The phylogenetic systematics of Spilomelinae and Pyraustinae (Lepidoptera: Pyraloidea: Crambidae) inferred from DNA and morphology

Spilomelinae and Pyraustinae form a species-rich monophylum of Crambidae (snout moths). Morphological distinction of the two groups has been difficult in the past, and the morphologically heterogenous Spilomelinae has not been broadly accepted as a natural group due to the lack of convincing apomorphies. In order to investigate potential apomorphic characters for Spilomelinae and Pyraustinae and to examine alternative phylogenetic hypotheses, we conduct a phylogenetic analysis using 6 molecular markers and 114 morphological characters of the adults representing 77 genera of Spilomelinae and 18 genera of Pyraustinae. The results of the analysis of the combined data strongly suggest that Spilomelinae and Pyraustinae are each monophyletic and sister to each other. Wurthiinae is confirmed as ingroup of Spilomelinae, and Sufetula Walker, 1859 as a non-spilomeline. Within Spilomelinae, several well supported clades are obtained, for which we propose a first phylogeny-based tribal classification, using nine available and four new names: Hydririni Minet, 1982 stat.rev., Lineodini Amsel, 1956 stat.rev., Udeini trib.n., Wurthiini Roepke, 1916 stat.rev., Agroterini Acloque, 1897 stat.rev., Spilomelini Guenée, 1854 stat.rev. (= Siginae Hampson, 1918), Herpetogrammatini trib.n., Hymeniini Swinhoe, 1900 stat.rev., Asciodini trib.n., Trichaeini trib.n., Steniini Guenée, 1854 stat.rev., Nomophilini Kuznetzov & Stekolnikov, 1979 stat.rev. and Margaroniini Swinhoe & Cotes, 1889 stat.rev. (= Dichocrociinae Swinhoe, 1900; = Hapaliadae Swinhoe, 1890; = Margarodidae Guenée, 1854). The available name Syleptinae Swinhoe, 1900 could not be assigned to any of the recovered clades. Three tribes are recognized in Pyraustinae: Euclastini Popescu-Gorj & Constantinescu, 1977 stat.rev., Portentomorphini Amsel, 1956 stat.rev. and Pyraustini Meyrick, 1890 stat.rev. (= Botydes Blanchard, 1840; = Ennychites Duponchel, 1845). The taxonomic status of Tetridia Warren, 1890, found to be sister to all other investigated Pyraustinae, needs further investigation. The four Spilomelinae tribes that are sister to all other, ‘euspilomeline’ tribes share several plesiomorphies with Pyraustinae. We provide morphological synapomorphies and descriptions for Spilomelinae, Pyraustinae and the subgroups recognised therein. These characters allow the assignment of additional 125 genera to Spilomelinae tribes, and additional 56 genera to Pyraustinae tribes. New and revised combinations are proposed: Nonazochis Amsel, 1956 syn.n. of Conchylodes Guenée, 1854, with Conchylodes graphialis (Schaus, 1912) comb.n.; Conchylodes octonalis (Zeller, 1873) comb.n. (from Lygropia); Hyperectis Meyrick, 1904 syn.n. of Hydriris Meyrick, 1885, with Hydriris dioctias (Meyick, 1904) comb.n., and Hydriris apicalis (Hampson, 1912) comb.n.; Conogethes pandamalis (Walker, 1859) comb.n. (from Dichocrocis); Arthromastix pactolalis (Guenée, 1854) comb.n. (from Syllepte); Prophantis coenostolalis (Hampson, 1899) comb.n. (from Thliptoceras); Prophantis xanthomeralis (Hampson, 1918) comb.n. (from Thliptoceras); Prophantis longicornalis (Mabille, 1900) comb.n. (from Syngamia); Charitoprepes apicipicta (Inoue, 1963) comb.n. (from Heterocnephes); Prenesta rubrocinctalis (Guenée, 1854) comb.n. (from Glyphodes); Alytana calligrammalis (Mabille, 1879) comb.n. (from Analyta). Epherema Snellen, 1892 stat.rev. with its type species E. abyssalis Snellen, 1892 comb.rev. is removed from synonymy with Syllepte Hübner, 1823. Ametrea Munroe, 1964 and Charitoprepes Warren, 1896 are transferred from Pyraustinae to Spilomelinae; Prooedema Hampson, 1891 from Spilomelinae to Pyraustinae; Aporocosmus Butler, 1886 from Spilomelinae to Odontiinae; Orthoraphis Hampson, 1896 from Spilomelinae to Lathrotelinae; Hydropionea Hampson, 1917, Plantegumia Amsel, 1956 and Munroe’s (1995) “undescribed genus ex Boeotarcha Meyrick” are transferred from Spilomelinae to Glaphyriinae.publishedVersio

Methods for designing treatments to reduce interior noise of predominant sources and paths in a single engine light aircraft

The sources and paths by which noise enters the cabin of a small single engine aircraft were determined through a combination of flight and laboratory tests. The primary sources of noise were found to be airborne noise from the propeller and engine casing, airborne noise from the engine exhaust, structureborne noise from the engine/propeller combination and noise associated with air flow over the fuselage. For the propeller, the primary airborne paths were through the firewall, windshield and roof. For the engine, the most important airborne path was through the firewall. Exhaust noise was found to enter the cabin primarily through the panels in the vicinity of the exhaust outlet although exhaust noise entering the cabin through the firewall is a distinct possibility. A number of noise control techniques were tried, including firewall stiffening to reduce engine and propeller airborne noise, to stage isolators and engine mounting spider stiffening to reduce structure-borne noise, and wheel well covers to reduce air flow noise

Eulerian simulation of the fluid dynamics of helicopter brownout

A computational model is presented that can be used to simulate the development of the dust cloud that can be entrained into the air when a helicopter is operated close to the ground in desert or dusty conditions. The physics of this problem, and the associated pathological condition known as ‘brownout’ where the pilot loses situational awareness as a result of his vision being occluded by dust suspended in the flow around the helicopter, is acknowledged to be very complex. The approach advocated here involves an approximation to the full dynamics of the coupled particulate-air system. Away from the ground, the model assumes that the suspended particles remain in near equilibrium under the action of aerodynamic forces. Close to the ground, this model is replaced by an algebraic sublayer model for the saltation and entrainment process. The origin of the model in the statistical mechanics of a distribution of particles governed by aerodynamic forces allows the validity of the method to be evaluated in context by comparing the physical properties of the suspended particulates to the local properties of the flow field surrounding the helicopter. The model applies in the Eulerian frame of reference of most conventional Computational Fluid Dynamics codes and has been coupled with Brown’s Vorticity Transport Model. Verification of the predictions of the coupled model against experimental data for particulate entrainment and transport in the flow around a model rotor are encouraging. An application of the coupled model to analyzing the differences in the geometry and extent of the dust clouds that are produced by single main rotor and tandem-rotor configurations as they decelerate to land has shown that the location of the ground vortex and the size of any regions of recirculatory flow, should they exist, play a primary role in governing the extent of the dust cloud that is created by the helicopter

Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

High-Resolution Structures and Orientations of Antimicrobial Peptides Piscidin 1 and Piscidin 3 in Fluid Bilayers Reveal Tilting, Kinking, and Bilayer Immersion

While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of 1H–15N dipolar couplings and 15N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound α-helical peptides. The tilt of the helical axis, τ, is between 83° and 93° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, ρ, is 235°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their τ angles (<10°) and significant difference in their ρ angles (∼25°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt ρ angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger ρ angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 Å more deeply inserted than p1 in PE/PG. In contrast to the ideal α-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted α-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie ∼1.2–3.6 Å below the plane defined by the C2 atoms of the lipid acyl chains

Reducing the risk of criminal exploitation using multi-systemic therapy (the RESET Study) : study protocol for a feasibility study and process evaluation

Background Child criminal exploitation is a form of child abuse that poses a serious risk to the welfare, safety, and wellbeing of young people. Multisystemic therapy (MST) is an intensive family and community-based intervention for young people with anti-social behavioral problems, many of whom will be at risk of criminal exploitation. This protocol describes a pilot feasibility study and process evaluation, designed to examine MST for children at risk of criminal exploitation. Methods This pilot feasibility study and process evaluation involves two phases with associated subphases: phase 1.1 involved the collaborative refinement of the logic model adapting MST for children at risk of criminal exploitation; phase 1.2 involved pre-pilot interviews with MST therapists, families, and young people; phase 2.1 is a pilot modeling study of MST for children at risk of criminal exploitation, and; Phase 2.2 is a process evaluation that will involve interviewing stakeholders, MST therapists and employees, families, and young people. The dataset for the process evaluation will include questionnaires completed by parents and young people at baseline, mid-treatment, end of treatment, and 6 months after treatment. We will supplement these data with participant-level data linkage from MST sites and services. Results Accrual to the pilot stage of this project opened on 6th August 2021 and is due to close on 31st May 2022. We aim to publish the results of this feasibility study and process evaluation in 2023. Conclusions The results of this feasibility study and process evaluation will inform the decision as to whether it is advisable to progress to a pilot clinical trial of MST for children at risk of criminal exploitation

Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K

SummaryBRAF is an attractive target for melanoma drug development. However, resistance to BRAF inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF inhibitors developed by chronic treatment of BRAFV600E melanoma cells with the BRAF inhibitor SB-590885; these cells are cross-resistant to other BRAF-selective inhibitors. Resistance involves flexible switching among the three RAF isoforms, underscoring the ability of melanoma cells to adapt to pharmacological challenges. IGF-1R/PI3K signaling was enhanced in resistant melanomas, and combined treatment with IGF-1R/PI3K and MEK inhibitors induced death of BRAF inhibitor-resistant cells. Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF-1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors

Transparent Development of the WHO Rapid Advice Guidelines

Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness