Innovation in Commercial Supersonic Aircraft with Candidate Engine for Next Generation Supersonic Aircraft

The objective of this design study and competition - Next Generation Supersonic Candidate Engine and Aircraft Design, is a response to a proposal and is motivated by NASA’s National Research Announcement in 2006. The requirements of this design study are provided by AIAA (American Institute of Aeronautics and Astronautics). The aircraft designed is a private business class. The aircraft engine performs at a maximum speed of Mach 1.8 and supersonic cruise speed of Mach 1.6 at 55,000 feet and a range of 4000 nmi. A generated mission profile through considerations in flight regime will drive the design involved in the development of aircraft characteristics. Interior cabin configurations are expected to support seating for up to 100 passengers. Using parametric cycle analysis, computational fluid dynamics, and system modeling/experimentation, a refined aircraft and engine design will be produced. Detailed analyses to meet the baseline requirements involve interpretation of trends of current generation aircraft engines are considered for the finalized design. The performance of the aircraft engine will involve calculations on wave drag, supersonic turbulent flow, and integrated methods of design of the nacelle enveloped within the aircraft fuselage. Through these various iterative methods, considerations in supersonic aircraft propulsion and aircraft design are presented. Projected technical specifications are to be implemented for the next generation of supersonic aircraft expected to be debuted in 2025. A robust composition of advanced material composites, methods of manufacturing, and forecasted advancements in technology are utilized to develop a proposal for the next generation of supersonic aircraft

Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

A broad‐spectrum synthesis of Tetravinylethylenes

The first general synthesis of compounds of the tetravinylethylene (TVE) family is reported. Ramirez‐type dibromo‐olefination of readily accessible penta‐1,4‐dien‐3‐ones generates 3,3‐dibromo[3]dendralenes, which undergo twofold Negishi, Suzuki–Miyaura or Mizoroki–Heck reactions with a wide variety of olefinic coupling partners. This route delivers a broad range of unsymmetrically substituted tetravinylethylenes with up to three different alkenyl substituents attached to the central C=C bond. The extensive scope of the approach is demonstrated by the preparation of the first higher order oligo‐alkenic through‐conjugated/cross‐conjugated hybrid compounds. An unsymmetrically substituted TVE is shown to undergo a domino electrocyclization–cycloaddition with high site‐selectivity and diastereoselectivity, thereby demonstrating the substantial synthetic potential of substituted TVEs for controlled, rapid structural complexity generation.This work was supported by the Australian Research Counci

In silico identification, synthesis and biological evaluation of novel tetrazole inhibitors of MurB

In the context of antibacterial drug discovery resurgence, novel therapeutic targets and new compounds with alternative mechanisms of action are of paramount importance. We focused on UDP-N- acetylenolpyruvylglucosamine reductase (i.e. MurB), an underexploited target enzyme that is involved in early steps of bacterial peptidoglycan biosynthesis. On the basis of the recently reported crystal structure of MurB in complex with NADP+ , a pharmacopohore model was generated and used in a virtual screening campaign with combined structure-based and ligand-based approaches. In order to explore chemical space around hit compounds, further similarity search and organic synthesis was employed to obtain several compounds with micromolar IC50 values on MurB. The best inhibitors in the reported series of 5-substituted tetrazol-2-yl acetamides were compounds 13, 26 and 30 with IC50 values of 34, 28 and 25 µM, respectively. None of the reported compounds possessed in vitro antimicrobial activity against S. aureus and E. coli

Estimating Increased Transient Water Storage With Increases in Beaver Dam Activity

Dam building by beaver (Castor spp.) slows water movement through montane valleys, increasing transient water storage and the diversity of residence times. In some cases, water storage created by beaver dam construction is correlated to changes in streamflow magnitude and timing. However, the total amount of additional surface and groundwater storage that beaver dams may create (and, thus, their maximum potential impact on streamflow) has not been contextualized in the water balance of larger river basins. We estimate the potential transient water storage increases that could be created at 5, 25, 50, and 100% of maximum modeled beaver dam capacity in the Bear River basin, USA, by adapting the height above nearest drainage (HAND) algorithm to spatially estimate surface water storage. Surface water storage estimates were combined with the MODFLOW groundwater model to estimate potential increases in groundwater storage throughout the basin. We tested four scenarios to estimate potential transient water storage increases resulting from the construction of 1179 to 34,897 beaver dams, and estimated surface water storage to range from 57.5 to 72.8 m3 per dam and groundwater storage to range from 182.2 to 313.3 m3 per dam. Overall, we estimate that beaver dam construction could increase transient water storage by up to 10.38 million m3 in the Bear River basin. We further contextualize beaver dam-related water storage increases with streamflow, reservoir, and snowpack volumes

The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization

Bacterial peptidoglycan glycosyltransferases (PGT) catalyse the essential polymerization of lipid II into linear glycan chains required for peptidoglycan biosynthesis. The PGT domain is composed of a large head subdomain and a smaller jaw subdomain and can be potently inhibited by the antibiotic moenomycin A (MoeA). We present an X-ray structure of the MoeA-bound Staphylococcus aureus monofunctional PGT enzyme, revealing electron density for a second MoeA bound to the jaw subdomain as well as the PGT donor site. Isothermal titration calorimetry confirms two drug-binding sites with markedly different affinities and positive cooperativity. Hydrophobic cluster analysis suggests that the membrane-interacting surface of the jaw subdomain has structural and physicochemical properties similar to amphipathic cationic α-helical antimicrobial peptides for lipid II recognition and binding. Furthermore, molecular dynamics simulations of the drug-free and -bound forms of the enzyme demonstrate the importance of the jaw subdomain movement for lipid II selection and polymerization process and provide molecular-level insights into the mechanism of peptidoglycan biosynthesis by PGTs

Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis

Diaryltriazene derivatives were synthesized and evaluated for their antimicrobial properties. Initial experiments showed some of these compounds to have activity against both methicillin-resistant strains of Staphylococus aureus (MRSA) and Mycobacterium smegmatis, with MICs of 0.02 and 0.03 μg/mL respectively. Those compounds with potent anti-staphylococcal and anti-mycobacterial activity were not found to act as growth inhibitors of mammalian cell lines or yeast. Furthermore, we demonstrated that one of the most active anti-MRSA diaryltriazene derivatives was subject to very low frequencies of resistance at <10−9. Whole genome sequencing of resistant isolates identified mutations in the enzyme that lysylates phospholipids. This could result in the modification of phospholipid metabolism and consequently the characteristics of the staphylococcal cell membrane, ultimately modifying the sensitivity of these pathogens to triazene challenge. Our work has therefore extended the potential range of triazenes, which could yield novel antimicrobials with low levels of resistance

First Light And Reionisation Epoch Simulations (FLARES) VIII. The Emergence of Passive Galaxies at z⩾5z \geqslant 5

Passive galaxies are ubiquitous in the local universe, and various physical channels have been proposed that lead to this passivity. To date, robust passive galaxy candidates have been detected up to $z \leqslant 5$, but it is still unknown if they exist at higher redshifts, what their relative abundances are, and what causes them to stop forming stars. We present predictions from the First Light And Reionisation Epoch Simulations (FLARES), a series of zoom simulations of a range of overdensities using the EAGLE code. Passive galaxies occur naturally in the EAGLE model at high redshift, and are in good agreement with number density estimates from HST and early JWST results at $3 \leqslant z \leqslant 5$. Due to the unique FLARES approach, we extend these predictions to higher redshifts, finding passive galaxy populations up to $z \sim 8$. Feedback from supermassive black holes is the main driver of passivity, leading to reduced gas fractions and star forming gas reservoirs. We find that passive galaxies at $z \geqslant 5$ are not identified in the typical UVJ selection space due to their still relatively young stellar populations, and present new rest--frame selection regions. We also present NIRCam and MIRI fluxes, and find that significant numbers of passive galaxies at $z \geqslant 5$ should be detectable in upcoming wide surveys with JWST. Finally, we present JWST colour distributions, with new selection regions in the observer--frame for identifying these early passive populations.Comment: 21 pages, 20 figures. Accepted to MNRA

An In Vitro Pipeline for Screening and Selection of Citrus-Associated Microbiota with Potential Anti-"Candidatus Liberibacter asiaticus" Properties.

Huanglongbing (HLB) is a destructive citrus disease that is lethal to all commercial citrus plants, making it the most serious citrus disease and one of the most serious plant diseases. Because of the severity of HLB and the paucity of effective control measures, we structured this study to encompass the entirety of the citrus microbiome and the chemistries associated with that microbial community. We describe the spatial niche diversity of bacteria and fungi associated with citrus roots, stems, and leaves using traditional microbial culturing integrated with culture-independent methods. Using the culturable sector of the citrus microbiome, we created a microbial repository using a high-throughput bulk culturing and microbial identification pipeline. We integrated an in vitro agar diffusion inhibition bioassay into our culturing pipeline that queried the repository for antimicrobial activity against Liberibacter crescens, a culturable surrogate for the nonculturable "Candidatus Liberibacter asiaticus" bacterium associated with HLB. We identified microbes with robust inhibitory activity against L. crescens that include the fungi Cladosporium cladosporioides and Epicoccum nigrum and bacterial species of Pantoea, Bacillus, and Curtobacterium Purified bioactive natural products with anti-"Ca. Liberibacter asiaticus" activity were identified from the fungus C. cladosporioides Bioassay-guided fractionation of an organic extract of C. cladosporioides yielded the natural products cladosporols A, C, and D as the active agents against L. crescens This work serves as a foundation for unraveling the complex chemistries associated with the citrus microbiome to begin to understand the functional roles of members of the microbiome, with the long-term goal of developing anti-"Ca Liberibacter asiaticus" bioinoculants that thrive in the citrus holosystem.IMPORTANCE Globally, citrus is threatened by huanglongbing (HLB), and the lack of effective control measures is a major concern of farmers, markets, and consumers. There is compelling evidence that plant health is a function of the activities of the plant's associated microbiome. Using Liberibacter crescens, a culturable surrogate for the unculturable HLB-associated bacterium "Candidatus Liberibacter asiaticus," we tested the hypothesis that members of the citrus microbiome produce potential anti-"Ca Liberibacter asiaticus" natural products with potential anti-"Ca Liberibacter asiaticus" activity. A subset of isolates obtained from the microbiome inhibited L. crescens growth in an agar diffusion inhibition assay. Further fractionation experiments linked the inhibitory activity of the fungus Cladosporium cladosporioides to the fungus-produced natural products cladosporols A, C, and D, demonstrating dose-dependent antagonism to L. crescens