Computational analysis of high resolution unsteady airloads for rotor aeroacoustics

The study of helicopter aerodynamic loading for acoustics applications requires the application of efficient yet accurate simulations of the velocity field induced by the rotor's vortex wake. This report summarizes work to date on the development of such an analysis, which builds on the Constant Vorticity Contour (CVC) free wake model, previously implemented for the study of vibratory loading in the RotorCRAFT computer code. The present effort has focused on implementation of an airload reconstruction approach that computes high resolution airload solutions of rotor/rotor-wake interactions required for acoustics computations. Supplementary efforts on the development of improved vortex core modeling, unsteady aerodynamic effects, higher spatial resolution of rotor loading, and fast vortex wake implementations have substantially enhanced the capabilities of the resulting software, denoted RotorCRAFT/AA (AeroAcoustics). Results of validation calculations using recently acquired model rotor data show that by employing airload reconstruction it is possible to apply the CVC wake analysis with temporal and spatial resolution suitable for acoustics applications while reducing the computation time required by one to two orders of magnitude relative to that required by direct calculations. Promising correlation with this body of airload and noise data has been obtained for a variety of rotor configurations and operating conditions

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Antarctic Surface Reflectivity Measurements from the ANITA-3 and HiCal-1 Experiments

The primary science goal of the NASA-sponsored ANITA project is measurement of ultra-high energy neutrinos and cosmic rays, observed via radio-frequency signals resulting from a neutrino- or cosmic ray- interaction with terrestrial matter (atmospheric or ice molecules, e.g.). Accurate inference of the energies of these cosmic rays requires understanding the transmission/reflection of radio wave signals across the ice-air boundary. Satellite-based measurements of Antarctic surface reflectivity, using a co-located transmitter and receiver, have been performed more-or-less continuously for the last few decades. Satellite-based reflectivity surveys, at frequencies ranging from 2--45 GHz and at near-normal incidence, yield generally consistent reflectivity maps across Antarctica. Using the Sun as an RF source, and the ANITA-3 balloon borne radio-frequency antenna array as the RF receiver, we have also measured the surface reflectivity over the interval 200-1000 MHz, at elevation angles of 12-30 degrees, finding agreement with the Fresnel equations within systematic errors. To probe low incidence angles, inaccessible to the Antarctic Solar technique and not probed by previous satellite surveys, a novel experimental approach ("HiCal-1") was devised. Unlike previous measurements, HiCal-ANITA constitute a bi-static transmitter-receiver pair separated by hundreds of kilometers. Data taken with HiCal, between 200--600 MHz shows a significant departure from the Fresnel equations, constant with frequency over that band, with the deficit increasing with obliquity of incidence, which we attribute to the combined effects of possible surface roughness, surface grain effects, radar clutter and/or shadowing of the reflection zone due to Earth curvature effects.Comment: updated to match publication versio

The impact of direct‐acting antiviral agents on liver and kidney transplant costs and outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146297/1/ajt14895_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146297/2/ajt14895.pd

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Binding of lac repressor-GFP fusion protein to lac operator sites inserted in the tobacco chloroplast genome examined by chromatin immunoprecipitation

Chromatin immunoprecipitation (ChIP) has been used to detect binding of DNA-binding proteins to sites in nuclear and mitochondrial genomes. Here, we describe a method for detecting protein-binding sites on chloroplast DNA, using modifications to the nuclear ChIP procedures. The method was developed using the lac operator (lacO)/lac repressor (LacI) system from Escherichia coli. The lacO sequences were integrated into a single site between the rbcL and accD genes in tobacco plastid DNA and homoplasmic transplastomic plants were crossed with transgenic tobacco plants expressing a nuclear-encoded plastid-targeted GFP-LacI fusion protein. In the progeny, the GFP-LacI fusion protein could be visualized in living tissues using confocal microscopy, and was found to co-localize with plastid nucleoids. Isolated chloroplasts from the lacO/GFP-LacI plants were lysed, treated with micrococcal nuclease to digest the DNA to fragments of ∼600 bp and incubated with antibodies to GFP and protein A-Sepharose. PCR analysis on DNA extracted from the immunoprecipitate demonstrated IPTG (isopropylthiogalactoside)-sensitive binding of GFP-LacI to lacO. Binding of GFP-LacI to endogenous sites in plastid DNA showing sequence similarity to lacO was also detected, but required reversible cross-linking with formaldehyde. This may provide a general method for the detection of binding sites on plastid DNA for specific proteins