Instrumentation design study for testing a hypersonic ramjet engine on the x-15 a-2. volume 2- preliminary design of in-flight thrust/drag measuring device

Inflight thrust and drag measuring device for hypersonic ramjet engine on X-15A-2 aircraf

Female Adult \u3cem\u3eAedes albopictus\u3c/em\u3e Suppression by \u3cem\u3eWolbachia\u3c/em\u3e-Infected Male Mosquitoes

Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can competitively mate and sterilize females at a level adequate to suppress a field population. Also, the unintended establishment of Wolbachia at the introduction site could result from horizontal transmission or inadvertent female release. In 2014, an Experimental Use Permit from the United States Environmental Protection Agency approved a pilot field trial in Lexington, Kentucky, USA. Here, we present data showing localized reduction of both egg hatch and adult female numbers. The artificial Wolbachia type was not observed to establish in the field. The results are discussed in relation to the applied use of Wolbachia-infected males as a biopesticide to suppress field populations of Ae. albopictus

Population Impacts of \u3cem\u3eWolbachia\u3c/em\u3e on \u3cem\u3eAedes albopictus\u3c/em\u3e

Prior studies have demonstrated that Wolbachia, a commonly occurring bacterium capable of manipulating host reproduction, can affect life history traits in insect hosts, which in turn can have population-level effects. Effects on hosts at the individual level are predicted to impact population dynamics, but the latter has not been examined empirically. Here, we describe a biological model system based on Aedes albopictus (Asian tiger mosquito) that allows for measurement of population dynamics, which has not been accomplished in prior field trials or laboratory designs. The results demonstrate the studied populations to be robust and allow for persistent, closed populations with overlapping generations, which are regulated solely through density-dependent, intraspecific competition for limited resources. Using a novel experimental design, we compare populations that are either uninfected or infected with Wolbachia. The results show differences that include population size, eclosion rates, adult survivorship, and fecundity. The aposymbiotic populations were generally larger and adults longer lived relative to the infected populations. The outcome is discussed in context with naturally occurring Wolbachia invasions, proposed autocidal strategies, and the utility of the developed system as a biological platform for hypothesis testing and improved parameterization

Dynamic instabilities in resonant tunneling induced by a magnetic field

We show that the addition of a magnetic field parallel to the current induces self sustained intrinsic current oscillations in an asymmetric double barrier structure. The oscillations are attributed to the nonlinear dynamic coupling of the current to the charge trapped in the well, and the effect of the external field over the local density of states across the system. Our results show that the system bifurcates as the field is increased, and may transit to chaos at large enough fields.Comment: 4 pages, 3 figures, accepted in Phys. Rev. Letter

Coordination of peroxide to the CuM center of peptidylglycine α-hydroxylating monooxygenase (PHM): Structural and computational study

Many bioactive peptides, such as hormones and neuropeptides, require amidation at the C terminus for their full biological activity. Peptidylglycine a-hydroxylating monooxygenase (PHM) performs the first step of the amidation reaction-the hydroxylation of peptidylglycine substrates at the Ca position of the terminal glycine. The hydroxylation reaction is copper- and O2-dependent and requires 2 equiv of exogenous reductant. The proposed mechanism suggests thatO2 is reduced by two electrons, each provided by one of two nonequivalent copper sites in PHM (CuH and CuM). The characteristics of the reduced oxygen species in the PHM reaction and the identity of the reactive intermediate remain uncertain. To further investigate the nature of the key intermediates in the PHM cycle, we determined the structure of the oxidized form of PHM complexed with hydrogen peroxide. In this 1.98-A° -resolution structure (hydro)peroxide binds solely to CuM in a slightly asymmetric side-on mode. The O-O interatomic distance of the copperbound ligand is 1.5 A ° , characteristic of peroxide/hydroperoxide species, and the Cu-O distances are 2.0 and 2.1 A ° . Density functional theory calculations using the first coordination sphere of the CuM active site as a model system show that the computed energies of the side-on L3CuM(II)-O2 2- species and its isomeric, end-on structure L3CuM(I)-O2 - are similar, suggesting that both these intermediates are significantly populated within the protein environment. This observation has important mechanistic implications. The geometry of the observed side-on coordinated peroxide ligand in L3CuM(II)O2 2- is in good agreement with the results of a hybrid quantum mechanical-molecular mechanical optimization of this species.Fil: Rudzka, Katarzyna. University Johns Hopkins; Estados UnidosFil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad de Buenos Aires; ArgentinaFil: Eipper, Betty. University Of Connecticut; Estados UnidosFil: Mains, Richard. University Of Connecticut; Estados UnidosFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires; ArgentinaFil: Amzel, L. Mario. University Johns Hopkins; Estados Unido

\u3cem\u3eWolbachia\u3c/em\u3e infections that reduce immature insect survival: predicted impacts on population replacement

BACKGROUND: The evolutionary success of Wolbachia bacteria, infections of which are widespread in invertebrates, is largely attributed to an ability to manipulate host reproduction without imposing substantial fitness costs. Here, we describe a stage-structured model with deterministic immature lifestages and a stochastic adult female lifestage. Simulations were conducted to better understand Wolbachia invasions into uninfected host populations. The model includes conventional Wolbachia parameters (the level of cytoplasmic incompatibility, maternal inheritance, the relative fecundity of infected females, and the initial Wolbachia infection frequency) and a new parameter termed relative larval viability (RLV), which is the survival of infected larvae relative to uninfected larvae. RESULTS: The results predict the RLV parameter to be the most important determinant for Wolbachia invasion and establishment. Specifically, the fitness of infected immature hosts must be close to equal to that of uninfected hosts before population replacement can occur. Furthermore, minute decreases in RLV inhibit the invasion of Wolbachia despite high levels of cytoplasmic incompatibility, maternal inheritance, and low adult fitness costs. CONCLUSIONS: The model described here takes a novel approach to understanding the spread of Wolbachia through a population with explicit dynamics. By combining a stochastic female adult lifestage and deterministic immature/adult male lifestages, the model predicts that even those Wolbachia infections that cause minor decreases in immature survival are unlikely to invade and spread within the host population. The results are discussed in relation to recent theoretical and empirical studies of natural population replacement events and proposed applied research, which would use Wolbachia as a tool to manipulate insect populations

Paper Session II-B - Strategies for Conducting Life Science Experiments Beyond Low Earth Orbit

Human exploration beyond low Earth orbit will require terrestrial life to survive and ultimately flourish in environments fundamentally different to those in which it has evolved. The effects of deep space and conditions on the surface of other planets must be studied to understand and reduce the risks to explorers, provide bioregenerative life support, and make full use of the broad research opportunities and scientific benefits offered by such unique environments. Though much is already known about biological adaptations to the space environment, key changes in terrestrial life may only be revealed over complete life cycles and across multiple generations living beyond Earth. The demands and potential risks of exploring and inhabiting other worlds necessitate a detailed understanding of these changes at all levels of biological organization, from genetic alterations to impacts on critical elements of reproduction, development, and aging. Results from experiments conducted beyond low Earth orbit will contribute to the safety of space exploration and address fundamental questions of life\u27s potential beyond its planet of origin. Research campaigns will include a combination of core studies and innovative, Pl-driven investigations. Multiple flight platforms-including free flyers and planetary bases-may support a range of manned and unmanned mission opportunities

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

Phthalate esters used as plasticizers in packed red blood cell storage bags may lead to progressive toxin exposure and the release of pro-inflammatory cytokines

Phthalate esters (PE's) are plasticizers used to soften PVC-based medical devices. PE's are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy. The leaching of PE's in donated packed red blood cells (PRBC) during storage was assessed. PRBC transfusion bags containing CPD/AS-1 (ADSOL) buffer were analyzed. Samples were collected on storage day 1 and day 42. Two PE's, di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), were measured by liquid chromatography coupled to mass spectrometry (LCMS). Interleukin-8 (IL-8) was measured by standard ELISA techniques. DEHP significantly increased from 34.3 µM (±20.0 SD) on day 1 to 433.2 µM (±131.2 SD) on day 42, a 12.6-fold increase. Similarly, MEHP significantly increased from 3.7 µM (±2.8 SD) on day 1 to 74.0 µM (±19.1 SD) on day 42, a 20.2-fold increase. Also, DEHP and MEHP increased the release of IL-8 from human umbilical vein endothelial cells (HUVEC). The transfusion of older units of PRBC could lead to an accumulation of PE's possibly resulting in inflammation and other effects. This accumulation could be exacerbated due to the decreased metabolism of PE's since trauma patients have a lower esterase activity, the enzymes responsible for metabolizing PE's. The effect of oxidative stress caused by PE's is discussed as a potential mechanism for increases in inflammation caused by older units of PRBC

InGaAs/InP hot electron transistors grown by chemical beam epitaxy

In this letter, we report on the dc performance of chemical beam epitaxy grown InGaAs/InP hot electron transistors (HETs). The highest observed differential β (dIC/dIB) is over 100. The HETs have Pd/Ge/Ti/Al shallow ohmic base contacts with diffusion lengths less than 300 Å. Furthermore, we also demonstrated ballistic transport of electrons in an InGaAs/InP HET by obtaining an energy distribution of electrons with ∼60 meV full width at half maximum. The measured conduction band discontinuity of InGaAs/InP is 250.3 meV, which is 39.8% of the band gap difference.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70748/2/APPLAB-61-2-189-1.pd