bluuebunny/crossref_metadata_2025 huggingface dataset:
Alula-Inspired Leading Edge Device for Low Reynolds Number Flight
Authors: Mandadzhiev Boris A. , Lynch Michael K. , Chamorro Leonardo P. , Wissa Aimy A.
Published: November 2016

Robust and predictable aerodynamic performance of unmanned aerial vehicles at the limits of their design envelope is critical for safety and mission adaptability. In order for a fixed wing aircraft to maintain the lift necessary for sustained flight at very low speeds and large angles of attack (AoA), the wing shape has to change. This is often achieved by using deployable aerodynamic surfaces, such as flaps or slats, from the wing leading or trailing edges. In nature, one such device is a feathered structure on birds’ wings called the alula. The span of the alula is 5% to 20% of the wing and is attached to the first digit of the wing. The goal of the current study is to understand the aerodynamic effects of the alula on wing performance. A series of wind tunnel experiments are performed to quantify the effect of various alula deployment parameters on the aerodynamic performance of a cambered airfoil (S1223). A full wind tunnel span wing, with a single alula located at the wing mid-span is tested under uniform low-turbulence flow at three Reynolds numbers, Re = 85,000, 106,00 and 146,000. An experimental matrix is developed to find the range of effectiveness of an alula-type device. The alula relative angle of attack measured measured from the mean chord of the airfoil is varied to modulate tip-vortex strength, while the alula deflection is varied to modulate the distance of the tip vortex to the wing surface. Lift and drag forces were measured using a six axis force transducer. The lift and drag coefficients showed the greatest sensitivity to the the alula relative angle of attack, increasing the normalized lift coefficient by as much as 80%. Improvements in lift are strongly correlated to higher alula angle, with β = 0° – 5°, while reduction in the drag coefficient is observed with higher alula tip deflection ratios and lower β angles. Results show that, as the wing angle of attack and Reynolds number are increased, the overall lift co-efficient improvement is diminished while the reduction in drag coefficient is higher.
Locate Damage Based on Change in Structural Shape Calculated From Uniform Load Surface
Authors: Yan Guirong , Zu Jianxin , Zhao Yi , Xiao Yan
Published: November 2016

Reticulated shell structures have been widely built for public assembly venues, where many people get together during events. Therefore, it is important to conduct condition assessment for this type of structure to ensure the safety of the general public. Considering that the member configuration of this type of structure may follow a regular pattern and damage in a local region may destroy the regular pattern, a damage detection approach based on the change in structural shape is proposed in this study. The change in structural shape can be obtained from the displacement at each joint. Since it may be difficult to measure displacements on this type of structure, it is proposed to use the uniform load surface calculated from the constructed modal flexibility matrix to represent displacements at joints. Therefore, this approach requires the measurement of acceleration responses, instead of displacement measurement. For validating the feasibility of the proposed approach, numerical simulations are conducted on a single-layer dome structure with different levels of damage severity considered. The obtained results verify that the proposed approach is capable of locating damage to exact members.
Optimal Design of 3D Printed Spiral Torsion Springs
Authors: Scarcia Umberto , Berselli Giovanni , Melchiorri Claudio , Ghinelli Manuele , Palli Gianluca
Published: November 2016

Spiral Torsion Springs (STS) are generally manufactured employing medium/high-carbon steel alloys shaped as thin rods with rectangular cross section. Meanwhile, plastic materials (e.g. ABS or PLA), currently used in freeform manufacturing processes, may not be suited for several applications, owing to the low material yield strength and the rather poor fatigue life. Despite the above-mentioned limitations, the main advantages of a 3D printing process, as compared to more traditional manufacturing techniques, are the design flexibility and the possibility to directly integrate elastic components within a joint mechanism produced as a single (monolithic) part. In particular, provided that the external forces acting on the spring coils are maintained within a certain threshold and that the spring geometry is suitably optimized, a reliable 3D-printed STS alternative to traditional steel springs is actually feasible. Given these premises, the main purpose of the present paper is to propose a model-based optimization algorithm that allows to optimally size STS for user-specified torque-deflection characteristics. Optimal STS geometries are then realized in ABS via Fused Deposition Manufacturing, and subsequently tested with a purposely-designed experimental set-up. Furthermore, the behavior of each STS sample (in terms of stiffness and equivalent Von Mises stress) is evaluated by means of non-linear finite elements analysis, in order to check the correspondence with the expected behavior. Finally, numerical and experimental results are provided, which demonstrate the prediction capabilities of the proposed modeling/optimization techniques, and confirm that well-behaved STS can be conceived and produced. Envisaged applications concern the development of smart structures for robot design, such as multi-articulated compliant robotic chains that can be used as low-cost manipulators (i.e. arm) or as mini-manipulators (i.e. fingers). The proposed approach effectively simplifies the production and the assembly of the mechanism, also allowing for an easier integration of embedded sensory-actuation systems.
Nonlinear Dynamic Models of Piezoelectric Nano-Stages
Authors: Mahmoodi S. Nima , Omidi Ehsan , Rankl Christian
Published: November 2016

High resolution imaging in scanning probe microscopes is conducted by rastering a sharp probe over a sample surface. The rastering is done using piezoelectric elements, converting applied voltage into mechanical motion. For example, imaging of a rectangular field of view is done by applying triangular waveforms with different frequencies to X and Y piezoelectric stage, respectively. A disadvantage of piezoelectric stages is their non-linear response to applied voltage. In addition to that, they show creep, i.e. moving even though the applied voltage is constant. This results in distortions of the acquired image. Furthermore, it can result in not precisely imaging the requested area. A common solution is to add position sensors to the piezoelectric stages and measure actual movements. By using a feedback it would be almost guaranteed that the piezoelectric stage moves as requested. The disadvantage of this approach is that it reduces the bandwidth and increases the noise. The aim of this paper is to study advanced piezoelectric stage models to better control the actual stage movement in an open-loop scan.
2-Scale Hierarchical Multiscale Modeling of Piezoresistive and Damage Response in Polymer Nanocomposite Bonded Explosive
Authors: Talamadupula Krishna K. , Chaurasia Adarsh K. , Seidel Gary D.
Published: November 2016

This paper builds on previous work done [1, 2] to explore the effective piezoresistive response of polymer bonded explosive (PBX) materials where the polymer medium is reinforced with carbon nanotubes (CNTs). In the present work, the nanocomposite binder is modeled explicitly as a piezoresistive material whose properties are determined from the nanoscale through a micromechanics based 2-scale hierarchical model connecting the nanoscale to the microscale grain structure. Electromechanical cohesive zones are used to model the interface between the grains and nanocomposite binder in order to characterize interface separation and the resulting piezoresistive effect. The overall microscale piezoresistive effect is measured by using the volume averaged properties of the microscale RVE. The hierarchical framework developed here is used to explore key features of the NCBX microstructure such as the effect of grain conductivity, weight percentage of CNTs used and nanocomposite gage factor.
Coupled Electromechanical Peristatic Simulation of Deformation and Damage Sensing in Granular Materials
Authors: Prakash Naveen , Seidel Gary D.
Published: November 2016

Energetic materials or explosives are a class of granular composite materials consisting of explosive grains dispersed in a polymer matrix. An accidental low velocity impact during transportation may cause damage in the material, which may lead to weakening and possibly ignition of the material. Traditional SHM methods such external sensors or imaging techniques may not reveal changes in the internal microstructure of the material. It is proposed that dispersing carbon nanotubes in the polymer phase of the explosive material will introduce piezoresistivity by which the health of the material can be monitored in real time. In this work, a coupled electromechanical computational framework is developed to investigate nanocomposites and applied to model deformation and damage sensing in nanocomposite bonded explosive materials.
Modeling Nanocomposite Piezoresistive Response With Electromechanical Cohesive Zone Material Point Method
Authors: Chaurasia Adarsh K. , Seidel Gary D.
Published: November 2016

In the current work, the Material Point Method (MPM) is extended to allow for interfacial discontinuities in problems with composite materials using cohesive zone (CZ) techniques. The proposed CZMPM is observed to result in smaller errors in the primary and secondary field variables, especially near the interface, for a given boundary value problem in comparison to the traditional MPM solution. The proposed CZMPM is used to solve an electromechanical test problem with a single fiber in the matrix medium. It is observed that the proposed CZMPM results in smaller local and volume averaged errors. The CZMPM is further used to evaluate the effective piezoresistive response of the nanoscale carbon nanotube (CNT)-polymer composite with electron hopping in between the nanotubes. The observed effective piezoresistive response exhibits features similar to those reported in the literature using finite element techniques for small strains. However, CZMPM allows for large deformations of the nanoscale representative volume element as presented in the current work.
Robust Self-Sensing in NiTi Actuators Using a Dual Measurement Technique
Authors: Gurley Austin , Lambert Tyler Ross , Beale David , Broughton Royall
Published: November 2016

Using a Shape Memory Alloy (SMA) actuator as both an actuator and a sensor provides huge benefits in cost reduction and miniaturization of robotic devices. Despite much effort, reliable and robust self-sensing (using the actuator as a position sensor) has not been achieved for general temperature, loading, hysteresis path, and fatigue conditions. Prior research has sought to model the intricacies of the electrical resistivity changes within the NiTi material. However, for the models to be solvable, nearly every previous technique only models the actuator within very specific boundary conditions. Here, we measure both the voltage across the entire NiTi wire and of a fixed-length segment of it; these dual measurements allow direct calculation of the actuator length without a material model. We review previous self-sensing literature, illustrate the mechanism design that makes the new technique possible, and use the dual measurement technique to determine the length of a single straight wire actuator under controlled conditions. This robust measurement can be used for feedback control in unknown ambient and loading conditions.
A Distributed-Parameter Flexoelectric Energy Harvester Model Accounting for Two-Way Coupling and Size Effects
Authors: Moura Adriane , Erturk Alper
Published: November 2016

We present a distributed-parameter electromechanical model and its modal analysis for flexoelectric energy harvesting using centrosymmetric dielectrics by accounting for both the direct and converse effects as well as size dependence of the coupling coefficient. Flexoelectricity is the generation of electric polarization in elastic dielectrics by the application of a non-uniform mechanical strain field, i.e. a strain gradient. In order to accompany atomistic simulations and experimental efforts at small scales, there is a growing need for high-fidelity device models that can also provide an analytical insight into size-dependent electro-elastodynamics of small structures that exhibit and exploit flexoelectricity. Particularly, although the conversion of mechanical energy into electrical energy (i.e. energy harvesting) is more related to the direct effect, it is necessary to accurately model the converse effect for thermodynamic consistency and completeness. To this end, we present a flexoelectric monolayer centrosymmetric energy harvester model (that yields no piezoelectric effect) for converting ambient vibration into electricity. The flexoelectric energy harvester model based on the Euler-Bernoulli beam theory is focused on strain gradient-induced polarization resulting from the bending (transverse) vibration modes in response to mechanical base excitation. Following recent efforts on the converse flexoelectric effect in finite samples, the proposed model accounts for two-way coupling, i.e. the direct and converse effects, and it also captures the effect of geometric scaling on the coupling coefficient. In addition to closed-form solutions of the electromechanical frequency response functions, various case studies are presented for a broad range of material and geometric parameters. Thickness dependence of the electromechanical coupling is analytically shown and is observed in simulations of the electromechanical frequency response functions as well.
Analysis of FBG Sensors Data for Pipeline Monitoring
Authors: Paolozzi Antonio , Felli Ferdinando , Vendittozzi Cristian , Paris Claudio , Asanuma Hiroshi
Published: November 2016

Pipelines for oil distribution may affect the environment when natural disasters such as landslides and earthquakes damage the infrastructures. Besides natural causes, illegal extraction of oil from the pipelines can produce significant environmental damage and sometimes loss of lives from explosions. During the spill, the fuel flow of the main stream theoretically reduces, but this variation is within the normal flow fluctuation and so it is not possible to detect this illegal activity using fuel flow measurements. Transducers based on Fiber Bragg Grating (FBG) sensors are very attractive for pipeline monitoring. In two previous works we proposed a new transducer for increasing the sensitivity of FBG sensors to detect illegal activities on the pipelines (drilling). In fact FBG sensors attached directly on the surface of the pipe are not capable to detect strain variations induced by a drill. This paper reports an update on the experimental results obtained on a real size pipeline and a theoretical study aimed to explain why a surface attached sensor does not work.
Polydopamine Coating for Thermal Insulation of Shape Memory Alloy Wires
Authors: Sahlabadi Mohammad , Zhao Yao , Jezler Kyle , Gardell David , Lee Harold H. , Ren Fei , Hutapea Parsaoran
Published: November 2016

Shape memory alloy (SMA) materials, such as Nickel Titanium (NiTi), can generate stress and strain during phase transformation induced by thermomechanical stimulation. Therefore, they may be used to construct active actuating devices for various biomedical applications such as smart surgical tools. Since temperature rise during the operation of SMA devices may damage the surrounding tissue, it is important to thermally shield such devices. We propose to use polydopamine (PDA) as an insulating coating for NiTi-based smart needles. PDA is a biomolecule (dopamine) derived polymer that can form conformal coating on various materials including NiTi. It is hypothesized that the surface temperature of the PDA coated needle can be reduced by the low thermal conductivity of PDA and the thermal resistance of the PDA/NiTi interface. Our experiments conducted in ambient air at room temperature showed that the coating reduced the surface temperature by as much as 45%. In this paper, we will present the thermal insulating performance of the PDA coating on NiTi wires. An experimental setup where the wire is embedded inside a gel phantom/tissue has been developed to simulate needle-tissue interaction. Effects of the coating thickness (material thermal resistance) and the number of layers (interfacial thermal resistance) will be discussed. 2D finite element analyses (FEA) were performed using ABAQUS to investigate the thermal distribution around the coated NiTi wires and the tissue gel phantom. In addition, using thermal distribution, potential tissue damage was assessed.
Structural Intensity Analysis of Periodic Elastic Structures With Frequency Stop Bands
Authors: Nouh M.
Published: November 2016

Periodic elastic structures consisting of self-repeating geometric or material arrangements exhibit unique wave propagation characteristics culminating in frequency stop bands, i.e. ranges of frequency where elastic waves can propagate the periodic medium. Such features make periodic structures appealing for a wide range of vibration suppression and noise control applications. Stop bands in periodic media are achieved via Bragg scattering of elastic which is attributed to impedance mismatches between the different constituents of the self-repeating cells. Stop band frequencies can be numerically predicted using mathematical models which generally utilize the Bloch wave theorem and a transfer matrix method to track the spatial and temporal parameters of the propagating waves from one cell to the next. Such analysis generates what is referred to as the band structure (or the dispersion curves) of the periodic medium which can be used to predict the location of the pass and stop bands. Although capable, these models become significantly more involved when analyzing structures with dissipative constituents and/or material damping and need further adjustments to account for complex elastic moduli and frequency dependent loss factors. A new approach is presented which relies on evaluating structural intensity parameters, such as the active vibrational power and energy transmission paths. It is shown that the steady-state spatial propagation of vibrational power caused by an external disturbance accurately reflects the wave propagation pattern in the periodic medium, and can thus be reverse engineered to numerically predict the stop band frequencies for different degrees of damping via a stop band index (SBI). The developed framework is mathematically applied to a one-dimensional periodic rod to validate the proposed method.
Investigation of Dynamic Behaviors of Flexible Beam Actuators Based on Magnetic Polymers
Authors: Reece Adam , Koo Jeong-Hoi
Published: November 2016

This study investigates the dynamic properties of Magneto-Rheological Elastomers (MRE) with hard magnetic particles used as bending actuators under an alternating magnetic field. As earlier studies demonstrated that a dispersion of hard magnetic particles in polymeric materials, aligned in a preferred orientation, cause rotational motion in the sample when a magnetic field is applied perpendicularly to the magnetization direction of the particles. They focused on static responses of MREs with hard magnetic particles. The primary goal of this study is to characterize the dynamic behavior of a flexible bending actuator based on MREs under alternating magnetic fields. In this study, samples from a previous study, consisting of barium hexaferrite particles at 30% concentrations by volume, were tested. A C-shaped electromagnet was constructed to apply alternating magnetic fields along the length of the sample. By securing only one end of the sample to the electromagnet, the sample is free to bend similar to a cantilever beam. Using this setup, the tip displacement of the sample was recorded using a precision load cell and a laser displacement sensor under various input magnetic field strengths and frequencies. The results show that increasing the voltage output or the magnetic field strength increases the displacement of the sample. The results also show that, as the frequency of the sinusoidal voltage input increases, the amplitude of the tip displacement of the sample decrease.
Application of Low-Cost Sensors for Estimation of Reference-Free Displacements Under Dynamic Loading for Railroad Bridges Safety
Authors: Gomez Jose A. , Ozdagli Ali I. , Moreu Fernando
Published: November 2016

The concept of SHM is that a sensing system on the structure monitors the system responses and notifies the owner about the condition of the structure. The aim of this paper is to propose an inexpensive SHM method employing low-cost sensors to monitor the railroad bridges. Traditional monitoring systems can have limitations regarding the deployment of wired sensors due to their high cost. In this paper, the utilization of low-cost sensors for live load monitoring of railroad bridges is explored. In this study an Arduino microcontroller along with an inexpensive accelerometer manufactured by Analog Devices were used as test platform. In order to determine the ability of the low-cost accelerometer to assess the condition of a vibrating structure, the sensor system was attached to an actuator simulating bridge vibrations and different types of frequencies and amplitudes were tested. The values obtained with the Arduino microcontroller are very similar to the commercial accelerometer while being 60 times cheaper, which shows the potential of investing on low-cost instrumentation for inexpensive monitoring of railroad bridges. The findings of this research indicate that low-cost sensors can be effectively utilized for structural health monitoring of railroad bridges.
A Nonlinear, Monolithic Structural-Material System for Vibration Energy Harvesting and Storage
Authors: Sundaresan Vishnu Baba , Harne Ryan L. , Hery Travis , Dai Quanqi
Published: November 2016

This research introduces an integrated vibration energy harvester and electrochemical energy storage device that can effectively convert ambient vibrations directly into stored electrochemical energy. The electrochemical energy storage device is an electrical double layer capacitor (EDLC) with an ionic redox transistor as its membrane separator. This ‘smart’ membrane separator directly rectifies the electrical energy generated by the transduction from the nonlinear energy harvester, creating an ionic polarization across the membrane separator for storage. This electrochemical gradient can be subsequently used for powering sensor electronics as required in various applications, including structural condition monitoring. The alternating voltage developed by the energy harvester (+/−5V around 100 Hz) is connected to an aqueous supercapacitor fabricated from nanofibrous carbon paper electrodes and a polypyrrole-based (PPy(DBS)) smart membrane separator. A potential below −400mV from the energy harvester applied to the supercapacitor turns the smart membrane separator ‘ON’ and results in a unidirectional ionic current of Li+ ions. As the potential developed by the harvester cycles above ∼50 mV, the membrane separator switches ‘OFF’ and prevents the discharge of the rectified current. This leads to a continuous polarization of ions towards electrical fields relevant for powering electronics. This article is the first description and demonstration of an energy harvesting and storage system that can directly convert the electrical energy from a vibration energy harvester into electrochemical energy without the use of passive circuit components for power rectification.
Envisioning Kanak Independence: A Cosmopolitan Future?
Authors: Robertson Scott
Published: November 2016

This article considers how the notion of independence might be reconciled with a cosmopolitan view of the world through an examination of how the Kanak nationalist movement in New Caledonia has envisaged the place of the non-Kanak majority in a future independent nation-state. Drawing on literature that criticises the over-bearing weight of Western universalism in cosmopolitan discourse, I show how Kanak independence calls for a moral re-centring of the political community that undermines French claims of a monopoly on universalism. In doing so, I explore how the Kanak independence movement engaged with the critique that it was intrinsically racist and exclusive and it’s wrestling with the question of how to affirm their identity as a people rather than as an ethnic group. I argue that Kanak views of independence reaffirm the possibility of locally constructed cosmopolitanisms.
Vernacular Cosmopolitanisms in Suburban Peripheries: A Case Study in Multicultural Sydney
Authors: Williamson Rebecca
Published: November 2016

This article examines different forms of cosmopolitanism that shape everyday spaces in a multicultural suburb at the periphery of urban and political dynamics of Sydney. I investigate two forms of cosmopolitanism: top-down cosmopolitanism as part of place-making strategies enacted by local government and associated parties, and ordinary intercultural encounters enacted in public spaces. The latter kind of vernacular cosmopolitanism does not necessarily fit with prevailing ideas of marketable diversity in the cosmopolitan city. The paper analyses these dynamics using a case study of Campsie, a peripheral multi-ethnic neighbourhood between Sydney’s Inner West and South West regions. The examples of vernacular exchange portrayed here point to the important role that space – as a social, political and material assemblage – plays in mediating the everyday performance of ‘ground-up’ cosmopolitanism. The paper argues that the dense web of spatially mediated interactions – ordinary cosmopolitanism – reveals values of civility and sociality that has the potential to foster inclusive urban spaces in multicultural cities.
Action Stations: Biological Cosmopolitanism at Play on Online Support Groups for Genetic Disorders
Authors: Herbst Pauline
Published: November 2016

This paper examines how 19 parents of children diagnosed with the inherited metabolic disorder medium-chain acyl coa dehydrogenase deficiency (MCADD) express their lived experience of the disorder on a closed New Zealand/Australia Facebook group. It shows how the diagnosis creates new geneticised subjects of both the child and the parents who care for her and that this diagnosis ties these families to the nation-state. Their online identity, tied to the care of their asymptomatically, ‘dis’ordered child, exists simultaneously with that of other identities linked to the ‘well’ child. As cosmopolitan subjects they move in and out of the socio-cultural environment constructed by the place in which they live and the health system linked to it, to engage with and in doing so, create, an entirely new group based around a shared condition. I suggest biological cosmopolitanism as an overarching framework to discuss how these parents of children caught in limbo between pathology and health, engage in a voluntary and mutually hospitable set of relationships on online support groups, characterised by mobility, openness and liberty.
Undermining Cosmopolitanism - Cyber-racism Narratives in Australia
Authors: Connelly Karen
Published: November 2016

Cyber-racism is a relatively new and yet increasingly pervasive form of racism that adds another dimension to the spread of race hate. Multi-cultural countries such as Australia share a concern for the effective development of online strategies to combat this problem, including through building community resilience. Understanding how cyber-racism impacts cosmopolitanism, as a key characteristic of multiculturalism, will give insight into how it can be countered. Cosmopolitanism can be described as an ideological concept that focuses on embracing cultural difference. More pragmatically, cosmopolitanism is a contextualized worldview that encourages and sustains productive engagement with cultural difference in multi-cultural societies. Social media such as Facebook has the potential to facilitate such a culturally inclusive worldview, or to work against it. Using a narrative approach, this research investigates a Facebook page that has been reported to the Online Hate Prevention Institute (OHPI) as racist. The findings of this research show that the worldview perpetuated in the narrative on this page is one of cultural exclusion, undermining the prospect of cosmopolitanism in Australia.
Cosmopolitan Methods and Recruiting the Urban Stranger in Aotearoa New Zealand
Authors: George Molly
Published: November 2016

This article emerges from the fieldwork experiences and methodological issues that arose while conducting fieldwork with older New Zealanders in two urban settings of diversity and multiculturalism in Aotearoa New Zealand. Some of the encountered methodological complexities are discussed, including the inherent complications around categorization and ethnicity when approaching the urban setting as the ethnographic field, particularly in a New Zealand context. I argue that serendipitous, fleeting interactions between ethnographer and those encountered in urban fields do not afford individuals the respectful time and space necessary to discuss matters of identity, such as ethnicity. I suggest, then, that the urban anthropologist is a peripheral stranger among other urban strangers and must employ an ethical, cosmopolitan detachment by refraining from ready categorizations in the urban field. With this discussion of cosmopolitanism-as-method, I thus present Aotearoa New Zealand as sitting at the periphery of an “anthropological gaze” that still prioritizes ethnic groupings.
Simulation of atomic layer deposition on nanoparticle agglomerates
Authors: Jin Wenjie , Kleijn Chris R. , van Ommen J. Ruud
Published: November 2016

Coated nanoparticles have many potential applications; production of large quantities is feasible by atomic layer deposition (ALD) on nanoparticles in a fluidized bed reactor. However, due to the cohesive interparticle forces, nanoparticles form large agglomerates, which influences the coating process. In order to study this influence, the authors have developed a novel computational modeling approach which incorporates (1) fully resolved agglomerates; (2) a self-limiting ALD half cycle reaction; and (3) gas diffusion in the rarefied regime modeled by direct simulation Monte Carlo. In the computational model, a preconstructed fractal agglomerate of up to 2048 spherical particles is exposed to precursor molecules that are introduced from the boundaries of the computational domain and react with the particle surfaces until these are fully saturated. With the computational model, the overall coating time for the nanoparticle agglomerate has been studied as a function of pressure, fractal dimension, and agglomerate size. Starting from the Gordon model for ALD coating within a cylindrical hole or trench [Gordon et al., Chem. Vap. Deposition 9, 73 (2003)], the authors also developed an analytic model for ALD coating of nanoparticles in fractal agglomerates. The predicted coating times from this analytic model agree well with the results from the computational model for Df = 2.5. The analytic model predicts that realistic agglomerates of O(109) nanoparticles require coating times that are 3–4 orders of magnitude larger than for a single particle.
Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria
Authors: Brust Tarsis F. , Morgenweck Jenny , Kim Susy A. , Rose Jamie H. , Locke Jason L. , Schmid Cullen L. , Zhou Lei , Stahl Edward L. , Cameron Michael D. , Scarry Sarah M. , Aubé Jeffrey , Jones Sara R. , Martin Thomas J. , Bohn Laura M.
Published: November 2016

Biased agonists of the kappa opioid receptor may relieve intractable itch without causing unwanted side effects.
A taste for the light
Authors: Wong Wei
Published: November 2016

A photoreceptor with homology to taste receptors enables worms to avoid excessive UV exposure.
De Novo
Emergence of Genetically Resistant Mutants of Mycobacterium tuberculosis from the Persistence Phase Cells Formed against Antituberculosis Drugs
In Vitro
Authors: Sebastian Jees , Swaminath Sharmada , Nair Rashmi Ravindran , Jakkala Kishor , Pradhan Atul , Ajitkumar Parthasarathi
Published: November 2016

Bacterial persisters are a subpopulation of cells that can tolerate lethal concentrations of antibiotics. However, the possibility of the emergence of genetically resistant mutants from antibiotic persister cell populations, upon continued exposure to lethal concentrations of antibiotics, remained unexplored. In the present study, we found that
Mycobacterium tuberculosis
cells exposed continuously to lethal concentrations of rifampin (RIF) or moxifloxacin (MXF) for prolonged durations showed killing, RIF/MXF persistence, and regrowth phases. RIF-resistant or MXF-resistant mutants carrying clinically relevant mutations in the
rpoB
or
gyrA
gene, respectively, were found to emerge at high frequency from the RIF persistence phase population. A Luria-Delbruck fluctuation experiment using RIF-exposed
M. tuberculosis
cells showed that the
rpoB
mutants were not preexistent in the population but were formed
de novo
from the RIF persistence phase population. The RIF persistence phase
M. tuberculosis
cells carried elevated levels of hydroxyl radical that inflicted extensive genome-wide mutations, generating RIF-resistant mutants. Consistent with the elevated levels of hydroxyl radical-mediated genome-wide random mutagenesis, MXF-resistant
M. tuberculosis
gyrA de novo
mutants could be selected from the RIF persistence phase cells. Thus, unlike previous studies, which showed emergence of genetically resistant mutants upon exposure of bacteria for short durations to sublethal concentrations of antibiotics, our study demonstrates that continuous prolonged exposure of
M. tuberculosis
cells to lethal concentrations of an antibiotic generates antibiotic persistence phase cells that form a reservoir for the generation of genetically resistant mutants to the same antibiotic or another antibiotic. These findings may have clinical significance in the emergence of drug-resistant tubercle bacilli.
Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa
Authors: Penrose Kerri J. , Wallis Carole L. , Brumme Chanson J. , Hamanishi Kristen A. , Gordon Kelley C. , Viana Raquel V. , Harrigan P. Richard , Mellors John W. , Parikh Urvi M.
Published: November 2016

A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1LAIcontaining bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC50) from 12 recombinant subtype C HIV-1LAIplasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC50s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC50of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC < 3). Mutations L100I and K103N were significantly more frequent in samples with >500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring.
Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding
Authors: Foissac Frantz , Blume Jörn , Tréluyer Jean-Marc , Tylleskär Thorkild , Kankasa Chipepo , Meda Nicolas , Tumwine James K. , Singata-Madliki Mandisa , Harper Kim , Illamola Silvia M. , Bouazza Naïm , Nagot Nicolas , Van de Perre Philippe , Blanche Stéphane , Hirt Déborah
Published: November 2016

The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.)
The capsule polysaccharide synthesis locus of streptococcus pneumoniae serotype 14: Identification of the glycosyl transferase gene cps14E
Authors: Kolkman M A , Morrison D A , Van Der Zeijst B A , Nuijten P J
Published: November 2016

To identify a chromosomal region of Streptococcus pneumoniae serotype 14 involved in capsule polysaccharide synthesis, two strategies were used: (i) Tn916 mutagenesis, followed by the characterization of four unencapsulated mutants, and (ii) cross-hybridization with a capsule polysaccharide synthesis gene (cps) probe from S. agalactiae, which has a structurally similar capsule. The two approaches detected the same chromosomal region consisting of two adjacent EcoRI fragments. One of these EcoRI fragments was cloned and hybridized with a cosmid library. This resulted in clone cMKO2. A similar cosmid clone was obtained from an unencapsulated Tn916 mutant, Spnl4.H. Sequence analysis of the two cosmid clones revealed that in the Tn916 mutant, a gene, cps14E, which is homologous to other bacterial genes encoding glycosyl transferases, had been inactivated. An open reading frame immediately downstream of cps14E, designated cps14F, shows no significant homology with any known genes or proteins. A functional assay showed that cps14E encodes a glycosyl transferase and that a gene-specific knockout mutant lacks this enzyme activity, whereas inactivation of cps14F does not have this effect.
Mecillinam resistance in Escherichia coli is conferred by loss of a second activity of the AroK protein
Authors: Vinella D , Gagny B , Joseleau-Petit D , D'Ari R , Cashel M
Published: November 2016

Mecillinam, a beta-lactam antibiotic specific to penicillin-binding protein 2 (PBP 2) in Escherichia coli, blocks cell wall elongation and, indirectly, cell division, but its lethality can be overcome by increased levels of ppGpp, the nucleotide effector of the stringent response. We have subjected an E. coli K-12 strain to random insertional mutagenesis with a mini-Tn10 element. One insertion, which was found to confer resistance to mecillinam in relA+ and relA strains, was mapped at 75.5 min on the E. coli map and was located between the promoters and the coding sequence of the aroK gene, which codes for shikimate kinase 1, one of two E. coli shikimate kinases, both of which are involved in aromatic amino acid biosynthesis. The mecillinam resistance conferred by the insertion was abolished in a delta relA delta spoT strain completely lacking ppGpp, and it thus depends on the presence of ppGpp. Furthermore, the insertion increased the ppGpp pool approximately twofold in a relA+ strain. However, this increase was not observed in relA strains, although the insertion still conferred mecillinam resistance in these backgrounds, showing that mecillinam resistance is not due to an increased ppGpp pool. The resistance was also abolished in an ftsZ84(Ts) strain under semipermissive conditions, and the aroK::mini-Tn10 allele partially suppressed ftsZ84(Ts); however, it did not increase the concentration of the FtsZ cell division protein. The insertion greatly decreased or abolished the shikimate kinase activity of AroK in vivo and in vitro. The two shikimate kinases of E. coli are not equivalent; the loss of AroK confers mecillinam resistance, whereas the loss of Arol, does not. Furthermore, the ability of the aroK mutation to confer mecillinam resistance is shown to be independent of polar effects on operon expression and of effects on the availability of aromatic amino acids or shikimic acid. Instead, we conclude that the AroK protein has a second activity, possibly related to cell division regulation, which confers mecillinam sensitivity. We were able to separate the AroK activities mutationally with an aroK mutant allele lacking shikimate kinase activity but still able to confer mecillinam sensitivity.
Comparative genomic analysis of the Haloferax volcanii DS2 and Halobacterium salinarium GRB contig maps reveals extensive rearrangement
Authors: St Jean A , Charlebois R L
Published: November 2016

Anonymous probes from the genome of Halobacterium salinarium GRB and 12 gene probes were hybridized to the cosmid clones representing the chromosome and plasmids of Halobacterium salinarium GRB and Haloferax volcanii DS2. The order of and pairwise distances between 35 loci uniquely cross-hybridizing to both chromosomes were analyzed in a search for conservation. No conservation between the genomes could be detected at the 15-kbp resolution used in this study. We found distinct sets of low-copy-number repeated sequences in the chromosome and plasmids of Halobacterium salinarium GRB, indicating some degree of partitioning between these replicons. We propose alternative courses for the evolution of the haloarchaeal genome: (i) that the majority of genomic differences that exist between genera came about at the inception of this group or (ii) that the differences have accumulated over the lifetime of the lineage. The strengths and limitations of investigating these models through comparative genomic studies are discussed.
Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage
Authors: Slupska M M , Baikalov C , Luther W M , Chiang J H , Wei Y F , Miller J H
Published: November 2016

We have cloned the human mutY gene (hMYH) from both genomic and cDNA libraries. The human gene contains 15 introns and is 7.1 kb long. The 16 exons encode a protein of 535 amino acids that displays 41% identity to the Escherichia coli protein, which provides an important function in the repair of oxidative damage to DNA and helps to prevent mutations from oxidative lesions. The human mutY gene maps on the short arm of chromosome 1, between p32.1 and p34.3.
Nitrate reductase activity and heterocyst suppression on nitrate in Anabaena sp. strain PCC 7120 require moeA
Authors: Ramaswamy K S , Endley S , Golden J W
Published: November 2016

Mutants of Anabaena sp. strain PCC 7120 that form heterocysts when grown on nitrate-containing media were isolated following nitrosoguanidine mutagenesis. Six independent mutants were isolated, and the characterization of one mutant, strain AMC260, which forms 6 to 8% heterocysts in the presence of nitrate, is presented. A 1.8-kb chromosomal fragment that complemented the AMC260 mutant was sequenced, and a 1.2-kb open reading frame, named moeA, was identified. The deduced amino acid sequence of the predicted Anabaena sp. strain PCC 7120 MoeA polypeptide shows 37% identity to MoeA from Escherichia coli, which is required for the synthesis of molybdopterin cofactor. Molybdopterin is required by various molybdoenzymes, such as nitrate reductase. Interruption of the moeA gene in Anabaena sp. strain PCC 7120 resulted in a strain, AMC364, that showed a phenotype similar to that of AMC260. We show that AMC260 and AMC364 lack methyl viologen-supported nitrate reductase activity. We conclude that the inability of the moeA mutants to metabolize nitrate results in heterocyst formation on nitrate-containing media. Northern (RNA) analysis detected a 1.5-kb moeA transcript in wild-type cells grown in the presence or absence of a combined nitrogen source.
Identification of a major cis-acting DNA element controlling the bidirectionally transcribed penicillin biosynthesis genes acvA (pcbAB) and ipnA (pcbC) of Aspergillus nidulans
Authors: Bergh K T , Litzka O , Brakhage A A
Published: November 2016

The beta-lactam antibiotic penicillin is produced as a secondary metabolite by some filamentous fungi. In this study, the molecular regulation of the Aspergillus (Emericella) nidulans penicillin biosynthesis genes acvA (pcbAB) and ipnA (pcbC) was analyzed. acvA and ipnA are divergently oriented and separated by an intergenic region of 872 bp. Translational fusions of acvA and ipnA with the two Escherichia coli reporter genes lacZ and uidA enabled us to measure the regulation of both genes simultaneously. A moving-window analysis of the 872-bp intergenic region indicated that the divergently oriented promoters are, at least in part, overlapping and share common regulatory elements. Removal of nucleotides -353 to -432 upstream of the acvA gene led to a 10-fold increase of acvA-uidA expression and simultaneously to a reduction of ipnA-lacZ expression to about 30%. Band shift assays and methyl interference analysis using partially purified protein extracts revealed that a CCAAT-containing DNA element within this region was specifically bound by a protein (complex), which we designated PENR1, for penicillin regulator. Deletion of 4 bp within the identified protein binding site caused the same contrary effects on acvA and ipnA expression as observed for all of the deletion clones which lacked nucleotides -353 to -432. The PENR1 binding site thus represents a major cis-acting DNA element. The intergenic regions of the corresponding genes of the beta-lactam-producing fungi Penicillium chrysogenum and Acremonium chrysogenum also diluted the complex formed between the A. nidulans probe and PENR1 in vitro, suggesting that these beta-lactam biosynthesis genes are regulated by analogous DNA elements and proteins.