bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Processing of Hybrid Shape Memory Alloy Composites
Authors: Lester Brian T. , Chemisky Yves , Lagoudas Dimitris C. , Geltmacher Andrew B. , Everett Richard K. , Qidwai Siddiq M.
Published: February 2012

The capability of using recoverable martensitic transformation to modify the residual stress-state of hybrid Shape Memory Alloy (SMA) composites is explored. It is shown that through careful selection of a thermomechanical loading path the composite can be “processed” such that the constituent phases have a beneficial residual stress-state. Specifically, for materials which have preferred loading conditions (i.e., compression versus tension) resulting in improved material properties, such processing places the considered phase into a preferred stress state. This processing is explored here by considering composites with an SMA phase whose constititutive behavior is described by a recent phenomenological model and an elasto-plastic second phase. To consider realistic microstructural effects, a 3D numerical representation of the composite is generated using microtomography. It is shown that through an actuation (isobaric) loading path, the martensitic transformation of the SMA phase generates irrecoverable strains in the elasto-plastic phase which, upon unloading, results in a favorable residual stress-state. To consider the applicability of this methodology for a variety of composites, the effect of thermal residual stresses due to thermal expansion mismatch is identified and matrix phases with different elastic moduli and plastic hardenings are considered. Specifically, it is shown that martensitic transformation is the driving force behind the generation of the new composite residual stress-state. Through computational simulation, it is shown that increased elastic moduli or plastic hardening coefficients of the elasto-plastic phase yield small increases in residual stresses.
Thermal Activation of Shape Memory Polymers Through Vascular Means
Authors: Phillips David M. , Baur Jeffery W.
Published: February 2012

Thermal activation of shape memory polymers requires a heating mechanism that will achieve a temperature range that exceeds a minimum triggering temperature but does not overheat the material. In laboratory practice, ovens are typically used to achieve a uniform temperature during testing. In practical applications, active heating schemes must be utilized that are robust enough to handle changing environmental conditions. In this work, we analyze the intricacies of vascular heating and cooling methodologies for shape memory polymers operating in an open environment. Our methodology is based on analytical modeling of the steady state surface temperature of shape memory polymers that incorporate vascular channels. With the material properties and environmental conditions, the model is used to predict appropriate channel geometry for triggering the shape memory polymer. Thermography is used to verify the model predictions for real systems of shape memory polymers.
Piezoresistive Reponse of Aligned Carbon Nanotube Arrays for Flow Sensing Applications
Authors: Maschmann Matthew R. , Ehlert Gregory J. , Baur Jeffery W.
Published: February 2012

We investigate the electromechanical sensing capabilities of aligned carbon nanotube (CNT) arrays as a means for a lightweight and simple electromechanical transduction element. CNT array heights of 25 and 350 μm are examined using a modified dynamic mechanical analyzer (DMA) to impart multiple strain-based test configurations while simultaneously measuring electrical resistance. Observed gauge factors range from 12.5 for the 25μm array to greater than 190 for the 350 μm array, with a peak sensitivity of 13,750 ohms/gram force achieved for the 350 μm array. The electromechanical response observed was independent of the examined frequency range, suggesting high fidelity sensory capabilities. Results of this study serve as a preliminary proof of concept for using CNT arrays as a transduction mechanism for a proposed artificial hair sensor for small air vehicles.
Operational Risk Assessment of Wind Turbine Structures Using Probabilistic Analysis of Aerodynamically Induced Vibrations
Authors: Velazquez Antonio , Swartz R. Andrew
Published: February 2012

The study of efficiency and safety for wind turbine structures under variable operating conditions is increasingly important for wind turbine design. Optimum aerodynamic performance of a wind turbine demands that serviceability effects and ultimate strength loads remain under safety design limits. From the perspective of wind turbine efficiency, variations in wind speed causes bluffing effects and vortex shedding that lead to vibration intensities in the longitudinal and transversal direction that can negatively impact aerodynamic performance of the turbine. From the perspective of wind turbine safety, variations in loading may lead to transient internal loads that threaten the safety of the structure. Inertial effects and asynchronous delays on rotational-force transmission may generate similar hazards. Monitoring and controlling displacement limits and load demands at critical tower locations can improve the efficiency of wind power generation, not to mention the structural performance of the turbine from both a strength and serviceability point of view. In this study, a probabilistic monitoring approach is developed to measure the response of the combined tower/nacelle/blade system to stochastic loading, estimate peak demand, and compare that demand to building code-derived estimates of structural resistance. Risk assessment is performed for the effects of along and across-wind forces in a framework of quantitative risk analysis with the goal of developing a near real-time estimate of structural risk that may be used to monitor safety and serviceability of the structure as well as regulate the aggressiveness of the controller that commands the blade angle of attack. To accomplish this goal, a numerical simulation of the aerodynamic performance of a wind turbine (including blades, the nacelle and the tower) is analyzed to study the interaction between the structural system and incoming flow. A model based on distributed-stationary random wind load profile for the combined along-wind and across-wind responses is implemented in Matlab to simulate full aero-elastic dynamic analysis to simulate tower with nacelle, hub, rotor and tower substructures. Self-weight, rotational, and axial effects of the blades, as well as lateral resistance of substructure elements are incorporated in the finite element model, including vortex-shedding effects on the wake zone. Reliability on the numerical solution is inspected on the tower structure by comparing the numerical solution with established experimental-analytical procedures.
Synergistic Wake Interactions in Aeroelastic Flutter Vibration Energy Harvester Arrays
Authors: Bryant Matthew , Mahtani Ranjeev L. , Garcia Ephrahim
Published: February 2012

This research experimentally investigates the operation of several aeroelastic flutter energy harvesters in an array. In order for such a wind energy harvesting array to operate effectively, it is important to understand the interaction between neighboring power harvesters including downstream wake effects, and how these interactions can be leveraged to maximize the output of the system. The fluttering motion of the energy harvester imparts an unsteady wake into the flow downstream of the device. Wind tunnel experiments with a pair of flutter energy harvesters show that this wake structure has significant effects on the oscillation amplitude, frequency, and power output of the trailing device. These wake interaction effects are shown to vary with the stream-wise and cross-stream separation distance between the two devices. At some separations, an advantageous frequency lock-in between the two devices occurs. When this occurs, the wake of the leading device adds constructively with the trailing device, causing larger oscillation amplitudes and higher power output in the trailing device. Experiments to characterize this variation in power output due to these wake interaction effects and to determine the optimal spacing of the energy harvesters are presented and discussed.
Generalized Eigensolution to Piecewise Continuous Distributed-Parameter Models of Piezoelectric Energy Harvesters Using the Transfer Matrix Method
Authors: Wickenheiser Adam M. , Reissman Timothy
Published: February 2012

Many multi-beam energy harvesters appearing in the literature require custom analytical or finite-element models to compute their eigensolutions and piezoelectric coupling effects. This paper discusses the use of the transfer matrix method to derive analytical solutions to beam structures with point-wise discontinuities or with lumped inertias between members or at the tip. In this method, transfer matrices are developed for the beam’s states (deflection, slope, shear force, and bending moment) analogously to the state transition matrix of a linear system. Euler-Bernoulli beam theory is used to derive transfer matrices for the uniform beam segments, and point transfer matrices are derived to handle discontinuities in the structure. The transfer matrix method is shown to be advantageous for analyzing complex structures because the size of the transfer matrix does not grow with increasing number of components in the structure. Furthermore, the same formulation can be used for a wide range of geometries, including arbitrary combinations of beam segments — single- or multi-layered — and lumped inertias. The eigensolution of the transfer matrix is shown to produce the natural frequencies and mode shapes for these structures. Subsequently, the electromechanical coupling effects are incorporated and the base excitation problem is considered. The electromechanical equations of motion are decoupled by mode and shown to be a generalization of existing analytical models. Parametric case studies are provided for beam structures with varying piezoelectric layer coverage.
The Development of a Closed-Loop Flight Controller for Localized Flow Control and Gust Alleviation Using Biomimetic Feathers on Aircraft Wings
Authors: Blower Christopher J. , Wickenheiser Adam M.
Published: February 2012

On avian wings, significant flow control is accomplished using localized control loops, both active and passive, between leading- and trailing-edge feathers. Conversely, most man-made flight control systems respond to perturbations in inertial measurements (global states) rather than the flow itself (local states). This paper presents the design of a distributed, biomimetic flow control system and a characterization of its performance compared to a wing with traditional control surfaces relying on inertial measurements. This new design consists of a skeletal wing structure with a network of feather-like panels installed on the upper and lower surfaces, extending beyond the trailing edge and replacing leading- and trailing-edge flaps/ailerons. Each feather is able to deform into and out of the boundary layer, thus permitting local airflow manipulation and transpiration through the wing. For this study, two airfoil sections are compared — a standard wing section with a trailing-edge flap, and section with multiple trailing-edge feathers. COMSOL Multiphysics is used to model the flow field under various flight conditions and flap deflections. A dynamics model of the wing is also simulated in order to compute the disturbances caused by wind gusts. Continuous gusts are simulated, and the disturbance rejection capabilities of the baseline and feathered wing cases are compared.
Amplitude Modulation of Nonlinear Piezoelectric Transducers for Ultrasonic Levitation
Authors: Mojrzisch Sebastian , Wallaschek Joerg
Published: February 2012

Ultrasonic levitation bearings are a new kind of bearing system that offers the advantages of air-bearings combined with dynamically adjustable supporting force without the need for pressurized air. Such systems are typically driven close or in their resonance frequency, due to energetic reasons. In this contribution the two possible driving methods, namely forced- and self-excitation, are compared in sense of their transient amplitude behavior in the presence of nonlinearities. It is known that during amplitude changes at high vibration amplitudes the system’s resonance frequency varies with Duffing-characteristic due to the nonlinear stiffness of piezoelectric material. It will be shown that self-excitation is the preferable driving method in sense of obtaining a high bandwidth of amplitude.
Multifunctional Liquid Crystal Polymeric Composites Embedded With Graphene Nano Platelets
Authors: Khan Muhammad Omer , Chan Ellen , Leung Siu N. , Naguib Hani , Dawson Francis , Adinkrah Vincent
Published: February 2012

This paper studies the development of new multifunctional liquid crystal polymeric composites filled with graphene nano platelets (GNPs) for electronic packaging applications. A series of parametric studies were conducted to study the effect of GNP content on the thermal conductivity of LCP-based nanocomposites. Graphene, ranging from 10 wt. % to 50 wt. %, were melt-compounded with LCP using a twin-screw compounder. The extrudates were ground and compression molded into small disc-shaped specimens. The thermal conductivity of LCP matrix was observed to have increased by more than 1000% where as the electrical conductivity increased by 13 orders of magnitude with the presence of 50 wt% GNP fillers. The morphology of the composites was analyzed using SEM micrographs to observe the dispersion of filler within the matrix. These thermally conductive composites represent potential cost-effective materials to injection mold three-dimensional, net-shape microelectronic enclosures with superior heat dissipation performance.
Polymer Skins With Switchable Roughness
Authors: Morris Nicholas J. , Gutierrez Joaquin M. , Barbero Ever J. , Cairns Darran R.
Published: February 2012

Polyvinyl alcohol (PVA) films with embedded electrically-responsive liquid crystal (LC) ellipsoids were fabricated to develop a membrane coating featuring tunable roughness. Membranes (∼30 microns thick) were placed between opposing pieces of indium-tin oxide (ITO) glass, creating electrodes for creation of a uniform electric field. Applied voltages ranged from 0V–350 V, as films were observed using an optical microscope. Thin-film interference patterns were observed in various regions of each film and were measured. Contour plots of film displacement were created and showed elevations across the observed region. The area of the first dark fringe regions, assumed to be in contact with the top glass surface, were measured as a function of applied voltage. The maximum displacement of the film was estimated to reach 1.5 microns and the area in contacted with the top glass surface increased 127% between 0–350 V. Finite element modelling results illustrate the influence of polarity on the roughness of the film surface.
Passive Multi-Source Energy Harvesting Schemes: Multiplicity of Piezoelectrics
Authors: Schlichting Alexander , Tiwari Rashi , Garcia Ephrahim
Published: February 2012

Energy harvesting technologies present a solution to decreasing battery size and to the in-situ recharging of batteries in mobile devices or wireless sensor nodes. Combining multiple energy harvesters to power one system can increase the viability of potential designs as solutions for many applications. This work uses LTspice circuit simulations to examine passive circuit topologies for a multiplicity of piezoelectrics as a multisource energy harvesting solution. The simulation results show increases in the maximum instantaneous power seen on the storage capacitor for both a series and parallel circuit topology. There is also an increase in the available voltage level for the series topology. However, these increases in output power and voltage are sensitive to differences in the harvester outputs. Therefore, passive multi-source topologies present a viable solution for combining the energy from a multiplicity of piezoelectric harvesters.
Bio-Inspired Flow Sensors Fabricated From Carbon Nanomaterials
Authors: Pinto Preston A. , Sarles Stephen A. , Leo Donald J. , Philen Michael , Champion Hunter A. , Black Sarah B. , Dorn Harry C.
Published: February 2012

Carbon-based flow sensors can be made by embedding carbon nanotubes (CNT) into a polymeric substrate. Specifically, when a conductive aqueous solution flows over the surface of the exposed CNT, a flow-dependent voltage is generated. The carbonaceous flow sensors fabricated in our work were all tested in salt water (5% NaCl). In order to measure the surface coverage of the CNT coated sensors, the electrical resistance across the surface of each sample was measured. Electrical Impedance Spectroscopy (EIS) measurements were also carried out in order to understand the electrical relationship between the sensor and the salt water. In order to study the surface topology and morphology of the flow sensors, scanning electron microscopy (SEM) was used. Voltage measurements of sensors with different levels of resistance were tested in varying fluid velocities. The least resistive sensor showed small, but detectable changes in voltages, while higher resistance sensors showed less response. On the other hand, the average current did not change with varying flow conditions for any of the sensors.
Characterization of Mechanical Properties in Multifunctional Structural-Energy Storage Nanocomposites for Lightweight Micro Autonomous Systems
Authors: Cole Daniel P. , Rivera Monica , Bundy Mark
Published: February 2012

A major concern in the design of micro-robotic systems is an on-board energy supply capable of providing the necessary power requirements, while limiting the volume/mass burden to the vehicle. The conventional solution to this design problem is to maximize the energy density of the on-board power supply. An alternative approach is to replace single-function structural components with multifunctional structural-energy storage materials. The mass and volume savings associated with the material substitution could potentially result in improved endurance and/or increased payload (e.g. video camera, microphone, chemical/biological sensors). In this study, carbon nanotube (CNT) based composites were used to fabricate structural-energy storage materials. Specifically, supercapacitor electrodes were constructed from paper covered with CNT ink and from polymer matrices infused with aligned CNT forests. The composites were subject to bulk mechanical tests in order to characterize their suitability as structural components in micro-autonomous systems. Tensile tests on the paper composites show directional and strain rate dependencies. The CNT-ink deposition process was found to degrade the elastic modulus of the paper by approximately 50%, although the tensile strength of the materials was largely unaffected. Preliminary electrical characterization of the CNT-coated electrode materials indicate that the nanomaterials potentially reach a percolation threshold after multiple depositions, resulting in a conductive surface network. Initial results indicate that improvements in the electrical properties of the CNT paper electrodes are met with reductions in the mechanical performance of the composites.
Testing of Novel Compliant Spines for Passive Wing Morphing
Authors: Wissa Aimy , Tummala Yashwanth , Hubbard James E. , Frecker Mary , Brown Alexander
Published: February 2012

Flapping wing Unmanned Aerial Vehicles (UAVs) or ornithopters are proliferating in both the civil and military markets. Ornithopters have the potential to combine the agility and maneuverability of rotary wing aircraft with excellent performance in low Reynolds number flight regimes. These traits promise optimized performance over multiple mission scenarios. Nature achieves this broad performance in birds using wing gaits that are optimized for a particular flight regime. The goal of this work is to improve the performance of ornithopters during steady level flight by passively implementing the Continuous Vortex Gait (CVG) found in natural avian flyers. In this paper we present new experimental results for a one degree of freedom (1DOF) compliant spine which was inserted into an experimental test ornithopter leading edge wing spar in order to achieve the desired kinematics. The lift and thrust along with electric power metrics at different flapping frequencies were measured using a six-channel load cell and a current senor, respectively. These metrics were determined for the test ornithopter both with and without the compliant spine insert. Initial results validate the ability of our compliant spine design to withstand the loads seen during flight at flapping frequencies of up to and including 5 Hz. For the ornithopter test platform used in the study, inserting the compliant spines into the wing leading edge spar accurately simulates the CVG increasing the mean lift by 16%, and reducing the power consumed by 45% without incurring any thrust penalties.
Design Optimization of a Compliant Spine for Dynamic Applications
Authors: Tummala Yashwanth , Wissa Aimy , Frecker Mary , Hubbard James E.
Published: February 2012

Ornithopters or flapping wing Unmanned Aerial Vehicles (UAVs) have potential applications in civil and military sectors. Amongst the UAVs, ornithopters have a unique ability to fly in low Reynolds number regions and also have the agility and maneuverability of a rotary wing aircraft. In nature, birds achieve such special characteristics by morphing their wings. The compliant spine (CS) design concept presented here represents a novel method of achieving wing morphing passively. In this paper, an optimal design method is developed that incorporates dynamic finite element analysis. To solve the CS design problem a new multi-objective optimization problem is formulated with three objective functions. The first objective function seeks to minimize the mass of the compliant spine. The second objective function seeks to maximize the deflection of the compliant spine for a particular dynamic loading condition. Finally, the third objective function seeks to minimize the stress in the design observed under the dynamic loading conditions experienced during flight. The deflections and stresses in the CS design are based on measured wing loads and are calculated by applying a sinusoidal forcing function at a prescribed forcing frequency. The optimization, performed via a controlled elitist genetic algorithm which is a variant of NSGA-II, is used to design CSs operating under dynamic conditions. Modal analysis and frequency response of an optimal compliant spine during the upstroke are also shown.
Modeling and Design of Building-Integrated Thermoelectrics
Authors: Headings Leon M. , Washington Gregory N.
Published: February 2012

The goal of this research is to develop a framework for replacing conventional heating and cooling systems with distributed, continuously and electrically controlled, building-integrated thermoelectric (BITE) heat pumps. The coefficient of performance of thermoelectric heat pumps increases as the temperature difference across them decreases and as the amplitude of temperature oscillations decreases. As a result, this research examines how thermal insulation and mass elements can be integrated with thermoelectrics as part of active multi-layer structures in order to minimize net energy consumption. In order to develop BITE systems, an explicit finite volume model was developed to model the dynamic thermal response of active multi-layer wall structures subjected to arbitrary boundary conditions (interior and exterior temperatures and interior heat loads) and control algorithms. Using this numerical model, the effects of wall construction on net system performance were examined. These simulation results provide direction for the ongoing development of BITE systems.
Active Detection of Structural Damage in Aluminum Alloy Using Magneto-Elastic Active Sensors (MEAS)
Authors: Conrad David , Zagrai Andrei
Published: February 2012

Many structural damage detection methods utilize piezoelectric sensors. While these sensors are efficient in supporting many structural health monitoring (SHM) methodologies, there are a few key disadvantages limiting their use. The disadvantages include the brittle nature of piezoceramics and their dependence of diagnostic results on the quality of the adhesive used in bonding the sensors. One viable alternative is the utilization of Magneto-Elastic Active Sensors (MEAS). Instead of mechanically creating elastic waves, MEAS induce eddy currents in the host structure which, along with an applied magnetic field, generate mechanical waves via the Lorentz force interaction. Since elastic waves are generated electromagnetically, MEAS do not require direct bonding to the host structure and its elements are not as fragile as PWAS. This work explores the capability of MEAS to detect damage in aluminum alloy. In particular, methodologies of detecting fatigue cracks in thin plates were explored. Specimens consisted of two identical aluminum plates featuring a machined slot to create a stress riser for crack formation. One specimen was subjected to cyclic fatigue load. MEAS were used to transmit elastic waves of different characteristics in order to explore several SHM methodologies. Experiments have shown that the introduction of fatigue cracks created measurable amplitude changes in the waves passing through the fatigued region of the aluminum plate. The phase indicated sensitivity to load conditions, but manifestation in the cracked region lacked stability. Nonlinear effects were studied using plate thickness resonance, which revealed birefringence due to local stresses at the site of the fatigue crack. The resonance spectrum has also shown a frequency decrease apparently due to stiffness loss. Preliminary results suggest opportunities for fatigue damage detection using MEAS. Application of MEAS for the diagnosis of complex structures is currently being investigated.
Structural Health Monitoring Technology for Aerospace Composite Propellant Tank
Authors: Banerjee Sourav , Messidoro Piero , Ferrarese Adriano , Beard Shawn , Banerjee Ritubarna
Published: February 2012

In this paper the experimental activities that were performed at Thales Alenia Space (TAS-I) System, Turin, Italy by Acellent Technologies Inc is presented. The final objective was defining a Vehicle / Vehicle Subsystem, built-in Health Management System which embeds self diagnosis and prognosis functions. Under this program a Composite Overwrapped Pressure Vessel (COPV) for space applications was monitored under pressure cycling (mechanical loading). The subscale demonstrator consisted of an aluminium metallic liner over wrapped by a CFRP layer. The metallic liner is seamless and manufactured by spin-forming. The liner material is aluminum AA6061 T6, with Yield Strength of 286 MPa, as declared by the bottle supplier (US Hydrospin); expected elongation to rupture is around 10%. The test was conducted for 3 days on a water filled COPV and at the end of three days the metal liner inside the propellant tank was cracked and caused water leakage. Acellent used a statistical data interpretation technique via feature extraction and data modeling approach to demonstrate that the system was able to generate the early alarm and also capable of localizing the damage which appeared at two hot spot locations.
Four-State Straintronics: Extremely Low Power Nanomagnetic Logic Using Multiferroics With Biaxial Anisotropy
Authors: D’Souza Noel M. , Atulasimha Jayasimha , Bandyopadhyay Supriyo
Published: February 2012

The authors had previously theoretically demonstrated that multiferroic nanomagnetic logic can be clocked in ∼1 GHz with few 100 kT/bit power dissipation which is ∼3 orders of magnitude more energy efficient than current CMOS transistor technology that dissipates several 100,000 kT/bit.. In this work, we propose the more novel concept of 4-state logic by numerically demonstrating the feasibity of an ultra low-power 4-state NOR logic gate using multiferroic nanomagnets with biaxial magnetocrystalline anisotropy. Here, the logic bits are encoded in the magnetization orientation of a nanoscale magnetostrictive layer elastically coupled to a piezoelectric layer. The piezoelectric layer can be clocked with a small electrostatic potential (∼0.2 V) to switch the magnetization of the magnetic layer. We also address logic propagation, where the accurate and unidirectional transfer of data from an input nanomagnet along an array of nanomagnets is needed. This is accomplished by devising an effective clocking scheme to the nanomagnet array, which allows for the realization of feasible logic circuits. Ultimately, this technology would enable higher order information processing, such as pattern recognition, to be performed in parallel at very high speeds while consuming extremely low power. Potential applications include high-density logic circuits, associative memory and neuromorphic computing.
Response to Comments on “Phonemic Diversity Supports a Serial Founder Effect Model of Language Expansion from Africa”
Authors: Atkinson Quentin D.
Published: February 2012

Concerns have been raised about my proposal that global phonemic diversity was shaped by a serial founder effect during the human expansion from Africa. I welcome this discussion of new data and alternative interpretations. Although this work highlights interesting questions for future research, it does not undermine support for a serial founder effect model of expansion of language from Africa.
Paradoxical Roots of “Social Construction”
Michael Polanyi and His Generation
Origins of the Social Construction of Science

by Mary Jo Nye

University of Chicago Press, Chicago, 2011. 427 pp. $45, £29. ISBN 9780226610634.
Authors: Kaiser David
Published: February 2012

Nye locates the roots of the "social turn" (highlighting the importance of social communities, behavioral norms, and personal commitments) in the scientific culture and political events of 1930s Europe.
It's All in the Symmetry
Authors: Abramson Jeff , Paz Aviv , Philipson Kenneth D.
Published: February 2012

The structure of a sodium-calcium exchange protein provides insight into the mechanism of Ca
2+
transport through the cell membrane.
The Endangered Bond
Authors: Schatz Gottfried
Published: February 2012

Creative ideas are children of solitude, yet are rarely conceived in isolation. This is particularly true in science, which thrives on reliable and precise communication across linguistic, social, and cultural barriers. The digital age has given us instant global communication, yet scientists still prefer to talk about shared values and scientific issues face to face. As a unifying bond for our scientific culture, nothing rivals the spoken word.
New Cystic Fibrosis Drug Offers Hope, at a Price
Authors: Kaiser Jocelyn
Published: February 2012

The new cystic fibrosis drug Kalydeco illustrates both the promise and peril of personalized medicine: It is extremely expensive and helps only 4% of people with the disease, or 1200 patients.
More Than One Way for Invaders to Wreak Havoc
Authors: Kerr Richard A.
Published: February 2012

A new paper published in the January issue of
GSA Today
holds invasions responsible for the failure to speciate in some marine animal groups in the Devonian period 380 million years ago.
Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population
Authors: Raache Rachida , Belanteur Khadidja , Amroun Habiba , Benyahia Amel , Heniche Amel , Azzouz Malha , Mimouni Safia , Gervais Thibaud , Latinne Dominique , Boudiba Aissa , Attal Nabila , Abbadi Mohamed Cherif
Published: February 2012

Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA-129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA.
Rapid Detection of Ampicillin Resistance in Escherichia coli by Quantitative Mass Spectrometry
Authors: Grundt A. , Findeisen P. , Miethke T. , Jäger E. , Ahmad-Nejad P. , Neumaier M.
Published: February 2012

Early targeted antimicrobial therapy helps decrease costs and prevents the spread of antimicrobial resistance, including in
Escherichia coli
, the most frequent Gram-negative bacterium that causes sepsis. Therefore, rapid susceptibility testing represents the major prerequisite for knowledge-based successful antimicrobial treatment. To accelerate testing for antibiotic susceptibility, we have developed a new mass spectrometry-based assay for antibiotic susceptibility testing (MAAST). For proof of principle, we present an ampicillin susceptibility test for
E. coli
with a turnaround time of 90 min upon growth detection.
Emergence of a
mutL
Mutation Causing Multilocus Sequence Typing–Pulsed-Field Gel Electrophoresis Discrepancy among Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient
Authors: García-Castillo María , Máiz Luis , Morosini María-Isabel , Rodríguez-Baños Mercedes , Suarez Lucrecia , Fernández-Olmos Ana , Baquero Fernando , Cantón Rafael , del Campo Rosa
Published: February 2012

A multilocus sequence type (MLST) shift (from ST242 to ST996) was detected in
Pseudomonas aeruginosa
isolates with a uniform pulsed-field gel electrophoresis (PFGE) pattern obtained from a chronically colonized patient. MLST mutational change involved the
mutL
gene with the consequent emergence of a hypermutable phenotype. This observation challenges the required neutrality of
mutL
as an appropriate marker in MLST and alerts researchers to the limitations of MLST-only-based population studies in chronic infections under constant antibiotic selective pressure.
Superior Induction of T Cell Responses to Conserved HIV-1 Regions by Electroporated Alphavirus Replicon DNA Compared to That with Conventional Plasmid DNA Vaccine
Authors: Knudsen Maria L. , Mbewe-Mvula Alice , Rosario Maximillian , Johansson Daniel X. , Kakoulidou Maria , Bridgeman Anne , Reyes-Sandoval Arturo , Nicosia Alfredo , Ljungberg Karl , Hanke Tomáš , Liljeström Peter
Published: February 2012

Vaccination using “naked” DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also,
in vivo
electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that
in vivo
electroporation increases CD8
+
T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8
+
T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.
The Latent Membrane Protein 1 (LMP1) Oncogene of Epstein-Barr Virus Can Simultaneously Induce and Inhibit Apoptosis in B Cells
Authors: Pratt Zachary L. , Zhang Jingzhu , Sugden Bill
Published: February 2012

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) regulates its own expression and the expression of human genes via its two functional moieties; the transmembrane domains of LMP1 are required to regulate its expression via the unfolded protein response (UPR) and autophagy in B cells, and the carboxy-terminal domain of LMP1 activates cellular signaling pathways that affect cellular proliferation and survival. An apparent anomaly in the complex regulation of the UPR and autophagy by LMP1 is that the induction of either pathway can lead to cellular death, yet neither EBV-infected B cells nor B cells expressing only LMP1 die. Thus, we sought to understand how B cells that express LMP1 survive. The transmembrane domains of LMP1 activated apoptosis in B cells, the apoptosis required the UPR, and the carboxy-terminal domain of LMP1 blocked this apoptosis. The expression of the mRNA ofBcl2a1, encoding an antiapoptotic homolog of BCL2, correlated directly with the expression of LMP1 in EBV-positive B-cell strains, and its expression inhibited the apoptosis induced by the transmembrane domains of LMP1. These findings illustrate how the carboxy-terminal domain of LMP1 supports survival of B cells in the presence of the deleterious effects of the complex regulation of this viral oncogene.
Hepatitis C Virus Induces CD81 and Claudin-1 Endocytosis
Authors: Farquhar Michelle J. , Hu Ke , Harris Helen J. , Davis Christopher , Brimacombe Claire L. , Fletcher Sarah J. , Baumert Thomas F. , Rappoport Joshua Z. , Balfe Peter , McKeating Jane A.
Published: February 2012

Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor-specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization.
Restoration of TLR3-Activated Myeloid Dendritic Cell Activity Leads to Improved Natural Killer Cell Function in Chronic Hepatitis B Virus Infection
Authors: Tjwa Eric T. T. L. , van Oord Gertine W. , Biesta Paula J. , Boonstra Andre , Janssen Harry L. A. , Woltman Andrea M.
Published: February 2012

There is increasing evidence that the function of NK cells in patients with chronic hepatitis B (CHB) infection is impaired. The underlying mechanism for the impaired NK cell function is still unknown. Since myeloid dendritic cells (mDC) are potent inducers of NK cells, we investigated the functional interaction of mDC and NK cells in CHB and the influence of antiviral therapy. Blood BDCA1
+
mDC and NK cells were isolated from 16 healthy controls or 39 CHB patients at baseline and during 6 months of antiviral therapy. After activation of mDC with poly(I · C) and gamma interferon (IFN-γ), mDC were cocultured with NK cells. Phenotype and function were analyzed in detail by flow cytometry and enzyme-linked immunosorbent assay. Our findings demonstrate that on poly(I · C)/IFN-γ-stimulated mDC from CHB patients, the expression of costimulatory molecules was enhanced, while cytokine production was reduced. In cocultures of poly(I · C)/IFN-γ-stimulated mDC and NK cells obtained from CHB patients, reduced mDC-induced NK cell activation (i.e., CD69 expression) and IFN-γ production compared to those in healthy individuals was observed. Antiviral therapy normalized mDC activity, since decreased expression of CD80 and CD86 on DC and of HLA-E on NK cells was observed, while poly(I · C)/IFN-γ-induced cytokine production by mDC was enhanced. In parallel, successful antiviral therapy resulted in improved mDC-induced NK cell activation and IFN-γ production. These data demonstrate that CHB patients display a diminished functional interaction between poly(I · C)/IFN-γ activated mDC and NK cells due to impaired mDC function, which can be partially restored by antiviral therapy. Enhancing this reciprocal interaction could reinforce the innate and thus the adaptive T cell response, and this may be an important step in achieving effective antiviral immunity.
A qualitative study of manufacturers' submissions to the UK NICE single technology appraisal process
Authors: Kaltenthaler Eva C , Dickson Rumona , Boland Angela , Carroll Christopher , Fitzgerald Patrick , Papaioannou Diana , Akehurst Ronald
Published: February 2012

Objectives

As part of the National Institute for Health and Clinical Excellence (NICE) Single Technology Appraisal (STA) process, manufacturers present submissions outlining the clinical and cost-effectiveness of new technologies. These submissions are critically appraised by Evidence Review Groups (ERGs), who produce a report, which forms part of the evidence considered by the NICE Appraisal Committees. The purpose of this research was first to identify common issues and concerns identified by the ERGs in their analyses of manufacturers' submissions (MS). The aim was then to use these as a basis to develop feedback for manufacturers.

Design

A qualitative study using a content analysis approach to examine two sources of evidence, the first 30 ERG reports and 21 clarification letters associated with these STAs.

Setting

UK HTA programme.

Primary and secondary outcome measures

Common issues and concerns in MS.

Results

There were positive comments regarding the quality of the MS, many of which were clearly written. The majority, however, were generally of poor quality and issues and concerns identified across the ERG reports and clarification letters included: criticisms related to the data being used especially data employed in the cost-effectiveness model, failure to perform a necessary analysis and poor reporting of processes used in the MS. Aspects of the decision problem were also often poorly or inadequately addressed by manufacturers. The majority of points raised for clarification related to the economic data analysis. Internal inconsistencies between the clinical and economic sections of the submission were frequently highlighted. These were used as the basis for the development of 12 suggestions for manufacturers.

Conclusions

Much can be done to improve the quality of MS in the NICE STA process. Suggestions include the need for clear and transparent reporting of methods and analyses.
Clustering of substance use and sexual risk behaviour in adolescence: analysis of two cohort studies
Authors: Jackson Caroline , Sweeting Helen , Haw Sally
Published: February 2012

Objectives

The authors aimed to examine whether changes in health risk behaviour rates alter the relationships between behaviours during adolescence, by comparing clustering of risk behaviours at different time points.

Design

Comparison of two cohort studies, the Twenty-07 Study (‘earlier cohort’, surveyed in 1987 and 1990) and the 11-16/16+ Study (‘later cohort’, surveyed 1999 and 2003).

Setting

Central Clydeside Conurbation around Glasgow City.

Participants

Young people who participated in the Twenty-07 and 11-16/16+ studies at ages 15 and 18–19.

Primary and secondary outcomes measures

The authors analysed data on risk behaviours in both early adolescence (started smoking prior to age 14, monthly drinking and ever used illicit drugs at age 15 and sexual intercourse prior to age 16) and late adolescence (age 18–19, current smoking, excessive drinking, ever used illicit drugs and multiple sexual partners) by gender and social class.

Results

Drinking, illicit drug use and risky sexual behaviour (but not smoking) increased between the earlier and later cohort, especially among girls. The authors found strong associations between substance use and sexual risk behaviour during early and late adolescence, with few differences between cohorts, or by gender or social class. Adjusted ORs for associations between each substance and sexual risk behaviour were around 2.00. The only significant between-cohort difference was a stronger association between female early adolescent smoking and early sexual initiation in the later cohort. Also, relationships between illicit drug use and both early sexual initiation and multiple sexual partners in late adolescence were significantly stronger among girls than boys in the later cohort.

Conclusions

Despite changes in rates, relationships between adolescent risk behaviours remain strong, irrespective of gender and social class. This indicates a need for improved risk behaviour prevention in young people, perhaps through a holistic approach, that addresses the broad shared determinants of various risk behaviours.
SELECTED TOPICS IN CLASSICAL INTEGRABILITY
Authors: DOIKOU ANASTASIA
Published: February 2012

Basic notions regarding classical integrable systems are reviewed. An algebraic description of the classical integrable models together with the zero curvature condition description is presented. The classical r-matrix approach for discrete and continuum classical integrable models is introduced. Using this framework the associated classical integrals of motion and the corresponding Lax pair are extracted based on algebraic considerations. Our attention is restricted to classical discrete and continuum integrable systems with periodic boundary conditions. Typical examples of discrete (Toda chain, discrete NLS model) and continuum integrable models (NLS, sine–Gordon models and affine Toda field theories) are also discussed.
CANONICAL METRICS ON CARTAN–HARTOGS DOMAINS
Authors: ZEDDA MICHELA
Published: February 2012

In this paper we address two problems concerning a family of domains MΩ(μ) ⊂ ℂn, called Cartan–Hartogs domains, endowed with a natural Kähler metric g(μ). The first one is determining when the metric g(μ) is extremal (in the sense of Calabi), while the second one studies when the coefficient a2in the Engliš expansion of Rawnsley ε-function associated to g(μ) is constant.