Noise Reduction in a Launch Vehicle Fairing Using Actively Tuned Loudspeakers

The Journal of the Acoustical Society of America. Apr, 2003  |  Pubmed ID: 12703709

Loudspeakers tuned as optimal acoustic absorbers can significantly reduce damaging, low frequency, reverberant noise in a full-scale launch vehicle fairing. Irregular geometry, changing payloads, and the compliant nature of the fairing hinder effective implementation of a passively tuned loudspeaker. A method of tuning the loudspeaker dynamics in real time is required to meet the application requirements. Through system identification, the dynamics of the enclosure can be identified and used to tune the dynamics of the loudspeaker for reduction of targeted, high intensity, low-frequency modes that dominate the acoustic response in the fairing. A loudspeaker model with desired dynamics serves as the reference model in a control law designed to tune the dynamics of a non-ideal loudspeaker to act as an optimal tuned absorber. Experimental results indicate that a tuned loudspeaker placed in the nose cone of the fairing significantly reduces acoustic energy and verifies results calculated from the simulation.

The Application of Smart Structures Toward Feedback Suppression in Amplified Acoustic Guitars

The Journal of the Acoustical Society of America. Jun, 2003  |  Pubmed ID: 12822791

Smart structures technology can be applied to amplified acoustic guitars to prevent instability resulting from acoustic feedback. This work presents a coupled model of the guitar dynamics and the acoustic feedback mechanism, and explains how a simple control loop using a piezoelectric ceramic actuator can be used to reduce the effects of acoustic feedback. In addition to model simulations, experimental results using a real system and a simple controller are presented. The results show that a significantly higher (7 dB) guitar output can be achieved before instability, without detrimentally affecting the amplified and unamplified guitar response.

Selection of Normalizer Genes in Conducting Relative Gene Expression Analysis of Embryos

Birth Defects Research. Part A, Clinical and Molecular Teratology. Aug, 2003  |  Pubmed ID: 14632301

In relative gene expression analysis, a reference gene for sample normalization is required for determining target expression changes among experimental treatment groups. Since some developmental toxicants secondarily cause general growth retardation and/or other general biological changes, commonly used housekeeping genes may not serve as accurate normalizers.

Developmental Toxicity of Artesunate and an Artesunate Combination in the Rat and Rabbit

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Dec, 2004  |  Pubmed ID: 15617018

The artemisinins are playing an increasingly important role in treating multidrug-resistant malaria. The artemisinin, artesunate, is currently in use in Southeast Asia and is advocated for use in Africa. In these areas, more than one million people die of malaria each year, with the highest mortality occurring in children and pregnant women. To test the developmental toxicity in ICH-compliant animal studies, embryofetal development studies were conducted in rats and rabbits treated with artesunate alone or a three-drug combination (CDA) consisting of chlorproguanil hydrochloride, Dapsone, and artesunate in the ratio 1.00:1.25:2.00. Developmental toxicity seen with CDA could be attributed to the administered dose of artesunate. The hallmark effect of artesunate exposure was a dramatic induction of embryo loss, apparent as abortions in rabbits and resorptions in both rats and rabbits. In addition, low incidences of cardiovascular malformations and a syndrome of skeletal defects were induced at or close to embryolethal doses of artesunate in both rats and rabbits. The cardiovascular malformations consisted of ventricular septal and vessel defects. The skeletal syndrome consisted of shortened and/or bent long bones and scapulae, misshapen ribs, cleft sternebrae, and incompletely ossified pelvic bones. These developmental effects were observed largely in the absence of any apparent maternal toxicity. The no or low adverse effect levels were in the range of 5 to 7 mg/kg/day artesunate. Encouragingly, no adverse drug-related developmental effects have been observed in a limited number of pregnant women (more than 100 first trimester and 600 second and third trimester) treated with artemisinins, primarily artesunate. Investigations of the mechanism of developmental toxicity are ongoing to attempt to determine whether rats and rabbits are more sensitive to artemisinins than humans.

What Causes Feedback in a Guitar or Microphone?

Scientific American. Sep, 2005  |  Pubmed ID: 16121864

Understanding the Elasticity of Fibronectin Fibrils: Unfolding Strengths of FN-III and GFP Domains Measured by Single Molecule Force Spectroscopy

Matrix Biology : Journal of the International Society for Matrix Biology. Apr, 2006  |  Pubmed ID: 16343877

While it is well established that fibronectin (FN) matrix fibrils are elastic, the mechanism of fibril elasticity during extension is still debated. To investigate the molecular origin of FN fibril elasticity, we used single molecule force spectroscopy (SMFS) to determine the unfolding behavior of a recombinant FN-III protein construct that contained eight FN-III domains ((1-8)FN-III) and two green fluorescent protein (GFP) domains. FN-III domains were distinguished from GFP domains by their shorter unfolding lengths. The unfolding strengths of both domains were determined for a wide range of pulling rates (50 to 1,745 nm/s). We found that the mechanical stabilities of FN-III and GFP domains were very similar to each other over the entire range of pulling speeds. FN fibrils containing GFP remain brightly fluorescent, even when stretched, meaning that GFP domains remain largely folded. Since GFP and FN-III have equal unfolding strengths, this suggests that FN-III domains are not extensively unraveled in stretched FN fibrils. Our results thus favor an alternative model, which invokes a conformational change from a compact to an extended conformation, as the basis for FN fibril elasticity.

The Crystal Structure of Human IRE1 Luminal Domain Reveals a Conserved Dimerization Interface Required for Activation of the Unfolded Protein Response

Proceedings of the National Academy of Sciences of the United States of America. Sep, 2006  |  Pubmed ID: 16973740

The unfolded protein response (UPR) is an evolutionarily conserved mechanism by which all eukaryotic cells adapt to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Inositol-requiring kinase 1 (IRE1) and PKR-related ER kinase (PERK) are two type I transmembrane ER-localized protein kinase receptors that signal the UPR through a process that involves homodimerization and autophosphorylation. To elucidate the molecular basis of the ER transmembrane signaling event, we determined the x-ray crystal structure of the luminal domain of human IRE1alpha. The monomer of the luminal domain comprises a unique fold of a triangular assembly of beta-sheet clusters. Structural analysis identified an extensive dimerization interface stabilized by hydrogen bonds and hydrophobic interactions. Dimerization creates an MHC-like groove at the interface. However, because this groove is too narrow for peptide binding and the purified luminal domain forms high-affinity dimers in vitro, peptide binding to this groove is not required for dimerization. Consistent with our structural observations, mutations that disrupt the dimerization interface produced IRE1alpha molecules that failed to either dimerize or activate the UPR upon ER stress. In addition, mutations in a structurally homologous region within PERK also prevented dimerization. Our structural, biochemical, and functional studies in vivo altogether demonstrate that IRE1 and PERK have conserved a common molecular interface necessary and sufficient for dimerization and UPR signaling.

Artesunate-induced Depletion of Embryonic Erythroblasts Precedes Embryolethality and Teratogenicity in Vivo

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Oct, 2006  |  Pubmed ID: 17066416

Artesunate (ART), an artemisinin antimalarial, is embryolethal and teratogenic in rats, with the most sensitive days being 10 and 11 postcoitum (pc), respectively (Clark et al.: Birth Defects Res B 71:380-394, 2004; White et al.: Birth Defects Res A 70:265, 2004).

Aberration Correction in Holographic Optical Tweezers

Optics Express. May, 2006  |  Pubmed ID: 19516565

Holographic or diffractive optical components are widely implemented using spatial light modulators within optical tweezers to form multiple, and/or modified traps. We show that by further modifying the hologram design to account for residual aberrations, the fidelity of the focused beams can be significantly improved, quantified by a spot sharpness metric. However, the impact this improvement has on the quality of the optical trap depends upon the particle size. For particle diameters on the order of 1 microm, aberration correction can improve the trap performance metric, which is the ratio of the mean square displacement of a corrected trap to an uncorrected trap, in excess of 25%, but for larger particles the trap performance is not unduly affected by the aberrations typically encountered in commercial spatial light modulators.

Aberration Correction in Holographic Optical Tweezers

Optics Express. May, 2006  |  Pubmed ID: 19516566

Holographic or diffractive optical components are widely implemented using spatial light modulators within optical tweezers to form multiple, and/or modified traps. We show that by further modifying the hologram design to account for residual aberrations, the fidelity of the focused beams can be significantly improved, quantified by a spot sharpness metric. However, the impact this improvement has on the quality of the optical trap depends upon the particle size. For particle diameters on the order of 1 microm, aberration correction can improve the trap performance metric, which is the ratio of the mean square displacement of a corrected trap to an uncorrected trap, in excess of 25%, but for larger particles the trap performance is not unduly affected by the aberrations typically encountered in commercial spatial light modulators.

Monitoring Kinetics of Surface Initiated Atom Transfer Radical Polymerization by Quartz Crystal Microbalance with Dissipation

Biointerphases. Mar, 2006  |  Pubmed ID: 20408613

This article reports that the kinetics of surface-initiated atom transfer radical polymerization can be quantified by the quartz crystal microbalance with dissipation (QCM-D) technique. The kinetics of in situ growth of poly(oligoethylene glycol methylmethacrylate) monitored on a gold-coated QCM-D sensor chip revealed that changes in the experimentally observed frequency (DeltaF) and dissipation (DeltaD) as a function of polymerization time were a function of the initiator density, and that the experimental response could be predicted from a continuum model.

A Stochastic, Cantilever Approach to the Evaluation of Solution Phase Thermodynamic Quantities

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2007  |  Pubmed ID: 17307881

A cantilever device based on competitive binding of an immobilized receptor to immobilized and soluble ligand and capable of measuring solution-phase thermodynamic quantities is described. Through multiple binary queries, the device stochastically measures the probability of the formation of a bound complex between immobilized protein and immobilized ligand as a function of soluble ligand concentration. The resulting binding isotherm is described by a binding polynomial consisting of the activities of soluble and immobilized ligand and binding constants for the association of immobilized protein with free and immobilized ligand. Evaluation of the polynomial reveals an association constant for the formation of a complex between immobilized ligand and immobilized protein close to that for the formation of complex between soluble protein and soluble ligand. The methodology lays the foundation for construction of practical portable sensing devices.

Pulling Geometry-induced Errors in Single Molecule Force Spectroscopy Measurements

Biophysical Journal. May, 2007  |  Pubmed ID: 17324999

In AFM-based single molecule force spectroscopy, it is tacitly assumed that the pulling direction coincides with the end-to-end vector of the molecule fragment being stretched. By systematically varying the position of the attachment point on the substrate relative to the AFM tip, we investigate empirically and theoretically the effect of the pulling geometry on force-extension characteristics of double-stranded DNA. We find that increasing the pulling angle can significantly lower the force of the characteristic overstretching transition and increase the width of the plateau feature beyond the canonical 70%. These effects, when neglected, can adversely affect the interpretation of measured force-extension relationships. We quantitatively evaluate force and extension errors originating from this "pulling angle effect" and stress the need to correct the pulling geometry when stretching rigid molecules with an AFM.

Controllable Porous Polymer Particles Generated by Electrospraying

Journal of Colloid and Interface Science. Jun, 2007  |  Pubmed ID: 17346734

In this paper, an electrospraying technique was applied to prepare polycaprolactone (PCL) polymer particles with a different microstructure. The PCL particles can be controlled to have a porous microstructure by tailoring the evaporation of solvents during the electrospraying process. The effect of various concentrations on the morphology and microstructure of PCL particles was investigated. The experiment has demonstrated the versatile capability of the electrohydrodynamic atomization process for preparing polymer PCL porous particles and fibers. The thermally induced and evaporation-induced phase separations are proposed as the main mechanisms for the porous microstructure formation. The results demonstrate that the electrospraying method is a simple, innovative and cost-effective method for preparing polymer particles with controllable microstructures.

Nanomechanical Fingerprints of UV Damage to DNA

Small (Weinheim an Der Bergstrasse, Germany). May, 2007  |  Pubmed ID: 17393552

Structural Acoustic Control of Plates with Variable Boundary Conditions: Design Methodology

The Journal of the Acoustical Society of America. Jul, 2007  |  Pubmed ID: 17614487

A method for optimizing a structural acoustic control system subject to variations in plate boundary conditions is provided. The assumed modes method is used to build a plate model with varying levels of rotational boundary stiffness to simulate the dynamics of a plate with uncertain edge conditions. A transducer placement scoring process, involving Hankel singular values, is combined with a genetic optimization routine to find spatial locations robust to boundary condition variation. Predicted frequency response characteristics are examined, and theoretically optimized results are discussed in relation to the range of boundary conditions investigated. Modeled results indicate that it is possible to minimize the impact of uncertain boundary conditions in active structural acoustic control by optimizing the placement of transducers with respect to those uncertainties.

Servo Control of an Optical Trap

Applied Optics. Aug, 2007  |  Pubmed ID: 17676096

A versatile optical trap has been constructed to control the position of trapped objects and ultimately to apply specified forces using feedback control. While the design, development, and use of optical traps has been extensive and feedback control has played a critical role in pushing the state of the art, few comprehensive examinations of feedback control of optical traps have been undertaken. Furthermore, as the requirements are pushed to ever smaller distances and forces, the performance of optical traps reaches limits. It is well understood that feedback control can result in both positive and negative effects in controlled systems. We give an analysis of the trapping limits as well as introducing an optical trap with a feedback control scheme that dramatically improves an optical trap's sensitivity at low frequencies.

Biocatalytic Microcontact Printing

The Journal of Organic Chemistry. Sep, 2007  |  Pubmed ID: 17705546

Immobilized biocatalytic lithography is presented as an application of soft lithography. In traditional microcontact printing, diffusion limits resolution of pattern transfer. By using an immobilized catalyst, the lateral resolution of microcontact printing would depend only on the length and flexibility of the tether (<2 nm) as opposed to diffusion (>100 nm). In the work, exonuclease reversibly immobilized on a relief-patterned stamp is used to ablate ssDNA monolayers Percent of ablation was determined via confocal fluorescence microscopy to be approximately 70%.

Inkless Microcontact Printing on Self-assembled Monolayers of Fmoc-protected Aminothiols

Journal of the American Chemical Society. Nov, 2007  |  Pubmed ID: 17949005

Time and Distance Dependence of Reversible Polymer Bridging Followed by Single-molecule Force Spectroscopy

Langmuir : the ACS Journal of Surfaces and Colloids. May, 2008  |  Pubmed ID: 18348580

Polymer bridging between surfaces plays an important role in a range of fundamental processes in the material and life sciences. Bridges formed by main-chain reversible polymers differ from their covalent analogs in that they can dynamically adjust their size and shape in response to external stimuli and have the potential to reform following bond scission. In this work, the time and distance dependence of main-chain reversible polymer bridge formation are studied using an atomic force microscope. The bridging process was studied using single-molecule force spectroscopy, and its dependence on the distance between surfaces and equilibration time was probed. The number of bridges formed decreases as the gap width increases, from approximately 2 bridges per 14 s equilibration at separations of 5-15 nm to approximately 0.5 bridges per 14 s equilibration at separations of 35-45 nm. The kinetics of bridge formation appear to be slightly faster at smaller separations.

Electrohydrodynamic Atomization: a Versatile Process for Preparing Materials for Biomedical Applications

Journal of Biomaterials Science. Polymer Edition. 2008  |  Pubmed ID: 18419939

Electrohydrodynamic atomization phenomena have increasingly attracted the attention of researchers who are interested in building micro- or nanometer architectures, such as fibers and encapsulated particles with a controllable microstructure. There are two main electrohydrodynamic atomization techniques: electrospraying and electrospinning. These techniques are unique processes in that they produce fibers and particles with dimensions that range from micrometers to nanometers depending on the processing parameters. This paper presents the principles, processes and potential biomedical applications for electrospraying and electrospinning of biomaterials. Both of these techniques offer great research opportunities. Emphasis will focus on the effects of processing parameters of electrohydrodynamic atomization on morphologies and microstructure of the final products. In addition, some potential applications are proposed based on the remarkable characteristics of the biomaterials generated using electrospraying and electrospinning.

An Adaptive System Identification Approach to Optical Trap Calibration

Optics Express. Mar, 2008  |  Pubmed ID: 18542538

A method of adaptive system identification for the modeling of an optical trap's system dynamics is presented. The system dynamics can be used to locate the corner frequency for trapping stiffness calibration using the power spectral method. The method is based on an adaptive least-mean-square (LMS) algorithm, which adjusts weights of a tapped delay line filter using a gradient descent method. The identified model is the inverse of the high order finite impulse response (FIR) filter. The model order is reduced using balanced model reduction, giving the corner frequency which can be used to calibrate the trapping stiffness. This method has an advantage over other techniques in that it is quick, does not explicitly require operator interaction, and can be acquired in real time. It is also a necessary step for an adaptive controller that can automatically update the controller for changes in the trap (e.g., power fluctuations) and for particles of different sizes and refractive indices.

Sensitive Periods for Developmental Toxicity of Orally Administered Artesunate in the Rat

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Aug, 2008  |  Pubmed ID: 18615704

Artesunate has been reported to cause embryolethality and malformations when administered orally to rats during organogenesis. The purpose of this study was to determine the most sensitive period(s) for the induction of these effects in order to provide clues about possible mechanisms and to identify a short treatment regimen for further studies.

Adaptive Disturbance Rejection in an Optical Trap

Applied Optics. Jul, 2008  |  Pubmed ID: 18617975

This article presents a method for characterizing the system dynamics of a trapped particle in real-time and designing a controller to minimize disturbances to the particle's position. Specifically, adaptive system identification is used to determine the trap characteristics and the actuator transfer function describing the mirror voltage to trap position path. Using an internal model control scheme combined with a filtered-x least-mean-square algorithm, adaptive control was used to create a controller that minimizes a frequency weighted mean-squared-error. The dynamics associated with multiple particle sizes and materials were experimentally determined under different power levels, each case resulting in different system dynamics and demonstrating positive control results. The adaptive system identification and the controller presented automate the process of system identification and control design, enabling the automation of optical trap controller design.

Minimizing Pulling Geometry Errors in Atomic Force Microscope Single Molecule Force Spectroscopy

Biophysical Journal. Oct, 2008  |  Pubmed ID: 18641069

In atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS), it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Recent studies, however, have indicated that the pulling geometry errors can drastically alter the measured force-extension relationship of molecules. Here we describe a software-based alignment method that repositions the cantilever such that it is located directly above the molecule's substrate attachment site. By aligning the applied force with the measurement axis, the molecule is no longer undergoing combined loading, and the full force can be measured by the cantilever. Simulations and experimental results verify the ability of the alignment program to minimize pulling geometry errors in AFM-SMFS studies.

Hydration and Conformational Mechanics of Single, End-tethered Elastin-like Polypeptides

Journal of the American Chemical Society. Aug, 2008  |  Pubmed ID: 18646848

We investigated the effect of temperature, ionic strength, solvent polarity, and type of guest residue on the force-extension behavior of single, end-tethered elastin-like polypeptides (ELPs), using single molecule force spectroscopy (SMFS). ELPs are stimulus-responsive polypeptides that contain repeats of the five amino acids Val-Pro-Gly-Xaa-Gly (VPGXG), where Xaa is a guest residue that can be any amino acid with the exception of proline. We fitted the force-extension data with a freely jointed chain (FJC) model which allowed us to resolve small differences in the effective Kuhn segment length distributions that largely arise from differences in the hydrophobic hydration behavior of ELP. Our results agree qualitatively with predictions from recent molecular dynamics simulations and demonstrate that hydrophobic hydration modulates the molecular elasticity for ELPs. Furthermore, our results show that SMFS, when combined with our approach for data analysis, can be used to study the subtleties of polypeptide-water interactions and thus provides a basis for the study of hydrophobic hydration in intrinsically unstructured biomacromolecules.

Artesunate: Developmental Toxicity and Toxicokinetics in Monkeys

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Aug, 2008  |  Pubmed ID: 18702116

The developmental toxicity, toxicokinetics, and hematological effects of the antimalarial drug, artesunate, were previously studied in rats and rabbits and have now been studied in cynomolgus monkeys.

Developmental Toxicity of Artesunate in the Rat: Comparison to Other Artemisinins, Comparison of Embryotoxicity and Kinetics by Oral and Intravenous Routes, and Relationship to Maternal Reticulocyte Count

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Aug, 2008  |  Pubmed ID: 18702118

The antimalarial, artesunate, is teratogenic and embryolethal in rats, with peak sensitivity on Days 10 and 11 postcoitum (pc).

Three-dimensional Parallel Holographic Micropatterning Using a Spatial Light Modulator

Optics Express. Sep, 2008  |  Pubmed ID: 18825231

We present a micropatterning method for the automatic transfer and arbitrary positioning of computer-generated three-dimensional structures within a substrate. The Gerchberg-Saxton algorithm and an electrically addressed spatial light modulator (SLM) are used to create and display phase holograms, respectively. A holographic approach to light manipulation enables arbitrary and efficient parallel photo-patterning. Multiple pyramidal microstructures were created simultaneously in a photosensitive adhesive. A scanning electron microscope was used to confirm successful replication of the desired microscale structures.

Controlled Rotation of Birefringent Particles in an Optical Trap

Applied Optics. Dec, 2008  |  Pubmed ID: 19037371

Optical traps have been used in a multitude of applications requiring the sensing and application of forces. However, optical traps also have the ability to accurately apply and sense torques. Birefringent particles experience a torque when trapped in elliptically polarized light. By measuring the frequency content of the exiting beam, the rotational rates can be set up in a feedback loop and actively controlled. Here we describe an optical trap with feedback torque control to maintain constant rotational rates despite the introduction of an increased drag on the particle. As a result, this research has the potential to advance the understanding of rotary motor proteins such as F1 ATPase.

A Simple and Practical Spreadsheet-Based Method to Extract Single-Molecule Dissociation Kinetics from Variable Loading-Rate Force Spectroscopy Data

The Journal of Physical Chemistry. C, Nanomaterials and Interfaces. Dec, 2008  |  Pubmed ID: 20011580

A Method for Atomic Force Microscopy Cantilever Stiffness Calibration Under Heavy Fluid Loading

The Review of Scientific Instruments. Dec, 2009  |  Pubmed ID: 20059166

This work presents a method for force calibration of rectangular atomic force microscopy (AFM) microcantilevers under heavy fluid loading. Theoretical modeling of the thermal response of microcantilevers is discussed including a fluid-structure interaction model of the cantilever-fluid system that incorporates the results of the fluctuation-dissipation theorem. This model is curve fit to the measured thermal response of a cantilever in de-ionized water and a cost function is used to quantify the difference between the theoretical model and measured data. The curve fit is performed in a way that restricts the search space to parameters that reflect heavy fluid loading conditions. The resulting fitting parameters are used to calibrate the cantilever. For comparison, cantilevers are calibrated using Sader's method in air and the thermal noise method in both air and water. For a set of eight cantilevers ranging in stiffness from 0.050 to 5.8 N/m, the maximum difference between Sader's calibration performed in air and the new method performed in water was 9.4%. A set of three cantilevers that violate the aspect ratio assumption associated with the fluid loading model (length-to-width ratios less than 3.5) ranged in stiffness from 0.85 to 4.7 N/m and yielded differences as high as 17.8%.

Single-Molecule Force Spectroscopy of DNA-Based Reversible Polymer Bridges: Surface Robustness and Homogeneity

Colloids and Surfaces. A, Physicochemical and Engineering Aspects. Aug, 2009  |  Pubmed ID: 21966095

Single-molecule force spectroscopy, as implemented in an atomic force microscope, provides a rarely-used method by which to monitor dynamic processes that occur near surfaces. Here, a methodology is presented and characterized that facilitates the study of polymer bridging across nanometer-sized gaps. The model system employed is that of DNA-based reversible polymers, and an automated procedure is introduced that allows the AFM tip-surface contact point to be automatically determined, and the distance d between opposing surfaces to be actively controlled. Using this methodology, the importance of several experimental parameters was systematically studied, e.g. the frequency of repeated tip/surface contacts, the area of the substrate surface sampled by the AFM, and the use of multiple AFM tips and substrates. Experiments revealed the surfaces to be robust throughout pulling experiments, so that multiple touches and pulls could be carried out on a single spot with no measurable affect on the results. Differences in observed bridging probabilities were observed, both on different spots on the same surface and, more dramatically, from one day to another. Data normalization via a reference measurement allows data from multiple days to be directly compared.

Towards Holonomic Control of Janus Particles in Optomagnetic Traps

Advanced Materials (Deerfield Beach, Fla.). Dec, 2009  |  Pubmed ID: 21049503

Versatile Synthesis and Micropatterning of Nonfouling Polymer Brushes on the Wafer Scale

Biointerphases. Jun, 2009  |  Pubmed ID: 20408717

In this article, the authors describe new approaches to synthesize and pattern surfaces with poly[oligo(ethylene glycol) methyl methacrylate] (POEGMA) polymer brushes synthesized by surface-initiated atom transfer radical polymerization. These patterned coatings confer "nonfouling" properties protein and cell resistance-to the surface in a biological milieu. The versatile routes for the synthesis of POEGMA demonstrated here offer clear advantages over other techniques previously used in terms of their simplicity, reliability, and ability to pattern large-area substrates. They also demonstrate that POEGMA polymer brushes can be patterned directly by photolithography, plasma ashing, and reactive ion etching to create patterns at the micro- and nanoscale over large areas with high throughput and repeatability, while preserving the protein and cell resistance of the POEGMA brush.

Fabrication of Elastin-like Polypeptide Nanoparticles for Drug Delivery by Electrospraying

Biomacromolecules. Jan, 2009  |  Pubmed ID: 19072041

The development of environmentally responsive drug carriers requires new methods for assembling stimuli-responsive nanoparticulates. This communication describes a novel application of electrospray to construct bioresponsive peptide-based particulates, which can encapsulate drugs. These particles are composed from genetically engineered elastin-like polypeptides (ELPs), a biodegradable, biocompatible, and bioresponsive polymer. To generate nanoparticles (300-400 nm in diameter), ELPs and drugs are codissolved in organic solvent, accelerated across a voltage gradient, dried by evaporation during transit, and collected from a target surface. These findings indicate that particle diameter, polydispersity, and morphology are strong functions of the solvent concentration, spraying voltage, and polymer molecular weight. Surprisingly, the loading of drug at 20 w/w% did not influence particle morphology; furthermore, drug release from these particles correlated with the pH-dependent solubility of the parent ELPs. These studies suggest that electrospray is an efficient and flexible method for generating stimuli-responsive drug particles.

Polymeric Particle Formation Through Electrospraying at Low Atmospheric Pressure

Journal of Biomedical Materials Research. Part B, Applied Biomaterials. Jul, 2009  |  Pubmed ID: 19107800

Electrospraying is a simple and versatile technique capable of producing polymeric particles. However, most investigations carried out thus far have been performed at ambient atmospheric pressure without studying the influences of pressure on the formation of polymeric particles. Here, we report our investigation on the effects of varying the pressure and the solution concentration on the microstructures of electrosprayed polymeric particles. Pressures are varied from ambient atmospheric pressure to 380 mmHg below ambient pressure, and solution concentrations are varied over a range of 3-7 w/v %. By varying these parameters, we manipulated the rate of solvent evaporation and the solidification of the electrosprayed particles. The results show that changes to the pressure had significant effects on the microstructure and morphology of poly(epsilon-caprolactone) (PCL) particles. The average particle size became larger as the chamber pressure decreased. At a solution concentration of 5 w/v % and a pressure 150 mmHg below ambient pressure, uniform and spherical PCL particles were generated. Electrospun fibers were formed when a solution concentration of 7 w/v % was used. The developed technique can be applied to prepare polymeric drug delivery carriers though a low-pressure-assisted spray-drying method, and is particularly suitable for fabricating delivery microspheres encapsulated with temperature-sensitive drugs and biomolecules.

UVA Generates Pyrimidine Dimers in DNA Directly

Biophysical Journal. Feb, 2009  |  Pubmed ID: 19186150

There is increasing evidence that UVA radiation, which makes up approximately 95% of the solar UV light reaching the Earth's surface and is also commonly used for cosmetic purposes, is genotoxic. However, in contrast to UVC and UVB, the mechanisms by which UVA produces various DNA lesions are still unclear. In addition, the relative amounts of various types of UVA lesions and their mutagenic significance are also a subject of debate. Here, we exploit atomic force microscopy (AFM) imaging of individual DNA molecules, alone and in complexes with a suite of DNA repair enzymes and antibodies, to directly quantify UVA damage and reexamine its basic mechanisms at a single-molecule level. By combining the activity of endonuclease IV and T4 endonuclease V on highly purified and UVA-irradiated pUC18 plasmids, we show by direct AFM imaging that UVA produces a significant amount of abasic sites and cyclobutane pyrimidine dimers (CPDs). However, we find that only approximately 60% of the T4 endonuclease V-sensitive sites, which are commonly counted as CPDs, are true CPDs; the other 40% are abasic sites. Most importantly, our results obtained by AFM imaging of highly purified native and synthetic DNA using T4 endonuclease V, photolyase, and anti-CPD antibodies strongly suggest that CPDs are produced by UVA directly. Thus, our observations contradict the predominant view that as-yet-unidentified photosensitizers are required to transfer the energy of UVA to DNA to produce CPDs. Our results may help to resolve the long-standing controversy about the origin of UVA-produced CPDs in DNA.

Embryotoxicity of the Artemisinin Antimalarials and Potential Consequences for Use in Women in the First Trimester

Reproductive Toxicology (Elmsford, N.Y.). Nov, 2009  |  Pubmed ID: 19447170

Single oral doses of artesunate, dihydroartemisinin, arteether and artemether administered to rats during a sensitive period of organogenesis caused embryo deaths and malformations (malformed long bones and ventricular septal defects). Extended oral dosing (12 days or more) of monkeys once daily with 12 mg/kg-d artesunate also caused embryo deaths. The initial embryotoxic effect in both species was to kill primitive erythroblasts which are present in the embryo for a few days of gestation in rats and several weeks in primates. The malformations that occurred in rats are attributed to a transient depletion of the primitive erythroblasts. In monkeys, when treatment at 12 mg/kg-d was shortened to 3 or 7 days, the embryos survived but likely suffered a transient loss of primitive erythroblasts. Limited clinical data including 123 first trimester pregnancies have not indicated any adverse effects on pregnancy. However, in rats and monkeys, the embryonic erythroblasts are much more sensitive to artemisinins than are erythroblasts in the adult bone marrow; the latter are indicated by decreases in reticulocyte count. Since decreases in reticulocyte count occur at therapeutic doses in humans, there is reason for concern that any treatment of pregnant women during the putative sensitive period (from approximately postconception Day 21 to approximately postconception week 9) that causes even minor decreases in adult reticulocyte count could also cause a marked depletion of embryonic erythroblasts which could lead to death or malformation of the embryo.

Electrosprayed Core-shell Microspheres for Protein Delivery

Chemical Communications (Cambridge, England). Jul, 2010  |  Pubmed ID: 20485844

This communication describes a single-step electrospraying technique that generates core-shell microspheres (CSMs) with encapsulated protein as the core and an amphiphilic biodegradable polymer as the shell. The protein release profiles of the electrosprayed CSMs showed steady release kinetics over 3 weeks without a significant initial burst.

A Versatile Diffractive Maskless Lithography for Single-shot and Serial Microfabrication

Optics Express. May, 2010  |  Pubmed ID: 20589036

We demonstrate a diffractive maskless lithographic system that is capable of rapidly performing both serial and single-shot micropatterning. Utilizing the diffractive properties of phase holograms displayed on a spatial light modulator, arbitrary intensity distributions were produced to form two and three dimensional micropatterns/structures in a variety of substrates. A straightforward graphical user interface was implemented to allow users to load templates and change patterning modes within the span of a few minutes. A minimum resolution of approximately 700 nm is demonstrated for both patterning modes, which compares favorably to the 232 nm resolution limit predicted by the Rayleigh criterion. The presented method is rapid and adaptable, allowing for the parallel fabrication of microstructures in photoresist as well as the fabrication of protein microstructures that retain functional activity.

Simultaneous Two-wavelength Transmission Quantitative Phase Microscopy with a Color Camera

Optics Letters. Aug, 2010  |  Pubmed ID: 20680075

We present a quantitative phase microscopy method that uses a Bayer mosaic color camera to simultaneously acquire off-axis interferograms in transmission mode at two distinct wavelengths. Wrapped phase information is processed using a two-wavelength algorithm to extend the range of the optical path delay measurements that can be detected using a single temporal acquisition. We experimentally demonstrate this technique by acquiring the phase profiles of optically clear microstructures without 2pi ambiguities. In addition, the phase noise contribution arising from spectral channel crosstalk on the color camera is quantified.

Localization of Artesunate and Its Derivatives in the Pregnant Rat and Fetus Following Oral Administration and Relationship to Developmental Toxicity

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Oct, 2010  |  Pubmed ID: 20717981

The antimalarial drug artesunate affects erythroid cells leading to developmental toxicity and adult reticulocytopenia. We report on a kinetic study in rats and the tissue distribution of radioactivity following oral administration of [(3)H]-artesunate to pregnant rats using quantitative whole-body autoradiography (QWBA).

Inkless Microcontact Printing on SAMs of Boc- and TBS-protected Thiols

Nano Letters. Jan, 2010  |  Pubmed ID: 19950928

We report a new inkless catalytic muCP technique that achieves accurate, fast, and complete pattern reproduction on SAMs of Boc- and TBS-protected thiols immobilized on gold using a polyurethane-acrylate stamp functionalized with covalently bound sulfonic acids. Pattern transfer is complete at room temperature just after one minute of contact and renders sub-200 nm size structures of chemically differentiated SAMs.

Catalytic Microcontact Printing on Chemically Functionalized H-terminated Silicon

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2010  |  Pubmed ID: 19950970

We report a novel inkless soft lithographic fabrication protocol that permits uniform parallel patterning of hydrogen-terminated silicon surfaces using catalytic elastomeric stamps. Pattern transfer is achieved catalytically via reaction between sulfonic acid moieties covalently bound to an elastomeric stamp and a Boc-functionalized SAM grafted to passivated silicon. The approach represents the first example of a soft lithographic printing technique that creates patterns of chemically distinctive SAMs on oxide-free silicon substrates.

Artesunate and Artelinic Acid: Association of Embryotoxicity, Reticulocytopenia, and Delayed Stimulation of Hematopoiesis in Pregnant Rats

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Feb, 2011  |  Pubmed ID: 21312322

The artemisinin antimalarials cause embryo death and malformations in animals by killing embryonic erythroblasts. Groups of pregnant rats (N = 4) were administered 35 and 48 µmol/kg artesunate and 17.2, 28.7, 48, 96, and 191 µmol/kg artelinic acid as a single oral dose on gestational day (GD) 12. Litters were examined on GD21. The ED(50) for embryo death with artelinic acid (23.4 µmol/kg) was just slightly lower than that for decreased reticulocyte count at 24 hr postdose (33.5 µmol/kg) and both had similarly steep dose responses (maximal effects of total litter loss and ∼60% decreases in reticulocyte count at 48 µmol/kg). Results with artesunate were similar. The correlation coefficient between embryo death and decreased reticulocyte count was 0.82 (p<0.01). The close relationship between embryotoxicity and reticulocytopenia is suggestive of a common mechanism-artemisinin-induced mitochondrial damage leading to cell death. At 9 days postdose, treatment with artesunate and artelinic acid also caused increases in counts of reticulocytes, lymphocytes, basophils, and monocytes (up to 3.7 ×, 1.7 ×, 4.7 ×, and 1.7 × control, respectively). This stimulation of hematopoiesis may have been mediated by the direct oxidative conversion of artesunate or artelinic acid to the artemisininyl hydroperoxide within the bone marrow cells or by an indirect increase in reactive oxygen species. The high correlation between embryotoxicity and reticulocytopenia further supports the assertion that therapeutic dosage regimens of artemisinins that cause decreases in reticulocyte count in pregnant women during the putative critical period (approximately postconception wk 3 to 9) are at risk of also causing adverse effects on the embryo.

Patterning NHS-terminated SAMs on Germanium

Langmuir : the ACS Journal of Surfaces and Colloids. May, 2011  |  Pubmed ID: 21504221

Here we report a simple, robust approach to patterning functional SAMs on germanium. The protocol relies on catalytic soft-lithographic pattern transfer from an elastomeric stamp bearing pendant immobilized sulfonic acid moieties to an NHS-functionalized bilayer molecular system comprising a primary ordered alkyl monolayer and a reactive ester secondary overlayer. The catalytic polyurethane-acrylate stamp was used to form micrometer-scale features of chemically distinct SAMs on germanium. The methodology represents the first example of patterned SAMs on germanium, a semiconductor material.

Soft-lithographic Approach to Functionalization and Nanopatterning Oxide-free Silicon

Langmuir : the ACS Journal of Surfaces and Colloids. May, 2011  |  Pubmed ID: 21520913

We report a simple, reliable high-throughput method for patterning passivated silicon with reactive organic monolayers and demonstrate selective functionalization of the patterned substrates with both small molecules and proteins. The approach completely protects silicon from chemical oxidation, provides precise control over the shape and size of the patterned features in the 100 nm domain, and gives rapid, ready access to chemically discriminated patterns that can be further functionalized with both organic and biological molecules.

Thermodynamic Modeling and Investigation of the Formation of Electrospun Collagen Fibers

Langmuir : the ACS Journal of Surfaces and Colloids. Oct, 2011  |  Pubmed ID: 21823663

Electrospun type I collagen fibers are very promising materials for tissue scaffold applications, but are typically fabricated from toxic solvents. Recently, electrospinning of type I collagen fibers by using environmentally friendly phosphate buffer saline (PBS)/ethanol solution has been explored. PBS/ethanol solvent systems offer better cell compatibility, but the high surface tension and high boiling point of the solvent system make the collagen difficult to electrospin and can cause inferior fiber morphology. In this study, the influence of solvent surface tension on the morphology of electrospun collagen fibers has been experimentally investigated and analyzed from a thermodynamics perspective. The analytical results indicate that solvents with high surface tension drive the formation of beads along the smaller, thinner fibers. In addition, beads with relatively small angular eccentricity were thermodynamically favorable. The experimental results presented herein corroborate the theoretical analysis and conclusions drawn from this study. The surface tension of the solvent has significant influence on the bead formation, especially in an aqueous system. The environmental humidity for the electrospinning process and the collagen concentration were also investigated. These parameters may result in variations of the evaporation-solidification rates, which consequently impact the formation and morphologies of electrospun collagen fibers. According to the thermodynamic analysis, uniform electrospun collagen fibers without beads can be obtained by manipulating solvent surface tension during the electrospinning process.

The Potential Role for Corticosterone in the Induction of Cleft Palate in Mice After Treatment with a Selective NK-1 Receptor Antagonist, Casopitant (GW679769B)

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Nov, 2011  |  Pubmed ID: 22127931

Background: Casopitant is a potent and selective NK-1 receptor antagonist that has shown clinical efficacy in the prevention of chemotherapy-induced and postoperative-induced nausea and vomiting. Methods: In an embryo-fetal development study, pregnant mice were given vehicle (sterile water) or doses of 30, 100, or 300 mg/kg/day casopitant on Gestation Day (GD) 6 to 15. Fetuses were evaluated for external, visceral, and skeletal abnormalities on GD 18. In a follow-on study to investigate casopitant-induced hormonal changes during the developmental period for palate formation, pregnant mice were given vehicle (sterile water) or 300 mg/kg/day casopitant once daily on GD 6 to 13. Blood was collected on GD 13 at various time-points for measurement of plasma adrenocorticotropic hormone and corticosterone (CRT) concentrations. Results: There was no evidence of developmental toxicity in mice at 30 or 100 mg/kg/day but 9% of fetuses at 300 mg/kg/day had cleft palate. Mice are sensitive to glucocorticoid-induced cleft palates, and NK-1 antagonists are known to modulate the hypothalamic-pituitary-adrenal axis leading to increases in corticosterone. On GD 13, mean plasma adrenocorticotropic hormone levels at 300 mg/kg/day were elevated by approximately twofold from vehicle-treated levels at 1 hr post-dose and mean plasma CRT levels were elevated by 3, 5, and 10-fold at 0.5, 1, and 2 hr post-dose, respectively. Conclusions: The increased level of CRT was in the range previously shown in the literature to cause cleft palates in mice and was likely the underlying mechanism behind casopitant-induced cleft palate in mice. Birth Defects Res (Part B) XX:1-9, 2011. © 2011 Wiley Periodicals, Inc.

Note: Curve Fit Models for Atomic Force Microscopy Cantilever Calibration in Water

The Review of Scientific Instruments. Nov, 2011  |  Pubmed ID: 22129023

Atomic force microscopy stiffness calibrations performed on commercial instruments using the thermal noise method on the same cantilever in both air and water can vary by as much as 20% when a simple harmonic oscillator model and white noise are used in curve fitting. In this note, several fitting strategies are described that reduce this difference to about 11%.

Reinforcement of Electrospun Membranes Using Nanoscale Al(2) O(3) Whiskers for Improved Tissue Scaffolds

Journal of Biomedical Materials Research. Part A. Jan, 2012  |  Pubmed ID: 22275136

Poly(ε-caprolactone) (PCL) is a promising material for tissue engineering applications; however, it can be difficult to create scaffolds with the morphology, hydrophilicity, and mechanical properties necessary to support tissue growth. Typically, pure PCL scaffolds have good cellular adhesion, but somewhat low mechanical properties (elastic modulus and tensile strength). This study addresses these issues by incorporating Al(2) O(3) whiskers as reinforcements within PCL membranes generated by electrospinning. Membranes were prepared with Al(2) O(3) content ranging from 1 to 20 wt % and characterized using XRD, TEM, and SEM to determine composition and morphology. The Al(2) O(3) whiskers were well dispersed within the PCL fibers, and the membranes had a highly porous morphology. The elastic modulus was significantly improved by the well aligned whisker reinforcements as verified by tensile testing. The cell morphology and proliferation studies demonstrate Al(2) O(3) whisker reinforced PCL scaffolds maintained the good biocompatibility. These improvements demonstrate that Al(2) O(3) whisker reinforced PCL scaffolds can be considered as a biocompatible material for tissue engineering and dental applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Effects of Artemisinins on Reticulocyte Count and Relationship to Possible Embryotoxicity in Confirmed and Unconfirmed Malarial Patients

Birth Defects Research. Part A, Clinical and Molecular Teratology. Feb, 2012  |  Pubmed ID: 22125126

Rat studies suggest that artemisinin-induced decreases in reticulocyte count are a marker for embryotoxicity (in one study, r = 0.82; p < 0.05). In clinical studies, therapeutic doses of artemisinins induced decreases in reticulocyte count that were larger in five of six groups of healthy volunteers (mean decreases of 47-75%) than in 12 groups of patients with malaria (mean decreases of 0-34% and incidences of low reticulocyte count of 0.6-18%). Malaria causes hypoferremia and drug concentrates in infected red cells so, among the explanations for the lesser decreases in patients, is that malaria protects against artemisinin-induced decreases in reticulocyte count by reducing the target tissue levels of active drug and/or ferrous iron which activates the drug to toxic free radicals. The disease could also protect against embryotoxicity in which case pregnant women without malaria would be at greater risk of artemisinin-induced embryotoxicity. Malaria protection against artesunate toxicity has been observed in rats. No artemisinin-induced embryotoxicity has been identified in limited numbers of women with confirmed malaria in the first trimester. However, in large parts of tropical Africa, malaria treatment is based on fever rather than confirmation of parasitemia and many pregnant women without malaria are exposed to antimalarials. No clinical studies have been conducted on uninfected women for whom pregnancy was identified and then an artemisinin was administered subsequently. Testing in rats and/or humans is needed to determine if malaria protects against reticulocytopenia and embryotoxicity and whether the parasite is a more or less sensitive target than the embryo and reticulocyte. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc.