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1.  Surface Characteristics and Bioactivity of a Novel Natural HA/Zircon Nanocomposite Coated on Dental Implants 
BioMed Research International  2014;2014:410627.
The surface characteristics of implant which influence the speed and strength of osseointegration include surface chemistry, crystal structure and crystallinity, roughness, strain hardening, and presence of impurities. The aim of this study was to evaluate the bioactivity and roughness of a novel natural hydroxyapatite/zircon (NHA/zircon) nanobiocomposite, coated on 316L stainless steel (SS) soaked in simulated body fluid (SBF). NHA/zircon nanobiocomposite was fabricated with 0 wt.%, 5 wt.%, 10 wt.%, and 15 wt.% of zircon in NHA using ball mill for 20 minutes. The composite mixture was coated on 316L SS using plasma spray method. The results are estimated using the scanning electron microscopy (SEM) observation to evaluate surface morphology, X-ray diffraction (XRD) to analyze phase composition, and transmission electron microscopy (TEM) technique to evaluate the shape and size of prepared NHA. Surfaces roughness tester was performed to characterize the coated nanocomposite samples. The maximum average Ra (14.54 μm) was found in the NHA 10 wt.% of zircon coating. In addition, crystallinity (Xc) was measured by XRD data, which indicated the minimum value (Xc = 41.1%) for the sample containing 10 wt.% of zircon. Maximum bioactivity occurred in the sample containing 10 wt.% of zircon, which was due to two reasons: first, the maximum roughness and, second, the minimum crystallinity of nanobiocomposite coating.
PMCID: PMC4009196  PMID: 24822204
2.  Localized Rejuvenation of a Crystal Mush Recorded in Zircon Temporal and Compositional Variation at the Lassen Volcanic Center, Northern California 
PLoS ONE  2014;9(12):e113157.
Zircon ages and trace element compositions from recent silicic eruptions in the Lassen Volcanic Center (LVC) allow for an evaluation of the timing and conditions of rejuvenation (reheating and mobilization of crystals) within the LVC magmatic system. The LVC is the southernmost active Cascade volcano and, prior to the 1980 eruption of Mount St. Helens, was the site of the only eruption in the Cascade arc during the last century. The three most recent silicic eruptions from the LVC were very small to moderate-sized lava flows and domes of dacite (1915 and 27 ka eruptions of Lassen Peak) and rhyodacite (1.1 ka eruption of Chaos Crags). These eruptions produced mixed and mingled lavas that contain a diverse crystal cargo, including zircon. 238U-230Th model ages from interior and surface analyses of zircon reveal ages from ∼17 ka to secular equilibrium (>350 ka), with most zircon crystallizing during a period between ∼60–200 ka. These data support a model for localized rejuvenation of crystal mush beneath the LVC. This crystal mush evidently is the remnant of magmatism that ended ∼190 ka. Most zircon are thought to have been captured from “cold storage” in the crystal mush (670–725°C, Hf >10,000 ppm, Eu/Eu* 0.25–0.4) locally remobilized by intrusion of mafic magma. A smaller population of zircon (>730°C, Hf <10,000 ppm, Eu/Eu* >0.4) grew in, and are captured from, rejuvenation zones. These data suggest the dominant method to produce eruptible melt within the LVC is small-scale, local rejuvenation of the crystal mush accompanied by magma mixing and mingling. Based on zircon stability, the time required to heat, erupt and then cool to background conditions is relatively short, lasting a maximum of 10 s–1000 s years. Rejuvenation events in the LVC are ephemeral and permit eruption within an otherwise waning and cooling magmatic body.
PMCID: PMC4254462  PMID: 25470726
3.  Diversity in early crustal evolution: 4100 Ma zircons in the Cathaysia Block of southern China 
Scientific Reports  2014;4:5143.
Zircons are crucial to understanding the first 500 Myr of crustal evolution of Earth. Very few zircons of this age (>4050 Ma) have been found other than from a ~300 km diameter domain of the Yilgarn Craton, Western Australia. Here we report SIMS U-Pb and O isotope ratios and trace element analyses for two ~4100 Ma detrital zircons from a Paleozoic quartzite at the Longquan area of the Cathaysia Block. One zircon (207Pb/206Pb age of 4127 ± 4 Ma) shows normal oscillatory zonation and constant oxygen isotope ratios (δ18O = 5.8 to 6.0‰). The other zircon grain has a ~4100 Ma magmatic core surrounded by a ~4070 Ma metamorphic mantle. The magmatic core has elevated δ18O (7.2 ± 0.2‰), high titanium concentration (53 ± 3.4 ppm) and a positive cerium anomaly, yielding anomalously high calculated oxygen fugacity (FMQ + 5) and a high crystallization temperature (910°C). These results are unique among Hadean zircons and suggest a granitoid source generated from dry remelting of partly oxidizing supracrustal sediments altered by surface waters. The ~4100 Ma dry melting and subsequent ~4070 Ma metamorphism provide new evidence for the diversity of the Earth's earliest crust.
PMCID: PMC4042129  PMID: 24888297
4.  Enhanced diffusion of Uranium and Thorium linked to crystal plasticity in zircon 
The effects of crystal-plasticity on the U-Th-Pb system in zircon is studied by quantitative microstructural and microchemical analysis of a large zircon grain collected from pyroxenite of the Lewisian Complex, Scotland. Electron backscatter diffraction (EBSD) mapping reveals a c.18° variation in crystallographic orientation that comprises both a gradual change in orientation and a series of discrete low-angle (<4°) boundaries. These microstructural data are consistent with crystal-plastic deformation of zircon associated with the formation and migration of dislocations. A heterogeneous pattern of dark cathodoluminescence, with the darkest domains coinciding with low-angle boundaries, mimics the deformation microstructure identified by EBSD. Geochemical data collected using the Sensitive High Resolution Ion MicroProbe (SHRIMP) shows a positive correlation between concentrations of the elements U, Th and Pb (ranging from 20–60 ppm, 30–110 ppm, and 14–36 ppm, respectively) and Th/U ratio (1.13 – 1.8) with the deformation microstructure. The highest measured concentrations and Th/U coincide with low-angle boundaries. This enrichment is interpreted to reflect enhanced bulk diffusion of U and Th due to the formation and migration of high-diffusivity dislocations. 207Pb/206Pb ages for individual analyses show no significant variation across the grain, and define a concordant, combined mean age of 2451 ± 14 Ma. This indicates that the grain was deformed shortly after initial crystallization, most probably during retrograde Inverian metamorphism at amphibolite facies conditions. The elevated Th over U and consistent 207Pb/206Pb ages indicates that deformation most likely occurred in the presence of a late-stage magmatic fluid that drove an increase in the Th/U during deformation. The relative enrichment of Th over U implies that Th/U ratio may not always be a robust indicator of crystallization environment. This study provides the first evidence of deformation-related modification of the U-Th system in zircon and has fundamental implications for the application and interpretation of zircon trace element data.
PMCID: PMC1769485  PMID: 17181855
5.  An Open System for Intravascular Ultrasound Imaging 
Visualization of the blood vessels can provide valuable morphological information for diagnosis and therapy strategies for cardiovascular disease. Intravascular ultrasound (IVUS) is able to delineate internal structures of vessel wall with fine spatial resolution. However, the developed IVUS is insufficient to identify the fibrous cap thickness and tissue composition of atherosclerotic lesions. Novel imaging strategies have been proposed, such as increasing the center frequency of ultrasound or using a modulated excitation technique to improve the accuracy of diagnosis. Dual-mode tomography combining IVUS with optical tomography has also been developed to determine tissue morphology and characteristics. The implementation of these new imaging methods requires an open system that allows users to customize the system for various studies. This paper presents the development of an IVUS system that has open structures to support various imaging strategies. The system design is based on electronic components and printed circuit board, and provides reconfigurable hardware implementation, programmable image processing algorithms, flexible imaging control, and raw RF data acquisition. In addition, the proposed IVUS system utilized a miniaturized ultrasound transducer constructed using PMN-PT single crystal for better piezoelectric constant and electromechanical coupling coefficient than traditional lead zirconate titanate (PZT) ceramics. Testing results showed that the IVUS system could offer a minimum detectable signal of 25 μV, allowing a 51 dB dynamic range at 47 dB gain, with a frequency range from 20 to 80 MHz. Finally, phantom imaging, in vitro IVUS vessel imaging, and multimodality imaging with photoacoustics were conducted to demonstrate the performance of the open system.
PMCID: PMC3760234  PMID: 23143570
6.  Targeted vertical cross-sectional imaging with handheld near-infrared dual axes confocal fluorescence endomicroscope 
Biomedical Optics Express  2013;4(2):322-330.
We demonstrate vertical cross-sectional (XZ-plane) images of near-infrared (NIR) fluorescence with a handheld dual axes confocal endomicroscope that reveals specific binding of a Cy5.5-labeled peptide to pre-malignant colonic mucosa. This view is perpendicular to the tissue surface, and is similar to that used by pathologists. The scan head is 10 mm in outer diameter (OD), and integrates a one dimensional (1-D) microelectromechanical systems (MEMS) X-axis scanner and a bulky lead zirconate titanate (PZT) based Z-axis actuator. The microscope images in a raster-scanning pattern with a ±6 degrees (mechanical) scan angle at ~3 kHz in the X-axis (fast) and up to 10 Hz (0–400 μm) in the Z-axis (slow). Vertical cross-sectional fluorescence images are collected with a transverse and axial resolution of 4 and 5 μm, respectively, over a field-of-view of 800 μm (width) × 400 μm (depth). NIR vertical cross-sectional fluorescence images of fresh mouse colonic mucosa demonstrate histology-like imaging performance with this miniature instrument.
PMCID: PMC3567718  PMID: 23412564
(170.1790) Confocal microscopy; (170.3880) Medical and biological imaging; (170.4580) Optical diagnostics for medicine; (170.5810) Scanning microscopy
7.  A three-degree-of-freedom thin-film PZT-actuated microactuator with large out-of-plane displacement 
A novel three degree-of-freedom microactuator based on thin-film lead-zirconate-titanate (PZT) is described with its detailed structural model. Its central rectangular-shaped mirror platform, also referred to as the stage, is actuated by four symmetric PZT bending legs such that each leg provides vertical translation for one corner of the stage. It has been developed to support real-time in vivo vertical cross-sectional imaging with a dual axes confocal endomicroscope for early cancer detection, having large displacements in three axes (z, θx, θy) and a relatively high bandwidth in the z-axis direction. Prototype microactuators closely meet the performance requirements for this application; in the out-of-plane (z-axis) direction, it has shown more than 177 μm of displacement and about 84 Hz of structural natural frequency, when two diagonal legs are actuated at 14V. With all four legs, another prototype of the same design with lighter stage mass has achieved more than 430 μm of out-of-plane displacement at 15V and about 200 Hz of bandwidth. The former design has shown approximately 6.4° and 2.9° of stage tilting about the x-axis and y-axis, respectively, at 14V. This paper also presents a modeling technique that uses experimental data to account for the effects of fabrication uncertainties in residual stress and structural dimensions. The presented model predicts the static motion of the stage within an average absolute error of 14.6 μm, which approaches the desired imaging resolution, 5 μm, and also reasonably anticipates the structural dynamic behavior of the stage. The refined model will support development of a future trajectory tracking controller for the system.
PMCID: PMC4262122  PMID: 25506131
piezoelectric actuator; multi-axis microactuator; microactuator modeling; PZT; endomicroscopy
8.  Fabrication and Performance of Endoscopic Ultrasound Radial Arrays Based on PMN-PT Single Crystal/Epoxy 1-3 Composite 
In this paper, 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) single crystal/epoxy 1–3 composite was used as the active material of the endoscopic ultrasonic radial array transducer, because this composite exhibited ultrahigh electromechanical coupling coefficient (kt = 0.81%), very low mechanical quality factor (Qm = 11) and relatively low acoustic impedance (Zt = 12 MRayls). A 6.91 MHz PMN-PT/epoxy 1–3 composite radial array transducer with 64 elements was tested in a pulse-echo response measurement. The −6-dB bandwidth of the composite array transducer was 102%, which was ~30% larger than that of traditional lead zirconate titanate array transducer. The two-way insertion loss was found to be −32.3 dB. The obtained results show that this broadband array transducer is promising for acquiring high-resolution endoscopic ultrasonic images in many clinical applications.
PMCID: PMC3056406  PMID: 21342833
9.  Ferroelectric translational antiphase boundaries in nonpolar materials 
Nature Communications  2014;5:3031.
Ferroelectric materials are heavily used in electro-mechanics and electronics. Inside the ferroelectric, domain walls separate regions in which the spontaneous polarization is differently oriented. Properties of ferroelectric domain walls can differ from those of the domains themselves, leading to new exploitable phenomena. Even more exciting is that a non-ferroelectric material may have domain boundaries that are ferroelectric. Many materials possess translational antiphase boundaries. Such boundaries could be interesting entities to carry information if they were ferroelectric. Here we show first that antiphase boundaries in antiferroelectrics may possess ferroelectricity. We then identify these boundaries in the classical antiferroelectric lead zirconate and evidence their polarity by electron microscopy using negative spherical-aberration imaging technique. Ab initio modelling confirms the polar bi-stable nature of the walls. Ferroelectric antiphase boundaries could make high-density non-volatile memory; in comparison with the magnetic domain wall memory, they do not require current for operation and are an order of magnitude thinner.
In ferroelectrics, the domain walls can have different properties than the domains themselves. Here, Wei et al. show that certain domain walls in antiferroelectric materials are ferroelectric, which makes them interesting candidates for new non-volatile memory concepts.
PMCID: PMC3941019  PMID: 24398704
10.  Large Stroke Vertical PZT Microactuator With High-Speed Rotational Scanning 
A thin-film piezoelectric microactuator using a novel combination of active vertical translational scanning and passive resonant rotational scanning is presented. Thin-film lead-zirconate-titanate unimorph bending beams surrounding a central platform provide nearly 200-μm displacement at 18 V with bandwidth greater than 200 Hz. Inside the platform, a mirror mount, or mirror surface, supported by silicon dioxide spring beams can be excited to resonance by low-voltage; high-frequency excitation of the outer PZT beams. Over ±5.5° mechanical resonance is obtained at 3.8 kHz and ±2 V. The combination of large translational vertical displacements and high-speed rotational scanning is intended to support real-time cross-sectional imaging in a dual axes confocal endomicroscope.
PMCID: PMC4262091  PMID: 25506187
Microactuators; piezoelectric transducers; microscopy
11.  Identifying the Volcanic Eruption Depicted in a Neolithic Painting at Çatalhöyük, Central Anatolia, Turkey 
PLoS ONE  2014;9(1):e84711.
A mural excavated at the Neolithic Çatalhöyük site (Central Anatolia, Turkey) has been interpreted as the oldest known map. Dating to ∼6600 BCE, it putatively depicts an explosive summit eruption of the Hasan Dağı twin-peaks volcano located ∼130 km northeast of Çatalhöyük, and a birds-eye view of a town plan in the foreground. This interpretation, however, has remained controversial not least because independent evidence for a contemporaneous explosive volcanic eruption of Hasan Dağı has been lacking. Here, we document the presence of andesitic pumice veneer on the summit of Hasan Dağı, which we dated using (U-Th)/He zircon geochronology. The (U-Th)/He zircon eruption age of 8.97±0.64 ka (or 6960±640 BCE; uncertainties 2σ) overlaps closely with 14C ages for cultural strata at Çatalhöyük, including level VII containing the “map” mural. A second pumice sample from a surficial deposit near the base of Hasan Dağı records an older explosive eruption at 28.9±1.5 ka. U-Th zircon crystallization ages in both samples range from near-eruption to secular equilibrium (>380 ka). Collectively, our results reveal protracted intrusive activity at Hasan Dağı punctuated by explosive venting, and provide the first radiometric ages for a Holocene explosive eruption which was most likely witnessed by humans in the area. Geologic and geochronologic lines of evidence thus support previous interpretations that residents of Çatalhöyük artistically represented an explosive eruption of Hasan Dağı volcano. The magmatic longevity recorded by quasi-continuous zircon crystallization coupled with new evidence for late-Pleistocene and Holocene explosive eruptions implicates Hasan Dağı as a potential volcanic hazard.
PMCID: PMC3885600  PMID: 24416270
12.  Isotopic evidence for continental ice sheet in mid-latitude region in the supergreenhouse Early Cretaceous 
Scientific Reports  2013;3:2732.
Cretaceous represents one of the hottest greenhouse periods in the Earth's history, but some recent studies suggest that small ice caps might be present in non-polar regions during certain periods in the Early Cretaceous. Here we report extremely negative δ18O values of −18.12‰ to −13.19‰ for early Aptian hydrothermal zircon from an A-type granite at Baerzhe in northeastern China. Given that A-type granite is anhydrous and that magmatic zircon of the Baerzhe granite has δ18O value close to mantle values, the extremely negative δ18O values for hydrothermal zircon are attributed to addition of meteoric water with extremely low δ18O, mostly likely transported by glaciers. Considering the paleoaltitude of the region, continental glaciation is suggested to occur in the early Aptian, indicating much larger temperature fluctuations than previously thought during the supergreenhouse Cretaceous. This may have impact on the evolution of major organism in the Jehol Group during this period.
PMCID: PMC3781392  PMID: 24061068
13.  Single crystal U–Pb zircon age and Sr–Nd isotopic composition of impactites from the Bosumtwi impact structure, Ghana: Comparison with country rocks and Ivory Coast tektites 
Chemical Geology  2010;275(3-4):254-261.
The 1.07 Myr old Bosumtwi impact structure (Ghana), excavated in 2.1–2.2 Gyr old supracrustal rocks of the Birimian Supergroup, was drilled in 2004. Here, we present single crystal U–Pb zircon ages from a suevite and two meta-graywacke samples recovered from the central uplift (drill core LB-08A), which yield an upper Concordia intercept age of ca. 2145 ± 82 Ma, in very good agreement with previous geochronological data for the West African Craton rocks in Ghana. Whole rock Rb–Sr and Sm–Nd isotope data of six suevites (five from inside the crater and one from outside the northern crater rim), three meta-graywacke, and two phyllite samples from core LB-08A are also presented, providing further insights into the timing of the metamorphism and a possibly related isotopic redistribution of the Bosumtwi crater rocks. Our Rb–Sr and Sm–Nd data show also that the suevites are mixtures of meta-greywacke and phyllite (and possibly a very low amount of granite). A comparison of our new isotopic data with literature data for the Ivory Coast tektites allows to better constrain the parent material of the Ivory Coast tektites (i.e., distal impactites), which is thought to consist of a mixture of metasedimentary rocks (and possibly granite), but with a higher proportion of phyllite (and shale) than the suevites (i.e., proximal impactites). When plotted in a Rb/Sr isochron diagram, the sample data points (n = 29, including literature data) scatter along a regression line, whose slope corresponds to an age of 1846 ± 160 Ma, with an initial Sr isotope ratio of 0.703 ± 0.002. However, due to the extensive alteration of some of the investigated samples and the lithological diversity of the source material, this age, which is in close agreement with a possible “metamorphic age” of ∼ 1.8–1.9 Ga tentatively derived from our U–Pb dating of zircons, is difficult to consider as a reliable metamorphic age. It may perhaps reflect a common ancient source whose Rb–Sr isotope systematics has not basically been reset on the whole rock scale during the Bosumtwi impact event, or even reflect another unknown geologic event.
PMCID: PMC2949568  PMID: 21037794
Impactite; U–Pb zircon; Sr–Nd isotopes; Bosumtwi crater; Ghana
14.  Timescales of Quartz Crystallization and the Longevity of the Bishop Giant Magma Body 
PLoS ONE  2012;7(5):e37492.
Supereruptions violently transfer huge amounts (100 s–1000 s km3) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ∼760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500–3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies.
PMCID: PMC3364253  PMID: 22666359
15.  In-Situ U–Pb Dating of Apatite by Hiroshima-SHRIMP: Contributions to Earth and Planetary Science 
Mass Spectrometry  2012;1(2):A0011.
The Sensitive High Resolution Ion MicroProbe (SHRIMP) is the first ion microprobe dedicated to geological isotopic analyses, especially in-situ analyses related to the geochronology of zircon. Such a sophisticated ion probe, which can attain a high sensitivity at a high mass resolution, based on a double focusing high mass-resolution spectrometer, designed by Matsuda (1974), was constructed at the Australian National University. In 1996, such an instrument was installed at Hiroshima University and was the first SHRIMP to be installed in Japan. Since its installation, our focus has been on the in-situ U–Pb dating of the mineral apatite, as well as zircon, which is a more common U-bearing mineral. This provides the possibility for extending the use of in-situ U–Pb dating from determining the age of formation of volcanic, granitic, sedimentary and metamorphic minerals to the direct determination of the diagenetic age of fossils and/or the crystallization age of various meteorites, which can provide new insights into the thermal history on the Earth and/or the Solar System. In this paper, we review the methodology associated with in-situ apatite dating and our contribution to Earth and Planetary Science over the past 16 years.
PMCID: PMC3775829  PMID: 24349912
in-situ analyses; U–Pb dating; SIMS; ion microprobe; chronology
16.  Proceedings of the 2010 National Toxicology Program Satellite Symposium 
Toxicologic pathology  2010;39(1):240-266.
The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Chicago, Illinois, in advance of the scientific symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an overview of mouse ovarian tumors.
PMCID: PMC3096448  PMID: 21177527
NTP Satellite Symposium; INHAND nomenclature; hepatocholangiocarcinoma; acinar-islet cell; preputial gland; hyaline glomerulopathy; eosinophilic substance; ependymoma; axonal degeneration; retinal gliosis; fibroadnexal hamartoma; intramural plaque; chloracne; ovary; cholangiocarcinoma
17.  Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling. 
Environmental Health Perspectives  1998;106(Suppl 6):1385-1393.
Systematic toxicity testing, using conventional toxicology methodologies, of single chemicals and chemical mixtures is highly impractical because of the immense numbers of chemicals and chemical mixtures involved and the limited scientific resources. Therefore, the development of unconventional, efficient, and predictive toxicology methods is imperative. Using carcinogenicity as an end point, we present approaches for developing predictive tools for toxicologic evaluation of chemicals and chemical mixtures relevant to environmental contamination. Central to the approaches presented is the integration of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) and quantitative structure--activity relationship (QSAR) modeling with focused mechanistically based experimental toxicology. In this development, molecular and cellular biomarkers critical to the carcinogenesis process are evaluated quantitatively between different chemicals and/or chemical mixtures. Examples presented include the integration of PBPK/PD and QSAR modeling with a time-course medium-term liver foci assay, molecular biology and cell proliferation studies. Fourier transform infrared spectroscopic analyses of DNA changes, and cancer modeling to assess and attempt to predict the carcinogenicity of the series of 12 chlorobenzene isomers. Also presented is an ongoing effort to develop and apply a similar approach to chemical mixtures using in vitro cell culture (Syrian hamster embryo cell transformation assay and human keratinocytes) methodologies and in vivo studies. The promise and pitfalls of these developments are elaborated. When successfully applied, these approaches may greatly reduce animal usage, personnel, resources, and time required to evaluate the carcinogenicity of chemicals and chemical mixtures.
PMCID: PMC1533423  PMID: 9860897
18.  Continuing Education Course #1: Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology 
Toxicologic pathology  2010;39(1):267-272.
The continuing education course “Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology” provided a thorough overview of commonly used imaging modalities and the logistics required for integration of small animal imaging into toxicologic pathology. Non-invasive imaging (NIN) is gaining acceptance as an important modality in toxicologic pathology. This technology allows non-terminal, time-course evaluation of functional and morphologic endpoints and can be used to translate biomarkers between preclinical animal models and human patients. Non-invasive imaging can support drug development as well as basic research in academic or industrial environments. An initial overview of theoretical principles was followed by focused presentations on magnetic resonance imaging (MRI)/magnetic resonance microscopy (MRM), positron emission tomography (PET)/single proton emission computed tomography (SPECT), ultrasonography (US, primarily focused on echocardiography), optical (bioluminescent) imaging, and computed tomography (CT). The choice of imaging modality will depend on the research question and the needed resolution.
PMCID: PMC3519422  PMID: 21147931
Non-invasive imaging; magnetic resonance imaging; computed tomography; ultrasound; positron emission tomography; single proton emission computed tomography; optical imaging
19.  Nanocolumnar Preferentially Oriented PSZT Thin Films Deposited on Thermally Grown Silicon Dioxide 
Nanoscale Research Letters  2008;4(1):29-33.
We report the first instance of deposition of preferentially oriented, nanocrystalline, and nanocolumnar strontium-doped lead zirconate titanate (PSZT) ferroelectric thin films directly on thermal silicon dioxide. No intermediate seed or activation layers were used between PSZT and silicon dioxide. The deposited thin films have been characterised using a combination of diffraction and microscopy techniques.
PMCID: PMC2894225  PMID: 20596364
PSZT thin films; Silicon dioxide; Nanocrystal; XRD; Microscopy
20.  High-overtone Self-Focusing Acoustic Transducers for High Frequency Ultrasonic Doppler 
Ultrasonics  2010;50(6):544-547.
This work reports the potential use of high-overtone self-focusing acoustic transducers for high frequency ultrasonic Doppler. By using harmonic frequencies of a thick bulk Lead Zirconate Titanate (PZT) transducer with a novel air-reflector Fresnel lens, we obtained strong ultrasound signals at 60 MHz (3rd harmonic) and 100 MHz (5th harmonic). Both experimental and theoretical analysis has demonstrated that the transducers can be applied to Doppler systems with high frequencies up to 100 MHz.
PMCID: PMC2856643  PMID: 20206371
Acoustic transducer; Self-focusing; Air-reflector; Doppler
21.  Nano-embossing technology on ferroelectric thin film Pb(Zr0.3,Ti0.7)O3 for multi-bit storage application 
Nanoscale Research Letters  2011;6(1):474.
In this work, we apply nano-embossing technique to form a stagger structure in ferroelectric lead zirconate titanate [Pb(Zr0.3, Ti0.7)O3 (PZT)] films and investigate the ferroelectric and electrical characterizations of the embossed and un-embossed regions, respectively, of the same films by using piezoresponse force microscopy (PFM) and Radiant Technologies Precision Material Analyzer. Attributed to the different layer thickness of the patterned ferroelectric thin film, two distinctive coercive voltages have been obtained, thereby, allowing for a single ferroelectric memory cell to contain more than one bit of data.
PMCID: PMC3211987  PMID: 21794156
22.  Particle manipulation in a microfluidic channel using acoustic trap 
Biomedical microdevices  2011;13(4):779-788.
A high frequency sound beam was employed to explore an experimental method that could control particle motions in a microfluidic device. A 24 MHz single element lead zirconate titanate (PZT) transducer was built to transmit a focused ultrasound of variable duty factors (pulse duration/pulse repetition time), and its 1–3 piezo-composite structure established a tight focusing with f-number (focal depth/aperture size) of one. The transducer was excited by the Chebyshev windowed chirp signal sweeping from 18 MHz to 30 MHz with a 50% of duty factor, in order to ensure that enough sound beams were penetrated into the microfluidic device. The device was fabricated from a polydimethylsiloxane (PDMS) mold, and had a main channel composed of three subchannels among which particles flowed in the middle. A 60~70 μm diameter single droplet in the flow could be trapped near the channel bifurcation, and subsequently diverted into the sheath flow by releasing or shifting the acoustic trap. Hence, the results showed the potential use of a focused sound beam in microfluidic devices, and further suggested that this method could be exploited in the development of ultrasound-based flow cytometry and cell sorting devices.
PMCID: PMC3217264  PMID: 21603963
Particle manipulation; Acoustic trap; High frequency transducer; Microfluidic device
23.  Sub-Frequency Interval Approach in Electromechanical Impedance Technique for Concrete Structure Health Monitoring 
Sensors (Basel, Switzerland)  2010;10(12):11644-11661.
The electromechanical (EM) impedance technique using piezoelectric lead zirconate titanate (PZT) transducers for structural health monitoring (SHM) has attracted considerable attention in various engineering fields. In the conventional EM impedance technique, the EM admittance of a PZT transducer is used as a damage indicator. Statistical analysis methods such as root mean square deviation (RMSD) have been employed to associate the damage level with the changes in the EM admittance signatures, but it is difficult to determine the location of damage using such methods. This paper proposes a new approach by dividing the large frequency (30–400 kHz) range into sub-frequency intervals and calculating their respective RMSD values. The RMSD of the sub-frequency intervals (RMSD-S) will be used to study the severity and location of damage. An experiment is carried out on a real size concrete structure subjected to artificial damage. It is observed that damage close to the PZT changes the high frequency range RMSD-S significantly, while the damage far away from the PZT changes the RMSD-S in the low frequency range significantly. The relationship between the frequency range and the PZT sensing region is also presented. Finally, a damage identification scheme is proposed to estimate the location and severity of damage in concrete structures.
PMCID: PMC3231059  PMID: 22163548
piezoelectric; Electromechanical Impedance (EMI); concrete; Structural Health Monitoring (SHM)
24.  A Piezoelectric Plethysmograph Sensor Based on a Pt Wire Implanted Lead Lanthanum Zirconate Titanate Bulk Ceramic 
Sensors (Basel, Switzerland)  2010;10(8):7146-7156.
This work reports on the development of a Lead Lanthanum Zirconate Titanate (PLZT) bulk ferroelectric poled ceramic structure as a Piezoelectric Plethysmograph (PZPG) sensor. The ceramic was implanted during its fabrication with a platinum (Pt) wire which works as an internal electrode. The ceramic was then submitted to an experimental setup in order to validate and determine the Pt-wire mechanical effects. This PZPG sensor was also mounted on a finger splint in order to measure the blood flow that results from the pulsations of blood occurring with each heartbeat. Fingertip pulses were recorded jointly with an ECG signal from a 25 year old male to compare the time shift; the PZPG sensor guarantees the electrical isolation of the patient. The proposed PZPG has several advantages: it can be adjusted for fingertip measurements, but it can easily be extended by means of spare bands, therefore making possible PZPG measurements from different body locations, e.g., forehead, forearm, knee, neck, etc.
PMCID: PMC3231161  PMID: 22163596
PLZT application; ceramic implants; plethysmography
25.  Nanocolumnar Preferentially Oriented PSZT Thin Films Deposited on Thermally Grown Silicon Dioxide 
Nanoscale Research Letters  2008;4(1):29-33.
We report the first instance of deposition of preferentially oriented, nanocrystalline, and nanocolumnar strontium-doped lead zirconate titanate (PSZT) ferroelectric thin films directly on thermal silicon dioxide. No intermediate seed or activation layers were used between PSZT and silicon dioxide. The deposited thin films have been characterised using a combination of diffraction and microscopy techniques.
PMCID: PMC2894225  PMID: 20596364
PSZT thin films; Silicon dioxide; Nanocrystal; XRD; Microscopy

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