Science.gov

Sample records for aberration corrected stem

  1. Brief history of the Cambridge STEM aberration correction project and its progeny.

    PubMed

    Brown, L Michael; Batson, Philip E; Dellby, Niklas; Krivanek, Ondrej L

    2015-10-01

    We provide a brief history of the project to correct the spherical aberration of the scanning transmission electron microscope (STEM) that started in Cambridge (UK) and continued in Kirkland (WA, USA), Yorktown Heights (NY, USA), and other places. We describe the project in the full context of other aberration correction research and related work, partly in response to the incomplete context presented in the paper "In quest of perfection in electron optics: A biographical sketch of Harald Rose on the occasion of his 80th birthday", recently published in Ultramicroscopy.

  2. Brief history of the Cambridge STEM aberration correction project and its progeny.

    PubMed

    Brown, L Michael; Batson, Philip E; Dellby, Niklas; Krivanek, Ondrej L

    2015-10-01

    We provide a brief history of the project to correct the spherical aberration of the scanning transmission electron microscope (STEM) that started in Cambridge (UK) and continued in Kirkland (WA, USA), Yorktown Heights (NY, USA), and other places. We describe the project in the full context of other aberration correction research and related work, partly in response to the incomplete context presented in the paper "In quest of perfection in electron optics: A biographical sketch of Harald Rose on the occasion of his 80th birthday", recently published in Ultramicroscopy. PMID:26094204

  3. Coalescence and sintering of Pt nanoparticles: in situ observation by aberration-corrected HAADF STEM.

    PubMed

    Asoro, M A; Kovar, D; Shao-Horn, Y; Allard, L F; Ferreira, P J

    2010-01-15

    An aberration-corrected JEOL 2200FS scanning-transmission electron microscope (STEM), equipped with a high-angle annular dark-field detector (HAADF), is used to monitor the coalescence and sintering of Pt nanoparticles with an average diameter of 2.8 nm. This in situ STEM capability is combined with an analysis methodology that together allows direct measurements of mass transport phenomena that are important in understanding how particle size influences coalescence and sintering at the nanoscale. To demonstrate the feasibility of this methodology, the surface diffusivity is determined from measurements obtained from STEM images acquired during the initial stages of sintering. The measured surface diffusivities are in reasonable agreement with measurements made on the surface of nanoparticles, using other techniques. In addition, the grain boundary mobility is determined from measurements made during the latter stages of sintering. PMID:19955618

  4. Coalescence and sintering of Pt nanoparticles: in situ observation by aberration-corrected HAADF STEM

    NASA Astrophysics Data System (ADS)

    Asoro, M. A.; Kovar, D.; Shao-Horn, Y.; Allard, L. F.; Ferreira, P. J.

    2010-01-01

    An aberration-corrected JEOL 2200FS scanning-transmission electron microscope (STEM), equipped with a high-angle annular dark-field detector (HAADF), is used to monitor the coalescence and sintering of Pt nanoparticles with an average diameter of 2.8 nm. This in situ STEM capability is combined with an analysis methodology that together allows direct measurements of mass transport phenomena that are important in understanding how particle size influences coalescence and sintering at the nanoscale. To demonstrate the feasibility of this methodology, the surface diffusivity is determined from measurements obtained from STEM images acquired during the initial stages of sintering. The measured surface diffusivities are in reasonable agreement with measurements made on the surface of nanoparticles, using other techniques. In addition, the grain boundary mobility is determined from measurements made during the latter stages of sintering.

  5. Aberration-corrected STEM imaging of Ag on gamma-Al2O3.

    PubMed

    Blom, Douglas A; Allard, Lawrence F; Narula, Chaitanya K; Moses-DeBusk, Melanie J

    2008-02-01

    Ag on gamma-alumina is a promising catalyst for hydrocarbon selective catalytic reduction in lean-burn gasoline and diesel engines for transportation applications. Although much is known about the mechanism of NOx reduction and the various intermediates, little agreement exists on the nature of the active silver species. In the present work, aberration-corrected STEM has provided new information about the nature of Ag on alumina both as impregnated and following treatments at various temperatures with exposure to simulated exhaust gas. Ex situ techniques have provided new insights into the evolution of Ag on alumina following exposure to temperature and simulated exhaust gas.

  6. Aberration corrected emittance exchange

    NASA Astrophysics Data System (ADS)

    Nanni, E. A.; Graves, W. S.

    2015-08-01

    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (rf) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by multiple orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dogleg emittance exchange setup with a five cell rf deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of an EEX line with emittances differing by four orders of magnitude, i.e., an initial transverse emittance of 1 pm-rad is exchanged with a longitudinal emittance of 10 nm-rad.

  7. Aberration-corrected STEM for atomic-resolution imaging and analysis.

    PubMed

    Krivanek, O L; Lovejoy, T C; Dellby, N

    2015-09-01

    Aberration-corrected scanning transmission electron microscopes are able to form electron beams smaller than 100 pm, which is about half the size of an average atom. Probing materials with such beams leads to atomic-resolution images, electron energy loss and energy-dispersive X-ray spectra obtained from single atomic columns and even single atoms, and atomic-resolution elemental maps. We review briefly how such electron beams came about, and show examples of applications. We also summarize recent developments that are propelling aberration-corrected scanning transmission electron microscopes in new directions, such as complete control of geometric aberration up to fifth order, and ultra-high-energy resolution EELS that is allowing vibrational spectroscopy to be carried out in the electron microscope.

  8. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).

    PubMed

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony

    2014-01-01

    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.

  9. Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).

    PubMed

    Kim, Taehyun; Bershteyn, Marina; Wynshaw-Boris, Anthony

    2014-01-01

    The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations. PMID:25482192

  10. Interfacial atomic structure analysis at sub-angstrom resolution using aberration-corrected STEM

    NASA Astrophysics Data System (ADS)

    Hsiao, Chien-Nan; Kuo, Shou-Yi; Lai, Fang-I.; Chen, Wei-Chun

    2014-10-01

    The atomic structure of a SiGe/Si epitaxial interface grown via molecular beam epitaxy on a single crystal silicon substrate was investigated using an aberration-corrected scanning transmittance electron microscope equipped with a high-angle annular dark-field detector and an energy-dispersive spectrometer. The accuracy required for compensation of the various residual aberration coefficients to achieve sub-angstrom resolution with the electron optics system was also evaluated. It was found that the interfacial layer was composed of a silicon single crystal, connected coherently to epitaxial SiGe nanolaminates. In addition, the distance between the dumbbell structures of the Si and Ge atoms was approximately 0.136 nm at the SiGe/Si interface in the [110] orientation. The corresponding fast Fourier transform exhibited a sub-angstrom scale point resolution of 0.78 Å. Furthermore, the relative positions of the atoms in the chemical composition line scan signals could be directly interpreted from the corresponding incoherent high-angle annular dark-field image.

  11. Aberration correction of unstable resonators

    NASA Technical Reports Server (NTRS)

    Lang, Robert J. (Inventor)

    1994-01-01

    Construction of aspheric reflectors for unstable resonator lasers to provide an arbitrary laser mode inside the resonator to correct aberrations of an output beam by the construction of the shape of an end reflector opposite the output reflector of the resonator cavity, such as aberrations resulting from refraction of a beam exiting the solid of the resonator having an index of refraction greater than 1 or to produce an aberration in the output beam that will precisely compensate for the aberration of an optical train into which the resonator beam is coupled.

  12. Identification of magnetic properties of few nm sized FePt crystalline particles by characterizing the intrinsic atom order using aberration corrected S/TEM.

    PubMed

    Biskupek, Johannes; Jinschek, Joerg R; Wiedwald, Ulf; Bendele, Markus; Han, Luyang; Ziemann, Paul; Kaiser, Ute

    2010-06-01

    Hard-magnetic nanomaterials like nanoparticles of FePt are of great interest because of their promising potential for data storage applications. The magnetic properties of FePt structures strongly differ whether the crystal phases are face centered cubic (fcc) or face centered tetragonal (fct). We evaluated aberration corrected HRTEM, electron diffraction and aberration corrected HAADF-STEM as methods to measure the chemical degree of order S that describes the ordering of Pt and Fe atoms within the crystals unit cells. S/TEM experiments are accompanied by image calculations. The findings are compared with results obtained from X-ray diffraction on a FePt film. Our results show that STEM is a reasonable fast approach over HRTEM and electron diffraction to locally determine the chemical degree of order S.

  13. Correction of Distributed Optical Aberrations

    SciTech Connect

    Baker, K; Olivier, S; Carrano, C; Phillion, D

    2006-02-12

    The objective of this project was to demonstrate the use of multiple distributed deformable mirrors (DMs) to improve the performance of optical systems with distributed aberrations. This concept is expected to provide dramatic improvement in the optical performance of systems in applications where the aberrations are distributed along the optical path or within the instrument itself. Our approach used multiple actuated DMs distributed to match the aberration distribution. The project developed the algorithms necessary to determine the required corrections and simulate the performance of these multiple DM systems.

  14. Double-aberration corrected TEM/STEM of solid acid nanocatalysts in the development of pharmaceutical NSAIDS

    NASA Astrophysics Data System (ADS)

    Yoshida, K.; Shiju, N.; Brown, R.; Wright, I.; Boyes, E. D.; Gai, P. L.

    2012-07-01

    We report nanostructural and physico-chemical studies in the development of an efficient low temperature heterogeneous catalytic process for nonsteroidal anti-inflammatory drugs (NSAIDS) such as N-acetyl-p-aminophenol (paracetamol or acetaminophen) on tungstated zirconia nanocatalysts. Using a double-aberration corrected TEM/STEM, modified in-house for in-situ studies at the sub-Angstrom level, we directly observed in real-time, the dynamic precursor transformation to the active catalyst. We quantified the observations with catalytic activity studies for the NSAIDS. The studies have provided the direct evidence for single tungsten promoter atoms and surface WOx species of <= 0.35 nm, with nanoclusters of WOx (0.6 to 1nm), located at grain boundaries on the surface of the zirconia nanoparticles. The correlation between the nanostructure and catalytic activity indicates that the species create Brønsted acid sites highly active for the low temperature process. The results open up opportunities for developing green heterogeneous methods for pharmaceuticals.

  15. STEM imaging of 47-pm-separated atomic columns by a spherical aberration-corrected electron microscope with a 300-kV cold field emission gun.

    PubMed

    Sawada, Hidetaka; Tanishiro, Yasumasa; Ohashi, Nobuhiro; Tomita, Takeshi; Hosokawa, Fumio; Kaneyama, Toshikatsu; Kondo, Yukihito; Takayanagi, Kunio

    2009-12-01

    A spherical aberration-corrected electron microscope has been developed recently, which is equipped with a 300-kV cold field emission gun and an objective lens of a small chromatic aberration coefficient. A dumbbell image of 47 pm spacing, corresponding to a pair of atomic columns of germanium aligned along the [114] direction, is resolved in high-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) with a 0.4-eV energy spread of the electron beam. The observed image was compared with a simulated image obtained by dynamical calculation.

  16. Direct observation of atomic columns in a Bi-2223 polycrystal by aberration-corrected STEM using a low accelerating voltage

    NASA Astrophysics Data System (ADS)

    Nagai, Takuro; Haruta, Mitsutaka; Kikuchi, Masashi; Zhang, Weizhu; Takeguchi, Masaki; Kimoto, Koji

    2014-05-01

    Aberration correction in scanning transmission electron microscopy (STEM) enables an atomic-scale probe size of ˜0.1 nm at a low accelerating voltage of 80 kV that avoids knock-on damage in materials including light elements such as oxygen. We used this advanced method of microscopy to directly observe atomic columns in a (Bi,Pb)2Sr2Ca2Cu3O10+δ (Bi-2223) superconducting wire produced by a powder-in-tube method. Using the atomic-number (Z) contrast mechanism, incoherent high-angle annular dark-field (HAADF) imaging clearly showed the atomic columns. Atomic displacements toward the boundary with a maximum magnitude of ˜0.26 nm enable each atomic layer to be continuous at edge grain boundaries (EGBs). The grains tend to be terminated with deficient (Bi,Pb)-O single layers at c-axis twist boundaries (TWBs) and small-angle asymmetrical tilt boundaries (ATBs); a quantitative HAADF analysis showed that the occupancies of the (Bi,Pb) sites around these boundaries are ˜0.66 and ˜0.72, respectively. Electron energy-loss spectroscopy (EELS) mapping successfully visualized atomic columns in the half-unit cell intergrowth of (Bi,Pb)2Sr2CaCu2O8+δ (Bi-2212) and (Bi,Pb)2Sr2Ca3Cu4O12+δ (Bi-2234) phases. Furthermore, the HAADF analysis indicated that the occupancy of the (Bi,Pb) sites is modulated between ˜0.88 and 1.0 along the diagonal direction of the primitive perovskite cell with the same period as the structural modulation.

  17. Aberration corrected environmental STEM (AC ESTEM) for dynamic in-situ gas reaction studies of nanoparticle catalysts

    NASA Astrophysics Data System (ADS)

    Boyes, E. D.; Gai, P. L.

    2014-06-01

    Environmental scanning transmission electron microscopy (ESTEM) with aberration correction (AC) has recently been added to the capabilities of the more established ETEM for analysis of heterogeneous nanoparticle based catalysts. It has helped to reveal the importance and potentially unique properties of individual atoms as active sites in their own right as well as pathways between established nanoparticles. A new capability is introduced for dynamic in-situ experiments under controlled conditions of specimen temperature and gas environment related to real world conditions pertinent to a range of industrial and societal priorities for new and improved chemical processes, materials, fuels, pharmaceutical products and processes, and in control or remediation of environmental emissions.

  18. Atomic-scale observation of migration and coalescence of Au nanoclusters on YSZ surface by aberration-corrected STEM.

    PubMed

    Li, Junjie; Wang, Zhongchang; Chen, Chunlin; Huang, Sumei

    2014-07-01

    Unraveling structural dynamics of noble metal nanoclusters on oxide supports is critical to understanding reaction process and origin of catalytic activity in heterogeneous catalysts. Here, we show that aberration-corrected scanning transmission electron microscopy can provide direct atomic-resolution imaging of surface migration, coalescence, and atomic rearrangement of Au clusters on an Y:ZrO₂ (YSZ) support. The high resolution enables us to reveal migration and coalescence process of Au clusters at the atomic scale, and to demonstrate that the coalesced clusters undergo a cooperative atomic rearrangement, which transforms the coherent into incoherent Au/YSZ interface. This approach can help to elucidate atomistic mechanism of catalytic activities and to develop novel catalysts with enhanced functionality.

  19. Phase and birefringence aberration correction

    DOEpatents

    Bowers, Mark; Hankla, Allen

    1996-01-01

    A Brillouin enhanced four wave mixing phase conjugate mirror corrects phase aberrations of a coherent electromagnetic beam and birefringence induced upon that beam. The stimulated Brillouin scattering (SBS) phase conjugation technique is augmented to include Brillouin enhanced four wave mixing (BEFWM). A seed beam is generated by a main oscillator which arrives at the phase conjugate cell before the signal beams in order to initiate the Brillouin effect. The signal beam which is being amplified through the amplifier chain is split into two perpendicularly polarized beams. One of the two beams is chosen to be the same polarization as some component of the seed beam, the other orthogonal to the first. The polarization of the orthogonal beam is then rotated 90.degree. such that it is parallel to the other signal beam. The three beams are then focused into cell containing a medium capable of Brillouin excitation. The two signal beams are focused such that they cross the seed beam path before their respective beam waists in order to achieve BEFWM or the two signal beams are focused to a point or points contained within the focused cone angle of the seed beam to achieve seeded SBS, and thus negate the effects of all birefringent and material aberrations in the system.

  20. Phase and birefringence aberration correction

    DOEpatents

    Bowers, M.; Hankla, A.

    1996-07-09

    A Brillouin enhanced four wave mixing phase conjugate mirror corrects phase aberrations of a coherent electromagnetic beam and birefringence induced upon that beam. The stimulated Brillouin scattering (SBS) phase conjugation technique is augmented to include Brillouin enhanced four wave mixing (BEFWM). A seed beam is generated by a main oscillator which arrives at the phase conjugate cell before the signal beams in order to initiate the Brillouin effect. The signal beam which is being amplified through the amplifier chain is split into two perpendicularly polarized beams. One of the two beams is chosen to be the same polarization as some component of the seed beam, the other orthogonal to the first. The polarization of the orthogonal beam is then rotated 90{degree} such that it is parallel to the other signal beam. The three beams are then focused into cell containing a medium capable of Brillouin excitation. The two signal beams are focused such that they cross the seed beam path before their respective beam waists in order to achieve BEFWM or the two signal beams are focused to a point or points contained within the focused cone angle of the seed beam to achieve seeded SBS, and thus negate the effects of all birefringent and material aberrations in the system. 5 figs.

  1. Aberration correction past and present.

    PubMed

    Hawkes, P W

    2009-09-28

    Electron lenses are extremely poor: if glass lenses were as bad, we should see as well with the naked eye as with a microscope! The demonstration by Otto Scherzer in 1936 that skillful lens design could never eliminate the spherical and chromatic aberrations of rotationally symmetric electron lenses was therefore most unwelcome and the other great electron optician of those years, Walter Glaser, never ceased striving to find a loophole in Scherzer's proof. In the wartime and early post-war years, the first proposals for correcting C(s) were made and in 1947, in a second milestone paper, Scherzer listed these and other ways of correcting lenses; soon after, Dennis Gabor invented holography for the same purpose. These approaches will be briefly summarized and the work that led to the successful implementation of quadupole-octopole and sextupole correctors in the 1990 s will be analysed. In conclusion, the elegant role of image algebra in describing image formation and processing and, above all, in developing new methods will be mentioned. PMID:19687058

  2. Behavior of Au species in Au/Fe2O3 catalysts characterized by novel in situ heating techniques and aberration-corrected STEM imaging.

    PubMed

    Allard, Lawrence F; Flytzani-Stephanopoulos, Maria; Overbury, Steven H

    2010-08-01

    The recent advent of a novel design of in situ heating technology for electron microscopes has permitted unprecedented control of elevated temperature studies of catalytic materials, particularly when coupled with the sub-Angström imaging performance of a modern aberration-corrected scanning transmission electron microscope (STEM). Using micro-electro-mechanical-systems (MEMS)-based Aduro heating chips from Protochips, Inc. (Raleigh, NC, USA) allows nearly instantaneous heating and cooling of catalyst powders, avoiding effects of temperature ramping as experienced with standard heating stages. The heating technology also provides stable operation limited only by the inherent drift in the microscope stage, thus allowing full image resolution to be achieved even at elevated temperatures. The present study details the use of both the high X-Y spatial resolution in both dark-field and simultaneous bright-field imaging, along with the high resolution in Z (depth sectioning) provided by the large probe incidence semiangle in the aberration-corrected instrument, to characterize the evolution of microstructure in a commercial Au/Fe2O3 water-gas shift catalyst during elevated temperature treatment. The phenomenon of Au diffusion to the surface of hematite support particles to form discrete crystalline Au nanoparticles in the 1-2 nm size range, after a prior leaching treatment to remove surface Au species has been characterized.

  3. Fine structural features of nanoscale zero-valent iron characterized by spherical aberration corrected scanning transmission electron microscopy (Cs-STEM).

    PubMed

    Liu, Airong; Zhang, Wei-xian

    2014-09-21

    An angstrom-resolution physical model of nanoscale zero-valent iron (nZVI) is generated with a combination of spherical aberration corrected scanning transmission electron microscopy (Cs-STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS) and electron energy-loss spectroscopy (EELS) on the Fe L-edge. Bright-field (BF), high-angle annular dark-field (HAADF) and secondary electron (SE) imaging of nZVI acquired by a Hitachi HD-2700 STEM show near atomic resolution images and detailed morphological and structural information of nZVI. The STEM-EDS technique confirms that the fresh nZVI comprises of a metallic iron core encapsulated with a thin layer of iron oxides or oxyhydroxides. SAED patterns of the Fe core suggest the polycrystalline structure in the metallic core and amorphous nature of the oxide layer. Furthermore, Fe L-edge of EELS shows varied structural features from the innermost Fe core to the outer oxide shell. A qualitative analysis of the Fe L(2,3) edge fine structures reveals that the shell of nZVI consists of a mixed Fe(II)/Fe(III) phase close to the Fe (0) interface and a predominantly Fe(III) at the outer surface of nZVI.

  4. Pulse compressor with aberration correction

    SciTech Connect

    Mankos, Marian

    2015-11-30

    In this SBIR project, Electron Optica, Inc. (EOI) is developing an electron mirror-based pulse compressor attachment to new and retrofitted dynamic transmission electron microscopes (DTEMs) and ultrafast electron diffraction (UED) cameras for improving the temporal resolution of these instruments from the characteristic range of a few picoseconds to a few nanoseconds and beyond, into the sub-100 femtosecond range. The improvement will enable electron microscopes and diffraction cameras to better resolve the dynamics of reactions in the areas of solid state physics, chemistry, and biology. EOI’s pulse compressor technology utilizes the combination of electron mirror optics and a magnetic beam separator to compress the electron pulse. The design exploits the symmetry inherent in reversing the electron trajectory in the mirror in order to compress the temporally broadened beam. This system also simultaneously corrects the chromatic and spherical aberration of the objective lens for improved spatial resolution. This correction will be found valuable as the source size is reduced with laser-triggered point source emitters. With such emitters, it might be possible to significantly reduce the illuminated area and carry out ultrafast diffraction experiments from small regions of the sample, e.g. from individual grains or nanoparticles. During phase I, EOI drafted a set of candidate pulse compressor architectures and evaluated the trade-offs between temporal resolution and electron bunch size to achieve the optimum design for two particular applications with market potential: increasing the temporal and spatial resolution of UEDs, and increasing the temporal and spatial resolution of DTEMs. Specialized software packages that have been developed by MEBS, Ltd. were used to calculate the electron optical properties of the key pulse compressor components: namely, the magnetic prism, the electron mirror, and the electron lenses. In the final step, these results were folded

  5. Quantitative analysis of interfacial strain in InAs/GaSb superlattices by aberration-corrected HRTEM and HAADF-STEM.

    PubMed

    Mahalingam, Krishnamurthy; Haugan, Heather J; Brown, Gail J; Eyink, Kurt G

    2013-04-01

    The strain distribution across interfaces in InAs/GaSb superlattices grown on (100)-GaSb substrates is investigated by aberration corrected transmission electron microscopy. Atomic resolution images of interfaces were obtained by conventional high resolution transmission electron microscopy (HRTEM), using the negative spherical-aberration imaging mode, and by scanning transmission electron microscopy (STEM), using the high-angle annular dark-field (HAADF) imaging mode. The local atomic displacements across interfaces were determined from these images using the peak pair algorithm, from which strain maps were calculated with respect to a reference lattice extracted from the GaSb substrate region. Both techniques yield consistent results, which reveal that the InAs-on-GaSb interface is nearly strain balanced, whereas the GaSb-on-InAs interface is in tensile strain, indicating that the prevalent bond type at this interface is Ga-As. In addition, the GaSb layers in the superlattice are compressively strained indicating the incorporation of In into these layers. Further analysis of the HAADF-STEM images indicates an estimated 4% In content in the GaSb layers and that the GaSb-on-InAs interface contributes to about 27% of the overall superlattice strain. The strain measurements in the InAs layers are in good agreement with the theoretical values determined from elastic constants. Furthermore, the overall superlattice strain determined from this analysis is also in good agreement with the measurements determined by high-resolution X-ray diffraction.

  6. Design and Performance Characteristics of the ORNL AdvancedMicroscopy Laboratory and JEOL 2200FS-AC Aberration-CorrectedSTEM/TEM

    SciTech Connect

    Allard, Lawrence F.; Blom, Douglas A.; O'Keefe, Michael A.; Mishina, S.

    2005-02-15

    At ORNL, the new Advanced Microscopy Laboratory (AML) has recently been completed, with two aberration-corrected instruments installed, and two more planned in the near future to fill the 4-laboratory building. The installed JEOL 2200FS-AC has demonstrated aTEM information limit of 0.9A. This limit is expected given the measured instrument parameters (HT and OL power supply stabilities, beam energy spread, etc.), and illustrates that the environmental influences are not adversely affecting the instrument performance. In STEM high-angle annular dark-field (HA-ADF) mode, images of a thin Si crystal in<110>zone axis orientation, after primary aberrations in the illuminating beam were optimally corrected, showed a significant vibration effect. The microscope is fitted with three magnetically levitated turbo pumps (one on the column at about the specimen position,and two near floor level) that pump the Omega energy filter and detector chamber. These pumps run at 48,000 rpm, precisely equivalent to 800Hz. It was determined that the upper turbo pump was contributing essentially all of the 800Hz signal to the image, and in fact that the pump was defective. After replacing the pump with one significantly quieter than the original, the Si atomic column image and associated diffractogram(Fig. 4b) show a much-reduced effect of the 800Hz signal, but still some residual effect from the turbo pump. The upper pump will be removed from the main column to an adjacent frame on the floor, and will have a large-diameter, well-damped, pump line to the original connection to the column to effectively isolate the pump from the column. If the 800Hz signal results from mechanical vibrations, they will be damped, and if the signal results from acoustic coupling to the column, it can be damped by appropriate acoustic materials.

  7. Atomic-resolution study of dislocation structures and interfaces in poly-crystalline thin film CdTe using aberration-corrected STEM

    NASA Astrophysics Data System (ADS)

    Paulauskas, Tadas; Colegrove, Eric; Buurma, Chris; Kim, Moon; Klie, Robert

    2014-03-01

    Commercial success of CdTe-based thin film photovoltaic devices stems from its nearly ideal direct band gap which very effectively couples to Sun's light spectrum as well as ease of manufacturing and low cost of these modules. However, to further improve the conversion efficiency beyond 20 percent, it is important to minimize the harmful effects of grain boundaries and lattice defects in CdTe. Direct atomic-scale characterization is needed in order identify the carrier recombination centers. Likewise, it is necessary to confirm that passivants in CdTe, such as Cl, are able to diffuse and bind to the target defects. In this study, we characterize dislocation structures and grain boundaries in poly-crystalline CdTe using aberration-corrected cold-field emission scanning transmission electron microscopy (STEM). The chemical composition of Shockley partial, Frank and Lomer-Cottrell dislocations is examined via atomic column-resolved X-ray energy dispersive (XEDS) and electron energy-loss spectroscopies (EELS). Segregation of Cl towards dislocation cores and grain boundaries is shown in CdCl2 treated samples. We also investigate interfaces in ultra-high-vacuum bonded CdTe bi-crystals with pre-defined misorientation angles which are intended to mimic grain boundaries. Funded by: DOE EERE Sunshot Award EE0005956.

  8. Migration of Single Iridium Atoms and Tri-iridium Clusters on MgO Surfaces. Aberration-Corrected STEM Imaging and ab-initio Calculations

    SciTech Connect

    Han, Chang W.; Iddir, Hakim; Uzun, Alper; Curtiss, Larry A.; Browning, Nigel D.; Gates, Bruce C.; Ortalan, Volkan

    2015-11-06

    To address the challenge of fast, direct atomic-scale visualization of the diffusion of atoms and clusters on surfaces, we used aberration-corrected scanning transmission electron microscopy (STEM) with high scan speeds (as little as ~0.1 s per frame) to visualize the diffusion of (1) a heavy atom (Ir) on the surface of a support consisting of light atoms, MgO(100), and (2) an Ir3 cluster on MgO(110). Sequential Z-contrast images elucidate the diffusion mechanisms, including the hopping of Ir1 and the rotational migration of Ir3 as two Ir atoms remain anchored to the surface. Density functional theory (DFT) calculations provided estimates of the diffusion energy barriers and binding energies of the iridium species to the surfaces. The results show how the combination of fast-scan STEM and DFT calculations allow real-time visualization and fundamental understanding of surface diffusion phenomena pertaining to supported catalysts and other materials.

  9. Optical advantages of astigmatic aberration corrected heliostats

    NASA Astrophysics Data System (ADS)

    van Rooyen, De Wet; Schöttl, Peter; Bern, Gregor; Heimsath, Anna; Nitz, Peter

    2016-05-01

    Astigmatic aberration corrected heliostats adapt their shape in dependence of the incidence angle of the sun on the heliostat. Simulations show that this optical correction leads to a higher concentration ratio at the target and thus in a decrease in required receiver aperture in particular for smaller heliostat fields.

  10. On the benefit of aberration-corrected HAADF-STEM for strain determination and its application to tailoring ferroelectric domain patterns.

    PubMed

    Tang, Y L; Zhu, Y L; Ma, X L

    2016-01-01

    Revealing strains on the unit-cell level is essential for understanding the particular performance of materials. Large-scale strain variations with a unit-cell resolution are important for studying ferroelectric materials since the spontaneous polarizations of such materials are strongly coupled with strains. Aberration-corrected high-angle-annular-dark-field scanning transmission electron microscopy (AC-HAADF-STEM) is not so sensitive to the sample thickness and therefore thickness gradients. Consequently it is extremely useful for large-scale strain determination, which can be readily extracted by geometrical phase analysis (GPA). Such a combination has various advantages: it is straightforward, accurate on the unit-cell scale, relatively insensitive to crystal orientation and therefore helpful for large-scale. We take a tetragonal ferroelectric PbTiO3 film as an example in which large-scale strains are determined. Furthermore, based on the specific relationship between lattice rotation and spontaneous polarization (Ps) at 180° domain-walls, the Ps directions are identified, which makes the investigation of ferroelectric domain structures accurate and straightforward. This method is proposed to be suitable for investigating strain-related phenomena in other ferroelectric materials.

  11. Aberration corrected Lorentz scanning transmission electron microscopy.

    PubMed

    McVitie, S; McGrouther, D; McFadzean, S; MacLaren, D A; O'Shea, K J; Benitez, M J

    2015-05-01

    We present results from an aberration corrected scanning transmission electron microscope which has been customised for high resolution quantitative Lorentz microscopy with the sample located in a magnetic field free or low field environment. We discuss the innovations in microscope instrumentation and additional hardware that underpin the imaging improvements in resolution and detection with a focus on developments in differential phase contrast microscopy. Examples from materials possessing nanometre scale variations in magnetisation illustrate the potential for aberration corrected Lorentz imaging as a tool to further our understanding of magnetism on this lengthscale.

  12. Zonal spherical aberration correction utilizing axial electrodes

    NASA Astrophysics Data System (ADS)

    Chao, Liang C.

    2005-01-01

    Spherical aberration is important in focused ion beam applications where large aperture angles are needed to obtain high beam currents because it results in large tails on the current density distribution. Merwe has shown that for coaxial lenses, negative spherical aberration can be found for rays pass through zonal regions. Merwe"s calculation is valid only for periodic or quasi-periodic lenses and requires a constant axial potential distribution. We have calculated zonal focusing properties of lenses with axial electrodes using nine-point finite difference method and direct ray tracing. Our calculation results indicate that an axial electrode protruding partially into the lens can correct the spherical aberration. When a three-element electrostatic lens is operated at deceleration mode, the introduction of an axial electrode creates zonal regions where the spherical aberration is negative. At deceleration mode, the induced surface charges on the axial electrode have an opposite sign relative to the primary beam. This is in agreement with our previous findings on the study of the correction of spherical aberration utilizing space charges. Same phenomenon was found when an axial electrode is used in conjunction with a cathode lens.

  13. Designing Aberration-Corrected Solid Unstable Resonators

    NASA Technical Reports Server (NTRS)

    Lang, Robert J.

    1994-01-01

    In improved method of designing solid unstable resonator of laser diode, shapes of mirrors calculated to yield specified mode. Ray tracing used to compute shape of initially unspecified end mirror, given shape of initially specified end mirror and specified output mode. No need to accept aberrations or suboptimal circular shapes, to make iterative design computations in effort to converge on desired mode, or to assume paraxiality of rays: Angles between rays and optical axis large, cross sections of surfaces noncircular, and computed shape of end mirror exact. End mirror corrects for all aberrations.

  14. Compact, holographic correction of aberrated telescopes.

    PubMed

    Andersen, G; Munch, J; Veitch, P

    1997-03-01

    We demonstrate a compact reflector telescope design that incorporates the holographic correction of a large, low-quality primary spherical mirror by using a laser beacon located at the center of curvature. The simple design makes use of conventional optics and is easily scalable to much larger apertures. Experimental results indicate diffraction-limited performance from a heavily aberrated 0.5-m-diameter spherical mirror.

  15. Variable zoom system with aberration correction capability

    NASA Astrophysics Data System (ADS)

    Lu, Yang; Stockbridge, Christopher R.; Hoffman, Samuel M.; Bifano, Thomas G.

    2012-07-01

    We describe experiments conducted with two deformable mirrors (DMs) at fixed locations in an optical microscope imaging system. In this configuration, the DM shapes are controlled to provide 2.5× zoom capability, to allow dynamic focus control and to compensate for aberrations of the fixed optical components. Zoom is achieved by simultaneously adjusting focal lengths of the two DMs, which are inserted between an infinity-corrected microscope objective and a tube lens. Image quality is measured using contrast modulation, and performance of the system is quantified, demonstrating an improved point spread function in the adaptively compensated system.

  16. An aberration-corrected STEM study of structural defects in epitaxial GaN thin films grown by ion beam assisted MBE.

    PubMed

    Poppitz, David; Lotnyk, Andriy; Gerlach, Jürgen W; Lenzner, Jörg; Grundmann, Marius; Rauschenbach, Bernd

    2015-06-01

    Ion-beam assisted molecular-beam epitaxy was used for direct growth of epitaxial GaN thin films on super-polished 6H-SiC(0001) substrates. The GaN films with different film thicknesses were studied using reflection high energy electron diffraction, X-ray diffraction, cathodoluminescence and primarily aberration-corrected scanning transmission electron microscopy techniques. Special attention was devoted to the microstructural characterization of GaN thin films and the GaN-SiC interface on the atomic scale. The results show a variety of defect types in the GaN thin films and at the GaN-SiC interface. A high crystalline quality of the produced hexagonal GaN thin films was demonstrated. The gained results are discussed.

  17. Aberration correction by maximizing generalized sharpness metrics.

    PubMed

    Fienup, J R; Miller, J J

    2003-04-01

    The technique of maximizing sharpness metrics has been used to estimate and compensate for aberrations with adaptive optics, to correct phase errors in synthetic-aperture radar, and to restore images. The largest class of sharpness metrics is the sum over a nonlinear point transformation of the image intensity. How the second derivative of the point nonlinearity varies with image intensity determines the effects of various metrics on the imagery. Some metrics emphasize making shadows darker, and other emphasize making bright points brighter. One can determine the image content needed to pick the best metric by computing the statistics of the image autocorrelation or of the Fourier magnitude, either of which is independent of the phase error. Computationally efficient, closed-form expressions for the gradient make possible efficient search algorithms to maximize sharpness.

  18. New experimental evidences of Au-Cu2S core-shell nanoparticles and atomic resolution imaging by aberration-corrected STEM

    NASA Astrophysics Data System (ADS)

    Khanal, Subarna; Casillas, Gilberto; Bhattarai, Nabraj; Velazquez-Salazar, J. Jesus; Yacaman, Miguel Jose

    2013-03-01

    Au-Cu2S core-shell nanoparticles present different properties than their monometallic counterparts, opening a wide range of possibilities for different applications. Au-Cu2S core-shell nanostructures have raised interest for their many applications in photoelectronic, sensing, catalysis and so on. Au and Au-Cu2S core-shell nanoparticles were prepared by using a modified polyol method. First Au seeds were prepared by reducing HAuCl4.xH2O in ethylene glycol (EG) in the presence of poly(vinylpyrrolidone) (PVP) as a polymer surfactant. Then Cu2S shells were overgrown on Au core seeds by reducing CuSO4 in EG with PVP. The morphology and structural characteristics of Au and Au-Cu2S nanostructures were studied in detail using scanning electron microcopy HITACHI S-5500 and high resolution transmission electron microscope (HRTEM), a resolution 0.19 nm. Moreover, the Cs-corrected scanning transmission electron microscopy (Cs-corrected STEM) technique allowed us to probe the structure at the atomic level of these nanoparticles revealing new structural information. We determined the structure of the four main polyhedral morphologies obtained in the synthesis: decahedral, icosahedral, triangular plates, and rods. This project was supported by grants from the National Center for Research Resources (5 G12RR013646-12) and the National Institute on Minority Health and Health Disparities (G12MD007591).

  19. Peripheral Aberrations and Image Quality for Contact Lens Correction

    PubMed Central

    Shen, Jie; Thibos, Larry N.

    2011-01-01

    Purpose Contact lenses reduced the degree of hyperopic field curvature present in myopic eyes and rigid contact lenses reduced sphero-cylindrical image blur on the peripheral retina, but their effect on higher order aberrations and overall optical quality of the eye in the peripheral visual field is still unknown. The purpose of our study was to evaluate peripheral wavefront aberrations and image quality across the visual field before and after contact lens correction. Methods A commercial Hartmann-Shack aberrometer was used to measure ocular wavefront errors in 5° steps out to 30° of eccentricity along the horizontal meridian in uncorrected eyes and when the same eyes are corrected with soft or rigid contact lenses. Wavefront aberrations and image quality were determined for the full elliptical pupil encountered in off-axis measurements. Results Ocular higher-order aberrations increase away from fovea in the uncorrected eye. Third-order aberrations are larger and increase faster with eccentricity compared to the other higher-order aberrations. Contact lenses increase all higher-order aberrations except 3rd-order Zernike terms. Nevertheless, a net increase in image quality across the horizontal visual field for objects located at the foveal far point is achieved with rigid lenses, whereas soft contact lenses reduce image quality. Conclusions Second order aberrations limit image quality more than higher-order aberrations in the periphery. Although second-order aberrations are reduced by contact lenses, the resulting gain in image quality is partially offset by increased amounts of higher-order aberrations. To fully realize the benefits of correcting higher-order aberrations in the peripheral field requires improved correction of second-order aberrations as well. PMID:21873925

  20. Correcting Aberrations in Complex Magnet Systems for Muon Cooling Channels

    SciTech Connect

    J.A. Maloney, B. Erdelyi, A. Afanaciev, R.P. Johnson, Y.S. Derbenev, V.S. Morozov

    2011-03-01

    Designing and simulating complex magnet systems needed for cooling channels in both neutrino factories and muon colliders requires innovative techniques to correct for both chromatic and spherical aberrations. Optimizing complex systems, such as helical magnets for example, is also difficult but essential. By using COSY INFINITY, a differential algebra based code, the transfer and aberration maps can be examined to discover what critical terms have the greatest influence on these aberrations.

  1. Correction of spherochromatic aberration by system of thin layers

    NASA Astrophysics Data System (ADS)

    Miks, A.; Novak, J.

    2005-08-01

    It is well-known from the theory of optical imaging that optical systems generally show a presence of a chromatic aberration, which originates from a variation of the refraction index of glass on the wavelength of light. The chromatic aberration must be well corrected in order to obtain a good quality of optical image. In practice, it is used a proper combination of optical elements manufactured from different types of optical glass with a different dispersion in order to suppress the chromatic aberration. Our work shows a way how to correct spherochromatic aberration using a system of thin aspherical layers. The equations are derived for determination of parameters of thin layers with respect to a required spherochromatic aberration.

  2. Lesion generation through ribs using histotripsy therapy without aberration correction.

    PubMed

    Kim, Yohan; Wang, Tzu-Yin; Xu, Zhen; Cain, Charles A

    2011-11-01

    This study investigates the feasibility of using high-intensity pulsed therapeutic ultrasound, or histotripsy, to non-invasively generate lesions through the ribs. Histotripsy therapy mechanically ablates tissue through the generation of a cavitation bubble cloud, which occurs when the focal pressure exceeds a certain threshold. We hypothesize that histotripsy can generate precise lesions through the ribs without aberration correction if the main lobe retains its shape and exceeds the cavitation initiation threshold and the secondary lobes remain below the threshold. To test this hypothesis, a 750-kHz focused transducer was used to generate lesions in tissue-mimicking phantoms with and without the presence of rib aberrators. In all cases, 8000 pulses with 16 to 18 MPa peak rarefactional pressure at a repetition frequency of 100 Hz were applied without aberration correction. Despite the high secondary lobes introduced by the aberrators, high-speed imaging showed that bubble clouds were generated exclusively at the focus, resulting in well-confined lesions with comparable dimensions. Collateral damage from secondary lobes was negligible, caused by single bubbles that failed to form a cloud. These results support our hypothesis, suggesting that histotripsy has a high tolerance for aberrated fields and can generate confined focal lesions through rib obstacles without aberration correction.

  3. Automated spherical aberration correction in scanning confocal microscopy

    NASA Astrophysics Data System (ADS)

    Yoo, H. W.; van Royen, M. E.; van Cappellen, W. A.; Houtsmuller, A. B.; Verhaegen, M.; Schitter, G.

    2014-12-01

    Mismatch between the refractive indexes of immersion media and glass coverslips introduces spherical aberrations in microscopes especially for high numerical aperture objectives. This contribution demonstrates an automated adjustment of the coverslip correction collar in scanning confocal microscopy to compensate for spherical aberrations due to coverslip thickness mismatch. With a motorized coverslip correction collar, the adjustment procedure consists of xz image scans, image processing, correction quality evaluation, the mismatch estimation, and eventually the optimal adjustment of the correction collar. For fast correction with less photodamage, coarse-fine Gaussian fitting algorithms are proposed and evaluated with various specimen for their estimation accuracy. The benefits of the proposed automated correction are demonstrated for various coverslips with biological specimens, showing the optimized resolution of the confocal microscope.

  4. Towards aberration correction of transcranial ultrasound using acoustic droplet vaporization.

    PubMed

    Haworth, Kevin J; Fowlkes, J Brian; Carson, Paul L; Kripfgans, Oliver D

    2008-03-01

    We report on the first experiments demonstrating the transcranial acoustic formation of stable gas bubbles that can be used for transcranial ultrasound aberration correction. It is demonstrated that the gas bubbles can be formed transcranially by phase-transitioning single, superheated, micron-size, liquid dodecafluoropentane droplets with ultrasound, a process known as acoustic droplet vaporization (ADV). ADV was performed at 550 kHz, where the skull is less attenuating and aberrating, allowing for higher-amplitudes to be reached at the focus. Additionally, it is demonstrated that time-reversal focusing at 1 MHz can be used to correct for transcranial aberrations with a single gas bubble acting as a point beacon. Aberration correction was performed using a synthetic aperture approach and verified by the realignment of the scattered waveforms. Under the conditions described below, time-reversal aberration correction using gas bubbles resulted in a gain of 1.9 +/- 0.3 in an introduced focusing factor. This is a small fraction of the gain anticipated from complete transmit-receive of a fully-populated two-dimensional array with sub-wavelength elements. (E-mail: khaworth@umich.edu).

  5. The three-dimensional point spread function of aberration-corrected scanning transmission electron microscopy.

    PubMed

    Lupini, Andrew R; de Jonge, Niels

    2011-10-01

    Aberration correction reduces the depth of field in scanning transmission electron microscopy (STEM) and thus allows three-dimensional (3D) imaging by depth sectioning. This imaging mode offers the potential for sub-Ångstrom lateral resolution and nanometer-scale depth sensitivity. For biological samples, which may be many microns across and where high lateral resolution may not always be needed, optimizing the depth resolution even at the expense of lateral resolution may be desired, aiming to image through thick specimens. Although there has been extensive work examining and optimizing the probe formation in two dimensions, there is less known about the probe shape along the optical axis. Here the probe shape is examined in three dimensions in an attempt to better understand the depth resolution in this mode. Examples are presented of how aberrations change the probe shape in three dimensions, and it is found that off-axial aberrations may need to be considered for focal series of large areas. It is shown that oversized or annular apertures theoretically improve the vertical resolution for 3D imaging of nanoparticles. When imaging nanoparticles of several nanometer size, regular STEM can thereby be optimized such that the vertical full-width at half-maximum approaches that of the aberration-corrected STEM with a standard aperture.

  6. Nanowire growth kinetics in aberration corrected environmental transmission electron microscopy

    DOE PAGES

    Chou, Yi -Chia; Panciera, Federico; Reuter, Mark C.; Stach, Eric A.; Ross, Frances M.

    2016-03-15

    Here, we visualize atomic level dynamics during Si nanowire growth using aberration corrected environmental transmission electron microscopy, and compare with lower pressure results from ultra-high vacuum microscopy. We discuss the importance of higher pressure observations for understanding growth mechanisms and describe protocols to minimize effects of the higher pressure background gas.

  7. Intrinsic instability of aberration-corrected electron microscopes.

    PubMed

    Schramm, S M; van der Molen, S J; Tromp, R M

    2012-10-19

    Aberration-corrected microscopes with subatomic resolution will impact broad areas of science and technology. However, the experimentally observed lifetime of the corrected state is just a few minutes. Here we show that the corrected state is intrinsically unstable; the higher its quality, the more unstable it is. Analyzing the contrast transfer function near optimum correction, we define an "instability budget" which allows a rational trade-off between resolution and stability. Unless control systems are developed to overcome these challenges, intrinsic instability poses a fundamental limit to the resolution practically achievable in the electron microscope.

  8. Holographic optical system for aberration corrections in laser Doppler velocimetry

    NASA Technical Reports Server (NTRS)

    Kim, R. C.; Case, S. K.; Schock, H. J.

    1985-01-01

    An optical system containing multifaceted holographic optical elements (HOEs) has been developed to correct for aberrations introduced by nonflat windows in laser Doppler velocimetry. The multifacet aberration correction approach makes it possible to record on one plate many sets of adjacent HOEs that address different measurement volume locations. By using 5-mm-diameter facets, it is practical to place 10-20 sets of holograms on one 10 x 12.5-cm plate, so that the procedure of moving the entire optical system to examine different locations may not be necessary. The holograms are recorded in dichromated gelatin and therefore are nonabsorptive and suitable for use with high-power argon laser beams. Low f-number optics coupled with a 90-percent efficient distortion-correcting hologram in the collection side of the system yield high optical efficiency.

  9. Phase aberration correction by correlation in digital holographic adaptive optics

    PubMed Central

    Liu, Changgeng; Yu, Xiao; Kim, Myung K.

    2013-01-01

    We present a phase aberration correction method based on the correlation between the complex full-field and guide-star holograms in the context of digital holographic adaptive optics (DHAO). Removal of a global quadratic phase term before the correlation operation plays an important role in the correction. Correlation operation can remove the phase aberration at the entrance pupil plane and automatically refocus the corrected optical field. Except for the assumption that most aberrations lie at or close to the entrance pupil, the presented method does not impose any other constraints on the optical systems. Thus, it greatly enhances the flexibility of the optical design for DHAO systems in vision science and microscopy. Theoretical studies show that the previously proposed Fourier transform DHAO (FTDHAO) is just a special case of this general correction method, where the global quadratic phase term and a defocus term disappear. Hence, this correction method realizes the generalization of FTDHAO into arbitrary DHAO systems. The effectiveness and robustness of this method are demonstrated by simulations and experiments. PMID:23669707

  10. Conformal dome aberration correction by designing the inner surface

    NASA Astrophysics Data System (ADS)

    Zhang, Wang; Chen, Shouqian; Fan, Zhigang

    2016-12-01

    The ray transmission models of optical domes were established, and the characteristics of the rays while passing through a hemispherical dome and a conformal dome were comparatively analysed. Acquiring the minimum deviated angles from the inner surface of the conformal dome was then determined to be the designing goal for reducing the dynamic aberrations. Based on this, the inner surface of the conformal dome was optimized and thus, the dynamic aberrations were reduced. Finally, a completely cooled conformal optical system was designed. The results show that the optical system have produced good imaging quality within all the fields of regard, which further illustrates that designing the inner surface of a conformal dome is an effective method for aberration correction.

  11. Spherical Aberration Corrections for the Electrostatic Gridded Lens

    SciTech Connect

    Pikin,A.

    2008-05-01

    Two methods of spherical aberration corrections of an electrostatic gridded lens have been studied with ray tracing simulations. Both methods are based on modifying electrostatic field on the periphery of the lens. In a simplest case such modification is done by extending the part of the grid support on its radial periphery in axial direction. In alternative method the electric field on the radial periphery of the lens is modified by applying an optimum voltage on an electrically isolated correcting electrode. It was demonstrated, that for a given focal length the voltage on this lens can be optimized for minimum aberration The performance of lenses is presented as a lens contribution to the beam RMS normalized emittance.

  12. An adaptive optic for correcting low-order wavefront aberrations

    SciTech Connect

    Thompson, C A; Wilhelmsen, J

    1999-09-02

    Adaptive Optics used for correcting low-order wavefront aberrations were tested and compared using interferometry, beam propagation, and a far-field test. Results confirm that the design and manufacturing specifications were met. Experimental data also confirms theoretical performance expectations, indicating the usefulness of these optics (especially in a laser-beam processing system), and identifying the resulting differences between the two fabrication methods used to make the optics.

  13. Transcranial phase aberration correction using beam simulations and MR-ARFI

    SciTech Connect

    Vyas, Urvi Kaye, Elena; Pauly, Kim Butts

    2014-03-15

    Purpose: Transcranial magnetic resonance-guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation-MR-ARFI technique to achieve aberration correction for transcranial MR-guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR-ARFI) to correct skull-caused phase aberrations. Methods: Skull-based numerical aberrations were obtained from a MR-guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focused ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR-ARFI images were used in the hybrid simulation-MR-ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16-aberration and 1024-aberration) was repeated three times. Results: The corrected MR-ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation-MR-ARFI technique resulted in an average increase in focal MR-ARFI phase of 44% for the 16-aberration case and 52% for the 1024-aberration case, and recovered 83% and 39% of the ideal MR-ARFI phase for the 16-aberrations and 1024-aberration case, respectively. Conclusions: Using one MR-ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation-MR-ARFI technique improved the maximum MR-ARFI phase of the beam's focus.

  14. Aberration-Corrected TEM Imaging of Oxygen Occupancy in YSZ.

    PubMed

    An, Jihwan; Koh, Ai Leen; Park, Joong Sun; Sinclair, Robert; Gür, Turgut M; Prinz, Fritz B

    2013-04-01

    We present atomic-scale imaging of oxygen columns and show quantitative analysis on the occupancy of the columns in yttria-stabilized zirconia (YSZ) using aberration-corrected TEM operated under the negative Cs condition. Also, individual contributions both from oxygen column occupancy and the static displacement of oxygen atoms due to occupancy change to the observed column intensities of TEM images were systematically investigated using HRTEM simulation. We found that oxygen column intensity is governed primarily by column occupancy rather than by static displacement of oxygen atoms. Utilizing the aberration-corrected TEM capability and HRTEM simulation results, we experimentally verified that oxygen vacancies segregate near the single grain boundary of a YSZ bicrystal. The methodology and the high spatial resolution characterization tool employed in the present study provide insights into the distribution of oxygen vacancies in the bulk as well as near grain boundaries and pave the way for further investigation and atomic-scale analysis in other important oxide materials.

  15. Seeing Inside Materials by Aberration-Corrected Electron Microscopy

    SciTech Connect

    Pennycook, Stephen J

    2011-01-01

    The recent successful correction of lens aberrations in the electron microscope has improved resolution by more than a factor of two in just a few years, bringing many benefits for the study of materials. These benefits extend significantly beyond enhanced resolution alone. Aberration correction gives higher resolution by allowing the objective lens to have a wider aperture, which also results in a reduced depth of field. This effect can be used to only focus specific sections inside materials for the first time. In this contribution we describe recent results exploiting this capability. Additionally, we show how combining the microscopy data with first-principles theory gives new insights into materials properties. We cover two applications, both involving heavy atoms in a lighter host. The first shows how single Hf atoms can be mapped in three dimensions inside the 1 nm-wide SiO2 region of a high dielectric constant device structure, and how a link to macroscopic device properties results through theoretical calculations. The second example is from the field of nanoscience, where individual Au atoms are imaged inside Si nanowires grown by a vapor-liquid-solid mechanism. The majority of Au atoms are probably injected by the highly energetic electron beam. However, their observed sites and atomic configurations represent at least meta-stable configurations and match well to results from density functional calculations.

  16. High order aberration and straylight evaluation after cataract surgery with implantation of an aspheric, aberration correcting monofocal intraocular lens

    PubMed Central

    Kretz, Florian T A; Tandogan, Tamer; Khoramnia, Ramin; Auffarth, Gerd U

    2015-01-01

    AIM To evaluate the quality of vision in respect to high order aberrations and straylight perception after implantation of an aspheric, aberration correcting, monofocal intraocular lens (IOL). METHODS Twenty-one patients (34 eyes) aged 50 to 83y underwent cataract surgery with implantation of an aspheric, aberration correcting IOL (Tecnis ZCB00, Abbott Medical Optics). Three months after surgery they were examined for uncorrected (UDVA) and corrected distance visual acuity (CDVA), contrast sensitivity (CS) under photopic and mesopic conditions with and without glare source, ocular high order aberrations (HOA, Zywave II) and retinal straylight (C-Quant). RESULTS Postoperatively, patients achieved a postoperative CDVA of 0.0 logMAR or better in 97.1% of eyes. Mean values of high order abberations were +0.02±0.27 (primary coma components) and -0.04±0.16 (spherical aberration term). Straylight values of the C-Quant were 1.35±0.44 log which is within normal range of age matched phakic patients. The CS measurements under mesopic and photopic conditions in combination with and without glare did not show any statistical significance in the patient group observed (P≥0.28). CONCLUSION The implantation of an aspherical aberration correcting monofocal IOL after cataract surgery resulted in very low residual higher order aberration (HOA) and normal straylight. PMID:26309872

  17. Studying Atomic Structures by Aberration-Corrected Transmission Electron Microscopy

    NASA Astrophysics Data System (ADS)

    Urban, Knut W.

    2008-07-01

    Seventy-five years after its invention, transmission electron microscopy has taken a great step forward with the introduction of aberration-corrected electron optics. An entirely new generation of instruments enables studies in condensed-matter physics and materials science to be performed at atomic-scale resolution. These new possibilities are meeting the growing demand of nanosciences and nanotechnology for the atomic-scale characterization of materials, nanosynthesized products and devices, and the validation of expected functions. Equipped with electron-energy filters and electron-energy loss spectrometers, the new instruments allow studies not only of structure but also of elemental composition and chemical bonding. The energy resolution is about 100 milli electron volts, and the accuracy of spatial measurements has reached a few picometers. However, understanding the results is generally not straightforward and only possible with extensive quantum-mechanical computer calculations.

  18. Studying atomic structures by aberration-corrected transmission electron microscopy.

    PubMed

    Urban, Knut W

    2008-07-25

    Seventy-five years after its invention, transmission electron microscopy has taken a great step forward with the introduction of aberration-corrected electron optics. An entirely new generation of instruments enables studies in condensed-matter physics and materials science to be performed at atomic-scale resolution. These new possibilities are meeting the growing demand of nanosciences and nanotechnology for the atomic-scale characterization of materials, nanosynthesized products and devices, and the validation of expected functions. Equipped with electron-energy filters and electron-energy-loss spectrometers, the new instruments allow studies not only of structure but also of elemental composition and chemical bonding. The energy resolution is about 100 milli-electron volts, and the accuracy of spatial measurements has reached a few picometers. However, understanding the results is generally not straightforward and only possible with extensive quantum-mechanical computer calculations. PMID:18653874

  19. Image transfer with spatial coherence for aberration corrected transmission electron microscopes.

    PubMed

    Hosokawa, Fumio; Sawada, Hidetaka; Shinkawa, Takao; Sannomiya, Takumi

    2016-08-01

    The formula of spatial coherence involving an aberration up to six-fold astigmatism is derived for aberration-corrected transmission electron microscopy. Transfer functions for linear imaging are calculated using the newly derived formula with several residual aberrations. Depending on the symmetry and origin of an aberration, the calculated transfer function shows characteristic symmetries. The aberrations that originate from the field's components, having uniformity along the z direction, namely, the n-fold astigmatism, show rotational symmetric damping of the coherence. The aberrations that originate from the field's derivatives with respect to z, such as coma, star, and three lobe, show non-rotational symmetric damping. It is confirmed that the odd-symmetric wave aberrations have influences on the attenuation of an image via spatial coherence. Examples of image simulations of haemoglobin and Si [211] are shown by using the spatial coherence for an aberration-corrected electron microscope.

  20. Phase-contrast imaging in aberration-corrected scanning transmission electron microscopy.

    PubMed

    Krumeich, F; Müller, E; Wepf, R A

    2013-06-01

    Although the presence of phase-contrast information in bright field images recorded with a scanning transmission electron microscope (STEM) has been known for a long time, its systematic exploitation for the structural characterization of materials began only with the availability of aberration-corrected microscopes that allow sufficiently large illumination angles. Today, phase-contrast STEM (PC-STEM) imaging represents an increasingly important alternative to the well-established HRTEM method. In both methods, the image contrast is coherently generated and thus depends not only on illumination and collection angles but on defocus and specimen thickness as well. By PC-STEM, a projection of the crystal potential is obtained in thin areas, with the scattering sites being represented either with dark or bright contrast at two different defocus values which are both close to Gaussian defocus. This imaging behavior can be further investigated by image simulations performed with standard HRTEM simulation software based on the principle of reciprocity. As examples for the application of this method, PC-STEM results obtained on metal nanoparticles and dodecagonal quasicrystals dd-(Ta,V)₁.₆Te are discussed.

  1. In vivo transcostal histotripsy therapy without aberration correction

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Vlaisavljevich, E.; Owens, G. E.; Allen, S. P.; Cain, C. A.; Xu, Z.

    2014-06-01

    This study investigates the in vivo therapeutic capabilities of transcostal histotripsy without using aberration correction mechanisms and its thermal impact on overlying tissues. Non-invasive liver treatments were conducted in eight pigs, with four lesions generated through transcostal windows with full ribcage obstruction and four lesions created through transabdominal windows without rib coverage. Treatments were performed by a 750 kHz focused transducer using 5 cycle pulses at 200 Hz PRF, with estimated in situ peak negative pressures of 13-17 MPa. Temperatures on overlying tissues including the ribs were measured with needle thermocouples inserted superficially beneath the skin. Treatments of approximately 40 min were applied, allowing overlying tissue temperatures to reach saturation. Lesions yielded statistically comparable ablation volumes of 3.6 ± 1.7 cm3 and 4.5 ± 2.0 cm3 in transcostal and transabdominal treatments, respectively. The average temperature increase observed in transcostal treatments was 3.9 ± 2.1 °C, while transabdominal treatments showed an increase of 1.7 ± 1.3 °C. No damage was seen on the ribcage or other overlying tissues. These results indicate that histotripsy can achieve effective treatment through the ribcage in vivo without requiring correction mechanisms, while inducing no substantial thermal effects or damage to overlying tissues. Such capabilities could benefit several non-invasive therapy applications involving transcostal treatment windows.

  2. Successive optimization for fast-phase aberration correction

    NASA Astrophysics Data System (ADS)

    Farouk, Zyad; Youssef, Abou-Bakr M.; Kadah, Yasser M.

    2003-05-01

    We propose two new methods that allow the determination of the phase delays corresponding to phase aberration efficiently. We derive a new optimization methodology to compute the best compensation phase delays in successive steps. In particular, we start with an array consisting of one element with a specific excitation pattern. Then, another element is added and the dynamic receive delays are iteratively computed such that the obtained echoes are optimal in strength. A third element is added and the process is repeated. This process continues until all elements in the aperture are added. Hence, instead of solving the conventional N-dimensional problem of adjusting the delays of N elements together to achieve optimal characteristics, we transform the problem into the one of solving N-1 consecutive one-dimensional optimization problems. Given the fact that the set of available delay values is finite, the one-dimensional problem is shown to be a classical combinatorial optimization problem. The other technique based on Fourier transform tries to align signals based on information from a single frequency selected as the center frequency of the probe. This method is simple, computationally efficient and lends itself to real-time implementation. The proposed methods were implemented to correct real data from a resolution phantom and the results particularly indicate the potential of the second method.

  3. Vision improvement by correcting higher-order aberrations with customized soft contact lenses in keratoconic eyes

    NASA Astrophysics Data System (ADS)

    Sabesan, Ramkumar; Jeong, Tae Moon; Carvalho, Luis; Cox, Ian G.; Williams, David R.; Yoon, Geunyoung

    2007-04-01

    Higher-order aberration correction in abnormal eyes can result in significant vision improvement, especially in eyes with abnormal corneas. Customized optics such as phase plates and customized contact lenses are one of the most practical, nonsurgical ways to correct these ocular higher-order aberrations. We demonstrate the feasibility of correcting higher-order aberrations and improving visual performance with customized soft contact lenses in keratoconic eyes while compensating for the static decentration and rotation of the lens. A reduction of higher-order aberrations by a factor of 3 on average was obtained in these eyes. The higher-order aberration correction resulted in an average improvement of 2.1 lines in visual acuity over the conventional correction of defocus and astigmatism alone.

  4. Sextupole system for the correction of spherical aberration

    DOEpatents

    Crewe, A.V.; Kopf, D.A.

    In an electron beam device in which an electron beam is developed and then focused by a lens to a particular spot, there is provided a means for eliminating spherical aberration. A sextupole electromagnetic lens is positioned between two focusing lenses. The interaction of the sextupole with the beam compensates for spherical aberration. (GHT)

  5. Study on the modification of measured wavefront aberration data for customized visual correction

    NASA Astrophysics Data System (ADS)

    Liu, Ming; Zhang, Yong; Zhang, Zhidong; Quan, Wei; An, Li

    2008-12-01

    Wavefront aberration of human eye is an important foundation for customized vision correction. In most current aberrometers, near infrared light is used to measure ocular wavefront aberration, whereas for customized visual correction, wavefront aberration data in visible range are required. With the measured wavefront aberration, corneal topography and eye's axial lengths data, individual eye models for twenty normal human eyes are constructed with the optical design software ZEMAX. Changing the incidence light wavelength and the refractive indexes of eye models, the values of defocus, astigmatism, higher-order aberrations in the measuring wavelength (833nm) and at the most sensitive wavelength of human eye (555nm) are obtained. Average focus shift between 833nm and 555nm is found to be about 0.94D, and different slightly for different individuals; the differences of astigmatism and higher-order aberrations between 833nm and 555nm are quite slight. For customized visual correction, the measured defocus value should be modified, whereas the measured astigmatism and higher-order aberrations could be used directly for the current correction precision. Individual eye model is a useful tool for accurate transformation of the measured wavefront aberration data into the data for visible spectrum.

  6. Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

    NASA Astrophysics Data System (ADS)

    Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

    2008-01-01

    Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

  7. Correction of chromatic aberrations at television registration of image through protective viewing systems

    NASA Astrophysics Data System (ADS)

    Kulyas, Oleg L.; Nikitin, Konstantin A.

    2016-03-01

    Ways of chromatic aberration in images are examined and analyzed which are generated at television supervision through protective glasses of a considerable thickness. The results of experimental check up of the given method of correction is introduced and described.

  8. Design of macro-filter-lens with simultaneous chromatic and geometric aberration correction.

    PubMed

    Prasad, Dilip K; Brown, Michael S

    2014-01-01

    A macro-filter-lens design that can correct for chromatic and geometric aberrations simultaneously while providing for a long focal length is presented. The filter is easy to fabricate since it involves two spherical surfaces and a planar surface. Chromatic aberration correction is achieved by making all the rays travel the same optical distance inside the filter element (negative meniscus). Geometric aberration is corrected for by the lens element (plano-convex), which makes the output rays parallel to the optic axis. This macro-filter-lens design does not need additional macro lenses and it provides an inexpensive and optically good (aberration compensated) solution for macro imaging of objects not placed close to the camera.

  9. Numerical spherical aberration correction method using spatial light modulator under deep-part fluorescence observation

    NASA Astrophysics Data System (ADS)

    Takiguchi, Yu; Takamoto, Hisayoshi; Kanada, Masamitsu; Inoue, Takashi; Matsumoto, Naoya; Terakawa, Susumu

    2014-03-01

    We have developed a confocal fluorescence laser scanning microscopy (CFLSM) incorporating a liquid crystal on silicon spatial light modulator (LCOS-SLM). To achieve high-resolution and high-contrast imaging for deeper part of the tissue with CFLSM, high numerical aperture objective lenses are required to tightly focus excitation light to meet Rayleigh limit(criterion) for the specimens. However, mismatch of refractive index at the boundary of interfacing materials, such as atmosphere, glass cover, and biological tissues, causes spherical aberration. Recently, we proposed a numerical method for correcting spherical aberration. In this method a pre-distorted wavefront pattern for aberration correction is calculated by ray tracing from a hypothetical focal point inside a specimen to the pupil plane. The resulting microscope can correct such spherical aberration. We observed 6.0μm fluorescent micro-beads dispersed three-dimensionally in agarose gel to confirm effectiveness of aberration correction. We reconstructed a three-dimensional image by taking 20 images by changing the depth with 1 μm interval and stacking them. It was apparent that the longitudinal/depth resolution was improved and that the intensity of fluorescence image was increased with aberration correction. While this method is applicable to other laser scanning microscopes, it has potential to enhance the signals for various super-resolution microscopic techniques, such as stimulated- emission-depletion (STED) fluorescence microscopy.

  10. Probing structures of nanomaterials using advanced electron microscopy methods, including aberration-corrected electron microscopy at the Angstrom scale.

    PubMed

    Gai, Pratibha L; Yoshida, Kenta; Shute, Carla; Jia, Xiaoting; Walsh, Michael; Ward, Michael; Dresselhaus, Mildred S; Weertman, Julia R; Boyes, Edward D

    2011-07-01

    Structural and compositional studies of nanomaterials of technological importance have been carried out using advanced electron microscopy methods, including aberration-corrected transmission electron microscopy (AC-TEM), AC-high angle annular dark field scanning TEM (AC-HAADF-STEM), AC-energy filtered TEM, electron-stimulated energy dispersive spectroscopy in the AC-(S)TEM and high-resolution TEM (HRTEM) with scanning tunneling microscopy (STM) holder. The AC-EM data reveal improvements in resolution and minimization in image delocalization. A JEOL 2200FS double-AC field emission gun TEM/STEM operating at 200 kV in the Nanocentre at the University of York has been used to image single metal atoms on crystalline supports in catalysts, grain boundaries in nanotwinned metals, and nanostructures of tetrapods. Joule heating studies using HRTEM integrated with an STM holder reveal in situ crystallization and edge reconstruction in graphene. Real-time in situ AC-HAADF-STEM studies at elevated temperatures are described. Dynamic in-column energy filtering in an AC environment provides an integral new approach to perform dynamic in situ studies with aberration correction. The new results presented here open up striking new opportunities for atomic scale studies of nanomaterials and indicate future development directions.

  11. 3-D stimulated emission depletion microscopy with programmable aberration correction.

    PubMed

    Lenz, Martin O; Sinclair, Hugo G; Savell, Alexander; Clegg, James H; Brown, Alice C N; Davis, Daniel M; Dunsby, Chris; Neil, Mark A A; French, Paul M W

    2014-01-01

    We present a stimulated emission depletion (STED) microscope that provides 3-D super resolution by simultaneous depletion using beams with both a helical phase profile for enhanced lateral resolution and an annular phase profile to enhance axial resolution. The 3-D depletion point spread function is realised using a single spatial light modulator that can also be programmed to compensate for aberrations in the microscope and the sample. We apply it to demonstrate the first 3-D super-resolved imaging of an immunological synapse between a Natural Killer cell and its target cell.

  12. Temporal integration property of stereopsis after higher-order aberration correction

    PubMed Central

    Kang, Jian; Dai, Yun; Zhang, Yudong

    2015-01-01

    Based on a binocular adaptive optics visual simulator, we investigated the effect of higher-order aberration correction on the temporal integration property of stereopsis. Stereo threshold for line stimuli, viewed in 550nm monochromatic light, was measured as a function of exposure duration, with higher-order aberrations uncorrected, binocularly corrected or monocularly corrected. Under all optical conditions, stereo threshold decreased with increasing exposure duration until a steady-state threshold was reached. The critical duration was determined by a quadratic summation model and the high goodness of fit suggested this model was reasonable. For normal subjects, the slope for stereo threshold versus exposure duration was about −0.5 on logarithmic coordinates, and the critical duration was about 200 ms. Both the slope and the critical duration were independent of the optical condition of the eye, showing no significant effect of higher-order aberration correction on the temporal integration property of stereopsis. PMID:26601010

  13. Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute myeloid leukemia.

    PubMed

    Mehrotra, B; George, T I; Kavanau, K; Avet-Loiseau, H; Moore, D; Willman, C L; Slovak, M L; Atwater, S; Head, D R; Pallavicini, M G

    1995-08-01

    Leukemia may be viewed as a clonal expansion of blast cells; however, the role of primitive cells and/or stem cells in disease etiology and progression is unclear. We investigated stem cell involvement in leukemia using fluorescence in situ hybridization (FISH), immunofluorescence labeling of hematopoietic subpopulations, and flow cytometric analysis/sorting to discriminate and quantify cytogenetically aberrant stem cells in 12 acute myeloid leukemia (AML) and three myelodysplastic (MDS) specimens. Flow cytometric analysis and sorting were used to discriminate and collect a primitive subpopulation enriched in stem cells expressing CD34+ and lacking CD33 and CD38 (CD34+lin-). A subpopulation containing progenitors and differentiating myeloid cells expressed CD34, CD33, and CD38 (CD34+lin+). Nine specimens contained less than 10% CD34+ cells and, thus, were considered to be CD34- leukemias. Mature lymphoid, myeloid, and erythroid subpopulations were sorted on the basis of antigen-linked immunofluorescence. Cytogenetically aberrant cells in sorted subpopulations were identified using FISH with enumerator probes selected on the basis of diagnosis karyotype. Cytogenetically aberrant CD34+lin- cells were present at frequencies between 9% and 99% in all specimens. CD34+lin- cytogenetically aberrant cells comprised between 0.05% and 11.9% of the marrow/blood specimens. Cytogenetically aberrant CD34+lin+ cells constituted 0.01% tp 56% of the marrow/blood population. These data demonstrate that aberrant cells are present in primitive CD34+ stem cell compartments, even in CD34- leukemias. Stem cell involvement was confirmed further by sorting lymphoid and erythroid subpopulations from eight specimens in which the predominant leukemic population lacked lymphoid/erythroid differentiation markers. In these specimens, as well as in multiple lineages, suggests involvement of a cell(s) with multilineage capabilities. The ability of aberrant CD34+lin- stem cells to contribute to

  14. Effect of correction of aberration dynamics on chaos in human ocular accommodation.

    PubMed

    Hampson, Karen M; Cufflin, Matthew P; Mallen, Edward A H

    2013-11-15

    We used adaptive optics to determine the effect of monochromatic aberration dynamics on the level of chaos in the accommodation control system. Four participants viewed a stationary target while the dynamics of their aberrations were either left uncorrected, defocus was corrected, or all aberrations except defocus were corrected. Chaos theory analysis was used to discern changes in the accommodative microfluctuations. We found a statistically significant reduction in the chaotic nature of the accommodation microfluctuations during correction of defocus, but not when all aberrations except defocus were corrected. The Lyapunov exponent decreased from 0.71 ± 0.07 D/s (baseline) to 0.55 ± 0.03 D/s (correction of defocus fluctuations). As the reduction of chaos in physiological signals is indicative of stress to the system, the results indicate that for the participants included in this study, fluctuations in defocus have a more profound effect than those of the other aberrations. There were no changes in the power spectrum between experimental conditions. Hence chaos theory analysis is a more subtle marker of changes in the accommodation control system and will be of value in the study of myopia onset and progression. PMID:24322122

  15. Modeling of Optical Aberration Correction using a Liquid Crystal Device

    NASA Technical Reports Server (NTRS)

    Xinghua, Wang; Bin, Wang; McManamon, Paul F.; Pouch, John J.; Miranda, Felix A.

    2006-01-01

    Gruneisen (sup 1-3), has shown that small, light weight, liquid crystal based devices can correct for the optical distortion caused by an imperfect primary mirror in a telescope and has discussed the efficiency of this correction. In this paper we expand on that work and propose a semi-analytical approach for quantifying the efficiency of a liquid crystal based wavefront corrector for this application.

  16. Correcting the aero-optical aberration of the supersonic mixing layer with adaptive optics: concept validation.

    PubMed

    Gao, Qiong; Jiang, Zongfu; Yi, Shihe; Xie, Wenke; Liao, Tianhe

    2012-06-10

    We describe an adaptive optics (AO) system for correcting the aero-optical aberration of the supersonic mixing layer and test its performance with numerical simulations. The AO system is based on the measurement of distributed Strehl ratios and the stochastic parallel gradient descent (SPGD) algorithm. The aero-optical aberration is computed by the direct numerical simulation of a two-dimensional supersonic mixing layer. When the SPGD algorithm is applied directly, the AO cannot give effective corrections. This paper suggests two strategies to improve the performance of the SPGD algorithm for use in aero-optics. The first one is using an iteration process keeping finite memory, and the second is based on the frozen hypothesis. With these modifications, the performance of AO is improved and the aero-optical aberration can be corrected to some noticeable extent. The possibility of experimental implementation is also discussed. PMID:22695671

  17. Imaging nanometre-scale structure in cells using in situ aberration correction.

    PubMed

    Fuller, C J; Straight, A F

    2012-10-01

    Accurate distance measurements of cellular structures on a length scale relevant to single macromolecules or macromolecular complexes present a major challenge for biological microscopy. In addition to the inherent challenges of overcoming the limits imposed by the diffraction of light, cells themselves are a complex and poorly understood optical environment. We present an extension of the high-resolution colocalization method to measure three dimensional distances between diffraction-limited objects using standard widefield fluorescence microscopy. We use this method to demonstrate that in three dimensions, cells intrinsically introduce a large and variable amount of chromatic aberration into optical measurements. We present a means of correcting this aberration in situ [termed 'Colocalization and In-situ Correction of Aberration for Distance Analysis' (CICADA)] by exploiting the fact that there is a linear relationship between the degree of aberration between different wavelengths. By labelling a cellular structure with redundantly multi-colour labelled antibodies, we can create an intracellular fiducial marker for correcting the individual aberrations between two different wavelengths in the same cells. Our observations demonstrate that with suitable corrections, nanometre scale three-dimensional distance measurements can be used to probe the substructure of macromolecular complexes within cells.

  18. High-resolution adaptive optics scanning laser ophthalmoscope with dual deformable mirrors for large aberration correction

    SciTech Connect

    Chen, D; Jones, S M; Silva, D A; Olivier, S S

    2007-01-25

    Scanning laser ophthalmoscopes with adaptive optics (AOSLO) have been shown previously to provide a noninvasive, cellular-scale view of the living human retina. However, the clinical utility of these systems has been limited by the available deformable mirror technology. In this paper, we demonstrate that the use of dual deformable mirrors can effectively compensate large aberrations in the human retina, making the AOSLO system a viable, non-invasive, high-resolution imaging tool for clinical diagnostics. We used a bimorph deformable mirror to correct low-order aberrations with relatively large amplitudes. The bimorph mirror is manufactured by Aoptix, Inc. with 37 elements and 18 {micro}m stroke in a 10 mm aperture. We used a MEMS deformable mirror to correct high-order aberrations with lower amplitudes. The MEMS mirror is manufactured by Boston Micromachine, Inc with 144 elements and 1.5 {micro}m stroke in a 3 mm aperture. We have achieved near diffraction-limited retina images using the dual deformable mirrors to correct large aberrations up to {+-} 3D of defocus and {+-} 3D of cylindrical aberrations with test subjects. This increases the range of spectacle corrections by the AO systems by a factor of 10, which is crucial for use in the clinical environment. This ability for large phase compensation can eliminate accurate refractive error fitting for the patients, which greatly improves the system ease of use and efficiency in the clinical environment.

  19. Practical spatial resolution of electron energy loss spectroscopy in aberration corrected scanning transmission electron microscopy.

    PubMed

    Shah, A B; Ramasse, Q M; Wen, J G; Bhattacharya, A; Zuo, J M

    2011-08-01

    The resolution of electron energy loss spectroscopy (EELS) is limited by delocalization of inelastic electron scattering rather than probe size in an aberration corrected scanning transmission electron microscope (STEM). In this study, we present an experimental quantification of EELS spatial resolution using chemically modulated 2×(LaMnO(3))/2×(SrTiO(3)) and 2×(SrVO(3))/2×(SrTiO(3)) superlattices by measuring the full width at half maxima (FWHM) of integrated Ti M(2,3), Ti L(2,3), V L(2,3), Mn L(2,3), La N(4,5), La N(2,3) La M(4,5) and Sr L(3) edges over the superlattices. The EELS signals recorded using large collection angles are peaked at atomic columns. The FWHM of the EELS profile, obtained by curve-fitting, reveals a systematic trend with the energy loss for the Ti, V, and Mn edges. However, the experimental FWHM of the Sr and La edges deviates significantly from the observed experimental tendency.

  20. Transmissive liquid-crystal device correcting primary coma aberration and astigmatism in laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

    2016-03-01

    Laser scanning microscopy allows 3D cross-sectional imaging inside biospecimens. However, certain aberrations produced can degrade the quality of the resulting images. We previously reported a transmissive liquid-crystal device that could compensate for the predominant spherical aberrations during the observations, particularly in deep regions of the samples. The device, inserted between the objective lens and the microscope revolver, improved the image quality of fixed-mouse-brain slices that were observed using two-photon excitation laser scanning microscopy, which was originally degraded by spherical aberration. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism, motivated by the fact that these asymmetric aberrations can also often considerably deteriorate image quality, even near the sample surface. The device's performance was evaluated by observing fluorescent beads using single-photon excitation laser scanning microscopy. The fluorescence intensity in the image of the bead under a cover slip tilted in the y-direction was increased by 1.5 times after correction by the device. Furthermore, the y- and z-widths of the imaged bead were reduced to 66% and 65%, respectively. On the other hand, for the imaged bead sucked into a glass capillary in the longitudinal x-direction, correction with the device increased the fluorescence intensity by 2.2 times compared to that of the aberrated image. In addition, the x-, y-, and z-widths of the bead image were reduced to 75%, 53%, and 40%, respectively. Our device successfully corrected several asymmetric aberrations to improve the fluorescent signal and spatial resolution, and might be useful for observing various biospecimens.

  1. Aberration and boresight error correction for conformal aircraft windows using the inner window surface and tilted fixed correctors.

    PubMed

    Zhao, Chunzhu; Cui, Qingfeng; Mao, Shan

    2016-04-01

    A static solution to aberrations and boresight error for tilted conformal aircraft windows at different look angles is reported. The solution uses the inner window surface to correct the window aberrations at a 0° look angle and uses fixed correctors behind the window to correct the residual window aberrations at other look angles. Then, the boresight error for the window at different look angles is corrected by tilting the fixed correctors. The principle of the solution is discussed, and a design example shows that the solution is effective in correcting the aberrations and boresight error for a tilted conformal aircraft window at different look angles.

  2. Correcting spherical aberrations induced by an unknown medium through determination of its refractive index and thickness.

    PubMed

    Iwaniuk, Daniel; Rastogi, Pramod; Hack, Erwin

    2011-09-26

    In imaging and focusing applications, spherical aberration induces axial broadening of the point spread function (PSF). A transparent medium between lens and object of interest induces spherical aberration. We propose a method that first obtains both the physical thickness and the refractive index of the aberration inducing medium in situ by measuring the induced focal shifts for paraxial and large angle rays. Then, the fourth order angle dependence of the optical path difference inside the medium is used to correct the spherical aberration using a phase-only spatial light modulator. The obtained measurement accuracy of 3% is sufficient for a complete compensation as demonstrated in a model microscope with NA 0.3 with glass plate induced axial broadening of the PSF by a factor of 5.

  3. Digital aberration correction of fluorescent images with coherent holographic image reconstruction by phase transfer (CHIRPT)

    NASA Astrophysics Data System (ADS)

    Field, Jeffrey J.; Bartels, Randy A.

    2016-03-01

    Coherent holographic image reconstruction by phase transfer (CHIRPT) is an imaging method that permits digital holographic propagation of fluorescent light. The image formation process in CHIRPT is based on illuminating the specimen with a precisely controlled spatio-temporally varying intensity pattern. This pattern is formed by focusing a spatially coherent illumination beam to a line focus on a spinning modulation mask, and image relaying the mask plane to the focal plane of an objective lens. Deviations from the designed spatio-temporal illumination pattern due to imperfect mounting of the circular modulation mask onto the rotation motor induce aberrations in the recovered image. Here we show that these aberrations can be measured and removed non-iteratively by measuring the disk aberration phase externally. We also demonstrate measurement and correction of systematic optical aberrations in the CHIRPT microscope.

  4. Energy-based adaptive focusing of waves: application to noninvasive aberration correction of ultrasonic wavefields

    PubMed Central

    Herbert, Eric; Pernot, Mathieu; Montaldo, Gabriel; Fink, Mathias; Tanter, Mickael

    2009-01-01

    An aberration correction method based on the maximization of the wave intensity at the focus of an emitting array is presented. The potential of this new adaptive focusing technique is investigated for ultrasonic focusing in biological tissues. The acoustic intensity is maximized non invasively through the direct measurement or indirect estimation of the beam energy at the focus for a series of spatially coded emissions. For ultrasonic waves, the acoustic energy at the desired focus can be indirectly estimated from the local displacements induced in tissues by the ultrasonic radiation force of the beam. Based on the measurement of these displacements, this method allows the precise estimation of the phase and amplitude aberrations and consequently the correction of aberrations along the beam travel path. The proof of concept is first performed experimentally using a large therapeutic array with strong electronic phase aberrations (up to 2π). Displacements induced by the ultrasonic radiation force at the desired focus are indirectly estimated using the time shift of backscattered echoes recorded on the array. The phase estimation is deduced accurately using a direct inversion algorithm which reduces the standard deviation of the phase distribution from σ = 1.89 before correction to σ = 0.53 following correction. The corrected beam focusing quality is verified using a needle hydrophone. The peak intensity obtained through the aberrator is found to be −7.69 dB below the reference intensity obtained without any aberration. Using the phase correction, a sharp focus is restored through the aberrator with a relative peak intensity of −0.89 dB. The technique is tested experimentally using a linear transmit/receive array through a real aberrating layer. The array is used to automatically correct its beam quality, as it both generates the radiation force with coded excitations and indirectly estimates the acoustic intensity at the focus with speckle tracking. This

  5. The correction of aberrations computed in the aperture plane of multifrequency microwave radiometer antennas

    NASA Technical Reports Server (NTRS)

    Schmidt, R. F.

    1984-01-01

    An analytical/numerical approach to identifying and correcting the aberrations introduced by a general displacement of the feed from the focal point of a single offset paraboloid antenna used in deployable radiometer systems is developed. A 15 meter reflector with 18 meter focal length is assumed for the analysis, which considers far field radiation pattern quality, focal region fields, and aberrations appearing in the aperture plane. The latter are obtained by ray tracing in the transmit mode and are expressed in terms of optical notation. Attention is given to the physical restraints imposed on corrective elements by real microwave systems and to the intermediate near field aspects of the problem in three dimensions. The subject of wave fronts and caustics in the receive mode is introduced for comparative purposes. Several specific examples are given for aberration reduction at eight beamwidths of scan at a frequency of 1.414 GHz.

  6. High performance Czerny-Turner imaging spectrometer with aberrations corrected by tilted lenses

    NASA Astrophysics Data System (ADS)

    Zhong, Xing; Zhang, Yuan; Jin, Guang

    2015-03-01

    The design of the high performance imaging spectrometer using low-cost plane grating is researched in this paper. In order to correct the aberrations well, under the guidance of the vector aberration theory, the modification of Czerny-Turner system with inserted tilt lenses is proposed. The novel design of a short-wave infrared imaging spectrometer working at between wavelengths of 1-2.5 μm is shown as an example, whose numerical aperture achieves 0.15 in image space. The aberrations are corrected well and the Modulation Transfer Function (MTF) performance is the same as the convex gratings systems. The smiles and keystones of the spectral image are acceptable. Advantages of the proposed design with a plane grating are obviously that the diffraction efficiency is high while the cost is very low.

  7. The correction of aberrations computed in the aperture plane of multifrequency microwave radiometer antennas

    NASA Astrophysics Data System (ADS)

    Schmidt, R. F.

    1984-05-01

    An analytical/numerical approach to identifying and correcting the aberrations introduced by a general displacement of the feed from the focal point of a single offset paraboloid antenna used in deployable radiometer systems is developed. A 15 meter reflector with 18 meter focal length is assumed for the analysis, which considers far field radiation pattern quality, focal region fields, and aberrations appearing in the aperture plane. The latter are obtained by ray tracing in the transmit mode and are expressed in terms of optical notation. Attention is given to the physical restraints imposed on corrective elements by real microwave systems and to the intermediate near field aspects of the problem in three dimensions. The subject of wave fronts and caustics in the receive mode is introduced for comparative purposes. Several specific examples are given for aberration reduction at eight beamwidths of scan at a frequency of 1.414 GHz.

  8. Exploring the depth range for three-dimensional laser machining with aberration correction.

    PubMed

    Salter, P S; Baum, M; Alexeev, I; Schmidt, M; Booth, M J

    2014-07-28

    The spherical aberration generated when focusing from air into another medium limits the depth at which ultrafast laser machining can be accurately maintained. We investigate how the depth range may be extended using aberration correction via a liquid crystal spatial light modulator (SLM), in both single point and parallel multi-point fabrication in fused silica. At a moderate numerical aperture (NA = 0.5), high fidelity fabrication with a significant level of parallelisation is demonstrated at the working distance of the objective lens, corresponding to a depth in the glass of 2.4 mm. With a higher numerical aperture (NA = 0.75) objective lens, single point fabrication is demonstrated to a depth of 1 mm utilising the full NA, and deeper with reduced NA, while maintaining high repeatability. We present a complementary theoretical model that enables prediction of the effectiveness of SLM based correction for different aberration magnitudes.

  9. Non-common path aberration correction in an adaptive optics scanning ophthalmoscope.

    PubMed

    Sulai, Yusufu N; Dubra, Alfredo

    2014-09-01

    The correction of non-common path aberrations (NCPAs) between the imaging and wavefront sensing channel in a confocal scanning adaptive optics ophthalmoscope is demonstrated. NCPA correction is achieved by maximizing an image sharpness metric while the confocal detection aperture is temporarily removed, effectively minimizing the monochromatic aberrations in the illumination path of the imaging channel. Comparison of NCPA estimated using zonal and modal orthogonal wavefront corrector bases provided wavefronts that differ by ~λ/20 in root-mean-squared (~λ/30 standard deviation). Sequential insertion of a cylindrical lens in the illumination and light collection paths of the imaging channel was used to compare image resolution after changing the wavefront correction to maximize image sharpness and intensity metrics. Finally, the NCPA correction was incorporated into the closed-loop adaptive optics control by biasing the wavefront sensor signals without reducing its bandwidth.

  10. Non-common path aberration correction in an adaptive optics scanning ophthalmoscope

    PubMed Central

    Sulai, Yusufu N.; Dubra, Alfredo

    2014-01-01

    The correction of non-common path aberrations (NCPAs) between the imaging and wavefront sensing channel in a confocal scanning adaptive optics ophthalmoscope is demonstrated. NCPA correction is achieved by maximizing an image sharpness metric while the confocal detection aperture is temporarily removed, effectively minimizing the monochromatic aberrations in the illumination path of the imaging channel. Comparison of NCPA estimated using zonal and modal orthogonal wavefront corrector bases provided wavefronts that differ by ~λ/20 in root-mean-squared (~λ/30 standard deviation). Sequential insertion of a cylindrical lens in the illumination and light collection paths of the imaging channel was used to compare image resolution after changing the wavefront correction to maximize image sharpness and intensity metrics. Finally, the NCPA correction was incorporated into the closed-loop adaptive optics control by biasing the wavefront sensor signals without reducing its bandwidth. PMID:25401020

  11. Device and method for creating Gaussian aberration-corrected electron beams

    DOEpatents

    McMorran, Benjamin; Linck, Martin

    2016-01-19

    Electron beam phase gratings have phase profiles that produce a diffracted beam having a Gaussian or other selected intensity profile. Phase profiles can also be selected to correct or compensate electron lens aberrations. Typically, a low diffraction order produces a suitable phase profile, and other orders are discarded.

  12. Chromatic Aberration Correction for Atomic Resolution TEM Imaging from 20 to 80 kV.

    PubMed

    Linck, Martin; Hartel, Peter; Uhlemann, Stephan; Kahl, Frank; Müller, Heiko; Zach, Joachim; Haider, Max; Niestadt, Marcel; Bischoff, Maarten; Biskupek, Johannes; Lee, Zhongbo; Lehnert, Tibor; Börrnert, Felix; Rose, Harald; Kaiser, Ute

    2016-08-12

    Atomic resolution in transmission electron microscopy of thin and light-atom materials requires a rigorous reduction of the beam energy to reduce knockon damage. However, at the same time, the chromatic aberration deteriorates the resolution of the TEM image dramatically. Within the framework of the SALVE project, we introduce a newly developed C_{c}/C_{s} corrector that is capable of correcting both the chromatic and the spherical aberration in the range of accelerating voltages from 20 to 80 kV. The corrector allows correcting axial aberrations up to fifth order as well as the dominating off-axial aberrations. Over the entire voltage range, optimum phase-contrast imaging conditions for weak signals from light atoms can be adjusted for an optical aperture of at least 55 mrad. The information transfer within this aperture is no longer limited by chromatic aberrations. We demonstrate the performance of the microscope using the examples of 30 kV phase-contrast TEM images of graphene and molybdenum disulfide, showing unprecedented contrast and resolution that matches image calculations. PMID:27563976

  13. Chromatic Aberration Correction for Atomic Resolution TEM Imaging from 20 to 80 kV

    NASA Astrophysics Data System (ADS)

    Linck, Martin; Hartel, Peter; Uhlemann, Stephan; Kahl, Frank; Müller, Heiko; Zach, Joachim; Haider, Max.; Niestadt, Marcel; Bischoff, Maarten; Biskupek, Johannes; Lee, Zhongbo; Lehnert, Tibor; Börrnert, Felix; Rose, Harald; Kaiser, Ute

    2016-08-01

    Atomic resolution in transmission electron microscopy of thin and light-atom materials requires a rigorous reduction of the beam energy to reduce knockon damage. However, at the same time, the chromatic aberration deteriorates the resolution of the TEM image dramatically. Within the framework of the SALVE project, we introduce a newly developed Cc/Cs corrector that is capable of correcting both the chromatic and the spherical aberration in the range of accelerating voltages from 20 to 80 kV. The corrector allows correcting axial aberrations up to fifth order as well as the dominating off-axial aberrations. Over the entire voltage range, optimum phase-contrast imaging conditions for weak signals from light atoms can be adjusted for an optical aperture of at least 55 mrad. The information transfer within this aperture is no longer limited by chromatic aberrations. We demonstrate the performance of the microscope using the examples of 30 kV phase-contrast TEM images of graphene and molybdenum disulfide, showing unprecedented contrast and resolution that matches image calculations.

  14. Training to improve contrast sensitivity in amblyopia: correction of high-order aberrations

    PubMed Central

    Liao, Meng; Zhao, Haoxing; Liu, Longqian; Li, Qian; Dai, Yun; Zhang, Yudong; Zhou, Yifeng

    2016-01-01

    Perceptual learning is considered a potential treatment for amblyopia even in adult patients who have progressed beyond the critical period of visual development because adult amblyopes retain sufficient visual plasticity. When perceptual learning is performed with the correction of high-order aberrations (HOAs), a greater degree of neural plasticity is present in normal adults and those with highly aberrated keratoconic eyes. Because amblyopic eyes show more severe HOAs than normal eyes, it is interesting to study the effects of HOA-corrected visual perceptual learning in amblyopia. In the present study, we trained twenty-six older child and adult anisometropic amblyopes while their HOAs were corrected using a real-time closed-loop adaptive optics perceptual learning system (AOPL). We found that adaptive optics (AO) correction improved the modulation transfer functions (MTFs) and contrast sensitivity functions (CSFs) of older children and adults with anisometropic amblyopia. When perceptual learning was performed with AO correction of the ocular HOAs, the improvements in visual function were not only demonstrated in the condition with AO correction but were also maintained in the condition without AO correction. Additionally, the learning effect with AO correction was transferred to the untrained visual acuity and fellow eyes in the condition without AO correction. PMID:27752122

  15. Octopole correction of geometric aberrations for high-current heavy-ion fusion beams

    SciTech Connect

    Ho, D.D.M.; Haber, I.; Crandall, K.R.; Brandon, S.T.

    1989-03-17

    The success of heavy-ion fusion depends critically on the ability to focus heavy-ion beams to millimeter-size spots. Third-order geometric aberrations caused by fringe fields of the final focusing quadrupoles can significantly distort the focal spot size calculated by first-order theory. We present a method to calculate the locations and strengths of the octopoles that are needed to correct these aberrations. Calculation indicates that the strengths of the octopoles are substantially less than that of the final focusing quadrupoles. 9 refs., 1 fig.

  16. Evolution of gold structure during thermal treatment of Au/FeOx catalysts revealed by aberration-corrected electron microscopy.

    PubMed

    Allard, Lawrence F; Borisevich, Albina; Deng, Weiling; Si, Rui; Flytzani-Stephanopoulos, Maria; Overbury, Steven H

    2009-06-01

    High-resolution aberration-corrected electron microscopy was performed on a series of catalysts derived from a parent material, 2 at.% Au/Fe(2)O(3) (WGC ref. no. 60C), prepared by co-precipitation and calcined in air at 400 degrees C, and a catalyst prepared by leaching surface gold from the parent catalyst and exposed to various treatments, including use in the water-gas shift reaction at 250 degrees C. Aberration-corrected JEOL 2200FS (JEOL USA, Peabody, MA) and Vacuum Generators HB-603U STEM instruments were used to image fresh, reduced, leached, used and re-oxidized catalyst samples. A new in situ heating technology (Protochips Inc., Raleigh, NC, USA), which permits full sub-Angström imaging resolution in the JEOL 2200FS was used to study the effects of temperature on the behavior of gold species. A remarkable stability of gold to redox treatments up to 400 degrees C, with atomic gold decorating step surfaces of iron oxide was identified. On heating the samples in vacuum to 700 degrees C, it was found that monodispersed gold began to sinter to form nanoparticles above 500 degrees C. Gold species internal to the iron oxide support material was shown to diffuse to the surface at elevated temperature, coalescing into discrete nanocrystals. The results demonstrate the value of in situ heating for understanding morphological changes in the catalyst with elevated temperature treatments.

  17. Phase-aberration correction using signals from point reflectors and diffuse scatterers: basic principles.

    PubMed

    Flax, S W; O'Donnell, M

    1988-01-01

    Methods for correction of phase aberrations induced by near-field variations in the index of refraction are explored. Using signals obtained from a sampled aperture (i.e. transducer array), phase aberrations can be accurately measured with a correlation approach similar to methods used in adaptive optics and radar. However, the method presented here has no need for a beacon or an ideal point reflector to act as a source for estimating phase errors. It uses signals from random collections of scatterers to determine phase aberrations accurately. Because there is no longer a need for a beacon signal, the method is directly applicable not only to medical ultrasound imaging but also to any coherent imaging system with a sampled aperture, such as radar and sonar.

  18. An aberration corrected photoemission electron microscope at the advanced light source

    SciTech Connect

    Feng, J.; MacDowell, A.A.; Duarte, R.; Doran, A.; Forest, E.; Kelez, N.; Marcus, M.; Munson, D.; Padmore, H.; Petermann, K.; Raoux, S.; Robin, D.; Scholl, A.; Schlueter, R.; Schmid, P.; Stohr, J.; Wan, W.; Wei, D.H.; Wu, Y.

    2003-11-01

    Design of a new aberration corrected Photoemission electron microscope PEEM3 at the Advanced Light Source is outlined. PEEM3 will be installed on an elliptically polarized undulator beamline and will be used for the study of complex materials at high spatial and spectral resolution. The critical components of PEEM3 are the electron mirror aberration corrector and aberration-free magnetic beam separator. The models to calculate the optical properties of the electron mirror are discussed. The goal of the PEEM3 project is to achieve the highest possible transmission of the system at resolutions comparable to our present PEEM2 system (50 nm) and to enable significantly higher resolution, albeit at the sacrifice of intensity. We have left open the possibility to add an energy filter at a later date, if it becomes necessary driven by scientific need to improve the resolution further.

  19. Aberration corrected STEM to study an ancient hair dyeing formula

    NASA Astrophysics Data System (ADS)

    Patriarche, G.; Van Elslande, E.; Castaing, J.; Walter, P.

    2014-05-01

    Lead-based chemistry was initiated in ancient Egypt for cosmetic preparation more than 4000 years ago. Here, we study a hair-dyeing recipe using lead salts described in text since Greco-Roman times. We report direct evidence about the shape and distribution of PbS nanocrystals that form within the hair during blackening.

  20. Chromosome aberrations, micronucleus and sperm head abnormalities in mice treated with natamycin, [corrected] a food preservative.

    PubMed

    Rasgele, Pinar Goc; Kaymak, Fisun

    2010-03-01

    Natamycin [corrected] is used as preservative in foods. The genotoxic effects of the food preservative natamycin [corrected] were evaluated using chromosome aberrations and micronucleus test in bone marrow cells and sperm head abnormality assays in mice. Blood samples were taken from mice and levels of total testosterone in serum were also determined. Natamycin [corrected] was intraperitoneally (ip) injected at 200, 400 and 800 mg/kg. Natamycin [corrected] did not induce chromosome aberrations but significantly increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm head abnormalities at all concentrations and treatment periods. It also decreased MI at all concentrations for 6, 12 and 24h treatment periods. Natamycin [corrected] decreased PCE/NCE ratio at all concentrations for 48h in female mice, for 24 and 48h treatment periods in male mice. At the 800 mg/kg concentration, natamycin [corrected] decreased PCE/NCE ratio for 24 and 72h in female mice. A dose dependent increase was observed in the percentage of sperm head abnormalities. The levels of serum testosterone decreased dose-dependently. The obtained results indicate that natamycin [corrected] is not clastogenic, but it is aneugenic in mice bone marrow and it is a potential germ cell mutagen in sperm cells.

  1. Characterization of surface metallic states in SrTiO3 by means of aberration corrected electron microscopy.

    PubMed

    Sánchez-Santolino, G; Tornos, J; Bruno, F Y; Cuellar, F A; Leon, C; Santamaría, J; Pennycook, S J; Varela, M

    2013-04-01

    An unusual conducting surface state can be produced in SrTiO3 substrates by irradiation with Argon ions from a plasma source, at low energy and high doses. The effects of irradiation are analyzed here by atomic force microscopy (AFM) and aberration corrected scanning transmission electron microscopy (STEM) combined with electron energy loss spectroscopy (EELS). Depth sensitive studies demonstrate the existence of a heavily damaged surface layer and an oxygen vacancy rich layer immediately underneath, both induced during the irradiation process. We find a clear dependence of the Ti oxidation state with the depth, with a very intense Ti(3+) component near the surface. Oxygen vacancies act as n-type doping by releasing electrons into the lattice and producing an insulator-to-metal transition, which explains the unusual metallic behavior of these samples.

  2. Correction of spherical aberrations of lenses by partially compensated beam parts

    NASA Astrophysics Data System (ADS)

    Becker, R.; Mücke, M.

    1999-05-01

    A self-consistent thermal compensation exhibits a radially dropping degree of space charge compensation. The amount of the central compensation as well as the radial variation is only dependent on the temperature of the compensating particles with respect to the potential variation in the uncompensated beam. This non-uniform compensation provides stronger beam spreading for the outer part of the beam and therefore may compensate the spherical aberration of lenses, when used in proper position of a beam line. We calculated this effect in a one-dimensional radial self-consistent analysis of space charge compensation for different ion temperatures and compared the radial behaviour of the field strength with a cubic power law, which gives best aberration correction. An ion temperature of 13% of the potential energy of the non compensated electron beam fits well for large radii with the cubic power law. We also present a schematic drawing for the construction of such a correction unit.

  3. Model-based sensor-less wavefront aberration correction in optical coherence tomography.

    PubMed

    Verstraete, Hans R G W; Wahls, Sander; Kalkman, Jeroen; Verhaegen, Michel

    2015-12-15

    Several sensor-less wavefront aberration correction methods that correct nonlinear wavefront aberrations by maximizing the optical coherence tomography (OCT) signal are tested on an OCT setup. A conventional coordinate search method is compared to two model-based optimization methods. The first model-based method takes advantage of the well-known optimization algorithm (NEWUOA) and utilizes a quadratic model. The second model-based method (DONE) is new and utilizes a random multidimensional Fourier-basis expansion. The model-based algorithms achieve lower wavefront errors with up to ten times fewer measurements. Furthermore, the newly proposed DONE method outperforms the NEWUOA method significantly. The DONE algorithm is tested on OCT images and shows a significantly improved image quality. PMID:26670496

  4. Apparatus for and method of correcting for aberrations in a light beam

    DOEpatents

    Sawicki, Richard H.

    1996-01-01

    A technique for adjustably correcting for aberrations in a light beam is disclosed herein. This technique utilizes first means which defines a flat, circular light reflecting surface having opposite reinforced circumferential edges and a central post and which is resiliently distortable, to a limited extent, into different concave and/or convex curvatures, which may be Gaussian-like, about the central axis, and second means acting on the first means for adjustably distorting the light reflecting surface into a particular selected one of the different curvatures depending upon the aberrations to be corrected for and for fixedly maintaining the curvature selected. In the embodiment disclosed, the light reflecting surface is adjustably distorted into the selected curvature by application of particular axial moments to the central post on the opposite side from the light reflecting surface and lateral moments to the circumference of the reflecting surface.

  5. Apparatus for and method of correcting for aberrations in a light beam

    DOEpatents

    Sawicki, R.H.

    1996-09-17

    A technique for adjustably correcting for aberrations in a light beam is disclosed herein. This technique utilizes first means which defines a flat, circular light reflecting surface having opposite reinforced circumferential edges and a central post and which is resiliently distortable, to a limited extent, into different concave and/or convex curvatures, which may be Gaussian-like, about the central axis, and second means acting on the first means for adjustably distorting the light reflecting surface into a particular selected one of the different curvatures depending upon the aberrations to be corrected for and for fixedly maintaining the curvature selected. In the embodiment disclosed, the light reflecting surface is adjustably distorted into the selected curvature by application of particular axial moments to the central post on the opposite side from the light reflecting surface and lateral moments to the circumference of the reflecting surface. 8 figs.

  6. Depth Sectioning with the Aberration-Corrected Scanning Transmission Electron Microscope

    SciTech Connect

    Borisevich, Albina Y; Lupini, Andrew R; Pennycook, Stephen J

    2006-01-01

    The ability to correct the aberrations of the probe-forming lens in the scanning transmission electron microscope provides not only a significant improvement in transverse resolution but in addition brings depth resolution at the nanometer scale. Aberration correction therefore opens up the possibility of 3D imaging by optical sectioning. Here we develop a definition for the depth resolution for scanning transmission electron microscope depth sectioning and present initial results from this method. Objects such as catalytic metal clusters and single atoms on various support materials are imaged in three dimensions with a resolution of several nanometers. Effective focal depth is determined by statistical analysis and the contributing factors are discussed. Finally, current challenges and future capabilities available through new instruments are discussed.

  7. Effects of higher-order aberration correction on stereopsis at different viewing durations.

    PubMed

    Kang, Jian; Xiao, Fei; Zhao, Junlei; Zhao, Haoxin; Hu, Yiyun; Tang, Guomao; Dai, Yun; Zhang, Yudong

    2015-07-01

    To better understand how the eye's optics affects stereopsis, we measured stereoacuity before and after higher-order aberration (HOA) correction with a binocular adaptive optics visual simulator. The HOAs were corrected either binocularly or monocularly in the better eye (the eye with better contrast sensitivity). A two-line stereo pattern served as the visual stimulus. Stereo thresholds at different viewing durations were obtained with the psychophysical method of constant stimuli. Binocular HOA correction led to significant improvement in stereoacuity. However, better eye HOA correction could bring either a bad degradation or a slight improvement in stereoacuity. As viewing duration increased, the stereo benefit approached the level of 1.0 for both binocular and better eye correction, suggesting that long viewing durations might weaken the effects of the eye's optical quality on stereopsis.

  8. Impact of dynamical scattering on quantitative contrast for aberration-corrected transmission electron microscope images.

    PubMed

    Wen, C; Smith, David J

    2016-10-01

    Aberration-corrected transmission electron microscope images taken under optimum-defocus conditions or processed offline can correctly reflect the projected crystal structure with atomic resolution. However, dynamical scattering, which will seriously influence image contrast, is still unavoidable. Here, the multislice image simulation approach was used to quantify the impact of dynamical scattering on the contrast of aberration-corrected images for a 3C-SiC specimen with changes in atomic occupancy and thickness. Optimum-defocus images with different spherical aberration (CS) coefficients, and structure images restored by deconvolution processing, were studied. The results show that atomic-column positions and the atomic occupancy for SiC 'dumbbells' can be determined by analysis of image contrast profiles only below a certain thickness limit. This limit is larger for optimum-defocus and restored structure images with negative CS coefficient than those with positive CS coefficient. The image contrast of C (or Si) atomic columns with specific atomic occupancy changes differently with increasing crystal thickness. Furthermore, contrast peaks for C atomic columns overlapping with neighboring peaks of Si atomic columns with varied Si atomic occupancy, which is enhanced with increasing crystal thickness, can be neglected in restored structure images, but the effect is substantial in optimum-defocus images.

  9. Imaging Single Atoms Using Secondary Electrons with an Aberration-Corrected Electron Microscope

    SciTech Connect

    Zhu, Y.; Inada, H.; Nakamura, K.; Wall, J.

    2009-09-20

    Aberration correction has embarked on a new frontier in electron microscopy by overcoming the limitations of conventional round lenses, providing sub-angstrom-sized probes. However, improvement of spatial resolution using aberration correction so far has been limited to the use of transmitted electrons both in scanning and stationary mode, with an improvement of 20-40%. In contrast, advances in the spatial resolution of scanning electron microscopes (SEMs), which are by far the most widely used instrument for surface imaging at the micrometre-nanometre scale, have been stagnant, despite several recent efforts. Here, we report a new SEM, with aberration correction, able to image single atoms by detecting electrons emerging from its surface as a result of interaction with the small probe. The spatial resolution achieved represents a fourfold improvement over the best-reported resolution in any SEM. Furthermore, we can simultaneously probe the sample through its entire thickness with transmitted electrons. This ability is significant because it permits the selective visualization of bulk atoms and surface ones, beyond a traditional two-dimensional projection in transmission electron microscopy. It has the potential to revolutionize the field of microscopy and imaging, thereby opening the door to a wide range of applications, especially when combined with simultaneous nanoprobe spectroscopy.

  10. A proposal for the holographic correction of incoherent aberrations by tilted reference waves.

    PubMed

    Röder, Falk; Lubk, Axel

    2015-05-01

    The recently derived general transfer theory for off-axis electron holography provides a new approach for reconstructing the electron wave beyond the conventional sideband information limit. Limited ensemble coherence of the electron beam between object and reference area leads to an attenuation of spatial frequencies of the object exit wave in the presence of aberrations of the objective lens. Concerted tilts of the reference wave under the condition of an invariant object exit wave are proposed to diminish the aberration impact on spatial frequencies even beyond the sideband information limit allowing its transfer with maximum possible contrast. In addition to the theoretical considerations outlined in detail, an experimental proof-of-principle is presented. A fully controlled tilt of the reference wave, however, remains as a promising task for the future. The use of a hologram series with varying reference wave tilt is considered for linearly synthesizing an effective aperture for the transfer into the sideband with broader bandwidth compared to conventional off-axis electron holography allowing us to correct the incoherent aberrations in transmission electron microscopy. Furthermore, tilting a reference wave with respect to a plane wave is expected to be an alternative way for measuring the coherent and incoherent aberrations of a transmission electron microscope. The capability of tilting the reference wave is expected to be beneficial for improving the signal-to-noise ratio in dark-field off-axis electron holography as well. PMID:25680104

  11. Design and progress toward a multi-conjugate adaptive optics system for distributed aberration correction

    SciTech Connect

    Baker, K; Olivier, S; Tucker, J; Silva, D; Gavel, D; Lim, R; Gratrix, E

    2004-08-17

    This article investigates the use of a multi-conjugate adaptive optics system to improve the field-of-view for the system. The emphasis of this research is to develop techniques to improve the performance of optical systems with applications to horizontal imaging. The design and wave optics simulations of the proposed system are given. Preliminary results from the multi-conjugate adaptive optics system are also presented. The experimental system utilizes a liquid-crystal spatial light modulator and an interferometric wave-front sensor for correction and sensing of the phase aberrations, respectively.

  12. Fast Correction Optics to Reduce Chromatic Aberrations in Longitudinally Compressed Ion Beams

    SciTech Connect

    Lidia, S.M.; Lee, E.P.; Ogata, D.; Seidl, P.A.; Waldron, W.L.; Lund, S.M.

    2009-04-30

    Longitudinally compressed ion beam pulses are currently employed in ion-beam based warm dense matter studies [1]. Compression arises from an imposed time-dependent longitudinal velocity ramp followed by drift in a neutralized channel. Chromatic aberrations in the final focusing system arising from this chirp increase the attainable beam spot and reduce the effective fluence on target. We report recent work on fast correction optics that remove the time-dependent beam envelope divergence and minimizes the beam spot on target. We present models of the optical element design and predicted ion beam fluence.

  13. Aberration correction during real time in vivo imaging of bone marrow with sensorless adaptive optics confocal microscope

    NASA Astrophysics Data System (ADS)

    Wang, Zhibin; Wei, Dan; Wei, Ling; He, Yi; Shi, Guohua; Wei, Xunbin; Zhang, Yudong

    2014-08-01

    We have demonstrated adaptive correction of specimen-induced aberration during in vivo imaging of mouse bone marrow vasculature with confocal fluorescence microscopy. Adaptive optics system was completed with wavefront sensorless correction scheme based on stochastic parallel gradient descent algorithm. Using image sharpness as the optimization metric, aberration correction was performed based upon Zernike polynomial modes. The experimental results revealed the improved signal and resolution leading to a substantially enhanced image contrast with aberration correction. The image quality of vessels at 38- and 75-μm depth increased three times and two times, respectively. The corrections allowed us to detect clearer bone marrow vasculature structures at greater contrast and improve the signal-to-noise ratio.

  14. Dynamic Aberration Correction for Conformal Window of High-Speed Aircraft Using Optimized Model-Based Wavefront Sensorless Adaptive Optics.

    PubMed

    Dong, Bing; Li, Yan; Han, Xin-Li; Hu, Bin

    2016-09-02

    For high-speed aircraft, a conformal window is used to optimize the aerodynamic performance. However, the local shape of the conformal window leads to large amounts of dynamic aberrations varying with look angle. In this paper, deformable mirror (DM) and model-based wavefront sensorless adaptive optics (WSLAO) are used for dynamic aberration correction of an infrared remote sensor equipped with a conformal window and scanning mirror. In model-based WSLAO, aberration is captured using Lukosz mode, and we use the low spatial frequency content of the image spectral density as the metric function. Simulations show that aberrations induced by the conformal window are dominated by some low-order Lukosz modes. To optimize the dynamic correction, we can only correct dominant Lukosz modes and the image size can be minimized to reduce the time required to compute the metric function. In our experiment, a 37-channel DM is used to mimic the dynamic aberration of conformal window with scanning rate of 10 degrees per second. A 52-channel DM is used for correction. For a 128 × 128 image, the mean value of image sharpness during dynamic correction is 1.436 × 10(-5) in optimized correction and is 1.427 × 10(-5) in un-optimized correction. We also demonstrated that model-based WSLAO can achieve convergence two times faster than traditional stochastic parallel gradient descent (SPGD) method.

  15. Dynamic Aberration Correction for Conformal Window of High-Speed Aircraft Using Optimized Model-Based Wavefront Sensorless Adaptive Optics.

    PubMed

    Dong, Bing; Li, Yan; Han, Xin-Li; Hu, Bin

    2016-01-01

    For high-speed aircraft, a conformal window is used to optimize the aerodynamic performance. However, the local shape of the conformal window leads to large amounts of dynamic aberrations varying with look angle. In this paper, deformable mirror (DM) and model-based wavefront sensorless adaptive optics (WSLAO) are used for dynamic aberration correction of an infrared remote sensor equipped with a conformal window and scanning mirror. In model-based WSLAO, aberration is captured using Lukosz mode, and we use the low spatial frequency content of the image spectral density as the metric function. Simulations show that aberrations induced by the conformal window are dominated by some low-order Lukosz modes. To optimize the dynamic correction, we can only correct dominant Lukosz modes and the image size can be minimized to reduce the time required to compute the metric function. In our experiment, a 37-channel DM is used to mimic the dynamic aberration of conformal window with scanning rate of 10 degrees per second. A 52-channel DM is used for correction. For a 128 × 128 image, the mean value of image sharpness during dynamic correction is 1.436 × 10(-5) in optimized correction and is 1.427 × 10(-5) in un-optimized correction. We also demonstrated that model-based WSLAO can achieve convergence two times faster than traditional stochastic parallel gradient descent (SPGD) method. PMID:27598161

  16. Dynamic Aberration Correction for Conformal Window of High-Speed Aircraft Using Optimized Model-Based Wavefront Sensorless Adaptive Optics

    PubMed Central

    Dong, Bing; Li, Yan; Han, Xin-li; Hu, Bin

    2016-01-01

    For high-speed aircraft, a conformal window is used to optimize the aerodynamic performance. However, the local shape of the conformal window leads to large amounts of dynamic aberrations varying with look angle. In this paper, deformable mirror (DM) and model-based wavefront sensorless adaptive optics (WSLAO) are used for dynamic aberration correction of an infrared remote sensor equipped with a conformal window and scanning mirror. In model-based WSLAO, aberration is captured using Lukosz mode, and we use the low spatial frequency content of the image spectral density as the metric function. Simulations show that aberrations induced by the conformal window are dominated by some low-order Lukosz modes. To optimize the dynamic correction, we can only correct dominant Lukosz modes and the image size can be minimized to reduce the time required to compute the metric function. In our experiment, a 37-channel DM is used to mimic the dynamic aberration of conformal window with scanning rate of 10 degrees per second. A 52-channel DM is used for correction. For a 128 × 128 image, the mean value of image sharpness during dynamic correction is 1.436 × 10−5 in optimized correction and is 1.427 × 10−5 in un-optimized correction. We also demonstrated that model-based WSLAO can achieve convergence two times faster than traditional stochastic parallel gradient descent (SPGD) method. PMID:27598161

  17. Synergistic enhancements of ultrasound image contrast with a combination of phase aberration correction and dual apodization with cross-correlation.

    PubMed

    Shin, Junseob; Yen, Jesse T

    2012-09-01

    Dual apodization with cross-correlation (DAX) is a novel adaptive beamforming technique which utilizes two distinct apodization functions in suppressing side lobes and clutter. Previous studies have shown that the performance of DAX in minimizing the effects of phase aberration diminishes with increasing aberrator strength. To achieve greater improvement in image contrast, we propose, in this paper, to combine DAX with a phase aberration correction algorithm based on nearest-neighbor cross-correlation (NNCC). Our simulation and experimental results presented in this work showed that the proposed method allows for synergistic enhancements of image contrast and achieves greater improvement in image quality than using DAX alone or phase aberration correction alone in the presence of weak and strong aberrators. Compared with standard delay-and-sum (DAS) beamforming, using the proposed method on simulated data with weak and strong aberrations increased the contrast-to-noise ratio (CNR) values from 4.10 to 10.96 and from 1.69 to 9.80, respectively. Experimental results were obtained using pork tissues of 4 and 10 mm thickness and a tissue-mimicking phantom. The CNR values increased from 3.74 to 9.72 for the 4-mm pork aberrator and from 1.27 to 8.17 for the 10-mm pork aberrator. PMID:23007784

  18. Smart microscope: an adaptive optics learning system for aberration correction in multiphoton confocal microscopy.

    PubMed

    Albert, O; Sherman, L; Mourou, G; Norris, T B; Vdovin, G

    2000-01-01

    Off-axis aberrations in a beam-scanning multiphoton confocal microscope are corrected with a deformable mirror. The optimal mirror shape for each pixel is determined by a genetic learning algorithm, in which the second-harmonic or two-photon fluorescence signal from a reference sample is maximized. The speed of the convergence is improved by use of a Zernike polynomial basis for the deformable mirror shape. This adaptive optical correction scheme is implemented in an all-reflective system by use of extremely short (10-fs) optical pulses, and it is shown that the scanning area of an f:1 off-axis parabola can be increased by nine times with this technique. PMID:18059779

  19. Theoretical aspects of image formation in the aberration-corrected electron microscope.

    PubMed

    Rose, H

    2010-04-01

    The theoretical aspects of image formation in the transmission electron microscope (TEM) are outlined and revisited in detail by taking into account the elastic and inelastic scattering. In particular, the connection between the exit wave and the scattering amplitude is formulated for non-isoplanatic conditions. Different imaging modes are investigated by utilizing the scattering amplitude and employing the generalized optical theorem. A novel obstruction-free anamorphotic phase shifter is proposed which enables one to shift the phase of the scattered wave by an arbitrary amount over a large range of spatial frequencies. In the optimum case, the phase of the scattered wave and the introduced phase shift add up to -pi/2 giving negative contrast. We obtain these optimum imaging conditions by employing an aberration-corrected electron microscope operating at voltages below the knock-on threshold for atom displacement and by shifting optimally the phase of the scattered electron wave. The optimum phase shift is achieved by adjusting appropriately the constant phase shift of the phase plate and the phase shift resulting from the defocus and the spherical aberration of the corrected objective lens. The realization of this imaging mode is the aim of the SALVE project (Sub-A Low-Voltage Electron microscope).

  20. Pitch-catch phase aberration correction of multiple isoplanatic patches for 3-D transcranial ultrasound imaging.

    PubMed

    Lindsey, Brooks D; Smith, Stephen W

    2013-03-01

    Having previously presented the ultrasound brain helmet, a system for simultaneous 3-D ultrasound imaging via both temporal bone acoustic windows, the scanning geometry of this system is utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals, followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3-D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e., several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing, or beacon, array, updates the transmit and receive delays of 5 isoplanatic patches within a 64° x 64° volume. In phantom experiments, color flow voxels above a common threshold have also increased by an average of 92%, whereas color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting that such a technique may be beneficial in the future for performing noninvasive 3-D color flow imaging of cerebrovascular disease, including stroke.

  1. Pitch–Catch Phase Aberration Correction of Multiple Isoplanatic Patches for 3-D Transcranial Ultrasound Imaging

    PubMed Central

    Lindsey, Brooks D.; Smith, Stephen W.

    2013-01-01

    Having previously presented the ultrasound brain helmet, a system for simultaneous 3-D ultrasound imaging via both temporal bone acoustic windows, the scanning geometry of this system is utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals, followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3-D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e., several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing, or beacon, array, updates the transmit and receive delays of 5 isoplanatic patches within a 64° × 64° volume. In phantom experiments, color flow voxels above a common threshold have also increased by an average of 92%, whereas color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting that such a technique may be beneficial in the future for performing noninvasive 3-D color flow imaging of cerebrovascular disease, including stroke. PMID:23475914

  2. Phase aberration correction by multi-stencils fast marching method using sound speed image in ultrasound computed tomography

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Lin, Hongxiang; Imoto, Haruka; Tamano, Satoshi; Takagi, Shu; Umemura, Shin-Ichiro; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-04-01

    Reflection image from ultrasound computed tomography (USCT) system can be obtained by synthetic aperture technique, however its quality is decreased by phase aberration caused by inhomogeneous media. Therefore, phase aberration correction is important to improve image quality. In this study, multi-stencils fast marching method (MSFMM) is employed for phase correction. The MSFMM is an accurate and fast solution of Eikonal equation which considers the refraction. The proposed method includes two steps. First, the MSFMM is used to compute sound propagation time from each element to each image gird point using sound speed image of USCT. Second, synthetic aperture technique is employed to obtain reflection image using the computed propagation time. To evaluate the proposed method, both numerical simulation and phantom experiment were conducted. With regard to numerical simulation, both quantitative and qualitative comparisons between reflection images with and without phase aberration correction were given. In the quantitative comparison, the diameters of point spread function (PSF) in reflection images of a two layer structure were presented. In the qualitative comparison, reflection images of simple circle and complex breast modes with phase aberration correction show higher quality than that without the correction. In respect to phantom experiment, a piece of breast phantom with artificial glandular structure inside was scanned by a USCT prototype, and the artificial glandular structure is able to be visible more clearly in the reflection image with phase aberration correction than in that without the correction. In this study, a phase aberration correction method by the MSFMM are proposed for reflection image of the USCT.

  3. Aberration-corrected scanning transmission electron microscopy for complex transition metal oxides

    NASA Astrophysics Data System (ADS)

    Qing-Hua, Zhang; Dong-Dong, Xiao; Lin, Gu

    2016-06-01

    Lattice, charge, orbital, and spin are the four fundamental degrees of freedom in condensed matter, of which the interactive coupling derives tremendous novel physical phenomena, such as high-temperature superconductivity (high-T c SC) and colossal magnetoresistance (CMR) in strongly correlated electronic system. Direct experimental observation of these freedoms is essential to understanding the structure-property relationship and the physics behind it, and also indispensable for designing new materials and devices. Scanning transmission electron microscopy (STEM) integrating multiple techniques of structure imaging and spectrum analysis, is a comprehensive platform for providing structural, chemical and electronic information of materials with a high spatial resolution. Benefiting from the development of aberration correctors, STEM has taken a big breakthrough towards sub-angstrom resolution in last decade and always steps forward to improve the capability of material characterization; many improvements have been achieved in recent years, thereby giving an in-depth insight into material research. Here, we present a brief review of the recent advances of STEM by some representative examples of perovskite transition metal oxides; atomic-scale mapping of ferroelectric polarization, octahedral distortions and rotations, valence state, coordination and spin ordering are presented. We expect that this brief introduction about the current capability of STEM could facilitate the understanding of the relationship between functional properties and these fundamental degrees of freedom in complex oxides. Project supported by the National Key Basic Research Project, China (Grant No. 2014CB921002), the Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDB07030200), and the National Natural Science Foundation of China (Grant Nos. 51522212 and 51421002).

  4. High-resolution microscopy with low-resolution objectives: correcting phase aberrations in Fourier ptychography

    NASA Astrophysics Data System (ADS)

    Konda, Pavan Chandra; Taylor, Jonathan M.; Harvey, Andrew R.

    2015-09-01

    The spatial resolution of a microscope is inversely proportionate to the sum of the objective numerical aperture (NA) and the illumination NA. Fourier Ptychography (FP) microscopy achieves high-resolution, wide-field imaging by the use of a low-NA, wide-field objective combined with time-sequential synthesis of high NA illumination using an array of LEDs. We describe reconstruction algorithms based on Fresnel propagation, rather than the traditional Fraunhofer propagation, which enables more accurate representation of LED illumination and hence reduced aberration in the image reconstruction. This also enables the new technique of Multi-Aperture Fourier Ptychography in the near-field. In this work the implementation of this algorithm is described together with some experimental results. The performance of this algorithm is validated by comparing to Fraunhofer based algorithm. More sophisticated update functions in the reconstruction procedures developed for FP are implemented with this algorithm and their performance is validated. The pupil phase can also be reconstructed during the reconstruction procedure hence allowing us to correct for the aberrations in the optical system without the need of any additional measurements.

  5. Chromatic aberration correction and deconvolution for UV sensitive imaging of fluorescent sterols in cytoplasmic lipid droplets.

    PubMed

    Wüstner, Daniel; Faergeman, Nils J

    2008-08-01

    Intrinsically fluorescent sterols, like dehydroergosterol (DHE), mimic cholesterol closely and are therefore suitable to determine cholesterol transport by fluorescence microscopy. Disadvantages of DHE are its low quantum yield, rapid bleaching, and the fact that its excitation and emission is in the UV region of the spectrum. Thus, one has to deal with chromatic aberration and low signal-to-noise ratio. We developed a method to correct for chromatic aberration between the UV channel and the red/green channel in multicolor imaging of DHE compared with the lipid droplet marker Nile Red in living macrophage foam cells and in adipocytes. We used deconvolution microscopy and developed image segmentation techniques to assess the DHE content of lipid droplets in both cell types in an automated manner. Pulse-chase studies and colocalization analysis were performed to monitor the redistribution of DHE upon adipocyte differentiation. DHE is targeted to transferrin-positive recycling endosomes in preadipocytes but associates with droplets in mature adipocytes. Only in adipocytes but not in foam cells fluorescent sterol was confined to the droplet-limiting membrane. We developed an approach to visualize and quantify sterol content of lipid droplets in living cells with potential for automated high content screening of cellular sterol transport.

  6. High-resolution microspectrometer with an aberration-correcting planar grating.

    PubMed

    Grabarnik, Semen; Emadi, Arvin; Wu, Huaiwen; de Graaf, Ger; Wolffenbuttel, Reinoud F

    2008-12-01

    A concept for a highly miniaturized spectrometer featuring a two-component design is presented. The first component is a planar chip that integrates an input slit and aberration-correcting diffraction grating with an image sensor and is fabricated using microelectromechanical systems (MEMS) technologies. Due to the fabrication in a simple MEMS batch process the essential elements of the spectrometer are automatically aligned, and a low fabrication cost per device can be achieved. The second component is a spherical mirror, which is the only external part. The optimized grating structure compensates for aberrations within the spectrometer operating range, resulting in a diffraction-limited performance of the spectrometer optics. The prototype of the device has been fabricated and characterized. It takes a volume of 0.5 cm(3) and provides a FWHM spectral resolution of 0.7 nm over a 350 nm bandwidth from 420 nm to 770 nm combined with an etendue of 7.4x10(-5) mm(2) sr. PMID:19037373

  7. Sub-Angstrom Low Voltage Performance of a Monochromated, Aberration-Corrected Transmission Electron Microscope

    PubMed Central

    Bell, David C.; Russo, Christopher J.; Benner, Gerd

    2011-01-01

    Lowering the electron energy in the transmission electron microscope allows for a significant improvement in contrast of light elements, and reduces knock-on damage for most materials. If low-voltage electron microscopes are defined as those with accelerating voltages below 100 kV, the introduction of aberration correctors and monochromators to the electron microscope column enables Ångstrom-level resolution, which was previously reserved for higher voltage instruments. Decreasing electron energy has three important advantages: 1) knock-on damage is lower, which is critically important for sensitive materials such as graphene and carbon nanotubes; 2) cross sections for electron-energy-loss spectroscopy increase, improving signal-to-noise for chemical analysis; 3) elastic scattering cross sections increase, improving contrast in high-resolution, zero-loss images. The results presented indicate that decreasing the acceleration voltage from 200 kV to 80 kV in a monochromated, aberration-corrected microscope enhances the contrast while retaining sub-angstrom resolution. These improvements in low-voltage performance are expected to produce many new results and enable a wealth of new experiments in materials science. PMID:20598206

  8. Bright-field imaging of compound semiconductors using aberration-corrected scanning transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Aoki, Toshihiro; Lu, Jing; McCartney, Martha R.; Smith, David J.

    2016-09-01

    This study reports the observation of six different zincblende compound semiconductors in [110] projection using large-collection-angle bright-field (LABF) imaging with an aberration-corrected scanning transmission electron microscope. Phase contrast is completely suppressed when the collection semi-angle is set equal to the convergence semi-angle and there are no reversals in image contrast with changes in defocus or thickness. The optimum focus for imaging closely separated pairs of atomic columns (‘dumbbells’) is unique and easily recognized, and the positions of atomic columns occupied by heavier atoms always have darker intensity than those occupied by lighter atoms. Thus, the crystal polarity of compound semiconductors can be determined unambiguously. Moreover, it is concluded that the LABF imaging mode will be highly beneficial for studying other more complicated heterostructures at the atomic scale.

  9. Identification of light elements in silicon nitride by aberration-corrected scanning transmission electron microscopy.

    PubMed

    Idrobo, Juan C; Walkosz, Weronika; Klie, Robert F; Oğüt, Serdar

    2012-12-01

    In silicon nitride structural ceramics, the overall mechanical and thermal properties are controlled by the atomic and electronic structures at the interface between the ceramic grains and the amorphous intergranular films (IGFs) formed by various sintering additives. In the last ten years the atomic arrangements of heavy elements (rare-earths) at the Si(3)N(4)/IGF interfaces have been resolved. However, the atomic position of light elements, without which it is not possible to obtain a complete description of the interfaces, has been lacking. This review article details the authors' efforts to identify the atomic arrangement of light elements such as nitrogen and oxygen at the Si(3)N(4)/SiO(2) interface and in bulk Si(3)N(4) using aberration-corrected scanning transmission electron microscopy.

  10. Three-dimensional locations of gold-labeled proteins in a whole mount eukaryotic cell obtained with 3 nm precision using aberration-corrected scanning transmission electron microscopy

    PubMed Central

    Dukes, Madeline J.; Ramachandra, Ranjan; Baudoin, Jean-Pierre; Jerome, W. Gray; de Jonge, Niels

    2011-01-01

    Three-dimensional (3D) maps of proteins within the context of whole cells are important for investigating cellular function. However, 3D reconstructions of whole cells are challenging to obtain using conventional transmission electron microscopy (TEM). We describe a methodology to determine the 3D locations of proteins labeled with gold nanoparticles on whole eukaryotic cells. The epidermal growth factor receptors on COS7 cells were labeled with gold nanoparticles, and critical-point dried whole-mount cell samples were prepared. 3D focal series were obtained with aberration-corrected scanning transmission electron microscopy (STEM), without tilting the specimen. The axial resolution was improved with deconvolution. The vertical locations of the nanoparticles in a whole-mount cell were determined with a precision of 3 nm. From the analysis of the variation of the axial positions of the labels we concluded that the cellular surface was ruffled. To achieve sufficient stability of the sample under the electron beam irradiation during the recording of the focal series, the sample was carbon coated. A quantitative method was developed to analyze the stability of the ultrastructure after electron beam irradiation using TEM. The results of this study demonstrate the feasibility of using aberration-corrected STEM to study the 3D nanoparticle distribution in whole cells. PMID:21440635

  11. Three-dimensional locations of gold-labeled proteins in a whole mount eukaryotic cell obtained with 3nm precision using aberration-corrected scanning transmission electron microscopy.

    PubMed

    Dukes, Madeline J; Ramachandra, Ranjan; Baudoin, Jean-Pierre; Gray Jerome, W; de Jonge, Niels

    2011-06-01

    Three-dimensional (3D) maps of proteins within the context of whole cells are important for investigating cellular function. However, 3D reconstructions of whole cells are challenging to obtain using conventional transmission electron microscopy (TEM). We describe a methodology to determine the 3D locations of proteins labeled with gold nanoparticles on whole eukaryotic cells. The epidermal growth factor receptors on COS7 cells were labeled with gold nanoparticles, and critical-point dried whole-mount cell samples were prepared. 3D focal series were obtained with aberration-corrected scanning transmission electron microscopy (STEM), without tilting the specimen. The axial resolution was improved with deconvolution. The vertical locations of the nanoparticles in a whole-mount cell were determined with a precision of 3nm. From the analysis of the variation of the axial positions of the labels we concluded that the cellular surface was ruffled. To achieve sufficient stability of the sample under electron beam irradiation during the recording of the focal series, the sample was carbon coated. A quantitative method was developed to analyze the stability of the ultrastructure after electron beam irradiation using TEM. The results of this study demonstrate the feasibility of using aberration-corrected STEM to study the 3D nanoparticle distribution in whole cells.

  12. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    NASA Astrophysics Data System (ADS)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  13. Aberration-corrected X-ray spectrum imaging and Fresnel contrast to differentiate nanoclusters and cavities in helium-irradiated alloy 14YWT

    SciTech Connect

    Miller, Michael K; Parish, Chad M

    2014-01-01

    Helium accumulation negatively impacts structural materials used in neutron-irradiated environments, such as fission and fusion reactors. Next-generation fission and fusion reactors will require structural materials, such as steels, resistant to large neutron doses yet see service temperatures in the range most affected by helium embrittlement. Previous work has indicated the difficulty of experimentally differentiating nanometer-sized helium bubbles from the Ti-Y-O rich nanoclustsers (NCs) in radiation-tolerant nanostructured ferritic alloys (NFAs). Because the NCs are expected to sequester helium away from grain boundaries and reduce embrittlement, experimental methods to study simultaneously the NC and bubble populations are needed. In this study, aberration-corrected scanning transmission electron microscopy (STEM) results combining high-collection-efficiency X-ray spectrum images (SIs), multivariate statistical analysis (MVSA), and Fresnel-contrast bright-field STEM imaging have been used for such a purpose. Results indicate that Fresnel-contrast imaging, with careful attention to TEM-STEM reciprocity, differentiates bubbles from NCs, and MVSA of X-ray SIs unambiguously identifies NCs. Therefore, combined Fresnel-contrast STEM and X-ray SI is an effective STEM-based method to characterize helium-bearing NFAs.

  14. In-situ Study of Dynamic Phenomena at Metal Nanosolder Interfaces Using Aberration Corrected Scanning Transmission Electron Microcopy.

    SciTech Connect

    Lu, Ping

    2014-10-01

    Controlling metallic nanoparticle (NP) interactions plays a vital role in the development of new joining techniques (nanosolder) that bond at lower processing temperatures but remain viable at higher temperatures. The pr imary objective of this project is t o develop a fundamental understanding of the actual reaction processes, associated atomic mechanisms, and the resulting microstructure that occur during thermally - driven bond formation concerning metal - metal nano - scale (%3C50nm) interfaces. In this LDRD pr oject, we have studied metallic NPs interaction at the elevated temperatures by combining in - situ transmission electron microscopy (TEM ) using an aberration - corrected scanning transmission electron microscope (AC - STEM) and atomic - scale modeling such as m olecular dynamic (MD) simulations. Various metallic NPs such as Ag, Cu and Au are synthesized by chemical routines. Numerous in - situ e xperiments were carried out with focus of the research on study of Ag - Cu system. For the first time, using in - situ STEM he ating experiments , we directly observed t he formation of a 3 - dimensional (3 - D) epitaxial Cu - Ag core - shell nanoparticle during the thermal interaction of Cu and Ag NPs at elevated temperatures (150 - 300 o C). The reaction takes place at temperatures as low as 150 o C and was only observed when care was taken to circumvent the effects of electron beam irradiation during STEM imaging. Atomic - scale modeling verified that the Cu - Ag core - shell structure is energetically favored, and indicated that this phenomenon is a nano - scale effect related to the large surface - to - volume ratio of the NPs. The observation potentially can be used for developing new nanosolder technology that uses Ag shell as the "glue" that stic ks the particles of Cu together. The LDRD has led to several journal publications and numerous conference presentations, and a TA. In addition, we have developed new TEM characterization techniques and phase

  15. Aberrant DNA methylation reprogramming during induced pluripotent stem cell generation is dependent on the choice of reprogramming factors.

    PubMed

    Planello, Aline C; Ji, Junfeng; Sharma, Vivek; Singhania, Rajat; Mbabaali, Faridah; Müller, Fabian; Alfaro, Javier A; Bock, Christoph; De Carvalho, Daniel D; Batada, Nizar N

    2014-01-01

    The conversion of somatic cells into pluripotent stem cells via overexpression of reprogramming factors involves epigenetic remodeling. DNA methylation at a significant proportion of CpG sites in induced pluripotent stem cells (iPSCs) differs from that of embryonic stem cells (ESCs). Whether different sets of reprogramming factors influence the type and extent of aberrant DNA methylation in iPSCs differently remains unknown. In order to help resolve this critical question, we generated human iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and cMYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28), and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identified Yamanaka-iPSC (Y-iPSC)-specific and Thomson-iPSC (T-iPSC)-specific recurrent aberrations. Strikingly, not only were the genomic locations of the aberrations different but also their types: reprogramming with Yamanaka factors mainly resulted in failure to demethylate CpGs, whereas reprogramming with Thomson factors mainly resulted in failure to methylate CpGs. Differences in the level of transcripts encoding DNMT3b and TET3 between Y-iPSCs and T-iPSCs may contribute partially to the distinct types of aberrations. Finally, de novo aberrantly methylated genes in Y-iPSCs were enriched for NANOG targets that are also aberrantly methylated in some cancers. Our study thus reveals that the choice of reprogramming factors influences the amount, location, and class of DNA methylation aberrations in iPSCs. These findings may provide clues into how to produce human iPSCs with fewer DNA methylation abnormalities. PMID:25408883

  16. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

    PubMed

    Davis, Hayley; Irshad, Shazia; Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc C; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen J; Greten, Florian R; Wang, Lai Mun; East, James E; Tomlinson, Ian; Leedham, Simon J

    2015-01-01

    Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

  17. A two-stage method to correct aberrations induced by slide slant in bright-field microscopy.

    PubMed

    Fan, Yilun; Bradley, Andrew P

    2016-08-01

    To achieve optimal image quality in bright field microscopy, the slide surface should be perpendicular to the optical axis of the microscope. However, in the recently proposed "slanted scan" slide acquisition technique, scan speed is increased by purposely slanting the slide by a small angle (of 3-5°) so that multiple focal depths can be imaged simultaneously. In this case, the slanted slide introduces a bend in the point spread function (PSF), resulting in a coma and other aberrations that degrade image quality. In this paper, we propose a two-stage deconvolution method specifically designed to correct the aberrations induced by a slanted scan, but with general applicability to high-resolution bright-field microscopy. Specifically, we initially apply phase deconvolution to correct the dominating coma aberration, before applying a conventional semi-blind deconvolution method to further improve image resolution and contrast. We also propose a novel method to estimate the degree of coma aberration and the PSF of the optics utilising actual cytology specimens. The efficacy of the proposed algorithm is demonstrated quantitatively on simulated data, against a ground-truth (object) image, and qualitatively on cervical cytology specimens. Results demonstrate both improved convergence speed of the two-stage approach, especially when correcting the bend in the PSF, and a resultant image quality that is comparable to a conventionally (flat) scanned specimen. PMID:27182660

  18. Aberration correction for direct laser written waveguides in a transverse geometry.

    PubMed

    Huang, L; Salter, P S; Payne, F; Booth, M J

    2016-05-16

    The depth dependent spherical aberration is investigated for ultrafast laser written waveguides fabricated in a transverse writing geometry using the slit beam shaping technique in the low pulse repetition rate regime. The axial elongation of the focus caused by the aberration leads to a distortion of the refractive index change, and waveguides designed as single mode become multimode. We theoretically estimate a depth range over which the aberration effects can be compensated simply by adjusting the incident laser power. If deeper fabrication is required, it is demonstrated experimentally that the aberration can be successfully removed using adaptive optics to fabricate single mode optical waveguides over a depth range > 1 mm. PMID:27409879

  19. Chromatic-aberration-corrected diffractive lenses for ultra-broadband focusing

    DOE PAGES

    Wang, Peng; Mohammad, Nabil; Menon, Rajesh

    2016-02-12

    We exploit the inherent dispersion in diffractive optics to demonstrate planar chromatic-aberration-corrected lenses. Specifically, we designed, fabricated and characterized cylindrical diffractive lenses that efficiently focus the entire visible band (450 nm to 700 nm) onto a single line. These devices are essentially pixelated, multi-level microstructures. Experiments confirm an average optical efficiency of 25% for a three-wavelength apochromatic lens whose chromatic focus shift is only 1.3 μm and 25 μm in the lateral and axial directions, respectively. Super-achromatic performance over the continuous visible band is also demonstrated with averaged lateral and axial focus shifts of only 1.65 μm and 73.6 μm,more » respectively. These lenses are easy to fabricate using single-step grayscale lithography and can be inexpensively replicated. Furthermore, these devices are thin (<3 μm), error tolerant, has low aspect ratio (<1:1) and offer polarization-insensitive focusing, all significant advantages compared to alternatives that rely on metasurfaces. Lastly, our design methodology offers high design flexibility in numerical aperture and focal length, and is readily extended to 2D.« less

  20. Chromatic-aberration-corrected diffractive lenses for ultra-broadband focusing

    PubMed Central

    Wang, Peng; Mohammad, Nabil; Menon, Rajesh

    2016-01-01

    We exploit the inherent dispersion in diffractive optics to demonstrate planar chromatic-aberration-corrected lenses. Specifically, we designed, fabricated and characterized cylindrical diffractive lenses that efficiently focus the entire visible band (450 nm to 700 nm) onto a single line. These devices are essentially pixelated, multi-level microstructures. Experiments confirm an average optical efficiency of 25% for a three-wavelength apochromatic lens whose chromatic focus shift is only 1.3 μm and 25 μm in the lateral and axial directions, respectively. Super-achromatic performance over the continuous visible band is also demonstrated with averaged lateral and axial focus shifts of only 1.65 μm and 73.6 μm, respectively. These lenses are easy to fabricate using single-step grayscale lithography and can be inexpensively replicated. Furthermore, these devices are thin (<3 μm), error tolerant, has low aspect ratio (<1:1) and offer polarization-insensitive focusing, all significant advantages compared to alternatives that rely on metasurfaces. Our design methodology offers high design flexibility in numerical aperture and focal length, and is readily extended to 2D. PMID:26868264

  1. Simple system of aberration correction for very large spherical primary mirrors

    NASA Astrophysics Data System (ADS)

    Beach, David A.

    2000-10-01

    Several large telescopes are now being proposed that would benefit from the cost reduction due to the use of spherical primary mirror. However, structural cost constraints require compact formats that tend to impose very high speeds, e.g. f/1.5, which renders difficult the correction of the resulting very large spherical aberration. A technique is described here in which a spherical concentric Cassegrain-like primary-secondary combination is followed by a simple catadioptric focal modifier. The spherical primary is 9m diameter, f/1.5, and the final focus is f/5 with a sub-arcsecond resolution over a 5 arcminute angular field for a passband of 480-850nm. Primary- secondary separation is only 11m and central obscuration is only 11% of pupil area. The two relatively small corrector components provide the functions of concentric meniscus and zonal corrector plate and are made from the same single glass- BK7 is the example given, but silica or any other preferred glass is possible. The relatively small zonal corrector is the only aspheric surface in the entire system. A related system is described elsewhere in which a 30 arcminute angular field can be achieved with a similar resolution, but with more complex glass requirements. However, supply of such exotic glasses may be difficult in large diameters, and the system presented here may find a place in some specialized applications.

  2. Estimating the number of hematopoietic or lymphoid stem cells giving rise to clonal chromosome aberrations in blood T lymphocytes.

    PubMed

    Nakano, M; Kodama, Y; Ohtaki, K; Itoh, M; Awa, A A; Cologne, J; Kusunoki, Y; Nakamura, N

    2004-03-01

    Quantifying the proliferative capacity of long-term hematopoietic stem cells in humans is important for bone marrow transplantation and gene therapy. Obtaining appropriate data is difficult, however, because the experimental tools are limited. We hypothesized that tracking clonal descendants originating from hematopoietic stem cells would be possible if we used clonal chromosome aberrations as unique tags of individual hematopoietic stem cells in vivo. Using FISH, we screened 500 blood T lymphocytes from each of 513 atomic bomb survivors and detected 96 clones composed of at least three cells with identical aberrations. The number of clones was inversely related to their population size, which we interpreted to mean that the progenitor cells were heterogeneous in the number of progeny that they could produce. The absolute number of progenitor cells contributing to the formation of the observed clones was estimated as about two in an unexposed individual. Further, scrutiny of ten clones revealed that lymphocyte clones could originate roughly equally from hematopoietic stem cells or from mature T lymphocytes, thereby suggesting that the estimated two progenitor cells are shared as one hematopoietic stem cell and one mature T cell. Our model predicts that one out of ten people bears a non- aberrant clone comprising >10% of the total lymphocytes, which indicates that clonal expansions are common and probably are not health-threatening. PMID:14982487

  3. Aberration correction for transcranial photoacoustic tomography of primates employing adjunct image data

    NASA Astrophysics Data System (ADS)

    Huang, Chao; Nie, Liming; Schoonover, Robert W.; Guo, Zijian; Schirra, Carsten O.; Anastasio, Mark A.; Wang, Lihong V.

    2012-06-01

    A challenge in photoacoustic tomography (PAT) brain imaging is to compensate for aberrations in the measured photoacoustic data due to their propagation through the skull. By use of information regarding the skull morphology and composition obtained from adjunct x-ray computed tomography image data, we developed a subject-specific imaging model that accounts for such aberrations. A time-reversal-based reconstruction algorithm was employed with this model for image reconstruction. The image reconstruction methodology was evaluated in experimental studies involving phantoms and monkey heads. The results establish that our reconstruction methodology can effectively compensate for skull-induced acoustic aberrations and improve image fidelity in transcranial PAT.

  4. Array elevation requirements in phase aberration correction using an 8x128 1.75D array

    NASA Astrophysics Data System (ADS)

    Fernandez, Anna T.; Dahl, Jeremy J.; Dumont, Douglas M.; Trahey, Gregg E.

    2002-04-01

    Accurate measurement of tissue aberrations is necessary for effective adaptive ultrasound imaging. Higher order arrays provide more elements and a larger array footprint over which echo signals can be acquired. This allows for better sampling of the aberrator in both the azimuthal and elevation dimensions. These measured aberration profiles can then be used to correct the timing of transmitted and received RF signals to generate new images. We acquired single channel RF data on a 6.7 MHz, 8 x 128 array (Tetrad Co.) operating at F/1.0 in azimuth and F/2.9 in elevation. This array was interfaced to a Siemens Elegra scanner, allowing for data acquisition during routine phantom and clinical scanning. One-dimensional and two-dimensional physical near-field aberrators were used while imaging speckle only and spherical cyst-mimicking phantoms. In some experiments, neighboring elements were electronically tied in elevation to form ``taller'' elements. We collected individual channel data on each of 6 physical rows and then on a combination of rows to form 3x128, 2x128, and 1x128 arrays over a 6x128 aperture of the array. A least-mean-squares algorithm was employed to estimate the arrival time error induced by the tissue for the different array geometries. These aberration measurements were used to correct the images. In addition, point target simulations were performed to characterize the algorithm's performance for all four different array configurations. We present the performance of the adaptive imaging algorithm and discuss methods of combining arrival time profiles from axial and lateral tissue regions to improve adaptive imaging performance. Contrast results in simulation and phantom experiments with different aberrators are presented. We also discuss, in the context of our aberration measurement profiles, the array geometry requirements for successful adaptive imaging and the effects of the aberrators on sidelobe strength and contrast measurement. Results from

  5. Aberration corrected 1.2-MV cold field-emission transmission electron microscope with a sub-50-pm resolution

    SciTech Connect

    Akashi, Tetsuya; Takahashi, Yoshio; Tanigaki, Toshiaki Shimakura, Tomokazu; Kawasaki, Takeshi; Furutsu, Tadao; Shinada, Hiroyuki; Osakabe, Nobuyuki; Müller, Heiko; Haider, Maximilian; Tonomura, Akira

    2015-02-16

    Atomic-resolution electromagnetic field observation is critical to the development of advanced materials and to the unveiling of their fundamental physics. For this purpose, a spherical-aberration corrected 1.2-MV cold field-emission transmission electron microscope has been developed. The microscope has the following superior properties: stabilized accelerating voltage, minimized electrical and mechanical fluctuation, and coherent electron emission. These properties have enabled to obtain 43-pm information transfer. On the bases of these performances, a 43-pm resolution has been obtained by correcting lens aberrations up to the third order. Observations of GaN [411] thin crystal showed a projected atomic locations with a separation of 44 pm.

  6. Progress on PEEM3 - An Aberration Corrected X-Ray PhotoemissionElectron Microscope at the ALS

    SciTech Connect

    MacDowell, Alastair A.; Feng, J.; DeMello, A.; Doran, A.; Duarte,R.; Forest, E.; Kelez, N.; Marcus, M.A.; Miller, T.; Padmore, H.A.; Raoux, S.; Robin, D.; Scholl, A.; Schlueter, R.; Schmid, P.; Stohr, J.; Wan, W.; Wei, D.H.; Wu, Y.

    2006-05-20

    A new ultrahigh-resolution photoemission electron microscope called PEEM3 is being developed and built at the Advanced Light Source (ALS). An electron mirror combined with a much-simplified magnetic dipole separator is to be used to provide simultaneous correction of spherical and chromatic aberrations. It is installed on an elliptically polarized undulator (EPU) beamline, and will be operated with very high spatial resolution and high flux to study the composition, structure, electric and magnetic properties of complex materials. The instrument has been designed and is described. The instrumental hardware is being deployed in 2 phases. The first phase is the deployment of a standard PEEM type microscope consisting of the standard linear array of electrostatic electron lenses. The second phase will be the installation of the aberration corrected upgrade to improve resolution and throughput. This paper describes progress as the instrument enters the commissioning part of the first phase.

  7. Direct imaging of lithium atoms in LiV₂O₄ by spherical aberration-corrected electron microscopy.

    PubMed

    Oshima, Yoshifumi; Sawada, Hidetaka; Hosokawa, Fumio; Okunishi, Eiji; Kaneyama, Toshikatsu; Kondo, Yukihito; Niitaka, Seiji; Takagi, Hidenori; Tanishiro, Yasumasa; Takayanagi, Kunio

    2010-01-01

    We visualized lithium atom columns in LiV₂O₄ crystals by combining scanning transmission electron microscopy with annular bright field (ABF) imaging using a spherical aberration-corrected electron microscope (R005) viewed from the [110] direction. The incident electron beam was coherent with a convergent angle of 30 mrad (semi-angle), and the detector collected scattered electrons over 20-30 mrad (semi-angle). The ABF image showed dark dots corresponding to lithium, vanadium and oxygen columns. PMID:20406731

  8. Higher-order aberrations and best-corrected visual acuity in Native American children with a high prevalence of astigmatism

    PubMed Central

    Miller, Joseph M.; Harvey, Erin M.; Schwiegerling, Jim

    2016-01-01

    Purpose To determine whether higher-order aberrations (HOAs) in children from a highly astigmatic population differ from population norms and whether HOAs are associated with astigmatism and reduced best-corrected visual acuity. Methods Subjects were 218 Tohono O’odham Native American children 5–9 years of age. Noncycloplegic HOA measurements were obtained with a handheld Shack-Hartmann sensor (SHS). Signed (z06s to z14s) and unsigned (z06u to z14u) wavefront aberration Zernike coefficients Z(3,−3) to Z(4,4) were rescaled for a 4 mm diameter pupil and compared to adult population norms. Cycloplegic refraction and best-corrected logMAR letter visual acuity (BCVA) were also measured. Regression analyses assessed the contribution of astigmatism (J0) and HOAs to BCVA. Results The mean root-mean-square (RMS) HOA of 0.191 ± 0.072 μm was significantly greater than population norms (0.100 ± 0.044 μm. All unsigned HOA coefficients (z06u to z14u) and all signed coefficients except z09s, z10s, and z11s were significantly larger than population norms. Decreased BCVA was associated with astigmatism (J0) and spherical aberration (z12u) but not RMS coma, with the effect of J0 about 4 times as great as z12u. Conclusions Tohono O’odham children show elevated HOAs compared to population norms. Astigmatism and unsigned spherical aberration are associated with decreased acuity, but the effects of spherical aberration are minimal and not clinically significant. PMID:26239206

  9. High resolution structural and compositional mapping of the SrTiO3/LaFeO3 interface using chromatic aberration corrected energy filtered imaging

    NASA Astrophysics Data System (ADS)

    Kabius, Bernd; Houben, Lothar; Dwyer, Christian; Colby, Robert; Chambers, Scott A.; Dunin-Borkowski, Rafal

    2014-03-01

    Interfaces between insulating polar perovskites have demonstrated a wealth of electronic and magnetic properties. Understanding and predicting the properties of a specific interface requires atomic level knowledge of interface structure and chemistry. Electron microscopy is capable of this task, and has been frequently applied to oxide interfaces using a combination of high-angle angular dark field scanning transmission electron microscopy (HAADF-STEM) and electron energy-loss spectroscopy (EELS). Energy-filtered TEM (EFTEM) captures a full image for a given energy losses, allowing a larger field of view than typical for STEM-EELS in far less time. However, EFTEM has not, to date, demonstrated the spatial resolution of STEM-EELS due to the limits set by chromatic aberration Cc. This study of LaFeO3/SrTiO3 demonstrates that Cc correction enhances the resolution of EFTEM for elemental mapping, allowing a unit cell-by-unit cell analysis of the concentration gradients across the SrTiO3/LaFeO3 interface. The charge distribution at the interface will be discussed. The research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory

  10. Some Considerations Regarding Pulsed Correction of Chromatic Aberrations in Final Focusing Systems

    SciTech Connect

    Bangerter, Roger

    2010-03-31

    overcome longitudinal space-charge forces; but these forces will remove part of the tilt as the beam compresses. Al Maschke suggested that it is possible to reduce the chromatic aberrations by applying a time-dependent transverse focusing correction to the beam upstream of the final focusing lenses [1]. At this point, because of the energy tilt, there is a correlation between longitudinal position in the beam and particle energy. In other words, the average beam energy at the tail of the beam is larger than the average beam energy at the head of the beam. If the beam is completely neutralized as it drifts toward the final focusing lenses, the kinetic energies of the individual particles will remain nearly unchanged during compression. In this case, it is possible, in principle, to apply some 'pre-focusing' to the higher energy particles (those nearer to the tail of the beam) to compensate for their weaker focusing in the final lenses. Although kinetic energies of individual particles are not conserved if the beam is not neutralized, one still expects a positive correlation between the particle energies at the beginning of compression and at the end of compression so correction is still assumed to be possible. It is important that the pulse duration is larger upstream than it is at the final focusing lenses. Larger pulse duration makes it easier, from an engineering standpoint, to supply the power needed to drive the pulsed correction elements. Nevertheless, it still appears impossible or very costly to provide the needed power for some specific cases that have been studied. In the remainder of this paper we ignore this issue and try to determine if there are other fundamental limitations on how well one might correct. We conclude that there are other important limitations.

  11. Open-loop wavefront sensing scheme for specimen aberrations correction in two-photon excited fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Aviles-Espinosa, Rodrigo; Andilla, Jordi; Porcar-Guezenec, Rafael; Levecq, Xavier; Artigas, David; Loza-Alvarez, Pablo

    2011-07-01

    The recent linkage between adaptive optics, a technique borrowed from astronomy and various imaging devices, has enabled to push forward their imaging capabilities by improving its contrast and resolution. A specific case is nonlinear microscopy (NLM) that, although it brings several inherent advantages (compared to linear fluorescence techniques) due to its nonlinear dependence on the excitation beam, its enhanced capabilities can be limited by the sample inhomogeneous structure. In this work, we demonstrate how these imaging capabilities can be enhanced by, employing adaptive optics in a two step correction process. Firstly, a closed-loop methodology aided by Shack-Hartman Wavefront sensing scheme is implemented for compensating the aberrations produced by the laser and the optical elements before the high numerical aperture microscope objective, resulting in a one-time calibration process. Then the residual aberrations are produced by the microscope objective and the sample. These are measured in a similar way as it is done in astronomy (employing a laser guide-star), using the two-photon excited fluorescence. The properties of this incoherent emission produced inside a test sample are compared to a genetically modified Caenorhabditis. elegans nematode expressing GFP showing that the emission of this protein (at 810nm) can be sensed efficiently with our WFS by modifying the exposure time. Therefore the recorded wavefront will capture the sample aberrations which are used to shape a deformable mirror in an open-loop configuration. This correction principle is demonstrated in a test sample by correcting aberrations in a "single-shot" resulting in a reduced sample exposure.

  12. Correction of Spherical Aberration in Grazing-Incidence X-ray Optics by Combination of Spherical-Concave Mirrors

    SciTech Connect

    Suzuki, Y.; Takeuchi, A.

    2011-09-09

    In grazing-incidence total-reflection mirror optics for x-rays, spherical aberrations and coma are the most serious aberrations for microfocusing and microimaging. High-resolution imaging is believed to be possible only when an aspherical mirror system is used. However, the spherical aberrations of a spherical-concave mirror in a grazing-incidence condition can be eliminated by sequential reflection of spherical mirrors of similar shapes. A sub-micrometer one-dimensional focusing is easily achieved by the spherical-aberration-corrected tandem-spherical mirror optics. By configuring four spherical mirrors in an analogy of the crossed mirror optics (Kirkpatrick-Baez optics), it is possible to achieve sub-micrometer focused beam size in the hard x-ray region. Preliminary experiments on x-ray microfocusing have been carried out at beamline 20XU of SPring-8, and a 0.5 {mu}mx0.4 {mu}m beam size was achieved at 8 keV.

  13. Field confinement with aberration correction for solid immersion lens based fluorescence correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Rao, Ramachandra; Mitic, Jelena; Serov, Alexandre; Leitgeb, Rainer A.; Lasser, Theo

    2007-03-01

    The solid immersion lens (SIL) as a tool for increasing the field confinement as well as providing optimal performance by aberration compensation in a confocal fluorescence correlation spectroscopy (FCS) system is illustrated here. Using Zernike polynomials we show that aberration compensation and the resultant pre-shaping of the incident wavefront enables near diffraction-limited performance. This is explained based on vectorial computations for high apertures in the Debye approximation. The obtained axial resolution parameters are compared with the obtained diffusion times in a SIL-FCS experiment for measurements in solutions done at the single molecule level.

  14. NrasG12D/+ promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions

    PubMed Central

    Wang, Jinyong; Kong, Guangyao; Liu, Yangang; Du, Juan; Chang, Yuan-I; Tey, Sin Ruow; Zhang, Xinmin; Ranheim, Erik A.; Saba-El-Leil, Marc K.; Meloche, Sylvain; Damnernsawad, Alisa; Zhang, Jingfang; Zhang, Jing

    2013-01-01

    Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated granulocyte macrophage colony-stimulating factor signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here, we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN-initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacologic and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. PMID:23687087

  15. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    PubMed Central

    Reddy, Avanish S.; Maletic-Savatic, Mirjana; Aguirre, Adan; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2−/− mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2−/− SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration. PMID:24391977

  16. Bayesian-based aberration correction and numerical diffraction for improved lensfree on-chip microscopy of biological specimens.

    PubMed

    Wong, Alexander; Kazemzadeh, Farnoud; Jin, Chao; Wang, Xiao Yu

    2015-05-15

    Lensfree on-chip microscopy is an emerging imaging technique that can be used to visualize and study biological specimens without the need for imaging lens systems. Important issues that can limit the performance of lensfree on-chip microscopy include interferometric aberrations, acquisition noise, and image reconstruction artifacts. In this study, we introduce a Bayesian-based method for performing aberration correction and numerical diffraction that accounts for all three of these issues to improve the effective numerical aperture (NA) and signal-to-noise ratio (SNR) of the reconstructed microscopic image. The proposed method was experimentally validated using the USAF resolution target as well as real waterborne Anabaena flos-aquae samples, demonstrating improvements in NA by ∼25% over the standard method, and improvements in SNR of 2.8 and 8.2 dB in the reconstructed image when compared to the reconstructed images produced using the standard method and a maximum likelihood estimation method, respectively.

  17. The structure of an Al-Rh-Cu decagonal quasicrystal studied by spherical aberration (Cs)-corrected scanning transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Hiraga, Kenji; Yasuhara, Akira; Yamamoto, Kazuki; Yubuta, Kunio

    2015-05-01

    The structure of an Al-Rh-Cu decagonal quasicrystal formed with two quasiperiodic planes along the periodic axis in an Al63Rh18.5Cu18.5 alloy has been studied by spherical aberration (Cs)-corrected high-angle annular detector dark-field (HAADF)- and annular bright-field (ABF)-scanning transmission electron microscopy (STEM). Heavy atoms of Rh and mixed sites (MSs) of Al and Cu atoms projected along the periodic axis can be clearly represented as separate bright dots in observed HAADF-STEM images, and consequently arrangements of Rh atoms and MSs on the two quasiperiodic planes can be directly determined from those of bright dots in the observed HAADF-STEM image. The Rh atoms are arranged in pentagonal tiling formed with pentagonal and star-shaped pentagonal tiles with an edge-length of 0.76 nm, and also MSs with a pentagonal arrangement are located in the pentagonal tiles with definite orientations. The star-shaped pentagonal tiles in the pentagonal tiling are arranged in τ2(τ: golden ratio)-inflated pentagonal tiling with a bond-length of 2 nm. From arrangements of Rh atoms placed in pentagonal tilings with a bond-length of 2 nm, which are generated by the projection of a five-dimensional hyper-cubic lattice, occupation domains in the perpendicular space are derived. Al atoms as well as Rh atoms and MSs are represented as dark dots in an observed ABF-STEM image, and arrangements of Al atoms in well-symmetric regions are discussed.

  18. Gaucher Disease-Induced Pluripotent Stem Cells Display Decreased Erythroid Potential and Aberrant Myelopoiesis

    PubMed Central

    Sgambato, Judi A.; Park, Tea Soon; Miller, Diana; Panicker, Leelamma M.; Sidransky, Ellen; Lun, Yu; Awad, Ola; Bentzen, Søren M.; Zambidis, Elias T.

    2015-01-01

    Gaucher disease (GD) is the most common lysosomal storage disease resulting from mutations in the lysosomal enzyme glucocerebrosidase (GCase). The hematopoietic abnormalities in GD include the presence of characteristic Gaucher macrophages that infiltrate patient tissues and cytopenias. At present, it is not clear whether these cytopenias are secondary to the pathological activity of Gaucher cells or a direct effect of GCase deficiency on hematopoietic development. To address this question, we differentiated induced pluripotent stem cells (iPSCs) derived from patients with types 1, 2, and 3 GD to CD34+/CD45+/CD43+/CD143+ hematopoietic progenitor cells (HPCs) and examined their developmental potential. The formation of GD-HPCs was unaffected. However, these progenitors demonstrated a skewed lineage commitment, with increased myeloid differentiation and decreased erythroid differentiation and maturation. Interestingly, myeloid colony-formation assays revealed that GD-HPCs, but not control-HPCs, gave rise to adherent, macrophage-like cells, another indication of abnormal myelopoiesis. The extent of these hematologic abnormalities correlated with the severity of the GCase mutations. All the phenotypic abnormalities of GD-HPCs observed were reversed by incubation with recombinant GCase, indicating that these developmental defects were caused by the mutated GCase. Our results show that GCase deficiency directly impairs hematopoietic development. Additionally, our results suggest that aberrant myelopoiesis might contribute to the pathological properties of Gaucher macrophages, which are central to GD manifestations. The hematopoietic developmental defects we observed reflect hematologic abnormalities in patients with GD, demonstrating the utility of GD-iPSCs for modeling this disease. Significance This study showed that hematopoietic progenitors from patients with Gaucher disease (GD) have intrinsic developmental abnormalities that reflect characteristic clinical

  19. Comparison of analytical and numerical approaches for CT-based aberration correction in transcranial passive acoustic imaging

    NASA Astrophysics Data System (ADS)

    Jones, Ryan M.; Hynynen, Kullervo

    2016-01-01

    Computed tomography (CT)-based aberration corrections are employed in transcranial ultrasound both for therapy and imaging. In this study, analytical and numerical approaches for calculating aberration corrections based on CT data were compared, with a particular focus on their application to transcranial passive imaging. Two models were investigated: a three-dimensional full-wave numerical model (Connor and Hynynen 2004 IEEE Trans. Biomed. Eng. 51 1693-706) based on the Westervelt equation, and an analytical method (Clement and Hynynen 2002 Ultrasound Med. Biol. 28 617-24) similar to that currently employed by commercial brain therapy systems. Trans-skull time delay corrections calculated from each model were applied to data acquired by a sparse hemispherical (30 cm diameter) receiver array (128 piezoceramic discs: 2.5 mm diameter, 612 kHz center frequency) passively listening through ex vivo human skullcaps (n  =  4) to emissions from a narrow-band, fixed source emitter (1 mm diameter, 516 kHz center frequency). Measurements were taken at various locations within the cranial cavity by moving the source around the field using a three-axis positioning system. Images generated through passive beamforming using CT-based skull corrections were compared with those obtained through an invasive source-based approach, as well as images formed without skull corrections, using the main lobe volume, positional shift, peak sidelobe ratio, and image signal-to-noise ratio as metrics for image quality. For each CT-based model, corrections achieved by allowing for heterogeneous skull acoustical parameters in simulation outperformed the corresponding case where homogeneous parameters were assumed. Of the CT-based methods investigated, the full-wave model provided the best imaging results at the cost of computational complexity. These results highlight the importance of accurately modeling trans-skull propagation when calculating CT-based aberration corrections

  20. Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites

    SciTech Connect

    Fontanarosa, Davide; Meer, Skadi van der; Bloemen-van Gurp, Esther; Stroian, Gabriela; Verhaegen, Frank

    2012-08-15

    Purpose: The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three-dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures. Methods: A correction, provided by a previously published density-based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated. Results: After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm. Conclusions: The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.

  1. Direct atomic-scale imaging of hydrogen and oxygen interstitials in pure niobium using atom-probe tomography and aberration-corrected scanning transmission electron microscopy.

    PubMed

    Kim, Yoon-Jun; Tao, Runzhe; Klie, Robert F; Seidman, David N

    2013-01-22

    Imaging the three-dimensional atomic-scale structure of complex interfaces has been the goal of many recent studies, due to its importance to technologically relevant areas. Combining atom-probe tomography and aberration-corrected scanning transmission electron microscopy (STEM), we present an atomic-scale study of ultrathin (~5 nm) native oxide layers on niobium (Nb) and the formation of ordered niobium hydride phases near the oxide/Nb interface. Nb, an elemental type-II superconductor with the highest critical temperature (T(c) = 9.2 K), is the preferred material for superconducting radio frequency (SRF) cavities in next-generation particle accelerators. Nb exhibits high solubilities for oxygen and hydrogen, especially within the RF-field penetration depth, which is believed to result in SRF quality factor losses. STEM imaging and electron energy-loss spectroscopy followed by ultraviolet laser-assisted local-electrode atom-probe tomography on the same needle-like sample reveals the NbO(2), Nb(2)O(5), NbO, Nb stacking sequence; annular bright-field imaging is used to visualize directly hydrogen atoms in bulk β-NbH.

  2. Direct imaging of light elements by annular dark-field aberration-corrected scanning transmission electron microscopy

    SciTech Connect

    Lotnyk, Andriy Poppitz, David; Gerlach, Jürgen W.; Rauschenbach, Bernd

    2014-02-17

    In this report, we show that an annular dark-field detector in an aberration-corrected scanning transmission electron microscope allows the direct observation of light element columns in crystalline lattices. At specific imaging conditions, an enhancement of the intensities of light element columns in the presence of heavy element columns is observed. Experimental results are presented for imaging the nitrogen and carbon atomic columns at the GaN-SiC interface and within the GaN and SiC compounds. The crystal polarity of GaN at the interface is identified. The obtained findings are discussed and are well supported by image simulations.

  3. Direct imaging of light elements by annular dark-field aberration-corrected scanning transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Lotnyk, Andriy; Poppitz, David; Gerlach, Jürgen W.; Rauschenbach, Bernd

    2014-02-01

    In this report, we show that an annular dark-field detector in an aberration-corrected scanning transmission electron microscope allows the direct observation of light element columns in crystalline lattices. At specific imaging conditions, an enhancement of the intensities of light element columns in the presence of heavy element columns is observed. Experimental results are presented for imaging the nitrogen and carbon atomic columns at the GaN-SiC interface and within the GaN and SiC compounds. The crystal polarity of GaN at the interface is identified. The obtained findings are discussed and are well supported by image simulations.

  4. Full correction for spatially distributed speed-of-sound in echo ultrasound based on measuring aberration delays via transmit beam steering.

    PubMed

    Jaeger, Michael; Robinson, Elise; Akarçay, H Günhan; Frenz, Martin

    2015-06-01

    Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique. PMID:25989072

  5. Full correction for spatially distributed speed-of-sound in echo ultrasound based on measuring aberration delays via transmit beam steering

    NASA Astrophysics Data System (ADS)

    Jaeger, Michael; Robinson, Elise; Günhan Akarçay, H.; Frenz, Martin

    2015-06-01

    Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique.

  6. Correction of thermal gradient errors in stem thermocouple hygrometers.

    PubMed

    Michel, B E

    1979-01-01

    Stem thermocouple hygrometers were subjected to transient and stable thermal gradients while in contact with reference solutions of NaCl. Both dew point and psychrometric voltages were directly related to zero offset voltages, the latter reflecting the size of the thermal gradient. Although slopes were affected by absolute temperature, they were not affected by water potential. One hygrometer required a correction of 1.75 bars water potential per microvolt of zero offset, a value that was constant from 20 to 30 C.

  7. Correction of Thermal Gradient Errors in Stem Thermocouple Hygrometers

    PubMed Central

    Michel, Burlyn E.

    1979-01-01

    Stem thermocouple hygrometers were subjected to transient and stable thermal gradients while in contact with reference solutions of NaCl. Both dew point and psychrometric voltages were directly related to zero offset voltages, the latter reflecting the size of the thermal gradient. Although slopes were affected by absolute temperature, they were not affected by water potential. One hygrometer required a correction of 1.75 bars water potential per microvolt of zero offset, a value that was constant from 20 to 30 C. PMID:16660685

  8. Correction of thermal gradient errors in stem thermocouple hygrometers.

    PubMed

    Michel, B E

    1979-01-01

    Stem thermocouple hygrometers were subjected to transient and stable thermal gradients while in contact with reference solutions of NaCl. Both dew point and psychrometric voltages were directly related to zero offset voltages, the latter reflecting the size of the thermal gradient. Although slopes were affected by absolute temperature, they were not affected by water potential. One hygrometer required a correction of 1.75 bars water potential per microvolt of zero offset, a value that was constant from 20 to 30 C. PMID:16660685

  9. Investigating a method for non-invasive ultrasound aberration correction through the skull bone

    NASA Astrophysics Data System (ADS)

    O'Reilly, Meaghan A.; Jones, Ryan M.; Hynynen, Kullervo

    2014-03-01

    Ultrasound imaging can be performed through narrow acoustic windows in the skull in order to minimize skull distortions. Alternatively, passive imaging using a larger aperture array can be used, which affords better resolution at the low frequencies that best penetrate the skull bone. However, to ensure image quality, it is necessary to correct for the distorting effects of the skull. In this study we examine a method to correct the distortions caused by a human skull using passive imaging of single microbubbles. The method is compared with images produced without phase correction, and those produced using a gold-standard invasive phase correction method. Using the non-invasive technique, the -6dB volume was found to vary by less than 22% from the invasive phase correction technique. By comparison, the -6dB volume when no correction was used was almost 300% larger than using the invasive correction technique. The bubblebased method introduced a positional error in the resulting image, which was most prevalent in the axial direction (on the order of 1 mm). The corrected image was biased by the location of the bubble used to calculate the correction terms. In the future, this method might be improved by using multiple bubbles to correct different regions of the image.

  10. Transcranial passive acoustic mapping with hemispherical sparse arrays using CT-based skull-specific aberration corrections: a simulation study.

    PubMed

    Jones, Ryan M; O'Reilly, Meaghan A; Hynynen, Kullervo

    2013-07-21

    The feasibility of transcranial passive acoustic mapping with hemispherical sparse arrays (30 cm diameter, 16 to 1372 elements, 2.48 mm receiver diameter) using CT-based aberration corrections was investigated via numerical simulations. A multi-layered ray acoustic transcranial ultrasound propagation model based on CT-derived skull morphology was developed. By incorporating skull-specific aberration corrections into a conventional passive beamforming algorithm (Norton and Won 2000 IEEE Trans. Geosci. Remote Sens. 38 1337-43), simulated acoustic source fields representing the emissions from acoustically-stimulated microbubbles were spatially mapped through three digitized human skulls, with the transskull reconstructions closely matching the water-path control images. Image quality was quantified based on main lobe beamwidths, peak sidelobe ratio, and image signal-to-noise ratio. The effects on the resulting image quality of the source's emission frequency and location within the skull cavity, the array sparsity and element configuration, the receiver element sensitivity, and the specific skull morphology were all investigated. The system's resolution capabilities were also estimated for various degrees of array sparsity. Passive imaging of acoustic sources through an intact skull was shown possible with sparse hemispherical imaging arrays. This technique may be useful for the monitoring and control of transcranial focused ultrasound (FUS) treatments, particularly non-thermal, cavitation-mediated applications such as FUS-induced blood-brain barrier disruption or sonothrombolysis, for which no real-time monitoring techniques currently exist.

  11. MAGNETIC LIQUID DEFORMABLE MIRRORS FOR ASTRONOMICAL APPLICATIONS: ACTIVE CORRECTION OF OPTICAL ABERRATIONS FROM LOWER-GRADE OPTICS AND SUPPORT SYSTEM

    SciTech Connect

    Borra, E. F.

    2012-08-01

    Deformable mirrors are increasingly used in astronomy. However, they still are limited in stroke for active correction of high-amplitude optical aberrations. Magnetic liquid deformable mirrors (MLDMs) are a new technology that has the advantages of high-amplitude deformations and low costs. In this paper, we demonstrate extremely high strokes and interactuator strokes achievable by MLDMs which can be used in astronomical instrumentation. In particular, we consider the use of such a mirror to suggest an interesting application for the next generation of large telescopes. We present a prototype 91 actuator deformable mirror made of a magnetic liquid (ferrofluid). This mirror uses a technique that linearizes the response of such mirrors by superimposing a large and uniform magnetic field on the magnetic field produced by an array of small coils. We discuss experimental results that illustrate the performance of MLDMs. A most interesting application of MLDMs comes from the fact they could be used to correct the aberrations of large and lower optical quality primary mirrors held by simple support systems. We estimate basic parameters of the needed MLDMs, obtaining reasonable values.

  12. Interaction between single gold atom and the graphene edge: A study via aberration-corrected transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Wang, Hongtao; Li, Kun; Cheng, Yingchun; Wang, Qingxiao; Yao, Yingbang; Schwingenschlögl, Udo; Zhang, Xixiang; Yang, Wei

    2012-04-01

    Interaction between single noble metal atoms and graphene edges has been investigated via aberration-corrected and monochromated transmission electron microscopy. A collective motion of the Au atom and the nearby carbon atoms is observed in transition between energy-favorable configurations. Most trapping and detrapping processes are assisted by the dangling carbon atoms, which are more susceptible to knock-on displacements by electron irradiation. Thermal energy is lower than the activation barriers in transition among different energy-favorable configurations, which suggests electron-beam irradiation can be an efficient way of engineering the graphene edge with metal atoms.Interaction between single noble metal atoms and graphene edges has been investigated via aberration-corrected and monochromated transmission electron microscopy. A collective motion of the Au atom and the nearby carbon atoms is observed in transition between energy-favorable configurations. Most trapping and detrapping processes are assisted by the dangling carbon atoms, which are more susceptible to knock-on displacements by electron irradiation. Thermal energy is lower than the activation barriers in transition among different energy-favorable configurations, which suggests electron-beam irradiation can be an efficient way of engineering the graphene edge with metal atoms. Electronic supplementary information (ESI) available: Additional Figures for characterization of mono-layer CVD graphene samples with free edges and Pt atoms decorations and analysis of the effect of electron irradiation; supporting movie on edge evolution. See DOI: 10.1039/c2nr00059h

  13. Transcranial passive acoustic mapping with hemispherical sparse arrays using CT-based skull-specific aberration corrections: a simulation study

    PubMed Central

    Jones, Ryan M.; O’Reilly, Meaghan A.; Hynynen, Kullervo

    2013-01-01

    The feasibility of transcranial passive acoustic mapping with hemispherical sparse arrays (30 cm diameter, 16 to 1372 elements, 2.48 mm receiver diameter) using CT-based aberration corrections was investigated via numerical simulations. A multi-layered ray acoustic transcranial ultrasound propagation model based on CT-derived skull morphology was developed. By incorporating skull-specific aberration corrections into a conventional passive beamforming algorithm (Norton and Won 2000 IEEE Trans. Geosci. Remote Sens. 38 1337–43), simulated acoustic source fields representing the emissions from acoustically-stimulated microbubbles were spatially mapped through three digitized human skulls, with the transskull reconstructions closely matching the water-path control images. Image quality was quantified based on main lobe beamwidths, peak sidelobe ratio, and image signal-to-noise ratio. The effects on the resulting image quality of the source’s emission frequency and location within the skull cavity, the array sparsity and element configuration, the receiver element sensitivity, and the specific skull morphology were all investigated. The system’s resolution capabilities were also estimated for various degrees of array sparsity. Passive imaging of acoustic sources through an intact skull was shown possible with sparse hemispherical imaging arrays. This technique may be useful for the monitoring and control of transcranial focused ultrasound (FUS) treatments, particularly non-thermal, cavitation-mediated applications such as FUS-induced blood-brain barrier disruption or sonothrombolysis, for which no real-time monitoring technique currently exists. PMID:23807573

  14. Transcranial passive acoustic mapping with hemispherical sparse arrays using CT-based skull-specific aberration corrections: a simulation study

    NASA Astrophysics Data System (ADS)

    Jones, Ryan M.; O'Reilly, Meaghan A.; Hynynen, Kullervo

    2013-07-01

    The feasibility of transcranial passive acoustic mapping with hemispherical sparse arrays (30 cm diameter, 16 to 1372 elements, 2.48 mm receiver diameter) using CT-based aberration corrections was investigated via numerical simulations. A multi-layered ray acoustic transcranial ultrasound propagation model based on CT-derived skull morphology was developed. By incorporating skull-specific aberration corrections into a conventional passive beamforming algorithm (Norton and Won 2000 IEEE Trans. Geosci. Remote Sens. 38 1337-43), simulated acoustic source fields representing the emissions from acoustically-stimulated microbubbles were spatially mapped through three digitized human skulls, with the transskull reconstructions closely matching the water-path control images. Image quality was quantified based on main lobe beamwidths, peak sidelobe ratio, and image signal-to-noise ratio. The effects on the resulting image quality of the source’s emission frequency and location within the skull cavity, the array sparsity and element configuration, the receiver element sensitivity, and the specific skull morphology were all investigated. The system’s resolution capabilities were also estimated for various degrees of array sparsity. Passive imaging of acoustic sources through an intact skull was shown possible with sparse hemispherical imaging arrays. This technique may be useful for the monitoring and control of transcranial focused ultrasound (FUS) treatments, particularly non-thermal, cavitation-mediated applications such as FUS-induced blood-brain barrier disruption or sonothrombolysis, for which no real-time monitoring techniques currently exist.

  15. Correcting spherical aberrations in a biospecimen using a transmissive liquid crystal device in two-photon excitation laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

    2015-10-01

    Two-photon excitation laser scanning microscopy has enabled the visualization of deep regions in a biospecimen. However, refractive-index mismatches in the optical path cause spherical aberrations that degrade spatial resolution and the fluorescence signal, especially during observation at deeper regions. Recently, we developed transmissive liquid-crystal devices for correcting spherical aberration without changing the basic design of the optical path in a conventional laser scanning microscope. In this study, the device was inserted in front of the objective lens and supplied with the appropriate voltage according to the observation depth. First, we evaluated the device by observing fluorescent beads in single- and two-photon excitation laser scanning microscopes. Using a 25× water-immersion objective lens with a numerical aperture of 1.1 and a sample with a refractive index of 1.38, the device recovered the spatial resolution and the fluorescence signal degraded within a depth of ±0.6 mm. Finally, we implemented the device for observation of a mouse brain slice in a two-photon excitation laser scanning microscope. An optical clearing reagent with a refractive index of 1.42 rendered the fixed mouse brain transparent. The device improved the spatial resolution and the yellow fluorescent protein signal within a depth of 0-0.54 mm.

  16. Correcting spherical aberrations in a biospecimen using a transmissive liquid crystal device in two-photon excitation laser scanning microscopy.

    PubMed

    Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

    2015-10-01

    Two-photon excitation laser scanning microscopy has enabled the visualization of deep regions in a biospecimen. However, refractive-index mismatches in the optical path cause spherical aberrations that degrade spatial resolution and the fluorescence signal, especially during observation at deeper regions. Recently, we developed transmissive liquid-crystal devices for correcting spherical aberration without changing the basic design of the optical path in a conventional laser scanning microscope. In this study, the device was inserted in front of the objective lens and supplied with the appropriate voltage according to the observation depth. First, we evaluated the device by observing fluorescent beads in single- and two-photon excitation laser scanning microscopes. Using a 25× water-immersion objective lens with a numerical aperture of 1.1 and a sample with a refractive index of 1.38, the device recovered the spatial resolution and the fluorescence signal degraded within a depth of 0.6 mm. Finally, we implemented the device for observation of a mouse brain slice in a two-photon excitation laser scanning microscope. An optical clearing reagent with a refractive index of 1.42 rendered the fixed mouse brain transparent. The device improved the spatial resolution and the yellow fluorescent protein signal within a depth of 0-0.54 mm. PMID:26244766

  17. Correcting spherical aberrations in a biospecimen using a transmissive liquid crystal device in two-photon excitation laser scanning microscopy.

    PubMed

    Tanabe, Ayano; Hibi, Terumasa; Ipponjima, Sari; Matsumoto, Kenji; Yokoyama, Masafumi; Kurihara, Makoto; Hashimoto, Nobuyuki; Nemoto, Tomomi

    2015-10-01

    Two-photon excitation laser scanning microscopy has enabled the visualization of deep regions in a biospecimen. However, refractive-index mismatches in the optical path cause spherical aberrations that degrade spatial resolution and the fluorescence signal, especially during observation at deeper regions. Recently, we developed transmissive liquid-crystal devices for correcting spherical aberration without changing the basic design of the optical path in a conventional laser scanning microscope. In this study, the device was inserted in front of the objective lens and supplied with the appropriate voltage according to the observation depth. First, we evaluated the device by observing fluorescent beads in single- and two-photon excitation laser scanning microscopes. Using a 25× water-immersion objective lens with a numerical aperture of 1.1 and a sample with a refractive index of 1.38, the device recovered the spatial resolution and the fluorescence signal degraded within a depth of 0.6 mm. Finally, we implemented the device for observation of a mouse brain slice in a two-photon excitation laser scanning microscope. An optical clearing reagent with a refractive index of 1.42 rendered the fixed mouse brain transparent. The device improved the spatial resolution and the yellow fluorescent protein signal within a depth of 0-0.54 mm.

  18. In situ observation on hydrogenation of Mg-Ni films using environmental transmission electron microscope with aberration correction

    SciTech Connect

    Matsuda, Junko; Yoshida, Kenta; Sasaki, Yukichi; Uchiyama, Naoki; Akiba, Etsuo

    2014-08-25

    In situ transmission electron microscopy (TEM) was performed to observe the hydrogenation of Mg-Ni films in a hydrogen atmosphere of 80–100 Pa. An aberration-corrected environmental TEM with a differential pumping system allows us to reveal the Angstrom-scale structure of the films in the initial stage of hydrogenation: first, nucleation and growth of Mg{sub 2}NiH{sub 4} crystals with a lattice spacing of 0.22 nm in an Mg-rich amorphous matrix of the film occurs within 20 s after the start of the high-resolution observation, then crystallization of MgH{sub 2} with a smaller spacing of 0.15 nm happens after approximately 1 min. Our in situ TEM method is also applicable to the analysis of other hydrogen-related materials.

  19. The Stanford Nanocharacterization Laboratory (SNL) and Recent Applications of an Aberration-Corrected Environmental Transmission Electron Microscope**

    PubMed Central

    Sinclair, Robert; Kempen, Paul Joseph; Chin, Richard; Koh, Ai Leen

    2014-01-01

    This article describes the establishment, over a period of ten years or so, of a multi-user, institution-wide facility for the characterization of materials and devices at the nano-scale. Emphasis is placed on the type of equipment that we have found to be most useful for our users, and the business strategy that maintains its operations. A central component of our facility is an aberration-corrected environmental transmission electron microscope and its application is summarized in the studies of plasmon energies of silver nanoparticles, the band gap of PbS quantum dots, atomic site occupancy near grain boundaries in yttria stabilized zirconia, the lithiation of silicon nanoparticles, in situ observations on carbon nanotube oxidation and the electron tomography of varicella zoster virus nucleocapsids. PMID:25364299

  20. Controlled polarity of sputter-deposited aluminum nitride on metals observed by aberration corrected scanning transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Harumoto, T.; Sannomiya, T.; Matsukawa, Y.; Muraishi, S.; Shi, J.; Nakamura, Y.; Sawada, H.; Tanaka, T.; Tanishiro, Y.; Takayanagi, K.

    2013-02-01

    The polarity determination process of sputter-deposited aluminum nitride (AlN) on metals has been analyzed using aberration corrected atomic resolution scanning transmission electron microscope. Direct growth of c-axis orientated AlN on face centered cubic metals (fcc) (111) with the local epitaxy has been observed, and the polarity was determined at the AlN/metal interface. We found that the AlN polarity can be controlled by the base metal layer: N-polarity AlN grows on Pt(111) while Al-polarity AlN forms on Al(111). Based on these results, the growth mechanism of AlN on metals is discussed.

  1. Controlled polarity of sputter-deposited aluminum nitride on metals observed by aberration corrected scanning transmission electron microscopy

    SciTech Connect

    Harumoto, T.; Sannomiya, T.; Matsukawa, Y.; Muraishi, S.; Shi, J.; Nakamura, Y.; Sawada, H.; Tanaka, T.; Tanishiro, Y.; Takayanagi, K.

    2013-02-28

    The polarity determination process of sputter-deposited aluminum nitride (AlN) on metals has been analyzed using aberration corrected atomic resolution scanning transmission electron microscope. Direct growth of c-axis orientated AlN on face centered cubic metals (fcc) (111) with the local epitaxy has been observed, and the polarity was determined at the AlN/metal interface. We found that the AlN polarity can be controlled by the base metal layer: N-polarity AlN grows on Pt(111) while Al-polarity AlN forms on Al(111). Based on these results, the growth mechanism of AlN on metals is discussed.

  2. Letter: A method for the chromatic aberration correction of a laser time of-flight mass analyzer.

    PubMed

    Sysoeva, Elizaveta A; Sysoev, Alexander A

    2016-01-01

    The new ion-optical system of the laser time-of-flight (TOF) mass spectrometer on the basis of two tandem wedge-shape reflectors has been offered and implemented. A new method of correcting chromatic aberration by the ion energy was proposed that used a wire electrode unit with adjustable potentials. This unit allows one to adjust the local TOF of the ions in a narrow energy range ± (1-2)% within the total ion packet with an energy spread of ± 20%. The method reduces the duration of the ion packets by up to 1.5ns, which enables us to obtain the restriction of resolution at a level not worse than R ~ 10500 for a TOF ~35 µs. The aim of the project is to increase the separation of isobaric ions to improve the limit of detection of the laser TOF-MS for the analysis of high-purity samples. PMID:27553736

  3. Anisotropic aberration correction using region of interest based digital adaptive optics in Fourier domain OCT.

    PubMed

    Kumar, Abhishek; Kamali, Tschackad; Platzer, René; Unterhuber, Angelika; Drexler, Wolfgang; Leitgeb, Rainer A

    2015-04-01

    In this paper a numerical technique is presented to compensate for anisotropic optical aberrations, which are usually present across the lateral field of view in the out of focus regions, in high resolution optical coherence tomography and microscopy (OCT/OCM) setups. The recorded enface image field at different depths in the tomogram is digitally divided into smaller sub-regions or the regions of interest (ROIs), processed individually using subaperture based digital adaptive optics (DAO), and finally stitched together to yield a final image with a uniform diffraction limited resolution across the entire field of view (FOV). Using this method, a sub-micron lateral resolution is achieved over a depth range of 218 [Formula: see text]for a nano-particle phantom sample imaged using a fiber based point scanning spectral domain (SD) OCM system with a limited depth of focus (DOF) of ~7 [Formula: see text]at a numerical aperture (NA) of 0.6. Thus, an increase in DOF by ~30x is demonstrated in this case. The application of this method is also shown in ex vivo mouse adipose tissue.

  4. Anisotropic aberration correction using region of interest based digital adaptive optics in Fourier domain OCT

    PubMed Central

    Kumar, Abhishek; Kamali, Tschackad; Platzer, René; Unterhuber, Angelika; Drexler, Wolfgang; Leitgeb, Rainer A.

    2015-01-01

    In this paper a numerical technique is presented to compensate for anisotropic optical aberrations, which are usually present across the lateral field of view in the out of focus regions, in high resolution optical coherence tomography and microscopy (OCT/OCM) setups. The recorded enface image field at different depths in the tomogram is digitally divided into smaller sub-regions or the regions of interest (ROIs), processed individually using subaperture based digital adaptive optics (DAO), and finally stitched together to yield a final image with a uniform diffraction limited resolution across the entire field of view (FOV). Using this method, a sub-micron lateral resolution is achieved over a depth range of 218 μmfor a nano-particle phantom sample imaged using a fiber based point scanning spectral domain (SD) OCM system with a limited depth of focus (DOF) of ~7 μmat a numerical aperture (NA) of 0.6. Thus, an increase in DOF by ~30x is demonstrated in this case. The application of this method is also shown in ex vivo mouse adipose tissue. PMID:25908999

  5. A speed of sound aberration correction algorithm for curvilinear ultrasound transducers in ultrasound-based image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Fontanarosa, Davide; Pesente, Silvia; Pascoli, Francesco; Ermacora, Denis; Abu Rumeileh, Imad; Verhaegen, Frank

    2013-03-01

    Conventional ultrasound (US) devices use the time of flight (TOF) of reflected US pulses to calculate distances inside the scanned tissues and thus create images. The speed of sound (SOS) is assumed to be constant in all human soft tissues at a generally accepted average value of 1540 m s-1. This assumption is a source of systematic errors up to several millimeters and of image distortion in quantitative US imaging. In this work, an extension of a method recently published by Fontanarosa et al (2011 Med. Phys. 38 2665-73) is presented: the aim is to correct SOS aberrations in three-dimensional (3D) US images in those cases where a spatially co-registered computerized tomography (CT) scan is also available; the algorithm is then applicable to a more general case where the lines of view (LOV) of the US device are not necessarily parallel and coplanar, thus allowing correction also for US transducers other than linear. The algorithm was applied on a multi-modality pelvic US phantom, scanned through three different liquid layers on top of the phantom with different SOS values; the results show that the correction restores a better match between the CT and the US images, reducing the differences to sub-millimeter agreement. Fifteen clinical cases of prostate cancer patients were also investigated: the SOS corrections of prostate centroids were on average +3.1 mm (max + 4.9 mm-min + 1.3 mm). This is in excellent agreement with reports in the literature on differences between measured prostate positions by US and other techniques, where often the discrepancy was attributed to other causes.

  6. Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections

    PubMed Central

    Jones, Ryan M.; O’Reilly, Meaghan A.; Hynynen, Kullervo

    2015-01-01

    Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981–5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11–0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors’ previous experimental measurements using source-based skull corrections O’Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285–1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood–brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position

  7. Lowered threshold energy for femtosecond laser induced optical breakdown in a water based eye model by aberration correction with adaptive optics.

    PubMed

    Hansen, Anja; Géneaux, Romain; Günther, Axel; Krüger, Alexander; Ripken, Tammo

    2013-06-01

    In femtosecond laser ophthalmic surgery tissue dissection is achieved by photodisruption based on laser induced optical breakdown. In order to minimize collateral damage to the eye laser surgery systems should be optimized towards the lowest possible energy threshold for photodisruption. However, optical aberrations of the eye and the laser system distort the irradiance distribution from an ideal profile which causes a rise in breakdown threshold energy even if great care is taken to minimize the aberrations of the system during design and alignment. In this study we used a water chamber with an achromatic focusing lens and a scattering sample as eye model and determined breakdown threshold in single pulse plasma transmission loss measurements. Due to aberrations, the precise lower limit for breakdown threshold irradiance in water is still unknown. Here we show that the threshold energy can be substantially reduced when using adaptive optics to improve the irradiance distribution by spatial beam shaping. We found that for initial aberrations with a root-mean-square wave front error of only one third of the wavelength the threshold energy can still be reduced by a factor of three if the aberrations are corrected to the diffraction limit by adaptive optics. The transmitted pulse energy is reduced by 17% at twice the threshold. Furthermore, the gas bubble motions after breakdown for pulse trains at 5 kilohertz repetition rate show a more transverse direction in the corrected case compared to the more spherical distribution without correction. Our results demonstrate how both applied and transmitted pulse energy could be reduced during ophthalmic surgery when correcting for aberrations. As a consequence, the risk of retinal damage by transmitted energy and the extent of collateral damage to the focal volume could be minimized accordingly when using adaptive optics in fs-laser surgery.

  8. Lowered threshold energy for femtosecond laser induced optical breakdown in a water based eye model by aberration correction with adaptive optics.

    PubMed

    Hansen, Anja; Géneaux, Romain; Günther, Axel; Krüger, Alexander; Ripken, Tammo

    2013-06-01

    In femtosecond laser ophthalmic surgery tissue dissection is achieved by photodisruption based on laser induced optical breakdown. In order to minimize collateral damage to the eye laser surgery systems should be optimized towards the lowest possible energy threshold for photodisruption. However, optical aberrations of the eye and the laser system distort the irradiance distribution from an ideal profile which causes a rise in breakdown threshold energy even if great care is taken to minimize the aberrations of the system during design and alignment. In this study we used a water chamber with an achromatic focusing lens and a scattering sample as eye model and determined breakdown threshold in single pulse plasma transmission loss measurements. Due to aberrations, the precise lower limit for breakdown threshold irradiance in water is still unknown. Here we show that the threshold energy can be substantially reduced when using adaptive optics to improve the irradiance distribution by spatial beam shaping. We found that for initial aberrations with a root-mean-square wave front error of only one third of the wavelength the threshold energy can still be reduced by a factor of three if the aberrations are corrected to the diffraction limit by adaptive optics. The transmitted pulse energy is reduced by 17% at twice the threshold. Furthermore, the gas bubble motions after breakdown for pulse trains at 5 kilohertz repetition rate show a more transverse direction in the corrected case compared to the more spherical distribution without correction. Our results demonstrate how both applied and transmitted pulse energy could be reduced during ophthalmic surgery when correcting for aberrations. As a consequence, the risk of retinal damage by transmitted energy and the extent of collateral damage to the focal volume could be minimized accordingly when using adaptive optics in fs-laser surgery. PMID:23761849

  9. Lowered threshold energy for femtosecond laser induced optical breakdown in a water based eye model by aberration correction with adaptive optics

    PubMed Central

    Hansen, Anja; Géneaux, Romain; Günther, Axel; Krüger, Alexander; Ripken, Tammo

    2013-01-01

    In femtosecond laser ophthalmic surgery tissue dissection is achieved by photodisruption based on laser induced optical breakdown. In order to minimize collateral damage to the eye laser surgery systems should be optimized towards the lowest possible energy threshold for photodisruption. However, optical aberrations of the eye and the laser system distort the irradiance distribution from an ideal profile which causes a rise in breakdown threshold energy even if great care is taken to minimize the aberrations of the system during design and alignment. In this study we used a water chamber with an achromatic focusing lens and a scattering sample as eye model and determined breakdown threshold in single pulse plasma transmission loss measurements. Due to aberrations, the precise lower limit for breakdown threshold irradiance in water is still unknown. Here we show that the threshold energy can be substantially reduced when using adaptive optics to improve the irradiance distribution by spatial beam shaping. We found that for initial aberrations with a root-mean-square wave front error of only one third of the wavelength the threshold energy can still be reduced by a factor of three if the aberrations are corrected to the diffraction limit by adaptive optics. The transmitted pulse energy is reduced by 17% at twice the threshold. Furthermore, the gas bubble motions after breakdown for pulse trains at 5 kilohertz repetition rate show a more transverse direction in the corrected case compared to the more spherical distribution without correction. Our results demonstrate how both applied and transmitted pulse energy could be reduced during ophthalmic surgery when correcting for aberrations. As a consequence, the risk of retinal damage by transmitted energy and the extent of collateral damage to the focal volume could be minimized accordingly when using adaptive optics in fs-laser surgery. PMID:23761849

  10. Canopy induced aberration correction in airborne electro-optical imaging systems

    NASA Astrophysics Data System (ADS)

    Harder, James A.; Sprague, Michaelene W.

    2011-11-01

    An increasing number of electro-optical systems are being used by pilots in tactical aircraft. This means that the afore mentioned systems must operate through the aircrafts canopy, unfortunately the canopy functions as a less than ideal lens element in the electro-optical sensor optical path. The canopy serves first and foremost as an aircraft structural component, considerations like minimizing the drag co-efficient and the ability to survive bird strikes take precedence over achieving optimal optical characteristics. This paper describes how the authors characterized the optical characteristics of an aircraft canopy. Families of modulation transfer functions were generated, for various viewing geometries through the canopy and for various electro-optical system entrance pupil diameters. These functions provided us with the means to significantly reduce the effect of the canopy "lens" on the performance of a representative electro-optical system, using an Astigmatic Corrector Lens. A comparison of the electro-optical system performance with and without correction is also presented.

  11. Simultaneous fluorescence and high-resolution bright-field imaging with aberration correction over a wide field-of-view with Fourier ptychographic microscopy (FPM) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chung, Jaebum; Kim, Jinho; Ou, Xiaoze; Horstmeyer, Roarke; Yang, Changhuei

    2016-03-01

    We present a method to acquire both fluorescence and high-resolution bright-field images with correction for the spatially varying aberrations over a microscope's wide field-of-view (FOV). First, the procedure applies Fourier ptychographic microscopy (FPM) to retrieve the amplitude and phase of a sample, at a resolution that significantly exceeds the cutoff frequency of the microscope objective lens. At the same time, FPM algorithm is able to leverage on the redundancy within the set of acquired FPM bright-field images to estimate the microscope aberrations, which usually deteriorate in regions further away from the FOV's center. Second, the procedure acquires a raw wide-FOV fluorescence image within the same setup. Lack of moving parts allows us to use the FPM-estimated aberration map to computationally correct for the aberrations in the fluorescence image through deconvolution. Overlaying the aberration-corrected fluorescence image on top of the high-resolution bright-field image can be done with accurate spatial correspondence. This can provide means to identifying fluorescent regions of interest within the context of the sample's bright-field information. An experimental demonstration successfully improves the bright-field resolution of fixed, stained and fluorescently tagged HeLa cells by a factor of 4.9, and reduces the error caused by aberrations in a fluorescence image by 31%, over a field of view of 6.2 mm by 9.3 mm. For optimal deconvolution, we show the fluorescence image needs to have a signal-to-noise ratio of ~18.

  12. Utilization of the excimer laser and a moving piezoelectric mirror to accomplish the customized contact lens ablation to correct high-order aberrations

    NASA Astrophysics Data System (ADS)

    de Matos, Luciana; Yasuoka, Fátima M. M.; Schor, Paulo; de Oliveira, Enos; Bagnato, Vanderlei S.; Carvalho, Luis A. V.

    2014-02-01

    The use of the Hartman-Shack sensor in ophthalmology allowed the identification of higher-order aberrations, which make possible the search for methods to correct them. Customized refractive surgery is one of the most successful methods, although there are patients which cannot be submitted to this surgery due to a variety of abnormal limiting factors such as cornea thickness and quantity of higher-order aberrations. Being this an irreversible process, the alternative is to develop a non-surgical method. This work proposes a method to obtain personalized contact lenses to correct high-order aberrations via the development of a customized ablation system using an excimer laser and a moving piezoelectric mirror. The process to produce such lenses consists of four steps. 1) The map of total aberrations of the patient's eye is measured by using an aberrometer with a Hartman-Shack sensor. 2) The measured aberration map is used to determine the maps for correction and related distribution of laser pulses for the ablation process with the excimer laser. 3) The lens production is performed following the same principle as customized refractive surgery. 4) The quality control of the lens is evaluated by two tests. 4.1) The lens is measured by a non-commercial lensometer, which is assembled specially for this measurement, as the ones commercially available are not capable of measuring asymmetric and irregular surfaces. 4.2) The evaluation of the lens-eye system is made using the aberrometer of the first step in order to verify the residual aberrations. Here, the lenses are ablated with a customized refractive surgery system.

  13. Active mirrors warped using Zernike polynomials for correcting off-axis aberrations of fixed primary mirrors. II. Optical testing and performance evaluation.

    NASA Astrophysics Data System (ADS)

    Moretto, G.; Lemaitre, G. R.; Bactivelane, T.; Wang, M.; Ferrari, M.; Mazzanti, S.; di Biagio, B.; Borra, E. F.

    1995-12-01

    We investigate the aspherization of an active mirror for correcting third and fifth-order aberrations. We use a stainless steel AISI 420 mirror with a controlled pressure load, two series of 12-punctual radial positions of force application distributed symmetrically in two concentric rings around the mirror. We obtain the wavefronts for Cv1, Sph3, Coma3, Astm3, Comatri, Astm5 as well as those of the added wavefronts. Although this active prototype mirror has general uses, our goal is to compensate the aberrations of a liquid mirror observing at large angles from the zenith.

  14. Wavefront correction for static and dynamic aberrations to within 1 second of the system shot in the NIF Beamlet demonstration facility

    SciTech Connect

    Hartley, R.; Kartz, M.; Behrendt, W.

    1996-10-01

    The laser wavefront of the NIF Beamlet demonstration system is corrected for static aberrations with a wavefront control system. The system operates closed loop with a probe beam prior to a shot and has a loop bandwidth of about 3 Hz. However, until recently the wavefront control system was disabled several minutes prior to the shot to allow time to manually reconfigure its attenuators and probe beam insertion mechanism to shot mode. Thermally-induced dynamic variations in gas density in the Beamlet main beam line produce significant wavefront error. After about 5-8 seconds, the wavefront error has increased to a new, higher level due to turbulence- induced aberrations no longer being corrected- This implies that there is a turbulence-induced aberration noise bandwidth of less than one Hertz, and that the wavefront controller could correct for the majority of turbulence-induced aberration (about one- third wave) by automating its reconfiguration to occur within one second of the shot, This modification was recently implemented on Beamlet; we call this modification the t{sub 0}-1 system.

  15. Separating strain from composition in unit cell parameter maps obtained from aberration corrected high resolution transmission electron microscopy imaging

    SciTech Connect

    Schulz, T.; Remmele, T.; Korytov, M.; Markurt, T.; Albrecht, M.; Duff, A.; Lymperakis, L.; Neugebauer, J.; Chèze, C.

    2014-01-21

    Based on the evaluation of lattice parameter maps in aberration corrected high resolution transmission electron microscopy images, we propose a simple method that allows quantifying the composition and disorder of a semiconductor alloy at the unit cell scale with high accuracy. This is realized by considering, next to the out-of-plane, also the in-plane lattice parameter component allowing to separate the chemical composition from the strain field. Considering only the out-of-plane lattice parameter component not only yields large deviations from the true local alloy content but also carries the risk of identifying false ordering phenomena like formations of chains or platelets. Our method is demonstrated on image simulations of relaxed supercells, as well as on experimental images of an In{sub 0.20}Ga{sub 0.80}N quantum well. Principally, our approach is applicable to all epitaxially strained compounds in the form of quantum wells, free standing islands, quantum dots, or wires.

  16. Focusing aberration corrections for ultrasonic inspections of disk forgings when using a surface compensating mirror and segmented annular phased array

    NASA Astrophysics Data System (ADS)

    Friedl, Jon Hiram, Jr.

    Phased array transducers are playing an increasing role in ultrasonic nondestructive evaluation inspection applications, and one area of their use is in the inspection of critical jet engine components such as titanium alloy turbine disk forgings. Inspection of these forging disks is performed during stages of their manufacturing, particularly at an intermediate stage when the forging disk has a deliberate "sonic shape." A forging's sonic shape, from which the final disk shape will be machined, is conducive to ultrasonic testing inspections due to its simple entry surfaces. These entry surfaces are primarily planar or conical surfaces. In prior work, forgings from General Electric Aircraft Engines, Pratt & Whitney, and Honeywell Engines and Systems were ultrasonically inspected through their planar interfaces, accomplished with a 10 MHz, segmented annular, compound spherical, phased array transducer designed to perform inspections through planar interfaces. Proof-of-concept research used this array along with surface compensating ultrasonic mirrors to inspect through the conical entry surfaces in these forgings. While successful, it was believed that the results of these inspections fell below what would be possible due to non-ideal focusing conditions and other focusing aberrations. To correct for focusing aberrations when inspecting through forging material planar and curved interfaces, three progressively more sophisticated ray-tracing algorithms were developed to generate delay time sets for phasing transducer array elements, including an initial 2D method from prior work, a refined 2D method designed to more accurately account for refraction at interfaces, and a 3D method designed for circumferentially phasing the segmented annular array. Ultrasonic inspections using these methods were performed on two sets of forging material specimens, with either planar or curved interfaces, thicknesses ranging from 0.2 inches to 2.7 inches, and each containing a 1/128-inch

  17. Aberrant epigenetic regulators control expansion of human CD34+ hematopoietic stem/progenitor cells

    PubMed Central

    Faridi, Farnaz; Ponnusamy, Kanagaraju; Quagliano-Lo Coco, Isabell; Chen-Wichmann, Linping; Grez, Manuel; Henschler, Reinhard; Wichmann, Christian

    2013-01-01

    Transcription is a tightly regulated process ensuring the proper expression of numerous genes regulating all aspects of cellular behavior. Transcription factors regulate multiple genes including other transcription factors that together control a highly complex gene network. The transcriptional machinery can be “hijacked” by oncogenic transcription factors, thereby leading to malignant cell transformation. Oncogenic transcription factors manipulate a variety of epigenetic control mechanisms to fulfill gene regulatory and cell transforming functions. These factors assemble epigenetic regulators at target gene promoter sequences, thereby disturbing physiological gene expression patterns. Retroviral vector technology and the availability of “healthy” human hematopoietic CD34+ progenitor cells enable the generation of pre-leukemic cell models for the analysis of aberrant human hematopoietic progenitor cell expansion mediated by leukemogenic transcription factors. This review summarizes recent findings regarding the mechanism by which leukemogenic gene products control human hematopoietic CD34+ progenitor cell expansion by disrupting the normal epigenetic program. PMID:24348510

  18. Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion.

    PubMed

    Yu, Jian-Bo; Jiang, Hao; Zhan, Ren-Ya

    2016-08-01

    Upregulation of the Notch signaling pathway in cancer stem cells and side population (SP) cells has a major role in maintenance, self-renewal and chemoresistance. The present study isolated a cancer stem cell-like SP accounting for 4.1% of a glioblastoma cell population using a Hoechst 33342 dye exclusion assay. In this glioblastoma SP, the expression of of Notch1 signaling proteins Notch1 intracellular domain and Hes‑1 was markedly upregulated. Furthermore, knockdown of Notch1 by RNA interference significantly diminished the neurosphere formation ability, self‑renewal and chemoresistance of the SP cells. In addition, the expression of the stem‑cell surface genes Oct‑4, Sox2 and Nanog in SP cells was significantly reduced and the sensitivity to the SP cells to chemotherapeutics was enhanced following Notch1 knockdown. In conclusion, the results of the present study suggested that upregulation of Notch1 is involved in the chemotherapy resistance and tumor recurrence of glioblastoma. Hence, the development of novel anti‑cancer drugs targeting the Notch1 signaling pathway may be a promising strategy for curing glioblastoma. PMID:27315154

  19. Nanoscale Energy-Filtered Scanning Confocal Electron Microscopy Using a Double-Aberration-Corrected Transmission Electron Microscope

    SciTech Connect

    Wang Peng; Behan, Gavin; Kirkland, Angus I.; Nellist, Peter D.; Takeguchi, Masaki; Hashimoto, Ayako; Mitsuishi, Kazutaka; Shimojo, Masayuki

    2010-05-21

    We demonstrate that a transmission electron microscope fitted with two spherical-aberration correctors can be operated as an energy-filtered scanning confocal electron microscope. A method for establishing this mode is described and initial results showing 3D chemical mapping with nanoscale sensitivity to height and thickness changes in a carbon film are presented. Importantly, uncorrected chromatic aberration does not limit the depth resolution of this technique and moreover performs an energy-filtering role, which is explained in terms of a combined depth and energy-loss response function.

  20. Two-photon polymerization setup enables experimental mapping and correction of spherical aberrations for improved macroscopic structure fabrication.

    PubMed

    Stichel, T; Hecht, B; Steenhusen, S; Houbertz, R; Sextl, G

    2016-09-15

    The two-photon photopolymerization of resins by focused laser light in principle enables the fabrication of structures with details below the diffraction limit. However, the method can be highly susceptible to aberrations, which hinders the fabrication of structures that are larger than, e.g., the working distance of the microscope objective. Here, two-photon polymerization is extended to the fabrication of macroscopic structures by making use of medium numerical-aperture microscope objectives. By introducing a substrate holder movable in the axial direction it is possible to keep the focusing conditions constant and to fabricate very large structures with heights that are not limited by the working distance of the objective. Moreover, the constant focusing conditions enable us to quantify spherical aberrations by experimental mapping of the optical point-spread function, which manifests itself in the shape of singe photo-polymerized voxels. By monitoring such shapes it is possible to minimize aberrations. Effective aberration control enables us to fabricate large but detailed biomedical scaffolds with interconnected pores, e.g., in the shape of a human stirrup bone.

  1. Correction of depth-dependent aberrations in 3D single-molecule localization and super-resolution microscopy.

    PubMed

    McGorty, Ryan; Schnitzbauer, Joerg; Zhang, Wei; Huang, Bo

    2014-01-15

    Single-molecule switching based super-resolution microscopy techniques have been extended into three dimensions through various 3D single-molecule localization methods. However, the localization accuracy in z can be severely degraded by the presence of aberrations, particularly the spherical aberration introduced by the refractive index mismatch when imaging into an aqueous sample with an oil immersion objective. This aberration confines the imaging depth in most experiments to regions close to the coverslip. Here we show a method to obtain accurate, depth-dependent z calibrations by measuring the point spread function (PSF) at the coverslip surface, calculating the microscope pupil function through phase retrieval, and then computing the depth-dependent PSF with the addition of spherical aberrations. We demonstrate experimentally that this method can maintain z localization accuracy over a large range of imaging depths. Our super-resolution images of a mammalian cell nucleus acquired between 0 and 2.5 μm past the coverslip show that this method produces accurate z localizations even in the deepest focal plane.

  2. Two-photon polymerization setup enables experimental mapping and correction of spherical aberrations for improved macroscopic structure fabrication.

    PubMed

    Stichel, T; Hecht, B; Steenhusen, S; Houbertz, R; Sextl, G

    2016-09-15

    The two-photon photopolymerization of resins by focused laser light in principle enables the fabrication of structures with details below the diffraction limit. However, the method can be highly susceptible to aberrations, which hinders the fabrication of structures that are larger than, e.g., the working distance of the microscope objective. Here, two-photon polymerization is extended to the fabrication of macroscopic structures by making use of medium numerical-aperture microscope objectives. By introducing a substrate holder movable in the axial direction it is possible to keep the focusing conditions constant and to fabricate very large structures with heights that are not limited by the working distance of the objective. Moreover, the constant focusing conditions enable us to quantify spherical aberrations by experimental mapping of the optical point-spread function, which manifests itself in the shape of singe photo-polymerized voxels. By monitoring such shapes it is possible to minimize aberrations. Effective aberration control enables us to fabricate large but detailed biomedical scaffolds with interconnected pores, e.g., in the shape of a human stirrup bone. PMID:27628374

  3. Correction of the sickle cell mutation in embryonic stem cells.

    PubMed

    Chang, Judy C; Ye, Lin; Kan, Yuet Wai

    2006-01-24

    Sickle cell anemia is one of the most common genetic diseases worldwide. Patients often suffer from anemia, painful crises, infections, strokes, and cardiopulmonary complications. Although current management has improved the quality of life and survival of patients, cure can be achieved only with bone marrow transplantation when histocompatible donors are available. The ES cell technology suggests that a therapeutic cloning approach may be feasible for treatment of this disease. Using a transgenic/knockout sickle cell anemia mouse model, which harbors 240 kb of human DNA sequences containing the beta(S)-globin gene, we prepared ES cells from blastocysts that had the sickle cells anemia genotype and carried out homologous recombination with DNA constructs that contained the beta(A)-globin gene. We obtained ES cells in which the beta(S) was corrected to the beta(A) sequence. Hematopoietic cells differentiated from these ES cells produced both hemoglobin A and hemoglobin S. This approach can be applied to human ES cells to correct the sickle mutation as well as beta-thalassemia mutations. PMID:16407095

  4. Correction of depth-induced spherical aberration for deep observation using two-photon excitation fluorescence microscopy with spatial light modulator

    PubMed Central

    Matsumoto, Naoya; Inoue, Takashi; Matsumoto, Akiyuki; Okazaki, Shigetoshi

    2015-01-01

    We demonstrate fluorescence imaging with high fluorescence intensity and depth resolution in which depth-induced spherical aberration (SA) caused by refractive-index mismatch between the medium and biological sample is corrected. To reduce the impact of SA, we incorporate a spatial light modulator into a two-photon excitation fluorescence microscope. Consequently, when fluorescent beads in epoxy resin were observed with this method of SA correction, the fluorescence signal of the observed images was ∼27 times higher and extension in the direction of the optical axes was ∼6.5 times shorter at a depth of ∼890 μm. Thus, the proposed method increases the depth observable at high resolution. Further, our results show that the method improved the fluorescence intensity of images of the fluorescent beads and the structure of a biological sample. PMID:26203383

  5. Aneurysm of aberrant right subclavian [corrected] artery arising from diverticulum of Kommerell. Report of a case with tracheal compression.

    PubMed

    Aoyagi, S; Akashi, H; Tayama, K; Fujino, T

    1997-07-01

    A 74-year-old woman presented with severe dyspnea without dysphagia. Computed tomographic scans and Digital subtraction angiography revealed the left aortic arch with an aberrant right subclavian artery arising from the Kommerell's diverticulum and tracheal compression. The aortic arch and the Kommerell's diverticulum were aneurysmal and were responsible for this compression. Surgical relief was accomplished by replacement of the aortic arch and reconstruction of the four brachiocephalic vessels with vascular prostheses through a median sternotomy incision extending into the right supraclavicular region.

  6. The Aberrant DNA Methylation Profile of Human Induced Pluripotent Stem Cells Is Connected to the Reprogramming Process and Is Normalized During In Vitro Culture

    PubMed Central

    Tesarova, Lenka; Simara, Pavel; Stejskal, Stanislav; Koutna, Irena

    2016-01-01

    The potential clinical applications of human induced pluripotent stem cells (hiPSCs) are limited by genetic and epigenetic variations among hiPSC lines and the question of their equivalency with human embryonic stem cells (hESCs). We used MethylScreen technology to determine the DNA methylation profile of pluripotency and differentiation markers in hiPSC lines from different source cell types compared to hESCs and hiPSC source cells. After derivation, hiPSC lines compromised a heterogeneous population characterized by variable levels of aberrant DNA methylation. These aberrations were induced during somatic cell reprogramming and their levels were associated with the type of hiPSC source cells. hiPSC population heterogeneity was reduced during prolonged culture and hiPSCs acquired an hESC-like methylation profile. In contrast, the expression of differentiation marker genes in hiPSC lines remained distinguishable from that in hESCs. Taken together, in vitro culture facilitates hiPSC acquisition of hESC epigenetic characteristics. However, differences remain between both pluripotent stem cell types, which must be considered before their use in downstream applications. PMID:27336948

  7. Identification of Proteins Related to Epigenetic Regulation in the Malignant Transformation of Aberrant Karyotypic Human Embryonic Stem Cells by Quantitative Proteomics

    PubMed Central

    Sun, Yi; Yang, Yixuan; Zeng, Sicong; Tan, Yueqiu; Lu, Guangxiu; Lin, Ge

    2014-01-01

    Previous reports have demonstrated that human embryonic stem cells (hESCs) tend to develop genomic alterations and progress to a malignant state during long-term in vitro culture. This raises concerns of the clinical safety in using cultured hESCs. However, transformed hESCs might serve as an excellent model to determine the process of embryonic stem cell transition. In this study, ITRAQ-based tandem mass spectrometry was used to quantify normal and aberrant karyotypic hESCs proteins from simple to more complex karyotypic abnormalities. We identified and quantified 2583 proteins, and found that the expression levels of 316 proteins that represented at least 23 functional molecular groups were significantly different in both normal and abnormal hESCs. Dysregulated protein expression in epigenetic regulation was further verified in six pairs of hESC lines in early and late passage. In summary, this study is the first large-scale quantitative proteomic analysis of the malignant transformation of aberrant karyotypic hESCs. The data generated should serve as a useful reference of stem cell-derived tumor progression. Increased expression of both HDAC2 and CTNNB1 are detected as early as the pre-neoplastic stage, and might serve as prognostic markers in the malignant transformation of hESCs. PMID:24465727

  8. The Aberrant DNA Methylation Profile of Human Induced Pluripotent Stem Cells Is Connected to the Reprogramming Process and Is Normalized During In Vitro Culture.

    PubMed

    Tesarova, Lenka; Simara, Pavel; Stejskal, Stanislav; Koutna, Irena

    2016-01-01

    The potential clinical applications of human induced pluripotent stem cells (hiPSCs) are limited by genetic and epigenetic variations among hiPSC lines and the question of their equivalency with human embryonic stem cells (hESCs). We used MethylScreen technology to determine the DNA methylation profile of pluripotency and differentiation markers in hiPSC lines from different source cell types compared to hESCs and hiPSC source cells. After derivation, hiPSC lines compromised a heterogeneous population characterized by variable levels of aberrant DNA methylation. These aberrations were induced during somatic cell reprogramming and their levels were associated with the type of hiPSC source cells. hiPSC population heterogeneity was reduced during prolonged culture and hiPSCs acquired an hESC-like methylation profile. In contrast, the expression of differentiation marker genes in hiPSC lines remained distinguishable from that in hESCs. Taken together, in vitro culture facilitates hiPSC acquisition of hESC epigenetic characteristics. However, differences remain between both pluripotent stem cell types, which must be considered before their use in downstream applications. PMID:27336948

  9. Gradient-based correction of chromatic aberration in the joint acquisition of color and near-infrared images

    NASA Astrophysics Data System (ADS)

    Sadeghipoor, Zahra; Lu, Yue M.; Süsstrunk, Sabine

    2015-02-01

    Chromatic aberration distortions such as wavelength-dependent blur are caused by imperfections in photographic lenses. These distortions are much more severe in the case of color and near-infrared joint acquisition, as a wider band of wavelengths is captured. In this paper, we consider a scenario where the color image is in focus, and the NIR image captured with the same lens and same focus settings is out-of-focus and blurred. To reduce chromatic aberration distortions, we propose an algorithm that estimates the blur kernel and deblurs the NIR image using the sharp color image as a guide in both steps. In the deblurring step, we retrieve the lost details of the NIR image by exploiting the sharp edges of the color image, as the gradients of color and NIR images are often correlated. However, differences of scene reflections and light in visible and NIR bands cause the gradients of color and NIR images to be different in some regions of the image. To handle this issue, our algorithm measures the similarities and differences between the gradients of the NIR and color channels. The similarity measures guide the deblurring algorithm to efficiently exploit the gradients of the color image in reconstructing high-frequency details of NIR, without discarding the inherent differences between these images. Simulation results verify the effectiveness of our algorithm, both in estimating the blur kernel and deblurring the NIR image, without producing ringing artifacts inherent to the results of most deblurring methods.

  10. Stem cell therapy and tissue engineering for correction of congenital heart disease

    PubMed Central

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects. PMID:26176009

  11. Restoring defect structures in 3C-SiC/Si (001) from spherical aberration-corrected high-resolution transmission electron microscope images by means of deconvolution processing.

    PubMed

    Wen, C; Wan, W; Li, F H; Tang, D

    2015-04-01

    The [110] cross-sectional samples of 3C-SiC/Si (001) were observed with a spherical aberration-corrected 300 kV high-resolution transmission electron microscope. Two images taken not close to the Scherzer focus condition and not representing the projected structures intuitively were utilized for performing the deconvolution. The principle and procedure of image deconvolution and atomic sort recognition are summarized. The defect structure restoration together with the recognition of Si and C atoms from the experimental images has been illustrated. The structure maps of an intrinsic stacking fault in the area of SiC, and of Lomer and 60° shuffle dislocations at the interface have been obtained at atomic level.

  12. Local symmetry breaking of a thin crystal structure of β-Si3N4 as revealed by spherical aberration corrected high-resolution transmission electron microscopy images.

    PubMed

    Kim, Hwang Su; Zhang, Zaoli; Kaiser, Ute

    2012-06-01

    This report is an extension of the study for structural imaging of 5-6 nm thick β-Si(3)N(4) [0001] crystal with a spherical aberration corrected transmission electron microscope by Zhang and Kaiser [2009. Structure imaging of β-Si(3)N(4) by spherical aberration-corrected high-resolution transmission electron microscopy. Ultramicroscopy 109, 1114-1120]. In this work, a local symmetry breaking with an uneven resolution of dumbbells in the six-membered rings revealed in the reported images in the study of Zhang and Kaiser has been analyzed in detail. It is found that this local asymmetry in the image basically is not relevant to a slight mistilt of the specimen and/or a beam tilt (coma). Rather the certain variation of the tetrahedral bond length of Si-N(4) in the crystal structure is found to be responsible for the uneven resolution with a local structural variation from region to region. This characteristic of the variation is also supposed to give a distorted lattice of apparently 2°-2.5° deviations from the perfect hexagonal unit cell as observed in the reported image in the work of Zhang and Kaiser. It is discussed that this variation may prevail only in a thin specimen with a thickness ranging ~≤ 5-6 nm. At the same time, it is noted that the average of the bond length variation is close to the fixed length known in a bulk crystal of β-Si(3)N(4).

  13. Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer’s disease

    PubMed Central

    Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

    2016-01-01

    Objective Among patients with Alzheimer’s disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. Materials and methods In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Results Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. Conclusion This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. PMID:27601903

  14. Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer’s disease

    PubMed Central

    Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

    2016-01-01

    Objective Among patients with Alzheimer’s disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. Materials and methods In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Results Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. Conclusion This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

  15. Barth Syndrome: From Mitochondrial Dysfunctions Associated with Aberrant Production of Reactive Oxygen Species to Pluripotent Stem Cell Studies

    PubMed Central

    Saric, Ana; Andreau, Karine; Armand, Anne-Sophie; Møller, Ian M.; Petit, Patrice X.

    2016-01-01

    Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS). Individuals with this X-linked multisystem disorder present cardiomyopathy (CM) (often dilated), skeletal muscle weakness, neutropenia, growth retardation, and 3-methylglutaconic aciduria. Biopsies of the heart, liver and skeletal muscle of patients have revealed mitochondrial malformations and dysfunctions. It is the purpose of this review to summarize recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated with TAZ mutations. Tafazzin is a mitochondrial phospholipidlysophospholipid transacylase that shuttles acyl groups between phospholipids and regulates the remodeling of cardiolipin (CL), a unique inner mitochondrial membrane phospholipid dimer consisting of two phosphatidyl residues linked by a glycerol bridge. After their biosynthesis, the acyl chains of CLs may be modified in remodeling processes involving up to three different enzymes. Their characteristic acyl chain composition depends on the function of tafazzin, although the enzyme itself surprisingly lacks acyl specificity. CLs are crucial for correct mitochondrial structure and function. In addition to their function in the basic mitochondrial function of ATP production, CLs play essential roles in cardiac function, apoptosis, autophagy, cell cycle regulation and Fe-S cluster biosynthesis. Recent developments in tafazzin research have provided strong insights into the link between mitochondrial dysfunction and the production of reactive oxygen species (ROS). An important tool has been the generation of BTHS-specific induced pluripotent stem cells (iPSCs) from BTHS patients. In a complementary approach, disease-specific mutations have been introduced into wild-type iPSC lines enabling direct comparison with isogenic controls. iPSC-derived cardiomyocytes were then characterized using biochemical and classical bioenergetic

  16. Axial ultrasound B-scans of the entire eye with a 20-MHz linear array: correction of crystalline lens phase aberration by applying Fermat's principle.

    PubMed

    Mateo, Tony; Chang, Alexandre; Mofid, Yassine; Pisella, Pierre-Jean; Ossant, Frederic

    2014-11-01

    In ophthalmic ultrasonography the crystalline lens is known to be the main source of phase aberration, causing a significant decrease in resolution and distortion effects on axial B-scans. This paper proposes a computationally efficient method to correct the phase aberration arising from the crystalline lens, including refraction effects using a bending ray tracing approach based on Fermat's principle. This method is used as a basis to perform eye-adapted beamforming (BF), with appropriate focusing delays for a 128-element 20-MHz linear array in both emission and reception. Implementation was achieved on an in-house developed experimental ultrasound scanning device, the ECODERM. The proposed BF was tested in vitro by imaging a wire phantom through an eye phantom consisting of a synthetic gelatin lens anatomically set up in an appropriate liquid (turpentine) to approach the in vivo velocity ratio. Both extremes of accommodation shapes of the human crystalline lens were investigated. The performance of the developed BF was evaluated in relation to that in homogeneous medium and compared to a conventional delay-and-sum (DAS) BF and a second adapted BF which was simplified to ignore the lens refraction. Global expectations provided by our method with the transducer array are reviewed by an analysis quantifying both image quality and spatial fidelity, as well as the detrimental effects of a crystalline lens in conventional reconstruction. Compared to conventional array imaging, the results indicated a two-fold improvement in the lateral resolution, greater sensitivity and a considerable reduction of spatial distortions that were sufficient to envisage reliable biometry directly in B-mode, especially phakometry. PMID:24988589

  17. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

    PubMed Central

    Raya, Ángel; Rodríguez-Pizà, Ignasi; Guenechea, Guillermo; Vassena, Rita; Navarro, Susana; Barrero, María José; Consiglio, Antonella; Castellà, Maria; Río, Paula; Sleep, Eduard; González, Federico; Tiscornia, Gustavo; Garreta, Elena; Aasen, Trond; Veiga, Anna; Verma, Inder M.; Surrallés, Jordi; Bueren, Juan; Belmonte, Juan Carlos Izpisúa

    2009-01-01

    The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications. PMID:19483674

  18. Camera processing with chromatic aberration.

    PubMed

    Korneliussen, Jan Tore; Hirakawa, Keigo

    2014-10-01

    Since the refractive index of materials commonly used for lens depends on the wavelengths of light, practical camera optics fail to converge light to a single point on an image plane. Known as chromatic aberration, this phenomenon distorts image details by introducing magnification error, defocus blur, and color fringes. Though achromatic and apochromatic lens designs reduce chromatic aberration to a degree, they are complex and expensive and they do not offer a perfect correction. In this paper, we propose a new postcapture processing scheme designed to overcome these problems computationally. Specifically, the proposed solution is comprised of chromatic aberration-tolerant demosaicking algorithm and post-demosaicking chromatic aberration correction. Experiments with simulated and real sensor data verify that the chromatic aberration is effectively corrected. PMID:25163060

  19. Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

    NASA Astrophysics Data System (ADS)

    Jaeger, Michael; Held, Gerrit; Preisser, Stefan; Peeters, Sara; Grünig, Michael; Frenz, Martin

    2014-03-01

    Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound.

  20. Evaluation of stacking faults and associated partial dislocations in AlSb/GaAs (001) interface by aberration-corrected high-resolution transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Wen, C.; Ge, B. H.; Cui, Y. X.; Li, F. H.; Zhu, J.; Yu, R.; Cheng, Z. Y.

    2014-11-01

    The stacking faults (SFs) in an AlSb/GaAs (001) interface were investigated using a 300 kV spherical aberration-corrected high-resolution transmission electron microscope (HRTEM). The structure and strain distribution of the single and intersecting (V-shaped) SFs associated with partial dislocations (PDs) were characterized by the [110] HRTEM images and geometric phase analysis, respectively. In the biaxial strain maps ɛxx and ɛyy, a SF can be divided into several sections under different strain states (positive or negative strain values). Furthermore, the strain state for the same section of a SF is in contrast to each other in ɛxx and ɛyy strain maps. The modification in the strain states was attributed to the variation in the local atomic displacements for the SF in the AlSb film on the GaAs substrate recorded in the lattice image. Finally, the single SF was found to be bounded by two 30° PDs. A pair of 30° PDs near the heteroepitaxial interface reacted to form a Lomer-Cottrell sessile dislocation located at the vertices of V-shaped SFs with opposite screw components. The roles of misfit dislocations, such as the PDs, in strain relaxation were also discussed.

  1. Evaluation of stacking faults and associated partial dislocations in AlSb/GaAs (001) interface by aberration-corrected high-resolution transmission electron microscopy

    SciTech Connect

    Wen, C.; Ge, B. H.; Cui, Y. X.; Li, F. H.; Zhu, J.; Yu, R.; Cheng, Z. Y.

    2014-11-15

    The stacking faults (SFs) in an AlSb/GaAs (001) interface were investigated using a 300 kV spherical aberration-corrected high-resolution transmission electron microscope (HRTEM). The structure and strain distribution of the single and intersecting (V-shaped) SFs associated with partial dislocations (PDs) were characterized by the [110] HRTEM images and geometric phase analysis, respectively. In the biaxial strain maps ε{sub xx} and ε{sub yy}, a SF can be divided into several sections under different strain states (positive or negative strain values). Furthermore, the strain state for the same section of a SF is in contrast to each other in ε{sub xx} and ε{sub yy} strain maps. The modification in the strain states was attributed to the variation in the local atomic displacements for the SF in the AlSb film on the GaAs substrate recorded in the lattice image. Finally, the single SF was found to be bounded by two 30° PDs. A pair of 30° PDs near the heteroepitaxial interface reacted to form a Lomer-Cottrell sessile dislocation located at the vertices of V-shaped SFs with opposite screw components. The roles of misfit dislocations, such as the PDs, in strain relaxation were also discussed.

  2. New advances of microRNAs in glioma stem cells, with special emphasis on aberrant methylation of microRNAs.

    PubMed

    Zhao, Bing; Bian, Er-Bao; Li, Jia; Li, Jun

    2014-09-01

    Malignant brain tumors are thought to be originate from a small population of cells that display stem cell properties, including the capacity of self-renewal, multipotent differentiation, initiation of tumor tissues. Cancer stem cells (CSCs) have been identified in gliomas in which they are named as glioma stem cells (GSCs). GSCs, sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Recently, increasing evidences have showed that miRNAs play a central role in GSCs. In this review we focus on the role of GSCs in gliomas and in the abnomal expression of miRNAs in GSCs. Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNAs by promoter DNA methylation is involved in the regulation of GSCs biology. Recent advances in understanding dysregulated expression of miRNAs and methylation of tumor-suppressor miRNAs in GSCs and their possible use as new therapeutic targets of gliomas.

  3. Quantitative ADF STEM: acquisition, analysis and interpretation

    NASA Astrophysics Data System (ADS)

    Jones, L.

    2016-01-01

    Quantitative annular dark-field in the scanning transmission electron microscope (ADF STEM), where image intensities are used to provide composition and thickness measurements, has enjoyed a renaissance during the last decade. Now in a post aberration-correction era many aspects of the technique are being revisited. Here the recent progress and emerging best-practice for such aberration corrected quantitative ADF STEM is discussed including issues relating to proper acquisition of experimental data and its calibration, approaches for data analysis, the utility of such data, its interpretation and limitations.

  4. Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes

    PubMed Central

    Naphade, Swati; Sharma, Jay; Chevronnay, Héloïse P. Gaide; Shook, Michael A.; Yeagy, Brian A.; Rocca, Celine J.; Ur, Sarah N.; Lau, Athena J.; Courtoy, Pierre J.; Cherqui, Stephanie

    2014-01-01

    Despite controversies on the potential of hematopoietic stem cells (HSCs) to promote tissue repair, we previously showed that HSC transplantation could correct cystinosis, a multi-systemic lysosomal storage disease, caused by a defective lysosomal membrane cystine transporter, cystinosin (CTNS). Addressing the cellular mechanisms, we here report vesicular cross-correction after HSC differentiation into macrophages. Upon co-culture with cystinotic fibroblasts, macrophages produced tunneling nanotubes (TNTs) allowing transfer of cystinosin-bearing lysosomes into Ctns-deficient cells, which exploited the same route to retrogradely transfer cystine-loaded lysosomes to macrophages, providing a bidirectional correction mechanism. TNT formation was enhanced by contact with diseased cells. In vivo, HSCs grafted to cystinotic kidneys also generated nanotubular extensions resembling invadopodia that crossed the dense basement membranes and delivered cystinosin into diseased proximal tubular cells. This is the first report of correction of a genetic lysosomal defect by bidirectional vesicular exchange via TNTs and suggests broader potential for HSC transplantation for other disorders due to defective vesicular proteins. PMID:25186209

  5. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    PubMed

    Dellambra, E; Vailly, J; Pellegrini, G; Bondanza, S; Golisano, O; Macchia, C; Zambruno, G; Meneguzzi, G; De Luca, M

    1998-06-10

    Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses. PMID:9650620

  6. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells.

    PubMed

    Hoban, Megan D; Cost, Gregory J; Mendel, Matthew C; Romero, Zulema; Kaufman, Michael L; Joglekar, Alok V; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R; Cooper, Aaron R; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E; Zhang, Lei; Rebar, Edward J; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D; Holmes, Michael C; Reik, Andreas; Hollis, Roger P; Kohn, Donald B

    2015-04-23

    Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By co-delivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers.

  7. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells

    PubMed Central

    Hoban, Megan D.; Cost, Gregory J.; Mendel, Matthew C.; Romero, Zulema; Kaufman, Michael L.; Joglekar, Alok V.; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R.; Cooper, Aaron R.; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E.; Zhang, Lei; Rebar, Edward J.; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D.; Holmes, Michael C.; Reik, Andreas; Hollis, Roger P.

    2015-01-01

    Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By codelivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34+ hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγnull mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34+ cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers. PMID:25733580

  8. Mapping magnetism with atomic resolution using aberrated electron probes

    NASA Astrophysics Data System (ADS)

    Idrobo, Juan; Rusz, Ján; McGuire, Michael A.; Symons, Christopher T.; Vatsavai, Ranga Raju; Lupini, Andrew R.

    2015-03-01

    In this talk, we report a direct experimental real-space mapping of magnetic circular dichroism with atomic resolution in aberration-corrected scanning transmission electron microscopy (STEM). Using an aberrated electron probe with customized phase distribution, we reveal with electron energy-loss (EEL) spectroscopy the checkerboard antiferromagnetic ordering of Mn moments in LaMnAsO by observing a dichroic signal in the Mn L-edge. The aberrated probes allow the collection of EEL spectra using the transmitted beam, which results in a magnetic circular dichroic signal with intrinsically larger signal-to-noise ratios than those obtained via nanodiffraction techniques (where most of the transmitted electrons are discarded). The novel experimental setup presented here, which can easily be implemented in aberration-corrected STEM, opens new paths for probing dichroic signals in materials with unprecedented spatial resolution. This research was supported by DOE SUFD MSED, by UT-Battelle, LLC, under Contract No. DE-AC05-00OR22725 with the US DOE, and by the Swedish Research Council and Swedish National Infrastructure for Computing (NSC center)

  9. Cosmic Aberration, and Its Correction

    ERIC Educational Resources Information Center

    Dixon, Robert

    2011-01-01

    Because the speed of light is finite, the further we look into space, the earlier we see. A galaxy seen 50 million light years away is 50 million years ago. How far out in space and how far back in time can we expect to see, and what should it look like? To a first approximation and ignoring local galactic interactions, the Hubble model of the…

  10. Disease-corrected hepatocyte-like cells from familial hypercholesterolemia-induced pluripotent stem cells.

    PubMed

    Fattahi, Faranak; Asgari, Samira; Pournasr, Behshad; Seifinejad, Ali; Totonchi, Mehdi; Taei, Adeleh; Aghdami, Nasser; Salekdeh, Ghasem Hosseini; Baharvand, Hossein

    2013-07-01

    The generation of human induced pluripotent stem cells (hiPSCs) from an individual patient provides a unique tool for disease modeling, drug discovery, and cell replacement therapies. Patient-specific pluripotent stem cells can be expanded in vitro and are thus suitable for genetic manipulations. To date, several genetic liver disorders have been modeled using patient-specific hiPSCs. Here, we present the generation of corrected hepatocyte-like cells (HLCs) from hiPSCs of a familial hypercholesterolemia (FH) patient with a homozygous mutation in the low-density lipoprotein receptor (LDLR) gene. We generated hiPSCs from a patient with FH with the mutated gene encoding a truncated non-functional receptor. In order to deliver normal LDLR to the defective cells, we used a plasmid vector carrying the normal receptor ORF to genetically transform the hiPSCs. The transformed cells were expanded and directed toward HLCs. Undifferentiated defective hiPSCs and HLCs differentiated from the defective hiPSCs did not have the ability to uptake labeled low-density lipoprotein (LDL) particles. The differentiated transformed hiPSCs showed LDL-uptake ability and the correction of disease phenotype as well as expressions of hepatocyte-specific markers. The functionality of differentiated cells was also confirmed by indo-cyanine green (ICG) uptake assay, PAS staining, inducible cyp450 activity, and oil red staining. These data suggest that hiPSC technology can be used for generation of disease-corrected, patient-specific HLCs with potential value for disease modeling and drug discovery as well as cell therapy applications in future.

  11. New formulations between spherical aberration and spherical aberration coefficient using the Abbe sine condition

    NASA Astrophysics Data System (ADS)

    Kang, Songgao; Lu, Kaichang; Zhu, Yafei

    1991-12-01

    The relationship between aberration and the aberration coefficient is the basic formulation in the field of aberration theory. The Seidel's formulations can only be used in the case of low performance (small aperture and small field), so that a set of correct relations between spherical aberration (SA) and spherical aberration coefficient (SAC) must be derived for the application of large aperture and small viewing field.

  12. A novel 3D absorption correction method for quantitative EDX-STEM tomography.

    PubMed

    Burdet, Pierre; Saghi, Z; Filippin, A N; Borrás, A; Midgley, P A

    2016-01-01

    This paper presents a novel 3D method to correct for absorption in energy dispersive X-ray (EDX) microanalysis of heterogeneous samples of unknown structure and composition. By using STEM-based tomography coupled with EDX, an initial 3D reconstruction is used to extract the location of generated X-rays as well as the X-ray path through the sample to the surface. The absorption correction needed to retrieve the generated X-ray intensity is then calculated voxel-by-voxel estimating the different compositions encountered by the X-ray. The method is applied to a core/shell nanowire containing carbon and oxygen, two elements generating highly absorbed low energy X-rays. Absorption is shown to cause major reconstruction artefacts, in the form of an incomplete recovery of the oxide and an erroneous presence of carbon in the shell. By applying the correction method, these artefacts are greatly reduced. The accuracy of the method is assessed using reference X-ray lines with low absorption.

  13. A novel 3D absorption correction method for quantitative EDX-STEM tomography.

    PubMed

    Burdet, Pierre; Saghi, Z; Filippin, A N; Borrás, A; Midgley, P A

    2016-01-01

    This paper presents a novel 3D method to correct for absorption in energy dispersive X-ray (EDX) microanalysis of heterogeneous samples of unknown structure and composition. By using STEM-based tomography coupled with EDX, an initial 3D reconstruction is used to extract the location of generated X-rays as well as the X-ray path through the sample to the surface. The absorption correction needed to retrieve the generated X-ray intensity is then calculated voxel-by-voxel estimating the different compositions encountered by the X-ray. The method is applied to a core/shell nanowire containing carbon and oxygen, two elements generating highly absorbed low energy X-rays. Absorption is shown to cause major reconstruction artefacts, in the form of an incomplete recovery of the oxide and an erroneous presence of carbon in the shell. By applying the correction method, these artefacts are greatly reduced. The accuracy of the method is assessed using reference X-ray lines with low absorption. PMID:26484792

  14. Aberrant high expression of immunoglobulin G in epithelial stem/progenitor-like cells contributes to tumor initiation and metastasis

    PubMed Central

    Wang, Fulin; Wang, Chong; Zhang, Jingxuan; Chu, Ming; Jiang, Dongyang; Xiao, Lin; Shao, Wenwei; Sheng, Zhengzuo; Tao, Xia; Huo, Lei; Yin, C. Cameron; Zhang, Youhui; Lee, Gregory; Huang, Jing; Li, Zihai; Qiu, Xiaoyan

    2015-01-01

    High expression of immunoglobulin G (IgG) in many non-B cell malignancies and its non-conventional roles in promoting proliferation and survival of cancer cells have been demonstrated. However, the precise function of non-B IgG remains incompletely understood. Here we define the antigen specificity of RP215, a monoclonal antibody that specifically recognizes the IgG in cancer cells. Using RP215, our study shows that IgG is overexpressed in cancer cells of epithelial lineage, especially cells with cancer stem/progenitor cell-like features. The RP215-recognized IgG is primarily localized on the cell surface, particularly lamellipodia-like structures. Cells with high IgG display higher migration, increased invasiveness and metastasis, and enhanced self-renewal and tumorgenecity ability in vitro and in vivo. Importantly, depletion of IgG in breast cancer leads to reduced adhesion, invasion and self-renewal and increased apoptosis of cancer cells. We conclude that high expression of IgG is a novel biomarker of tumor progression, metastasis and cancer stem cell maintenance and demonstrate the potential therapeutic benefits of RP215-recognized IgG targeted strategy. PMID:26472025

  15. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

    PubMed Central

    Yusa, Kosuke; Rashid, S. Tamir; Strick-Marchand, Helene; Varela, Ignacio; Liu, Pei-Qi; Paschon, David E.; Miranda, Elena; Ordóñez, Adriana; Hannan, Nick; Rouhani, Foad Jafari; Darche, Sylvie; Alexander, Graeme; Marciniak, Stefan J.; Fusaki, Noemi; Hasegawa, Mamoru; Holmes, Michael C.; Di Santo, James P.; Lomas, David A.; Bradley, Allan; Vallier, Ludovic

    2011-01-01

    Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders1,2,3,4. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications3,5. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome6. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of hIPSCs. Here, we show that a combination of zinc finger nucleases (ZFNs)7 and piggyBac8,9 technology in hIPSCs can achieve bi-allelic correction of a point mutation (Glu342Lys) in the α1-antitrypsin (A1AT, also called SERPINA1) gene that is responsible for α1-antitrypsin deficiency (A1ATD). Genetic correction of hIPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle for the potential of combining hIPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies. PMID:21993621

  16. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning.

    PubMed

    Aiuti, Alessandro; Slavin, Shimon; Aker, Memet; Ficara, Francesca; Deola, Sara; Mortellaro, Alessandra; Morecki, Shoshana; Andolfi, Grazia; Tabucchi, Antonella; Carlucci, Filippo; Marinello, Enrico; Cattaneo, Federica; Vai, Sergio; Servida, Paolo; Miniero, Roberto; Roncarolo, Maria Grazia; Bordignon, Claudio

    2002-06-28

    Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID. PMID:12089448

  17. Aberrant patterns of X chromosome inactivation in a new line of human embryonic stem cells established in physiological oxygen concentrations.

    PubMed

    de Oliveira Georges, Juliana Andrea; Vergani, Naja; Fonseca, Simone Aparecida Siqueira; Fraga, Ana Maria; de Mello, Joana Carvalho Moreira; Albuquerque, Maria Cecília R Maciel; Fujihara, Litsuko Shimabukuro; Pereira, Lygia Veiga

    2014-08-01

    One of the differences between murine and human embryonic stem cells (ESCs) is the epigenetic state of the X chromosomes in female lines. Murine ESCs (mESCs) present two transcriptionally active Xs that will undergo the dosage compensation process of XCI upon differentiation, whereas most human ESCs (hESCs) spontaneously inactivate one X while keeping their pluripotency. Whether this reflects differences in embryonic development of mice and humans, or distinct culture requirements for the two kinds of pluripotent cells is not known. Recently it has been shown that hESCs established in physiological oxygen levels are in a stable pre-XCI state equivalent to that of mESCs, suggesting that culture in low oxygen concentration is enough to preserve that epigenetic state of the X chromosomes. Here we describe the establishment of two new lines of hESCs under physiological oxygen level and the characterization of the XCI state in the 46,XX line BR-5. We show that a fraction of undifferentiated cells present XIST RNA accumulation and single H3K27me foci, characteristic of the inactive X. Moreover, analysis of allele specific gene expression suggests that pluripotent BR-5 cells present completely skewed XCI. Our data indicate that physiological levels of oxygen are not sufficient for the stabilization of the pre-XCI state in hESCs.

  18. Aberrant patterns of X chromosome inactivation in a new line of human embryonic stem cells established in physiological oxygen concentrations.

    PubMed

    de Oliveira Georges, Juliana Andrea; Vergani, Naja; Fonseca, Simone Aparecida Siqueira; Fraga, Ana Maria; de Mello, Joana Carvalho Moreira; Albuquerque, Maria Cecília R Maciel; Fujihara, Litsuko Shimabukuro; Pereira, Lygia Veiga

    2014-08-01

    One of the differences between murine and human embryonic stem cells (ESCs) is the epigenetic state of the X chromosomes in female lines. Murine ESCs (mESCs) present two transcriptionally active Xs that will undergo the dosage compensation process of XCI upon differentiation, whereas most human ESCs (hESCs) spontaneously inactivate one X while keeping their pluripotency. Whether this reflects differences in embryonic development of mice and humans, or distinct culture requirements for the two kinds of pluripotent cells is not known. Recently it has been shown that hESCs established in physiological oxygen levels are in a stable pre-XCI state equivalent to that of mESCs, suggesting that culture in low oxygen concentration is enough to preserve that epigenetic state of the X chromosomes. Here we describe the establishment of two new lines of hESCs under physiological oxygen level and the characterization of the XCI state in the 46,XX line BR-5. We show that a fraction of undifferentiated cells present XIST RNA accumulation and single H3K27me foci, characteristic of the inactive X. Moreover, analysis of allele specific gene expression suggests that pluripotent BR-5 cells present completely skewed XCI. Our data indicate that physiological levels of oxygen are not sufficient for the stabilization of the pre-XCI state in hESCs. PMID:24633531

  19. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease.

    PubMed

    Hamilton, Laura K; Dufresne, Martin; Joppé, Sandra E; Petryszyn, Sarah; Aumont, Anne; Calon, Frédéric; Barnabé-Heider, Fanie; Furtos, Alexandra; Parent, Martin; Chaurand, Pierre; Fernandes, Karl J L

    2015-10-01

    Lipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer's disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer's disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs.

  20. Hematopoietic Stem Cell and Gene Therapy Corrects Primary Neuropathology and Behavior in Mucopolysaccharidosis IIIA Mice

    PubMed Central

    Langford-Smith, Alexander; Wilkinson, Fiona L; Langford-Smith, Kia J; Holley, Rebecca J; Sergijenko, Ana; Howe, Steven J; Bennett, William R; Jones, Simon A; Wraith, JE; Merry, Catherine LR; Wynn, Robert F; Bigger, Brian W

    2012-01-01

    Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo disease) is a neurodegenerative disorder caused by a deficiency in the lysosomal enzyme sulfamidase (SGSH), catabolizing heparan sulfate (HS). Affected children present with severe behavioral abnormalities, sleep disturbances, and progressive neurodegeneration, leading to death in their second decade. MPS I, a similar neurodegenerative disease accumulating HS, is treated successfully with hematopoietic stem cell transplantation (HSCT) but this treatment is ineffectual for MPS IIIA. We compared HSCT in MPS IIIA mice using wild-type donor cells transduced ex vivo with lentiviral vector-expressing SGSH (LV-WT-HSCT) versus wild-type donor cell transplant (WT-HSCT) or lentiviral-SGSH transduced MPS IIIA cells (LV-IIIA-HSCT). LV-WT-HSCT results in 10% of normal brain enzyme activity, near normalization of brain HS and GM2 gangliosides, significant improvements in neuroinflammation and behavioral correction. Both WT-HSCT and LV-IIIA-HSCT mediated improvements in GM2 gangliosides and neuroinflammation but were less effective at reducing HS or in ameliorating abnormal HS sulfation and had no significant effect on behavior. This suggests that HS may have a more significant role in neuropathology than neuroinflammation or GM2 gangliosides. These data provide compelling evidence for the efficacy of gene therapy in conjunction with WT-HSCT for neurological correction of MPS IIIA where conventional transplant is ineffectual. PMID:22547151

  1. Determination of aberration center of Ronchigram for automated aberration correctors in scanning transmission electron microscopy.

    PubMed

    Sannomiya, Takumi; Sawada, Hidetaka; Nakamichi, Tomohiro; Hosokawa, Fumio; Nakamura, Yoshio; Tanishiro, Yasumasa; Takayanagi, Kunio

    2013-12-01

    A generic method to determine the aberration center is established, which can be utilized for aberration calculation and axis alignment for aberration corrected electron microscopes. In this method, decentering induced secondary aberrations from inherent primary aberrations are minimized to find the appropriate axis center. The fitness function to find the optimal decentering vector for the axis was defined as a sum of decentering induced secondary aberrations with properly distributed weight values according to the aberration order. Since the appropriate decentering vector is determined from the aberration values calculated at an arbitrary center axis, only one aberration measurement is in principle required to find the center, resulting in /very fast center search. This approach was tested for the Ronchigram based aberration calculation method for aberration corrected scanning transmission electron microscopy. Both in simulation and in experiments, the center search was confirmed to work well although the convergence to find the best axis becomes slower with larger primary aberrations. Such aberration center determination is expected to fully automatize the aberration correction procedures, which used to require pre-alignment of experienced users. This approach is also applicable to automated aperture positioning.

  2. Myeloid/Microglial Driven Autologous Hematopoietic Stem Cell Gene Therapy Corrects a Neuronopathic Lysosomal Disease

    PubMed Central

    Sergijenko, Ana; Langford-Smith, Alexander; Liao, Ai Y; Pickford, Claire E; McDermott, John; Nowinski, Gabriel; Langford-Smith, Kia J; Merry, Catherine LR; Jones, Simon A; Wraith, J Edmond; Wynn, Robert F; Wilkinson, Fiona L; Bigger, Brian W

    2013-01-01

    Mucopolysaccharidosis type IIIA (MPSIIIA) is a lysosomal storage disorder caused by mutations in N-sulfoglucosamine sulfohydrolase (SGSH), resulting in heparan sulfate (HS) accumulation and progressive neurodegeneration. There are no treatments. We previously demonstrated improved neuropathology in MPSIIIA mice using lentiviral vectors (LVs) overexpressing SGSH in wild-type (WT) hematopoietic stem cell (HSC) transplants (HSCTs), achieved via donor monocyte/microglial engraftment in the brain. However, neurological disease was not corrected using LVs in autologous MPSIIIA HSCTs. To improve brain expression via monocyte/microglial specificity, LVs expressing enhanced green fluorescent protein (eGFP) under ubiquitous phosphoglycerate kinase (PGK) or myeloid-specific promoters were compared in transplanted HSCs. LV-CD11b-GFP gave significantly higher monocyte/B-cell eGFP expression than LV-PGK-GFP or LV-CD18-GFP after 6 months. Subsequently, autologous MPSIIIA HSCs were transduced with either LV-PGK-coSGSH or LV-CD11b-coSGSH vectors expressing codon-optimized SGSH and transplanted into MPSIIIA mice. Eight months after HSCT, LV-PGK-coSGSH vectors produced bone marrow SGSH (576% normal activity) similar to LV-CD11b-coSGSH (473%), but LV-CD11b-coSGSH had significantly higher brain expression (11 versus 7%), demonstrating improved brain specificity. LV-CD11b-coSGSH normalized MPSIIIA behavior, brain HS, GM2 ganglioside, and neuroinflammation to WT levels, whereas LV-PGK-coSGSH partly corrected neuropathology but not behavior. We demonstrate compelling evidence of neurological disease correction using autologous myeloid driven lentiviral-HSC gene therapy in MPSIIIA mice. PMID:23748415

  3. Correction.

    PubMed

    2015-11-01

    In the article by Heuslein et al, which published online ahead of print on September 3, 2015 (DOI: 10.1161/ATVBAHA.115.305775), a correction was needed. Brett R. Blackman was added as the penultimate author of the article. The article has been corrected for publication in the November 2015 issue. PMID:26490278

  4. The potential of bone marrow stem cells to correct liver dysfunction in a mouse model of Wilson's disease.

    PubMed

    Allen, Katrina J; Cheah, Daphne M Y; Lee, Xiao Ling; Pettigrew-Buck, Nicole E; Vadolas, Jim; Mercer, Julian F B; Ioannou, Panayiotis A; Williamson, Robert

    2004-01-01

    Metabolic liver diseases are excellent targets for correction using novel stem cell, hepatocyte, and gene therapies. In this study, the use of bone marrow stem cell transplantation to correct liver disease in the toxic milk (tx) mouse, a murine model for Wilson's disease, was evaluated. Preconditioning with sublethal irradiation, dietary copper loading, and the influence of cell transplantation sites were assessed. Recipient tx mice were sublethally irradiated (4 Gy) prior to transplantation with bone marrow stem cells harvested from normal congenic (DL) littermates. Of 46 transplanted tx mice, 11 demonstrated genotypic repopulation in the liver. Sublethal irradiation was found to be essential for donor cell engraftment and liver repopulation. Dietary copper loading did not improve cell engraftment and repopulation results. Both intravenously and intrasplenically transplanted cells produced similar repopulation successes. Direct evidence of functionality and disease correction following liver repopulation was observed in the 11 mice where liver copper levels were significantly reduced when compared with mice with no liver repopulation. The reversal of copper loading with bone marrow cells is similar to the level of correction seen when normal congenic liver cells are used. Transplantation of bone marrow cells partially corrects the metabolic phenotype in a mouse model for Wilson's disease.

  5. Aberrant microRNA expression likely controls RAS oncogene activation during malignant transformation of human prostate epithelial and stem cells by arsenic.

    PubMed

    Ngalame, Ntube N O; Tokar, Erik J; Person, Rachel J; Xu, Yuanyuan; Waalkes, Michael P

    2014-04-01

    Inorganic arsenic (iAs), a human carcinogen, potentially targets the prostate. iAs malignantly transforms the RWPE-1 human prostate epithelial line to CAsE-PE cells, and a derivative normal stem cell (SC) line, WPE-stem, to As-Cancer SC (As-CSC) line. MicroRNAs (miRNA) are noncoding but exert negative control on expression by degradation or translational repression of target mRNAs. Aberrant miRNA expression is important in carcinogenesis. A miRNA array of CAsE-PE and As-CSC revealed common altered expression in both for pathways concerning oncogenesis, miRNA biogenesis, cell signaling, proliferation, and tumor metastasis and invasion. The KRAS oncogene is overexpressed in CAsE-PE cells but not by mutation or promoter hypomethylation, and is intensely overexpressed in As-CSC cells. In both transformants, decreased miRNAs targeting KRAS and RAS superfamily members occurred. Reduced miR-134, miR-373, miR-155, miR-138, miR-205, miR-181d, miR-181c, and let-7 in CAsE-PE cells correlated with increased target RAS oncogenes, RAN, RAB27A, RAB22A mRNAs, and KRAS protein. Reduced miR-143, miR-34c-5p, and miR-205 in As-CSC correlated with increased target RAN mRNA, and KRAS, NRAS, and RRAS proteins. The RAS/ERK and PI3K/PTEN/AKT pathways control cell survival, differentiation, and proliferation, and when dysregulated promote a cancer phenotype. iAs transformation increased expression of activated ERK kinase in both transformants and altered components of the PI3K/PTEN/AKT pathway including decreased PTEN and increases in BCL2, BCL-XL, and VEGF in the absence of AKT activation. Thus, dysregulated miRNA expression may be linked to RAS activation in both transformants.

  6. [The surgical correction of the right aortic arch with aberrant left subclavian artery and left ligamentum arteriosum--a rare case from clinical practice].

    PubMed

    Baev, B; Nachev, G; Chirkov, A

    1995-01-01

    Reports on the surgical management of the vascular ring formed by the right aortic arch with aberrant retroesophageal left subclavian artery and left ligamentum arteriosum are relatively few. The authors present a case of a thirty-three-year old woman with cough, dysphonia and stridor without dysphagia. Surgical management which was performed through a bilateral thoracotomy with transversal sternotomy, included division of the ligamentum arteriosum and of the aberrant left subclavian artery and suture of the latter. There was no need to resect the Kommerell's diverticulum, because of lack of any dysphagia despite of the well documented severe compression of the esophagus. The authors experience proved that in difficult cases the bilateral thoracotomy and transversal sternotomy is an useful approach to perform complete surgical repair of this abnormality.

  7. Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon ((28)Si) ions.

    PubMed

    Rithidech, Kanokporn Noy; Honikel, Louise M; Reungpathanaphong, Paiboon; Tungjai, Montree; Jangiam, Witawat; Whorton, Elbert B

    2015-11-01

    Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to (28)Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n (28)Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p<0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n (28)Si ions. Slight increases in the levels of 5 mC were observed in all treatment groups, as compared to the sham-control level. In contrast, there was a significant reduction in levels of 5 hmC (ANOVA, p<0.01). Since these endpoints were evaluated in the same mouse, our data suggested for the first time a link between a reduction in 5 hmC and genomic instability in HSPC-derived myeloid colonies of CBA/CaJ mice exposed to 300 Me

  8. Corrections

    NASA Astrophysics Data System (ADS)

    2012-09-01

    The feature article "Material advantage?" on the effects of technology and rule changes on sporting performance (July pp28-30) stated that sprinters are less affected by lower oxygen levels at high altitudes because they run "aerobically". They run anaerobically. The feature about the search for the Higgs boson (August pp22-26) incorrectly gave the boson's mass as roughly 125 MeV it is 125 GeV, as correctly stated elsewhere in the issue. The article also gave a wrong value for the intended collision energy of the Superconducting Super Collider, which was designed to collide protons with a total energy of 40 TeV.

  9. Correction.

    PubMed

    2015-05-22

    The Circulation Research article by Keith and Bolli (“String Theory” of c-kitpos Cardiac Cells: A New Paradigm Regarding the Nature of These Cells That May Reconcile Apparently Discrepant Results. Circ Res. 2015:116:1216-1230. doi: 10.1161/CIRCRESAHA.116.305557) states that van Berlo et al (2014) observed that large numbers of fibroblasts and adventitial cells, some smooth muscle and endothelial cells, and rare cardiomyocytes originated from c-kit positive progenitors. However, van Berlo et al reported that only occasional fibroblasts and adventitial cells derived from c-kit positive progenitors in their studies. Accordingly, the review has been corrected to indicate that van Berlo et al (2014) observed that large numbers of endothelial cells, with some smooth muscle cells and fibroblasts, and more rarely cardiomyocytes, originated from c-kit positive progenitors in their murine model. The authors apologize for this error, and the error has been noted and corrected in the online version of the article, which is available at http://circres.ahajournals.org/content/116/7/1216.full ( PMID:25999426

  10. Accommodative lag and fluctuations when optical aberrations are manipulated.

    PubMed

    Gambra, Enrique; Sawides, Lucie; Dorronsoro, Carlos; Marcos, Susana

    2009-06-09

    We evaluated the accommodative response to a stimulus moving from 0 to 6 D following a staircase function under natural, corrected, and induced optical aberrations, using an adaptive-optics (AO) electromagnetic deformable mirror. The accommodative response of the eye (through the mirror) and the change of aberrations were measured on 5 subjects using a Hartmann-Shack wavefront sensor operating at 12.8 Hz. Five conditions were tested: (1) natural aberrations, (2) AO correction of the unaccommodated state and induction (over 6-mm pupils) of (3) +1 microm and (4) -1 microm of spherical aberration and (5) -2 microm of vertical coma. Four subjects showed a better accommodative response with AO correction than with their natural aberrations. The induction of negative spherical aberration also produced a better accommodative response in the same subjects. Accommodative lag increased in all subjects when positive spherical aberration and coma were induced. Fluctuations of the accommodative response (computed during each 1-D period of steady accommodation) increased with accommodative response when high-order aberrations were induced. The largest fluctuations occurred for induced negative spherical aberration and the smallest for natural and corrected aberrations. The study demonstrates that aberrations influence accommodative lag and fluctuations of accommodation and that correcting aberrations improves rather than compromises the accommodative response.

  11. Quantitative atom column position analysis at the incommensurate interfaces of a (PbS)(1.14)NbS(2) misfit layered compound with aberration-corrected HRTEM.

    PubMed

    Garbrecht, M; Spiecker, E; Tillmann, K; Jäger, W

    2011-02-01

    Aberration-corrected HRTEM is applied to explore the potential of NCSI contrast imaging to quantitatively analyse the complex atomic structure of misfit layered compounds and their incommensurate interfaces. Using the (PbS)(1.14)NbS(2) misfit layered compound as a model system it is shown that atom column position analyses at the incommensurate interfaces can be performed with precisions reaching a statistical accuracy of ±6pm. The procedure adopted for these studies compares experimental images taken from compound regions free of defects and interface modulations with a structure model derived from XRD experiments and with multi-slice image simulations for the corresponding NCSI contrast conditions used. The high precision achievable in such experiments is confirmed by a detailed quantitative analysis of the atom column positions at the incommensurate interfaces, proving a tetragonal distortion of the monochalcogenide sublattice.

  12. Three traps in stellar aberration

    NASA Astrophysics Data System (ADS)

    Liebscher, Dierck-E.; Brosche, Peter

    The effect of aberration seems to be one of the simplest in astronomical observations. Nevertheless, it has a long and pertaining history of misunderstanding and wrong interpretation. In the time just before the advent of the theory of relativity, aberration and drag of the aether (as found in Michelson's experiment) are interpreted as contradiction. This contradiction vanishes with the theory of relativity. More obstinate is the misunderstanding that the aberration depends on the relative velocity of source and observer. In the twenties, some physicists and astronomers believed that the consequences of such a relativity, wrongly supposed but never found, would constitute a firm argument against Einstein's theory (Hayn, Tomaschek, Osten, v. Brunn, Courvoisier, Mohorovicic). History forgot their argument, but it is difficult to find a correct explanation of their error (Emden). Instead, the subject is forgotten, and one can conjecture it because of the political side of the argument. This attitude takes its revenge: Misunderstandings are still handed down from textbook to textbook.

  13. New Frontier in Regenerative Medicine: Site-Specific Gene Correction in Patient-Specific Induced Pluripotent Stem Cells

    PubMed Central

    Garate, Zita; Davis, Brian R.; Quintana-Bustamante, Oscar

    2013-01-01

    Abstract Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle, to differentiate into any cell type of the human body. Since Yamanaka and colleagues first reported the generation of hiPSCs in 2007, significant efforts have been made to understand the reprogramming process and to generate hiPSCs with potential for clinical use. On the other hand, the development of gene-editing platforms to increase homologous recombination efficiency, namely DNA nucleases (zinc finger nucleases, TAL effector nucleases, and meganucleases), is making the application of locus-specific gene therapy in human cells an achievable goal. The generation of patient-specific hiPSC, together with gene correction by homologous recombination, will potentially allow for their clinical application in the near future. In fact, reports have shown targeted gene correction through DNA-Nucleases in patient-specific hiPSCs. Various technologies have been described to reprogram patient cells and to correct these patient hiPSCs. However, no approach has been clearly more efficient and safer than the others. In addition, there are still significant challenges for the clinical application of these technologies, such as inefficient differentiation protocols, genetic instability resulting from the reprogramming process and hiPSC culture itself, the efficacy and specificity of the engineered DNA nucleases, and the overall homologous recombination efficiency. To summarize advances in the generation of gene corrected patient-specific hiPSCs, this review focuses on the available technological platforms, including their strengths and limitations regarding future therapeutic use of gene-corrected hiPSCs. PMID:23675640

  14. Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells.

    PubMed

    Wu, Yuxuan; Zhou, Hai; Fan, Xiaoying; Zhang, Ying; Zhang, Man; Wang, Yinghua; Xie, Zhenfei; Bai, Meizhu; Yin, Qi; Liang, Dan; Tang, Wei; Liao, Jiaoyang; Zhou, Chikai; Liu, Wujuan; Zhu, Ping; Guo, Hongshan; Pan, Hong; Wu, Chunlian; Shi, Huijuan; Wu, Ligang; Tang, Fuchou; Li, Jinsong

    2015-01-01

    Spermatogonial stem cells (SSCs) can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene-modified animals. However, successful genetic manipulation of SSCs has been limited, partially due to complexity and low efficiency of currently available genetic editing techniques. Here, we show that efficient genetic modifications can be introduced into SSCs using the CRISPR-Cas9 system. We used the CRISPR-Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs. The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes. Round spermatids were generated and, after injection into mature oocytes, supported the production of heterozygous offspring displaying the corresponding mutant phenotypes. Furthermore, a disease-causing mutation in Crygc (Crygc(-/-)) that pre-existed in SSCs could be readily repaired by CRISPR-Cas9-induced nonhomologous end joining (NHEJ) or homology-directed repair (HDR), resulting in SSC lines carrying the corrected gene with no evidence of off-target modifications as shown by whole-genome sequencing. Fertilization using round spermatids generated from these lines gave rise to offspring with the corrected phenotype at an efficiency of 100%. Our results demonstrate efficient gene editing in mouse SSCs by the CRISPR-Cas9 system, and provide the proof of principle of curing a genetic disease via gene correction in SSCs.

  15. TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.

    PubMed

    Ramalingam, Sivaprakash; Annaluru, Narayana; Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

    2014-01-01

    Generation and precise genetic correction of patient-derived hiPSCs have great potential in regenerative medicine. Such targeted genetic manipulations can now be achieved using gene-editing nucleases. Here, we report generation of cystic fibrosis (CF) and Gaucher's disease (GD) hiPSCs respectively from CF (homozygous for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase (GBA) 1448T>C mutation] patient fibroblasts, using CCR5- specific TALENs. Site-specific addition of loxP-flanked Oct4/Sox2/Klf4/Lin28/Nanog/eGFP gene cassette at the endogenous CCR5 site of patient-derived disease-specific primary fibroblasts induced reprogramming, giving rise to both monoallele (heterozygous) and biallele CCR5-modified hiPSCs. Subsequent excision of the donor cassette was done by treating CCR5-modified CF and GD hiPSCs with Cre. We also demonstrate site-specific correction of sickle cell disease (SCD) mutations at the endogenous HBB locus of patient-specific hiPSCs [TNC1 line that is homozygous for mutated β- globin alleles (βS/βS)], using HBB-specific TALENs. SCD-corrected hiPSC lines showed gene conversion of the mutated βS to the wild-type βA in one of the HBB alleles, while the other allele remained a mutant phenotype. After excision of the loxP-flanked DNA cassette from the SCD-corrected hiPSC lines using Cre, we obtained secondary heterozygous βS/βA hiPSCs, which express the wild-type (βA) transcript to 30-40% level as compared to uncorrected (βS/βS) SCD hiPSCs when differentiated into erythroid cells. Furthermore, we also show that TALEN-mediated generation and genetic correction of disease-specific hiPSCs did not induce any off-target mutations at closely related sites.

  16. Aberrant Wnt/β-catenin signaling and elevated expression of stem cell proteins are associated with osteosarcoma side population cells of high tumorigenicity.

    PubMed

    Yi, Xi-Jun; Zhao, Yu-Hua; Qiao, Li-Xiang; Jin, Chun-Lei; Tian, Jing; Li, Qiu-Shi

    2015-10-01

    According to the cancer stem cell theory, the presence of a small sub‑population of cancer cells, termed cancer stem cells (CSCs), have a significant implication on cancer treatment and are responsible for tumor recurrence. Previous studies have reported that alterations in the Wnt/β‑catenin signaling are crucial in the maintenance of CSCs. In the present study, the characteristic features and activation of Wnt/β‑catenin signaling in CSCs from osteosarcoma, an aggressive human bone tumor, were investigated. In total, ~2.1% of the cancer stem‑like side population (SP) cells were identified in the osteosarcoma samples. The results of subsequent western blot and reverse transcription‑quantitative polymerase chain reaction analyses revealed that the protein levels of β‑catenin and cyclin D1 were markedly upregulated in the fluorescence‑activated cell sorted osteosarcoma SP cells. In addition, the elevated expression levels of stem cell proteins, including CD133, nestin Oct‑4, Sox‑2 and Nanog were significantly higher in the SP cells, which contributed to self‑renewal and enhanced the proliferation rate of the SP cells. Furthermore, the SP cells were found to be highly invasive and able to form tumors in vivo. Taken together, these data suggested that the identification of novel anticancer drugs, which suppress the Wnt/β‑catenin signaling and its downstream pathway may assist in eradicating osteosarcoma stem cells.

  17. Factor VIII delivered by hematopoietic stem cell-derived B cells corrects the phenotype of hemophilia A mice

    PubMed Central

    Ramezani, Ali; Zweier-Renn, Lynnsey A.; Hawley, Robert G.

    2011-01-01

    Summary The main impediments to clinical application of hematopoietic stem cell (HSC) gene therapy for treatment of hemophilia A are the bone marrow transplant-related risks and the potential for insertional mutagenesis caused by retroviral vectors. To circumvent these limitations, we have adapted a nonmyeloablative conditioning regimen and directed factor VIII (FVIII) protein synthesis to B lineage cells using an insulated lentiviral vector containing an immunoglobulin heavy chain enhancer-promoter. Transplantation of lentiviral vector-modified HSCs resulted in therapeutic levels of FVIII in the circulation of all transplanted mice for the duration of the study (6 months). Immunostaining of spleen cells showed that the majority of FVIII was synthesized by B220+ B cells and CD138+ plasma cells. Subsequent challenge with recombinant FVIII elicited at most a minor anti-FVIII antibody response, demonstrating induction of immune hyporesponsiveness. All transplant recipients exhibited clot formation and survived tail clipping, indicating correction of their hemophilic phenotype. Therapeutic levels of FVIII could be transferred to secondary recipients by bone marrow transplantation, confirming gene transfer into long-term repopulating HSCs. Moreover, short-term therapeutic FVIII levels could also be achieved in secondary recipients by adoptive transfer of HSC-derived splenic B cells. Our findings support pursuit of B cell-directed protein delivery as a potential clinical approach to treat hemophilia A and other disorders correctable by systemically distributed proteins. PMID:21264447

  18. Image-based EUVL aberration metrology

    NASA Astrophysics Data System (ADS)

    Fenger, Germain Louis

    A significant factor in the degradation of nanolithographic image fidelity is optical wavefront aberration. As resolution of nanolithography systems increases, effects of wavefront aberrations on aerial image become more influential. The tolerance of such aberrations is governed by the requirements of features that are being imaged, often requiring lenses that can be corrected with a high degree of accuracy and precision. Resolution of lithographic systems is driven by scaling wavelength down and numerical aperture (NA) up. However, aberrations are also affected from the changes in wavelength and NA. Reduction in wavelength or increase in NA result in greater impact of aberrations, where the latter shows a quadratic dependence. Current demands in semiconductor manufacturing are constantly pushing lithographic systems to operate at the diffraction limit; hence, prompting a need to reduce all degrading effects on image properties to achieve maximum performance. Therefore, the need for highly accurate in-situ aberration measurement and correction is paramount. In this work, an approach has been developed in which several targets including phase wheel, phase disk, phase edges, and binary structures are used to generate optical images to detect and monitor aberrations in extreme ultraviolet (EUV) lithographic systems. The benefit of using printed patterns as opposed to other techniques is that the lithography system is tested under standard operating conditions. Mathematical models in conjunction with iterative lithographic simulations are used to determine pupil phase wavefront errors and describe them as combinations of Zernike polynomials.

  19. Quantitative fluctuation electron microscopy in the STEM: methods to identify, avoid, and correct for artifacts.

    PubMed

    Li, Tian T; Bogle, Stephanie N; Abelson, John R

    2014-10-01

    Fluctuation electron microscopy can reveal the nanoscale order in amorphous materials via the statistical variance in the scattering intensity as a function of position, scattering vector, and resolution. However, several sources of experimental artifacts can seriously affect the magnitude of the variance peaks. The use of a scanning transmission electron microscope for data collection affords a convenient means to check whether artifacts are present. As nanodiffraction patterns are collected in serial, any spatial or temporal dependence of the scattering intensity across the series can easily be detected. We present examples of the major types of artifact and methods to correct the data or to avoid the problem experimentally. We also re-cast the statistical formalism used to identify sources of noise in view of the present results. The present work provides a basis on which to perform fluctuation electron microscopy with a high level of reliability and confidence in the quantitative magnitude of the data.

  20. Gene Editing in Human Pluripotent Stem Cells: Choosing the Correct Path

    PubMed Central

    Singh, Amar M.; Adjan Steffey, Valeriya V.; Yeshi, Tseten; Allison, Daniel W.

    2015-01-01

    The recent emergence of targeted nucleases has opened up new opportunities for performing genetic modifications with human pluripotent stem cells (hPSCs). These modifications can range from the creation of a routine knock-out to the more challenging single point-mutation. For both the new and established user, deciding on the best approach for the specific modification of interest can be an arduous task, as new and improved technologies are rapidly and continuously being developed. The choices between the reagents and methodologies depends entirely on the end-goal of the experiments and the locus to be modified. Investigators need to decide on the best nuclease to use for each experiment from among Zinc-Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 that would result in the highest likelihood of success with the fewest pitfalls. Furthermore, there have been significant improvements over the first-generation nucleases, such as the development of the dimeric CRISPR RNA-guided Fok1 nucleases (RFNs, marketed as NextGEN™ CRISPR) that reduces the “off-target” mutation rate, providing further options for investigators. Should researchers need to perform a point mutation, then considerations must be made between using single-stranded oligo-deoxynucleotides (ssODN) as the donor for homology-directed repair or utilizing a selection cassette within a donor vector in combination with an excision-only piggyBac™ transposase to leave a seamless edit. In this review, we will provide a general overview of the current technologies, along with methodologies for generating point mutations, while considering both their pros and cons. PMID:26702451

  1. A large aberrant stem ichthyosauriform indicating early rise and demise of ichthyosauromorphs in the wake of the end-Permian extinction.

    PubMed

    Jiang, Da-Yong; Motani, Ryosuke; Huang, Jian-Dong; Tintori, Andrea; Hu, Yuan-Chao; Rieppel, Olivier; Fraser, Nicholas C; Ji, Cheng; Kelley, Neil P; Fu, Wan-Lu; Zhang, Rong

    2016-01-01

    Contrary to the fast radiation of most metazoans after the end-Permian mass extinction, it is believed that early marine reptiles evolved slowly during the same time interval. However, emerging discoveries of Early Triassic marine reptiles are questioning this traditional view. Here we present an aberrant basal ichthyosauriform with a hitherto unknown body design that suggests a fast radiation of early marine reptiles. The new species is larger than coeval marine reptiles and has an extremely small head and a long tail without a fluke. Its heavily-built body bears flattened and overlapping gastral elements reminiscent of hupehsuchians. A phylogenetic analysis places the new species at the base of ichthyosauriforms, as the sister taxon of Cartorhynchus with which it shares a short snout with rostrally extended nasals. It now appears that ichthyosauriforms evolved rapidly within the first one million years of their evolution, in the Spathian (Early Triassic), and their true diversity has yet to be fully uncovered. Early ichthyosauromorphs quickly became extinct near the Early-Middle Triassic boundary, during the last large environmental perturbation after the end-Permian extinction involving redox fluctuations, sea level changes and volcanism. Marine reptile faunas shifted from ichthyosauromorph-dominated to sauropterygian-dominated composition after the perturbation. PMID:27211319

  2. A large aberrant stem ichthyosauriform indicating early rise and demise of ichthyosauromorphs in the wake of the end-Permian extinction

    PubMed Central

    Jiang, Da-Yong; Motani, Ryosuke; Huang, Jian-Dong; Tintori, Andrea; Hu, Yuan-Chao; Rieppel, Olivier; Fraser, Nicholas C.; Ji, Cheng; Kelley, Neil P.; Fu, Wan-Lu; Zhang, Rong

    2016-01-01

    Contrary to the fast radiation of most metazoans after the end-Permian mass extinction, it is believed that early marine reptiles evolved slowly during the same time interval. However, emerging discoveries of Early Triassic marine reptiles are questioning this traditional view. Here we present an aberrant basal ichthyosauriform with a hitherto unknown body design that suggests a fast radiation of early marine reptiles. The new species is larger than coeval marine reptiles and has an extremely small head and a long tail without a fluke. Its heavily-built body bears flattened and overlapping gastral elements reminiscent of hupehsuchians. A phylogenetic analysis places the new species at the base of ichthyosauriforms, as the sister taxon of Cartorhynchus with which it shares a short snout with rostrally extended nasals. It now appears that ichthyosauriforms evolved rapidly within the first one million years of their evolution, in the Spathian (Early Triassic), and their true diversity has yet to be fully uncovered. Early ichthyosauromorphs quickly became extinct near the Early-Middle Triassic boundary, during the last large environmental perturbation after the end-Permian extinction involving redox fluctuations, sea level changes and volcanism. Marine reptile faunas shifted from ichthyosauromorph-dominated to sauropterygian-dominated composition after the perturbation. PMID:27211319

  3. Combining Single Strand Oligodeoxynucleotides and CRISPR/Cas9 to Correct Gene Mutations in β-Thalassemia-induced Pluripotent Stem Cells.

    PubMed

    Niu, Xiaohua; He, Wenyin; Song, Bing; Ou, Zhanhui; Fan, Di; Chen, Yuchang; Fan, Yong; Sun, Xiaofang

    2016-08-01

    β-Thalassemia (β-Thal) is one of the most common genetic diseases in the world. The generation of patient-specific β-Thal-induced pluripotent stem cells (iPSCs), correction of the disease-causing mutations in those cells, and then differentiation into hematopoietic stem cells offers a new therapeutic strategy for this disease. Here, we designed a CRISPR/Cas9 to specifically target the Homo sapiens hemoglobin β (HBB) gene CD41/42(-CTTT) mutation. We demonstrated that the combination of single strand oligodeoxynucleotides with CRISPR/Cas9 was capable of correcting the HBB gene CD41/42 mutation in β-Thal iPSCs. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm mutation correction, we verified that the purified clones retained full pluripotency and exhibited normal karyotyping. Additionally, whole-exome sequencing showed that the mutation load to the exomes was minimal after CRISPR/Cas9 targeting. Furthermore, the corrected iPSCs were selected for erythroblast differentiation and restored the expression of HBB protein compared with the parental iPSCs. This method provides an efficient and safe strategy to correct the HBB gene mutation in β-Thal iPSCs. PMID:27288406

  4. The imbalanced expression of adenosine receptors in an epilepsy model corrected using targeted mesenchymal stem cell transplantation.

    PubMed

    Huicong, Kang; Zheng, Xue; Furong, Wang; Zhouping, Tang; Feng, Xu; Qi, Hu; Xiaoyan, Liu; Xiaojiang, Huang; Na, Zhang; Ke, Xu; Zheng, Zeng; Suiqiang, Zhu

    2013-12-01

    Adenosine inhibits epileptic episodes by interacting with G-protein-coupled receptors. This study examined the mechanism by which the inhibitory effect of adenosine becomes impaired during epileptogenesis. Dynamic changes in adenosine A1 receptors (A1Rs) and A2a receptors (A2aRs) were investigated in a kindling model of epilepsy. RT-PCR, Western blotting, and immunofluorescence results indicated that expression of A1Rs was increased in the hippocampus 24 h after kindling, but progressively decreased 1 and 6 months after kindling. Opposite changes were seen in the expression of A2aRs. This bidirectional change resulted in an imbalance between A1Rs and A2aRs and dysregulation of the adenosine system. Autologous mesenchymal stem cell (MSC) transplantation was used to correct this disorder and avoid side effects of systematic adenosine therapy. Paramagnetic iron oxide particles were used to mark and track the MSCs in vivo using MRI. The results indicated that the transplanted cells migrated along the callosum and settled at the ependymal layer. The MSCs displayed a relatively long survival time, at least 3 months. The improved AR expression and EEG findings suggested that MSC transplantation was a potentially effective means of treating refractory epilepsy.

  5. Interpreting Chromosome Aberration Spectra

    NASA Technical Reports Server (NTRS)

    Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

    2007-01-01

    Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

  6. Tuning fifth-order aberrations in a Quadrupole-Octupole Corrector

    SciTech Connect

    Lupini, Andrew R; Pennycook, Stephen J

    2012-01-01

    The resolution of conventional electron microscopes is usually limited by spherical aberration. Microscopes equipped with aberration-correctors are then primarily limited by higher-order, chromatic, and misalignment aberrations. In particular the Nion third-order aberration correctors installed on machines with a low energy spread and possessing sophisticated alignment software were limited by the uncorrected fifth-order aberrations. Here we show how the Nion fifth-order aberration corrector can be used to adjust and reduce some of the fourth and fifth-order aberrations in a probe-corrected scanning transmission electron microscope.

  7. Correcting Hubble Vision.

    ERIC Educational Resources Information Center

    Shaw, John M.; Sheahen, Thomas P.

    1994-01-01

    Describes the theory behind the workings of the Hubble Space Telescope, the spherical aberration in the primary mirror that caused a reduction in image quality, and the corrective device that compensated for the error. (JRH)

  8. STEM?!?!

    ERIC Educational Resources Information Center

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  9. Comparison of Aberrations After Standard and Customized Refractive Surgery

    NASA Astrophysics Data System (ADS)

    Fang, L.; He, X.; Wang, Y.

    2013-09-01

    To detect possible differences in residual wavefront aberrations between standard and customized laser refractive surgery based onmathematical modeling, the residual optical aberrations after conventional and customized laser refractive surgery were compared accordingto the ablation profile with transition zone. The results indicated that ablation profile has a significant impact on the residual aberrations.The amount of residual aberrations for conventional correction is higher than that for customized correction. Additionally, the residualaberrations for high myopia eyes are markedly larger than those for moderate myopia eyes. For a 5 mm pupil, the main residual aberrationterm is coma and yet it is spherical aberration for a 7 mm pupil. When the pupil diameter is the same as optical zone or greater, themagnitudes of residual aberrations is obviously larger than that for a smaller pupil. In addition, the magnitudes of the residual fifth orsixth order aberrations are relatively large, especially secondary coma in a 6 mm pupil and secondary spherical aberration in a 7 mm pupil.Therefore, the customized ablation profile may be superior to the conventional correction even though the transition zone and treatmentdecentration are taken into account. However, the customized ablation profile will still induce significant amount of residual aberrations.

  10. Reactivation of latently infected HIV-1 viral reservoirs and correction of aberrant alternative splicing in the LMNA gene via AMPK activation: Common mechanism of action linking HIV-1 latency and Hutchinson-Gilford progeria syndrome.

    PubMed

    Finley, Jahahreeh

    2015-09-01

    AMPK, a master regulator of cellular metabolism which has been shown to activate PKC-theta (θ) and is essential for T cell activation, may modulate the splicing activities of SRp55 as well as enhance a p32-mediated inhibition of ASF/SF2-induced alternative splicing, potentially correcting aberrant alternative splicing in the LMNA gene and reactivating latent viral HIV-1 reservoirs. Moreover, similar epigenetic modifications and cell cycle regulators also characterize the analogous stages of premature senescence in progeroid cells and latency in HIV-1 infected T cells. AMPK-activating compounds including metformin and resveratrol may thus embody a novel treatment paradigm linking the pathophysiology of HGPS with that of HIV-1 latency.

  11. Robust method for TALEN-edited correction of pF508del in patient-specific induced pluripotent stem cells.

    PubMed

    Camarasa, María Vicenta; Gálvez, Víctor Miguel

    2016-02-09

    Cystic fibrosis is one of the most frequent inherited rare diseases, caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Apart from symptomatic treatments, therapeutic protocols for curing the disease have not yet been established. The regeneration of genetically corrected, disease-free epithelia in cystic fibrosis patients is envisioned by designing a stem cell/genetic therapy in which patient-derived pluripotent stem cells are genetically corrected, from which target tissues are derived. In this framework, we present an efficient method for seamless correction of pF508del mutation in patient-specific induced pluripotent stem cells by gene edited homologous recombination. Gene edition has been performed by transcription activator-like effector nucleases and a homologous recombination donor vector which contains a PiggyBac transposon-based double selectable marker cassette.This new method has been designed to partially avoid xenobiotics from the culture system, improve cell culture efficiency and genome stability by using a robust culture system method, and optimize timings. Overall, once the pluripotent cells have been amplified for the first nucleofection, the procedure can be completed in 69 days, and can be easily adapted to edit and change any gene of interest.

  12. Dynamics of the eye's wave aberration.

    PubMed

    Hofer, H; Artal, P; Singer, B; Aragón, J L; Williams, D R

    2001-03-01

    It is well known that the eye's optics exhibit temporal instability in the form of microfluctuations in focus; however, almost nothing is known of the temporal properties of the eye's other aberrations. We constructed a real-time Hartmann-Shack (HS) wave-front sensor to measure these dynamics at frequencies as high as 60 Hz. To reduce spatial inhomogeneities in the short-exposure HS images, we used a low-coherence source and a scanning system. HS images were collected on three normal subjects with natural and paralyzed accommodation. Average temporal power spectra were computed for the wave-front rms, the Seidel aberrations, and each of 32 Zernike coefficients. The results indicate the presence of fluctuations in all of the eye's aberration, not just defocus. Fluctuations in higher-order aberrations share similar spectra and bandwidths both within and between subjects, dropping at a rate of approximately 4 dB per octave in temporal frequency. The spectrum shape for higher-order aberrations is generally different from that for microfluctuations of accommodation. The origin of these measured fluctuations is not known, and both corneal/lenticular and retinal causes are considered. Under the assumption that they are purely corneal or lenticular, calculations suggest that a perfect adaptive optics system with a closed-loop bandwidth of 1-2 Hz could correct these aberrations well enough to achieve diffraction-limited imaging over a dilated pupil. PMID:11265680

  13. Identification and correction of spectral contamination in 2H/1H and 18O/16O measured in leaf, stem, and soil water.

    PubMed

    Schultz, Natalie M; Griffis, Timothy J; Lee, Xuhui; Baker, John M

    2011-11-15

    Plant water extracts typically contain organic materials that may cause spectral interference when using isotope ratio infrared spectroscopy (IRIS), resulting in errors in the measured isotope ratios. Manufacturers of IRIS instruments have developed post-processing software to identify the degree of contamination in water samples, and potentially correct the isotope ratios of water with known contaminants. Here, the correction method proposed by an IRIS manufacturer, Los Gatos Research, Inc., was employed and the results were compared with those obtained from isotope ratio mass spectrometry (IRMS). Deionized water was spiked with methanol and ethanol to create correction curves for δ(18)O and δ(2)H. The contamination effects of different sample types (leaf, stem, soil) and different species from agricultural fields, grasslands, and forests were compared. The average corrections in leaf samples ranged from 0.35 to 15.73‰ for δ(2)H and 0.28 to 9.27‰ for δ(18)O. The average corrections in stem samples ranged from 1.17 to 13.70‰ for δ(2)H and 0.47 to 7.97‰ for δ(18)O. There was no contamination observed in soil water. Cleaning plant samples with activated charcoal had minimal effects on the degree of spectral contamination, reducing the corrections, by on average, 0.44‰ for δ(2)H and 0.25‰ for δ(18)O. The correction method eliminated the discrepancies between IRMS and IRIS for δ(18)O, and greatly reduced the discrepancies for δ(2)H. The mean differences in isotope ratios between IRMS and the corrected IRIS method were 0.18‰ for δ(18)O, and -3.39‰ for δ(2)H. The inability to create an ethanol correction curve for δ(2)H probably caused the larger discrepancies. We conclude that ethanol and methanol are the primary compounds causing interference in IRIS analyzers, and that each individual analyzer will probably require customized correction curves. PMID:22006400

  14. Aberrations of the cathode objective lens up to fifth order.

    PubMed

    Tromp, R M; Wan, W; Schramm, S M

    2012-08-01

    In this paper we discuss a topic that was close to Prof. Gertrude Rempfer s interests for many years. On this occasion of her 100th birthday, we remember and honor Gertrude for her many outstanding contributions, and for the inspiring example that she set. We derive theoretical expressions for the aberration coefficients of the uniform electrostatic field up to 5th order and compare these with raytracing calculations for the cathode lens used in Low Energy Electron Microscopy and Photo Electron Emission Microscopy experiments. These higher order aberration coefficients are of interest for aberration corrected experiments in which chromatic (C(c)) and spherical (C₃) aberrations of the microscope are set to zero. The theoretical predictions are in good agreement with the results of raytracing. Calculations of image resolution using the Contrast Transfer Function method show that sub-nanometer resolution is achievable in an aberration corrected LEEM system. PMID:22188906

  15. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases.

    PubMed

    Sebastiano, Vittorio; Maeder, Morgan L; Angstman, James F; Haddad, Bahareh; Khayter, Cyd; Yeo, Dana T; Goodwin, Mathew J; Hawkins, John S; Ramirez, Cherie L; Batista, Luis F Z; Artandi, Steven E; Wernig, Marius; Joung, J Keith

    2011-11-01

    The combination of induced pluripotent stem cell (iPSC) technology and targeted gene modification by homologous recombination (HR) represents a promising new approach to generate genetically corrected, patient-derived cells that could be used for autologous transplantation therapies. This strategy has several potential advantages over conventional gene therapy including eliminating the need for immunosuppression, avoiding the risk of insertional mutagenesis by therapeutic vectors, and maintaining expression of the corrected gene by endogenous control elements rather than a constitutive promoter. However, gene targeting in human pluripotent cells has remained challenging and inefficient. Recently, engineered zinc finger nucleases (ZFNs) have been shown to substantially increase HR frequencies in human iPSCs, raising the prospect of using this technology to correct disease causing mutations. Here, we describe the generation of iPSC lines from sickle cell anemia patients and in situ correction of the disease causing mutation using three ZFN pairs made by the publicly available oligomerized pool engineering method (OPEN). Gene-corrected cells retained full pluripotency and a normal karyotype following removal of reprogramming factor and drug-resistance genes. By testing various conditions, we also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an open-source method to achieve efficient, transgene-free correction of monogenic disease mutations in patient-derived iPSCs. Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications.

  16. Efficient phase contrast imaging in STEM using a pixelated detector. Part 1: experimental demonstration at atomic resolution.

    PubMed

    Pennycook, Timothy J; Lupini, Andrew R; Yang, Hao; Murfitt, Matthew F; Jones, Lewys; Nellist, Peter D

    2015-04-01

    We demonstrate a method to achieve high efficiency phase contrast imaging in aberration corrected scanning transmission electron microscopy (STEM) with a pixelated detector. The pixelated detector is used to record the Ronchigram as a function of probe position which is then analyzed with ptychography. Ptychography has previously been used to provide super-resolution beyond the diffraction limit of the optics, alongside numerically correcting for spherical aberration. Here we rely on a hardware aberration corrector to eliminate aberrations, but use the pixelated detector data set to utilize the largest possible volume of Fourier space to create high efficiency phase contrast images. The use of ptychography to diagnose the effects of chromatic aberration is also demonstrated. Finally, the four dimensional dataset is used to compare different bright field detector configurations from the same scan for a sample of bilayer graphene. Our method of high efficiency ptychography produces the clearest images, while annular bright field produces almost no contrast for an in-focus aberration-corrected probe.

  17. Efficient phase contrast imaging in STEM using a pixelated detector. Part 1: Experimental demonstration at atomic resolution

    DOE PAGES

    Pennycook, Timothy J.; Lupini, Andrew R.; Yang, Hao; Murfitt, Matthew F.; Jones, Lewys; Nellist, Peter D.

    2014-10-15

    In this paper, we demonstrate a method to achieve high efficiency phase contrast imaging in aberration corrected scanning transmission electron microscopy (STEM) with a pixelated detector. The pixelated detector is used to record the Ronchigram as a function of probe position which is then analyzed with ptychography. Ptychography has previously been used to provide super-resolution beyond the diffraction limit of the optics, alongside numerically correcting for spherical aberration. Here we rely on a hardware aberration corrector to eliminate aberrations, but use the pixelated detector data set to utilize the largest possible volume of Fourier space to create high efficiency phasemore » contrast images. The use of ptychography to diagnose the effects of chromatic aberration is also demonstrated. In conclusion, the four dimensional dataset is used to compare different bright field detector configurations from the same scan for a sample of bilayer graphene. Our method of high efficiency ptychography produces the clearest images, while annular bright field produces almost no contrast for an in-focus aberration-corrected probe.« less

  18. Efficient phase contrast imaging in STEM using a pixelated detector. Part 1: Experimental demonstration at atomic resolution

    SciTech Connect

    Pennycook, Timothy J.; Lupini, Andrew R.; Yang, Hao; Murfitt, Matthew F.; Jones, Lewys; Nellist, Peter D.

    2014-10-15

    In this paper, we demonstrate a method to achieve high efficiency phase contrast imaging in aberration corrected scanning transmission electron microscopy (STEM) with a pixelated detector. The pixelated detector is used to record the Ronchigram as a function of probe position which is then analyzed with ptychography. Ptychography has previously been used to provide super-resolution beyond the diffraction limit of the optics, alongside numerically correcting for spherical aberration. Here we rely on a hardware aberration corrector to eliminate aberrations, but use the pixelated detector data set to utilize the largest possible volume of Fourier space to create high efficiency phase contrast images. The use of ptychography to diagnose the effects of chromatic aberration is also demonstrated. In conclusion, the four dimensional dataset is used to compare different bright field detector configurations from the same scan for a sample of bilayer graphene. Our method of high efficiency ptychography produces the clearest images, while annular bright field produces almost no contrast for an in-focus aberration-corrected probe.

  19. Anisoplanatism in adaptive optics systems due to pupil aberrations

    SciTech Connect

    Bauman, B

    2005-08-01

    Adaptive optics systems typically include an optical relay that simultaneously images the science field to be corrected and also a set of pupil planes conjugate to the deformable mirror of the system. Often, in the optical spaces where DM's are placed, the pupils are aberrated, leading to a displacement and/or distortion of the pupil that varies according to field position--producing a type of anisoplanatism, i.e., a degradation of the AO correction with field angle. The pupil aberration phenomenon is described and expressed in terms of Seidel aberrations. An expression for anisoplanatism as a function of pupil distortion is derived, an example of an off-axis parabola is given, and a convenient method for controlling pupil-aberration-generated anisoplanatism is proposed.

  20. Phase from chromatic aberrations.

    PubMed

    Waller, Laura; Kou, Shan Shan; Sheppard, Colin J R; Barbastathis, George

    2010-10-25

    We show that phase objects may be computed accurately from a single color image in a brightfield microscope, with no hardware modification. Our technique uses the chromatic aberration that is inherent to every lens-based imaging system as a phase contrast mechanism. This leads to a simple and inexpensive way of achieving single-shot quantitative phase recovery by a modified Transport of Intensity Equation (TIE) solution, allowing real-time phase imaging in a traditional microscope. PMID:21164620

  1. Cosmological parameter estimation: impact of CMB aberration

    SciTech Connect

    Catena, Riccardo; Notari, Alessio E-mail: notari@ffn.ub.es

    2013-04-01

    The peculiar motion of an observer with respect to the CMB rest frame induces an apparent deflection of the observed CMB photons, i.e. aberration, and a shift in their frequency, i.e. Doppler effect. Both effects distort the temperature multipoles a{sub lm}'s via a mixing matrix at any l. The common lore when performing a CMB based cosmological parameter estimation is to consider that Doppler affects only the l = 1 multipole, and neglect any other corrections. In this paper we reconsider the validity of this assumption, showing that it is actually not robust when sky cuts are included to model CMB foreground contaminations. Assuming a simple fiducial cosmological model with five parameters, we simulated CMB temperature maps of the sky in a WMAP-like and in a Planck-like experiment and added aberration and Doppler effects to the maps. We then analyzed with a MCMC in a Bayesian framework the maps with and without aberration and Doppler effects in order to assess the ability of reconstructing the parameters of the fiducial model. We find that, depending on the specific realization of the simulated data, the parameters can be biased up to one standard deviation for WMAP and almost two standard deviations for Planck. Therefore we conclude that in general it is not a solid assumption to neglect aberration in a CMB based cosmological parameter estimation.

  2. Chromosome transplantation as a novel approach for correcting complex genomic disorders.

    PubMed

    Paulis, Marianna; Castelli, Alessandra; Susani, Lucia; Lizier, Michela; Lagutina, Irina; Focarelli, Maria Luisa; Recordati, Camilla; Uva, Paolo; Faggioli, Francesca; Neri, Tui; Scanziani, Eugenio; Galli, Cesare; Lucchini, Franco; Villa, Anna; Vezzoni, Paolo

    2015-11-01

    Genomic disorders resulting from large rearrangements of the genome remain an important unsolved issue in gene therapy. Chromosome transplantation, defined as the perfect replacement of an endogenous chromosome with a homologous one, has the potential of curing this kind of disorders. Here we report the first successful case of chromosome transplantation by replacement of an endogenous X chromosome carrying a mutation in the Hprt genewith a normal one in mouse embryonic stem cells (ESCs), correcting the genetic defect. The defect was also corrected by replacing the Y chromosome with an X chromosome. Chromosome transplanted clones maintained in vitro and in vivo features of stemness and contributed to chimera formation. Genome integrity was confirmed by cytogenetic and molecular genome analysis. The approach here proposed, with some modifications, might be used to cure various disorders due to other X chromosome aberrations in induced pluripotent stem (iPS) cells derived from affected patients. PMID:26485770

  3. Light elements quantitative x-ray microanalysis of thin samples in STEM. Absorption correction using EELS data

    NASA Astrophysics Data System (ADS)

    Banchet, V.; Michel, J.; Jallot, E.; Laurent-Maquin, D.; Balossier, G.

    2003-07-01

    Quantification of low Z elements like oxygen by energy-dispersive x-ray spectrometry requires x-rays absorption correction even the in the case of thin films analysis in scanning transmission electron microscope. Absorption correction needs the knowledge of the sample local mass thickness. The purpose of this paper is to propose a method which allows the obtainment of the sample local mass thickness and then permits the quantification of all the elements of the sample using the quantification ratio method. Combining electron energy loss spectroscopy measured relative specimen thickness, and x-rays characteristic peaks intensities, we determine with an iterative process the local mass thickness and the absorption corrected elemental weight concentrations. We validate our method with four standard samples (SiO, SiO2, CaSiO3 and Li4SiO4) by the determination of the O/Si atomic ratio. We also ensure the method by analysing a native bioactive glass sample of known composition and of inhomogeneous mass thickness.

  4. Application of STEM characterization for investigating radiation effects in BCC Fe-based alloys

    DOE PAGES

    Parish, Chad M.; Field, Kevin G.; Certain, Alicia G.; Wharry, Janelle P.

    2015-04-20

    This paper provides a general overview of advanced scanning transmission electron microscopy (STEM) techniques used for characterization of irradiated BCC Fe-based alloys. Advanced STEM methods provide the high-resolution imaging and chemical analysis necessary to understand the irradiation response of BCC Fe-based alloys. The use of STEM with energy dispersive x-ray spectroscopy (EDX) for measurement of radiation-induced segregation (RIS) is described, with an illustrated example of RIS in proton- and self-ion irradiated T91. Aberration-corrected STEM-EDX for nanocluster/nanoparticle imaging and chemical analysis is also discussed, and examples are provided from ion-irradiated oxide dispersion strengthened (ODS) alloys. In conclusion, STEM techniques for void,more » cavity, and dislocation loop imaging are described, with examples from various BCC Fe-based alloys.« less

  5. Application of STEM characterization for investigating radiation effects in BCC Fe-based alloys

    SciTech Connect

    Parish, Chad M.; Field, Kevin G.; Certain, Alicia G.; Wharry, Janelle P.

    2015-04-20

    This paper provides a general overview of advanced scanning transmission electron microscopy (STEM) techniques used for characterization of irradiated BCC Fe-based alloys. Advanced STEM methods provide the high-resolution imaging and chemical analysis necessary to understand the irradiation response of BCC Fe-based alloys. The use of STEM with energy dispersive x-ray spectroscopy (EDX) for measurement of radiation-induced segregation (RIS) is described, with an illustrated example of RIS in proton- and self-ion irradiated T91. Aberration-corrected STEM-EDX for nanocluster/nanoparticle imaging and chemical analysis is also discussed, and examples are provided from ion-irradiated oxide dispersion strengthened (ODS) alloys. In conclusion, STEM techniques for void, cavity, and dislocation loop imaging are described, with examples from various BCC Fe-based alloys.

  6. Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

    PubMed Central

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

    2016-01-01

    Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  7. Influences of reference plane and direction of measurement on eye aberration measurement

    NASA Astrophysics Data System (ADS)

    Atchison, David A.; Charman, W. Neil

    2005-12-01

    We explored effects of measurement conditions on wave aberration estimates for uncorrected, axially myopic model eyes. Wave aberrations were initially referenced to either the anterior corneal pole or the natural entrance pupil of symmetrical eye models, with rays traced into the eye from infinity (into the eye) to simulate normal vision, into the eye from infinity and then back out of the eye from the retinal intercepts (into/out of the eye), or out of the eye from the retinal fovea (out of the eye). The into-the-eye and out-of-the-eye ray traces gave increases in spherical aberration as myopia increased, but the into/out-of-the-eye ray trace showed little variation in spherical aberration. Reference plane choice also affected spherical aberration. Corresponding residual aberrations were calculated after the models had been optically corrected, either by placing the object or image plane at the paraxial far point or by modifying corneas to simulate laser ablation corrections. Correcting aberrations by ablation was more complete if the original aberrations were referenced to the cornea rather than to the entrance pupil. For eyes corrected by spectacle lenses, failure to allow for effects of pupil magnification on apparent entrance pupil diameter produced larger changes in measured aberrations. The general findings regarding choice of reference plane and direction of measurement were found to be equally applicable to eyes that lacked rotational symmetry.

  8. Clinical and immunological correction of DOCK8 deficiency by allogeneic hematopoietic stem cell transplantation following a reduced toxicity conditioning regimen.

    PubMed

    Boztug, Heidrun; Karitnig-Weiß, Cäcilia; Ausserer, Bernd; Renner, Ellen D; Albert, Michael H; Sawalle-Belohradsky, Julie; Belohradsky, Bernd H; Mann, Georg; Horcher, Ernst; Rümmele-Waibel, Alexandra; Geyeregger, Rene; Lakatos, Karoly; Peters, Christina; Lawitschka, Anita; Matthes-Martin, Susanne

    2012-10-01

    Dedicator of cytokinesis 8 protein (DOCK8) deficiency is a combined immunodeficiency disorder characterized by an expanding clinical picture with typical features of recurrent respiratory or gastrointestinal tract infections, atopic eczema, food allergies, chronic viral infections of the skin, and blood eosinophilia often accompanied by elevated serum IgE levels. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT). We report a patient with early severe manifestation of DOCK8 deficiency, who underwent unrelated allogeneic HSCT at the age of 3 years following a reduced toxicity conditioning regimen. The transplant course was complicated by pulmonary aspergilloma pretransplantation, adenovirus (ADV) reactivation, and cytomegalovirus (CMV) pneumonitis 4 weeks after transplantation. With antifungal and antiviral treatment the patient recovered. Seven months after transplantation the patient is in excellent clinical condition. Eczematous rash, chronic viral skin infections, and food allergies have subsided, associated with normalization of IgE levels and absolute numbers of eosinophils. Chimerism analysis shows stable full donor chimerism. DOCK8 deficiency can be successfully cured by allogeneic HSCT. This treatment option should be considered early after diagnosis, as opportunistic infections and malignancies that occur more frequently during the natural course of the disease are associated with higher morbidity and mortality. PMID:22897717

  9. Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma

    PubMed Central

    Pirozzi, Giuseppe; Gringeri, Enrico; Boetto, Riccardo; Di Domenico, Marina; Zavan, Barbara; Ferraro, Giuseppe A.; Cillo, Umberto

    2015-01-01

    Liver cancer is the fifth most commonly diagnosed malignancy and the second most frequent cause of cancer death in men worldwide. Amongst liver cancers, hepatocellular carcinoma (HCC) represents the major histological subtype and it is one of the most common malignant human tumors worldwide. Research into the molecular biology of hepatocarcinogenesis has identified several biomarkers, which could provide additional informations in order to better understand the biology of HCC. A large number of biomarkers have been shown to have potential predictive significance and a wide variety of molecular markers have been proven to be excellent diagnostic tools for HCC but it is difficult to characterize HCC with a single biomarker. Thus, signatures of a combination of biomarkers may be more valuable for the diagnosis, staging and prognosis of HCC. Specifically, a correlation of HCC-CSCs phenotype to specific hepatic cancer subtypes and to specific clinical and pathological features has not yet been reported in human liver tumors. In this view we will first discuss the possible sources of liver stem cells and their relation with liver cancer development and we will secondly focus on the prognostic significance of clinical and pathological features of HCC. PMID:26097877

  10. Correction of the disease phenotype in canine leukocyte adhesion deficiency using ex vivo hematopoietic stem cell gene therapy

    PubMed Central

    Bauer, Thomas R.; Hai, Mehreen; Tuschong, Laura M.; Burkholder, Tanya H.; Gu, Yu-chen; Sokolic, Robert A.; Ferguson, Cole; Dunbar, Cynthia E.; Hickstein, Dennis D.

    2006-01-01

    Canine leukocyte adhesion deficiency (CLAD) represents the canine counter-part of the human disease leukocyte adhesion deficiency (LAD). Defects in the leukocyte integrin CD18 adhesion molecule in both CLAD and LAD lead to recurrent, life-threatening bacterial infections. We evaluated ex vivo retroviral-mediated gene therapy in CLAD using 2 nonmyeloablative conditioning regimens—200 cGy total body irradiation (TBI) or 10 mg/kg busulfan—with or without posttransplantation immunosuppression. In 6 of 11 treated CLAD dogs, therapeutic levels of CD18+ leukocytes were achieved. Conditioning with either TBI or busulfan allowed long-term engraftment, and immunosuppression was not required for efficacy. The percentage of CD18+ leukocytes in the peripheral blood progressively increased over 6 to 8 months after infusion to levels ranging from 1.26% to 8.37% at 1-year follow-up in the 6 dogs. These levels resulted in reversal or moderation of the severe CLAD phenotype. Linear amplification–mediated polymerase chain reaction assays indicated polyclonality of insertion sites. These results describe ex vivo hematopoietic stem cell gene transfer in a disease-specific, large animal model using 2 clinically applicable conditioning regimens, and they provide support for the use of nonmyeloablative conditioning regimens in preclinical protocols of retroviral-mediated gene transfer for nonmalignant hematopoietic diseases such as LAD. PMID:16868255

  11. Using aberrant behaviors as reinforcers for autistic children.

    PubMed Central

    Charlop, M H; Kurtz, P F; Casey, F G

    1990-01-01

    In a series of experiments, we assessed the efficacy of using autistic children's aberrant behaviors as reinforcers to increase their correct task responding. In Experiment 1, reinforcer conditions of stereotypy, food, and varied (food or stereotypy) were compared. In Experiment 2, the conditions were delayed echolalia, food, and varied (food or delayed echolalia), and in Experiment 3, perseverative behavior was compared with stereotypy and food as potential reinforcers. A multielement design was used for all comparisons, and side-effect measures were recorded during and after teaching sessions as well as at home. Results indicated that, in general, task performance was highest when brief opportunities to engage in aberrant behaviors were provided as reinforcers. Edibles were associated with the lowest performance. Furthermore, no negative side effects (e.g., an increase in aberrant behaviors) occurred. The results are discussed in terms of suggesting a more pragmatic treatment approach by addressing the contingent use of autistic children's aberrant behaviors as reinforcers. PMID:2373653

  12. Using aberrant behaviors as reinforcers for autistic children.

    PubMed

    Charlop, M H; Kurtz, P F; Casey, F G

    1990-01-01

    In a series of experiments, we assessed the efficacy of using autistic children's aberrant behaviors as reinforcers to increase their correct task responding. In Experiment 1, reinforcer conditions of stereotypy, food, and varied (food or stereotypy) were compared. In Experiment 2, the conditions were delayed echolalia, food, and varied (food or delayed echolalia), and in Experiment 3, perseverative behavior was compared with stereotypy and food as potential reinforcers. A multielement design was used for all comparisons, and side-effect measures were recorded during and after teaching sessions as well as at home. Results indicated that, in general, task performance was highest when brief opportunities to engage in aberrant behaviors were provided as reinforcers. Edibles were associated with the lowest performance. Furthermore, no negative side effects (e.g., an increase in aberrant behaviors) occurred. The results are discussed in terms of suggesting a more pragmatic treatment approach by addressing the contingent use of autistic children's aberrant behaviors as reinforcers.

  13. Promotion of chondrogenesis of marrow stromal stem cells by TGF-β3 fusion protein in vivo. [corrected].

    PubMed

    Wu, Wei; Dan, Yang; Yang, Shu-hua; Yang, Cao; Shao, Zeng-wu; Xu, Wei-hua; Li, Jin; Liu, Xian-zhe; Zheng, Dong

    2013-10-01

    The purpose of this study was to investigate the repair of the osteoarthritis(OA)-induced cartilage injury by transfecting the new TGF-β3 fusion protein (LAP-MMP-mTGF-β3) with targeted therapy function into the bone marrow-derived mesenchymal stem cells (MSCs) in rats. The recombinant of pIRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector pIRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat embryos by RT-PCR and inserted into the upstream and downstream of MMP from pIRES-EGFP-MMP respectively, so as to construct the recombinant plasmid of pIRES-EGFP-LAP-MMP-mTGF-β3. pIRES-EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cultured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction (ACLT). The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Green and graded by Mankin's scale. pIRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein (39 kD) was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury. PMID:24142722

  14. Diffractively corrected counter-rotating Risley prisms.

    PubMed

    Nie, Xin; Yang, Hongfang; Xue, Changxi

    2015-12-10

    Using the vector refraction equation and the vector diffraction equation, we obtain the expressions of the direction cosines of the refractive rays for the two wedge prisms, and the direction cosines of the diffractive rays for two wedge grisms, in which diffractive gratings were etched into the prism faces to correct the chromatic aberrations. A mathematical model between the two vector equations is proposed to compare the difference angle chromatic aberrations when the Risley prisms/grisms are rotating at different angles. We conclude that the use of diffractively corrected prisms offers a new method to correct chromatic aberrations in Risley prisms. PMID:26836873

  15. Diffractively corrected counter-rotating Risley prisms.

    PubMed

    Nie, Xin; Yang, Hongfang; Xue, Changxi

    2015-12-10

    Using the vector refraction equation and the vector diffraction equation, we obtain the expressions of the direction cosines of the refractive rays for the two wedge prisms, and the direction cosines of the diffractive rays for two wedge grisms, in which diffractive gratings were etched into the prism faces to correct the chromatic aberrations. A mathematical model between the two vector equations is proposed to compare the difference angle chromatic aberrations when the Risley prisms/grisms are rotating at different angles. We conclude that the use of diffractively corrected prisms offers a new method to correct chromatic aberrations in Risley prisms.

  16. Chromosome Aberrations in Astronauts

    NASA Technical Reports Server (NTRS)

    George, Kerry A.; Durante, M.; Cucinotta, Francis A.

    2007-01-01

    A review of currently available data on in vivo induced chromosome damage in the blood lymphocytes of astronauts proves that, after protracted exposure of a few months or more to space radiation, cytogenetic biodosimetry analyses of blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk. Recent studies indicate that biodosimetry estimates from single spaceflights lie within the range expected from physical dosimetry and biophysical models, but very large uncertainties are associated with single individual measurements and the total sample population remains low. Retrospective doses may be more difficult to estimate because of the fairly rapid time-dependent loss of "stable" aberrations in blood lymphocytes. Also, biodosimetry estimates from individuals who participate in multiple missions, or very long (interplanetary) missions, may be complicated by an adaptive response to space radiation and/or changes in lymphocyte survival and repopulation. A discussion of published data is presented and specific issues related to space radiation biodosimetry protocols are discussed.

  17. Treating hemoglobinopathies using gene-correction approaches: promises and challenges.

    PubMed

    Cottle, Renee N; Lee, Ciaran M; Bao, Gang

    2016-09-01

    Hemoglobinopathies are genetic disorders caused by aberrant hemoglobin expression or structure changes, resulting in severe mortality and health disparities worldwide. Sickle cell disease (SCD) and β-thalassemia, the most common forms of hemoglobinopathies, are typically treated using transfusions and pharmacological agents. Allogeneic hematopoietic stem cell transplantation is the only curative therapy, but has limited clinical applicability. Although gene therapy approaches have been proposed based on the insertion and forced expression of wild-type or anti-sickling β-globin variants, safety concerns may impede their clinical application. A novel curative approach is nuclease-based gene correction, which involves the application of precision genome-editing tools to correct the disease-causing mutation. This review describes the development and potential application of gene therapy and precision genome-editing approaches for treating SCD and β-thalassemia. The opportunities and challenges in advancing a curative therapy for hemoglobinopathies are also discussed. PMID:27314256

  18. Image Ellipticity from Atmospheric Aberrations

    SciTech Connect

    de Vries, W H; Olivier, S S; Asztalos, S J; Rosenberg, L J; Baker, K L

    2007-03-06

    We investigate the ellipticity of the point-spread function (PSF) produced by imaging an unresolved source with a telescope, subject to the effects of atmospheric turbulence. It is important to quantify these effects in order to understand the errors in shape measurements of astronomical objects, such as those used to study weak gravitational lensing of field galaxies. The PSF modeling involves either a Fourier transform of the phase information in the pupil plane or a ray-tracing approach, which has the advantage of requiring fewer computations than the Fourier transform. Using a standard method, involving the Gaussian weighted second moments of intensity, we then calculate the ellipticity of the PSF patterns. We find significant ellipticity for the instantaneous patterns (up to more than 10%). Longer exposures, which we approximate by combining multiple (N) images from uncorrelated atmospheric realizations, yield progressively lower ellipticity (as 1/{radical}N). We also verify that the measured ellipticity does not depend on the sampling interval in the pupil plane using the Fourier method. However, we find that the results using the ray-tracing technique do depend on the pupil sampling interval, representing a gradual breakdown of the geometric approximation at high spatial frequencies. Therefore, ray tracing is generally not an accurate method of modeling PSF ellipticity induced by atmospheric turbulence unless some additional procedure is implemented to correctly account for the effects of high spatial frequency aberrations. The Fourier method, however, can be used directly to accurately model PSF ellipticity, which can give insights into errors in the statistics of field galaxy shapes used in studies of weak gravitational lensing.

  19. Phase aberration effects in elastography.

    PubMed

    Varghese, T; Bilgen, M; Ophir, J

    2001-06-01

    In sonography, phase aberration plays a role in the corruption of sonograms. Phase aberration does not have a significant impact on elastography, if statistically similar phase errors are present in both the pre- and postcompression signals. However, if the phase errors are present in only one of the pre- or postcompression signal pairs, the precision of the strain estimation process will be reduced. In some cases, increased phase errors may occur only in the postcompression signal due to changes in the tissue structure with the applied compression. Phase-aberration effects increase with applied strain and may be viewed as an image quality derating factor, much like frequency-dependent attenuation or undesired lateral tissue motion. In this paper, we present a theoretical and simulation study of the effects of phase aberration on the elastographic strain-estimation process, using the strain filter approach.

  20. Adaptive optics full-field OCT: a resolution almost insensitive to aberrations (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xiao, Peng; Fink, Mathias; Boccara, A. Claude

    2016-03-01

    A Full-Field OCT (FFOCT) setup coupled to a compact transmissive liquid crystal spatial light modulator (LCSLM) is used to induce or correct aberrations and simulate eye examinations. To reduce the system complexity, strict pupil conjugation was abandoned. During our work on quantifying the effect of geometrical aberrations on FFOCT images, we found that the image resolution is almost insensitive to aberrations. Indeed if the object channel PSF is distorted, its interference with the reference channel conserves the main feature of an unperturbed PSF with only a reduction of the signal level. This unique behavior is specific to the use of a spatially incoherent illumination. Based on this, the FFOCT image intensity was used as the metric for our wavefront sensorless correction. Aberration correction was first conducted on an USAF resolution target with the LSCLM as both aberration generator and corrector. A random aberration mask was induced, and the low-order Zernike Modes were corrected sequentially according to the intensity metric function optimization. A Ficus leaf and a fixed mouse brain tissue slice were also imaged to demonstrate the correction of sample self-induced wavefront distortions. After optimization, more structured information appears for the leaf imaging. And the high-signal fiber-like myelin fiber structures were resolved much more clearly after the whole correction process for mouse brain imaging. Our experiment shows the potential of this compact AO-FFOCT system for aberration correction imaging. This preliminary approach that simulates eyes aberrations correction also opens the path to a simple implementation of FFOCT adaptive optics for retinal examinations.

  1. Development of optical design algorithms on the base of the exact (all orders) geometrical aberration theory

    NASA Astrophysics Data System (ADS)

    Hristov, Boian A.

    2011-10-01

    The process of optical design today is both an art and a science mainly due to the lack of exact and suitable aberration theory. In this paper we propose an exact (without any approximations) analytical aberration theory. It describes exactly the relations between the on-axis image aberrations and on-axis object aberrations via so called relative parameters, real aperture incidence angles, real aperture slope angles, refraction indexes and object distance. The image field aberrations (distortion, astigmatism, tangential curvature, sagittal curvature and field curvature) are described in a mathematically exact way by means of relative parameters, real incidence angles and slope angles of the chief rays, refraction indexes, object distance and corresponding object aberrations. For the image tangential coma and image sagittal coma we propose differential formulae. To verify the correction of every single aberration we use the commercial program OSLO. The differences between our and OSLO results for each aberration (except for the tangential and sagittal coma) are less than 1x10-8 mm. In addition we propose some exact aberration's correction algorithms for a very distant object and variety of constructive design solutions which confirm the truth of the proposed theory.

  2. DNA Repair Defects and Chromosomal Aberrations

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  3. Correction of defective CFTR/ENaC function and tightness of cystic fibrosis airway epithelium by amniotic mesenchymal stromal (stem) cells.

    PubMed

    Carbone, Annalucia; Castellani, Stefano; Favia, Maria; Diana, Anna; Paracchini, Valentina; Di Gioia, Sante; Seia, Manuela; Casavola, Valeria; Colombo, Carla; Conese, Massimo

    2014-08-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with most of the mortality given by the lung disease. Human amniotic mesenchymal stromal (stem) cells (hAMSCs) hold great promise for regenerative medicine in the field of lung disease; however, their potential as therapeutics for CF lung disease has not been fully explored. In the present study, hAMSCs were analysed in co-cultures on Transwell filters with CF immortalized airway epithelial cells (CFBE41o- line) at different ratios to exploit their potency to resume basic defects associated with CF. The results show that F-actin content was increased in co-cultures as compared with CF cells and actin was reorganized to form stress fibres. Confocal microscopy studies revealed that co-cultures had a tendency of increased expression of occludin and ZO-1 at the intercellular borders, paralleled by a decrease in dextran permeability, suggestive of more organized tight junctions (TJs). Spectrofluorometric analysis of CFTR function demonstrated that hAMSC-CFBE co-cultures resumed chloride transport, in line with the appearance of the mature Band C of CFTR protein by Western blotting. Moreover, hAMSC-CFBE co-cultures, at a 1:5 ratio, showed a decrease in fluid absorption, as opposed to CFBE cell monolayers that displayed a great rate of fluid resorption from the apical side. Our data show that human amniotic MSCs can be used in co-culture with CF respiratory epithelial cells to model their engraftment into the airways and have the potential to resume a tight epithelium with partial correction of the CF phenotype.

  4. Correction of defective CFTR/ENaC function and tightness of cystic fibrosis airway epithelium by amniotic mesenchymal stromal (stem) cells.

    PubMed

    Carbone, Annalucia; Castellani, Stefano; Favia, Maria; Diana, Anna; Paracchini, Valentina; Di Gioia, Sante; Seia, Manuela; Casavola, Valeria; Colombo, Carla; Conese, Massimo

    2014-08-01

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with most of the mortality given by the lung disease. Human amniotic mesenchymal stromal (stem) cells (hAMSCs) hold great promise for regenerative medicine in the field of lung disease; however, their potential as therapeutics for CF lung disease has not been fully explored. In the present study, hAMSCs were analysed in co-cultures on Transwell filters with CF immortalized airway epithelial cells (CFBE41o- line) at different ratios to exploit their potency to resume basic defects associated with CF. The results show that F-actin content was increased in co-cultures as compared with CF cells and actin was reorganized to form stress fibres. Confocal microscopy studies revealed that co-cultures had a tendency of increased expression of occludin and ZO-1 at the intercellular borders, paralleled by a decrease in dextran permeability, suggestive of more organized tight junctions (TJs). Spectrofluorometric analysis of CFTR function demonstrated that hAMSC-CFBE co-cultures resumed chloride transport, in line with the appearance of the mature Band C of CFTR protein by Western blotting. Moreover, hAMSC-CFBE co-cultures, at a 1:5 ratio, showed a decrease in fluid absorption, as opposed to CFBE cell monolayers that displayed a great rate of fluid resorption from the apical side. Our data show that human amniotic MSCs can be used in co-culture with CF respiratory epithelial cells to model their engraftment into the airways and have the potential to resume a tight epithelium with partial correction of the CF phenotype. PMID:24894806

  5. Impact of astigmatism and high-order aberrations on subjective best focus.

    PubMed

    Marcos, Susana; Velasco-Ocana, Miriam; Dorronsoro, Carlos; Sawides, Lucie; Hernandez, Martha; Marin, Gildas

    2015-08-01

    We studied the role of native astigmatism and ocular aberrations on best-focus setting and its shift upon induction of astigmatism in 42 subjects (emmetropes, myopes, hyperopes, with-the-rule [WTR] and against-the-rule [ATR] myopic astigmats). Stimuli were presented in a custom-developed adaptive optics simulator, allowing correction for native aberrations and astigmatism induction (+1 D; 6-mm pupil). Best-focus search consisted on randomized-step interleaved staircase method. Each subject searched best focus for four different images, and four different conditions (with/without aberration correction, with/without astigmatism induction). The presence of aberrations induced a significant shift in subjective best focus (0.4 D; p < 0.01), significantly correlated (p = 0.005) with the best-focus shift predicted from optical simulations. The induction of astigmatism produced a statistically significant shift of the best-focus setting in all groups under natural aberrations (p = 0.001), and in emmetropes and in WTR astigmats under corrected aberrations (p < 0.0001). Best-focus shift upon induced astigmatism was significantly different across groups, both for natural aberrations and AO-correction (p < 0.0001). Best focus shifted in opposite directions in WTR and ATR astigmats upon induction of astigmatism, symmetrically with respect to the best-focus shift in nonastigmatic myopes. The shifts are consistent with a bias towards vertical and horizontal retinal blur in WTR and ATR astigmats, respectively, indicating adaptation to native astigmatism.

  6. Sexual aberration or instinctual vicissitude? Revisiting freud's "the sexual aberrations".

    PubMed

    Phillips, Sidney H

    2014-04-01

    The author reconsiders Freud's "The Sexual Aberrations," the first of his Three Essays on the Theory of Sexuality (1905), in light of contemporary psychoanalytic theory. Are the concepts of sexual aberration and norm still viable? The author argues that they are necessary but insufficient elements in current theory. He then presents a competing model in which sexuality can be reduced to a more elemental level of disturbance and wish, where it is an expression of a nonsexual wish--for example, to possess or control the object to eliminate separateness. The author presents clinical material to demonstrate this alternative model. PMID:24777366

  7. Eye aberration analysis with Zernike polynomials

    NASA Astrophysics Data System (ADS)

    Molebny, Vasyl V.; Chyzh, Igor H.; Sokurenko, Vyacheslav M.; Pallikaris, Ioannis G.; Naoumidis, Leonidas P.

    1998-06-01

    New horizons for accurate photorefractive sight correction, afforded by novel flying spot technologies, require adequate measurements of photorefractive properties of an eye. Proposed techniques of eye refraction mapping present results of measurements for finite number of points of eye aperture, requiring to approximate these data by 3D surface. A technique of wave front approximation with Zernike polynomials is described, using optimization of the number of polynomial coefficients. Criterion of optimization is the nearest proximity of the resulted continuous surface to the values calculated for given discrete points. Methodology includes statistical evaluation of minimal root mean square deviation (RMSD) of transverse aberrations, in particular, varying consecutively the values of maximal coefficient indices of Zernike polynomials, recalculating the coefficients, and computing the value of RMSD. Optimization is finished at minimal value of RMSD. Formulas are given for computing ametropia, size of the spot of light on retina, caused by spherical aberration, coma, and astigmatism. Results are illustrated by experimental data, that could be of interest for other applications, where detailed evaluation of eye parameters is needed.

  8. Intracavity adaptive correction of a 10 kW, solid-state, heat-capacity laser.

    SciTech Connect

    LaFortune, K N; Hurd, R L; Johansson, E M; Dane, C B; Fochs, S N; Brase, J M

    2004-01-12

    The Solid-State, Heat-Capacity Laser (SSHCL), under development at Lawrence Livermore National Laboratory is a large aperture (100 cm{sup 2}), confocal, unstable resonator requiring near-diffraction-limited beam quality. There are two primary sources of the aberrations in the system: residual, static aberrations from the fabrication of the optical components and predictable, time-dependent, thermally-induced index gradients within the gain medium. A deformable mirror placed within the cavity is used to correct the aberrations that are sensed externally with a Shack-Hartmann wavefront sensor. Although it is more challenging than external correction, intracavity correction enables control of the mode growth within the resonator, resulting in the ability to correct a more aberrated system longer. The overall system design, measurement techniques and correction algorithms are discussed. Experimental results from initial correction of the static aberrations and dynamic correction of the time-dependent aberrations are presented.

  9. Intracavity adaptive correction of a 10 kW, solid-state, heat-capacity laser

    SciTech Connect

    LaFortune, K N; Hurd, R L; Brase, J M; Yamamoto, R M

    2004-05-13

    The Solid-State, Heat-Capacity Laser (SSHCL), under development at Lawrence Livermore National Laboratory (LLNL) is a large aperture (100 cm{sup 2}), confocal, unstable resonator requiring near-diffraction-limited beam quality. There are two primary sources of the aberrations in the system: residual, static aberrations from the fabrication of the optical components and predictable, time-dependent, thermally-induced index gradients within the gain medium. A deformable mirror placed within the cavity is used to correct the aberrations that are sensed externally with a Shack-Hartmann wavefront sensor. Although the complexity of intracavity adaptive correction is greater than that of external correction, it enables control of the mode growth within the resonator, resulting in the ability to correct a more aberrated system longer. The overall system design, measurement techniques and correction algorithms are discussed. Experimental results from initial correction of the static aberrations and dynamic correction of the time-dependent aberrations are presented.

  10. Overcoming Polarization Aberrations In Microscopy

    NASA Astrophysics Data System (ADS)

    Hansen, Eric W.

    1988-06-01

    A long-standing problem in polarized light microscopy has been the inability, due to polarization aberrations, to achieve simultaneously high spatial resolution and high contrast. The rotation of the plane of polarization at oblique interfaces between crossed polars causes the pupil function to resemble a dark cross rather than being uniformly dark. Likewise, the point spread function has the visual appearance of a four-leaf clover rather than the ideal Airy disk, and is also space-variant. Images formed with these systems are severely degraded. In this paper the theory of polarization aberrations is applied to the analysis of three solutions to this problem: Reducing the system aperture to block troublesome high-aperture rays; the AVEC-POL method, in which high bias compensation introduces counterbalancing aberrations; and the polarization rectifier, an optical element designed to introduce equal and opposite rotations of the electric vector.

  11. Aberrant DNA Methylation in Keratoacanthoma

    PubMed Central

    Nakagawa, Hidemi

    2016-01-01

    Background Keratoacanthoma (KA) is a self-limiting epidermal tumor for which histopathological examination sometimes suggests malignancy. Based on inconsistent clinical views, KA can be regarded as both a benign tumor and a variant of squamous cell carcinoma (SCC). Aberrant DNA methylation frequently occurs in malignant tumors but it scarcely occurs in benign tumors. Whether aberrant methylation occurs in KA has not been previously examined. Objective The aim is to elucidate whether aberrant methylation of CpG islands (CGI) containing a high density of cytosine-guanine dinucleotide (CpG) sites occurs in KA. Methods Five SCC cell lines, two cultured samples of normal human epidermal keratinocytes (NHEKs), 18 clinical SCC samples, and 21 clinical KA samples were analyzed with Infinium HumanMethylation450 BeadChips, quantitative real-time methylation-specific PCR (RT-MSP) and/or bisulfite sequencing. Results Genome-wide analyses of NHEK, KA, and SCC indicated that there was a greater number of aberrantly hypermethylated CGIs in SCC than in KA and there were aberrantly hypermethylated CGIs which are common in both. Among the common hypermethylated CGIs, RT-MSP and bisulfite sequencing targeting CGIs located on CCDC17, PVR, and MAP3K11 gene bodies also showed that methylation levels were significantly higher in KA than in normal epidermis. Statistical analyses suggested that the methylation level of CGI located on PVR in SCC might be correlated to lymph node metastasis (P = 0.013, Mann-Whitney U test) and that the methylation level of CGI in MAP3K11 in KA might be correlated to age (P = 0.031, linear regression analysis). Conclusion Aberrant DNA methylation occurs in KA. PMID:27788211

  12. How To Measure Gravitational Aberration?

    NASA Astrophysics Data System (ADS)

    Krizek, M.; Solcova, A.

    2007-08-01

    In 1905, Henri Poincaré predicted the existence of gravitational waves and assumed that their speed c[g] would be that of the speed of light c. If the gravitational aberration would also have the same magnitude as the aberration of light, we would observe several paradoxical phenomena. For instance, the orbit of two bodies of equal mass would be unstable, since two attractive forces arise that are not in line and hence form a couple. This tends to increase the angular momentum, period, and total energy of the system. This can be modelled by a system of ordinary differential equations with delay. A big advantage of computer simulation is that we can easily perform many test for various possible values of the speed of gravity [1]. In [2], Carlip showed that gravitational aberration in general relativity is almost cancelled out by velocity-dependent interactions. This means that rays of sunlight are not parallel to the attractive gravitational force of the Sun, i.e., we do not see the Sun in the direction of its attractive force, but slightly shifted about an angle less than 20``. We show how the actual value of the gravitational aberration can be obtained by measurement of a single angle at a suitable time instant T corresponding to the perihelion of an elliptic orbit. We also derive an a priori error estimate that expresses how acurately T has to be determined to attain the gravitational aberration to a prescribed tolerance. [1] M. Křížek: Numerical experience with the finite speed of gravitational interaction, Math. Comput. Simulation 50 (1999), 237-245. [2] S. Carlip: Aberration and the speed of gravity, Phys. Lett. A 267 (2000), 81-87.

  13. Chromosome Aberrations by Heavy Ions

    NASA Astrophysics Data System (ADS)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  14. Color correction strategies in optical design

    NASA Astrophysics Data System (ADS)

    Pfisterer, Richard N.; Vorndran, Shelby D.

    2014-12-01

    An overview of color correction strategies is presented. Starting with basic first-order aberration theory, we identify known color corrected solutions for doublets and triplets. Reviewing the modern approaches of Robb-Mercado, Rayces-Aguilar, and C. de Albuquerque et al, we find that they confirm the existence of glass combinations for doublets and triplets that yield color corrected solutions that we already know exist. Finally we explore the use of the y, ӯ diagram in conjunction with aberration theory to identify the solution space of glasses capable of leading to color corrected solutions in arbitrary optical systems.

  15. Eigenfunction analysis of stochastic backscatter for characterization of acoustic aberration in medical ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Varslot, Trond; Krogstad, Harald; Mo, Eirik; Angelsen, Bjørn A.

    2004-06-01

    Presented here is a characterization of aberration in medical ultrasound imaging. The characterization is optimal in the sense of maximizing the expected energy in a modified beamformer output of the received acoustic backscatter. Aberration correction based on this characterization takes the form of an aberration correction filter. The situation considered is frequently found in applications when imaging organs through a body wall: aberration is introduced in a layer close to the transducer, and acoustic backscatter from a scattering region behind the body wall is measured at the transducer surface. The scattering region consists of scatterers randomly distributed with very short correlation length compared to the acoustic wavelength of the transmit pulse. The scatterer distribution is therefore assumed to be δ correlated. This paper shows how maximizing the expected energy in a modified beamformer output signal naturally leads to eigenfunctions of a Fredholm integral operator, where the associated kernel function is a spatial correlation function of the received stochastic signal. Aberration characterization and aberration correction are presented for simulated data constructed to mimic aberration introduced by the abdominal wall. The results compare well with what is obtainable using data from a simulated point source.

  16. A discussion of two wavefront aberration correction procedures.

    PubMed

    Steinberg, B D

    1992-10-01

    This review paper discusses the basic properties of two adaptive signal processing procedures for dealing with weak scattering in a phased array transducer system. A fundamental improvement in the lateral resolution of ultrasonic echo scanners will result if the weight vector of a large phased array transducer can be modified to account for distortion in the propagation medium. Lateral resolution in most tissue is limited to a few mm by wavefront-distortion-induced sound-speed variations. One important wavefront-distortion source is scattering from local speed variations within large and reasonably homogeneous tissue beds such as the liver. Scattering disperses some energy from the beam and perturbs the wavefront, thereby distorting the image and limiting the resolution to the scale of the distortion. Often, such scattering is weak, meaning that most of the energy in the beam is unscattered. The total field at the receiving transducer is the vector sum of the unscattered and scattered fields. In weak scattering the unscattered field is dominant and the resultant field can be treated as the unscattered field plus a perturbation. The net effect is primarily a distorted phasefront, while the amplitude or modulus of the wavefront remains reasonably intact. Refraction and strong scattering effect the wavefront more severely and are less responsive to these algorithms.

  17. Tomographic diffractive microscopy and multiview profilometry with flexible aberration correction.

    PubMed

    Liu, H; Bailleul, J; Simon, B; Debailleul, M; Colicchio, B; Haeberlé, O

    2014-02-01

    We have developed a tomographic diffractive microscope in reflection, which permits observation of sample surfaces with an improved lateral resolution, compared to a conventional holographic microscope. From the same set of data, high-precision measurements can be performed on the shape of the reflective surface by reconstructing the phase of the diffracted field. Doing so allows for several advantages compared to classical holographic interferometric measurements: improvement in lateral resolution, easier phase unwrapping, reduction of the coherent noise, combined with the high-longitudinal precision provided by interferometric phase measurements. We demonstrate these capabilities by imaging various test samples. PMID:24514193

  18. Chromosome aberrations in workers exposed to arsenic.

    PubMed

    Beckman, G; Beckman, L; Nordenson, I

    1977-08-01

    The occurrence of chromosome aberrations was studied in short-term cultured lymphocytes from nine workers exposed to arsenic at the Rönnskär smeltery in northern Sweden. In the smelter workers, 87 aberrations were found in 819 mitoses. The number of aberrations varied individually from 0 to 25 aberrations per 100 cells. In a control material 13 aberrations were found in 1012 mitoses. The frequency of chromosome aberrations was significantly increased among the smelter workers, but due to the simultaneous exposure to other agents the effect of arsenic per se can not be assessed with certainty.

  19. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design. PMID:27557003

  20. Clinical importance of spherical and chromatic aberration on the accommodative response in contact lens wear

    NASA Astrophysics Data System (ADS)

    Wahlberg, M.; Lindskoog Pettersson, A.; Rosén, R.; Nilsson, M.; Unsbo, P.; Brautaset, R.

    2011-11-01

    The aim of this study was to evaluate the accommodation response under both mono- and polychromatic light while varying the amount of spherical aberration. It is thought that chromatic and spherical aberrations are directional cues for the accommodative system and could affect response time, velocity or lag. Spherical aberration is often eliminated in modern contact lenses in order to enhance image quality in the unaccommodated eye. This study was divided into two parts. The first part was done to evaluate the amount of spherical and other Zernike aberrations in the unaccommodated eye when uncorrected and with two types of correction (trial lens and spherical-aberration controlled contact lens) and the second part evaluated the dynamic accommodation responses obtained when wearing each of the corrections under polychromatic and monochromatic conditions. Measurements of accommodation showed no significant differences in time, velocity and lag of accommodation after decreasing the spherical aberration with a contact lens, neither in monochromatic nor polychromatic light. It is unlikely that small to normal changes of spherical aberration in white light or monochromatic mid-spectral light affect directional cues for the accommodative system, not in white light or mid-spectral monochromatic light, since the accommodative response did not show any change.

  1. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  2. Phase Aberrations in Diffraction Microscopy

    SciTech Connect

    Marchesini, S; Chapman, H N; Barty, A; Howells, M R; Spence, J H; Cui, C; Weierstall, U; Minor, A M

    2005-09-29

    In coherent X-ray diffraction microscopy the diffraction pattern generated by a sample illuminated with coherent x-rays is recorded, and a computer algorithm recovers the unmeasured phases to synthesize an image. By avoiding the use of a lens the resolution is limited, in principle, only by the largest scattering angles recorded. However, the imaging task is shifted from the experiment to the computer, and the algorithm's ability to recover meaningful images in the presence of noise and limited prior knowledge may produce aberrations in the reconstructed image. We analyze the low order aberrations produced by our phase retrieval algorithms. We present two methods to improve the accuracy and stability of reconstructions.

  3. The Effect of Optical Aberrations on Laser-Induced Gas Breakdown.

    NASA Astrophysics Data System (ADS)

    Ryan, Daniel Joseph

    Over the past twenty years, much work has gone into developing a theoretical model for laser-induced gas breakdown. Out of all this work evolved the theories of multiphoton absorption and inverse Bremsstrahlung absorption. These two theories together provide a reasonable explanation of the processes of laser-induced gas breakdown. There are, however, many experimental results which are not in agreement with the theoretical results. One of the reasons for this is that aberrations in the focusing optics have, for the most part, been ignored in the studies of gas breakdown. The work presented in this dissertation examines the effects of aberrations on the imaging quality of lenses and on the energy distribution at the focal plane. Experimental results are shown comparing gas breakdown threshold for near diffraction limited lenses and for lenses having many wavelengths of aberrations. The results of the calculations on imaging performance and breakdown thresholds are then used to generate the aberration calibration curve. The calibration curve is a plot of the relationship between the number of wavelengths of aberrations and the percent of the total energy entering the aperture of the lens which is actually within the diffraction limited spot. Knowing the aberration characteristics of a lens, a corrected breakdown threshold intensity can be determined. A breakdown model which includes the effects of aberrations employs the aberration calibration curve to determine the intensity, assumes a diffraction limited spot size, and models the focal volume as an oblate spheroid. Presently accepted solutions to the continuity equation are then adaptable to include the effects of aberrations using these definitions of intensity, spot size and focal volume. The experimental results indicate the effectiveness of the aberration calibration curve in accounting for the contribution of aberrations in gas breakdown. The curve was successfully applied to previously published results

  4. Membrane-based deformable mirror: intrinsic aberrations and alignment issues

    NASA Astrophysics Data System (ADS)

    Raja Bayanna, A.; Louis, Rohan E.; Chatterjee, S.; Mathew, Shibu K.; Venkatakrishnan, P.

    2015-03-01

    A Deformable Mirror (DM) is an important component of an Adaptive Optics system. It is known that an on-axis spherical/parabolic optical component, placed at an angle to the incident beam introduces defocus as well as astigmatism in the image plane. Although the former can be compensated by changing the focal plane position, the latter cannot be removed by mere optical re-alignment. Since the DM is to be used to compensate a turbulence-induced curvature term in addition to other aberrations, it is necessary to determine the aberrations induced by such (curved DM surface) an optical element when placed at an angle (other than 0 degree) of incidence in the optical path. To this effect, we estimate to a first order, the aberrations introduced by a DM as a function of the incidence angle and deformation of the DM surface. We record images using a simple setup in which the incident beam is reflected by a 37 channel Micro-machined Membrane Deformable Mirror for various angles of incidence. It is observed that astigmatism is a dominant aberration which was determined by measuring the difference between the tangential and sagital focal planes. We justify our results on the basis of theoretical simulations and discuss the feasibility of using such a system for adaptive optics considering a trade-off between wavefront correction and astigmatism due to deformation.

  5. Wide-field aberration corrector for spherical gossamer primary mirrors

    NASA Astrophysics Data System (ADS)

    Beach, David A.

    2000-10-01

    If gossamer primary mirrors were to be constructed in a spherical form, it would be possible to arrange a simple null- test in situ. However, spherical mirrors would require correction of the large amount of spherical aberration created in pupils that generally will be greater than 2 m diameter. The design requirement is for diffraction-limited performance over a useful angular field. The otherwise excellent wide- field design solutions of the classical Schmidt and Maksutov are inapplicable in gossamer structures because of the mass and size penalty of large refractive components. However, it is possible for this mode of correction to be achieved near the prime focus by means of pupil transfer optics that minify the large entrance pupil down to more acceptable dimensions. A problem with these solutions is constraint of field coverage due to pupil aberrations created by the large spherical aberration of the primary mirror. This leads the designer towards slower primaries and the penalty of larger, heavier structures. A solution is presented here for spherical primaries with speeds up to f/4. This is based on the 'KiwiStar' principle presented here in 1997, in which a large spherical catoptric is combined by pupil-transfer with a smaller spherical catadioptric to give well corrected wide field images of high speed. This system is well suited to correction at the prime focus of large spherical mirrors, and has only one relatively small weak aspheric surface to provide zonal correction, all other surfaces being spherical. An example is presented of a 4 m diameter, f/2.5 system that is diffraction-limited over the whole of a 0.25 degree field (43 mm diameter), for a bandpass of 486 - 850 nm.

  6. Relations between Neurological Aberrations and Psychological Dysfunctions in Children with Serious Language Problems.

    ERIC Educational Resources Information Center

    Bo, Ola O.; And Others

    1992-01-01

    Relationships between neuropsychological aberrations and psychological dysfunction were studied for 20 Swedish children (average age around 10 years at first testing) with serious language problems through (1) electroencephalography; (2) brain stem response audiometry; (3) magnetic resonance imaging; and (4) brain electric activity mapping by…

  7. Political Correctness--Correct?

    ERIC Educational Resources Information Center

    Boase, Paul H.

    1993-01-01

    Examines the phenomenon of political correctness, its roots and objectives, and its successes and failures in coping with the conflicts and clashes of multicultural campuses. Argues that speech codes indicate failure in academia's primary mission to civilize and educate through talk, discussion, thought,166 and persuasion. (SR)

  8. Chromosome aberrations induced by zebularine in triticale.

    PubMed

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation. PMID:27334255

  9. STEM, STEM Education, STEMmania

    ERIC Educational Resources Information Center

    Sanders, Mark

    2009-01-01

    In this article, the author introduces integrative STEM (science, technology, engineering, and/or mathematics) education and discusses the importance of the program. The notion of integrative STEM education includes approaches that explore teaching and learning between/among any two or more of the STEM subject areas, and/or between a STEM subject…

  10. The misalignment induced aberrations of TMA telescopes.

    PubMed

    Thompson, Kevin P; Schmid, Tobias; Rolland, Jannick P

    2008-12-01

    The next major space-borne observatory, the James Webb Space Telescope, will be a 6.6M field-biased, obscured, three-mirror anastigmat (TMA). Over the used field of view, the performance of TMA telescopes is dominated by 3(rd) order misalignment aberrations. Here it is shown that two dominant 3(rd) order misalignment aberrations arise for any TMA telescope. One aberration, field constant 3(rd) order coma is a well known misalignment aberration commonly seen in two-mirror Ritchey Chretien telescopes. The second aberration, field-asymmetric, field-linear, 3(rd) order astigmatism is a new and unique image orientation dependence with field derived here for the first time using nodal aberration theory.

  11. Aberrations of ellipsoidal reflectors for unit magnification.

    PubMed

    Mielenz, K D

    1974-12-01

    Ellipsoidal reflectors are useful for the 1:1 imaging of small objects without spherical and chromatic aberration. The magnitude of the off-axis aberrations of such reflectors is computed by application of Fermat's principle to the Hamiltonian point characteristic. The limiting form of the mirror aperture for which these aberrations do not exceed a set tolerance is an ellipse whose semiaxes depend on object size and angle of incidence. PMID:20134811

  12. Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease

    SciTech Connect

    Kleinerman, R.A.; Boice, J.D. Jr.; Inskip, P.D.; Tarone, R.E.; Littlefield, L.G.; Sayer, A.M.; Cookfair, D.L.; Wactawski-Wende, J.

    1994-07-01

    Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow. High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received. 30 refs., 4 tabs.

  13. Depth aberrations characterization in linear and nonlinear microscopy schemes using a Shack-Hartmann wavefront sensor

    NASA Astrophysics Data System (ADS)

    Aviles-Espinosa, Rodrigo; Andilla, Jordi; Porcar-Guezenec, Rafael; Levecq, Xavier; Artigas, David; Loza-Alvarez, Pablo

    2012-03-01

    The performance of imaging devices such as linear and nonlinear microscopes (NLM) can be limited by the optical properties of the imaged sample. Such an important aspect has already been described using theoretical models due to the difficulties of implementing a direct wavefront sensing scheme. However, these only stand for simple interfaces and cannot be generalized to biological samples given its structural complexity. This has leaded to the development of sensor-less adaptive optics (AO) implementations. In this approach, aberrations are iteratively corrected trough an image related parameter (aberrations are not measured), being prone of causing sample damage. In this work, we perform a practical implementation of a Shack-Hartman wavefront sensor to compensate for sample induced aberrations, demonstrating its applicability in linear and NLM. We perform an extensive analysis of wavefront distortion effects through different depths employing phantom samples. Aberration effects originated by the refractive index mismatch and depth are quantified using the linear and nonlinear guide-star concept. More over we analyze offaxis aberrations in NLM, an important aspect that is commonly overlooked. In this case spherical aberration behaves similarly to the wavefront error compared with the on-axis case. Finally we give examples of aberration compensation using epi-fluorescence and nonlinear microscopy.

  14. Influence of aberrations in microholographic recording

    NASA Astrophysics Data System (ADS)

    Katayama, Ryuichi

    2015-11-01

    The influence of various types of aberrations (spherical, coma, and astigmatic) of recording and readout beams on the readout signal in a microholographic recording was investigated through a numerical simulation. The simulation conditions were that the wavelength of the laser was 405 nm and the numerical aperture of the objective lenses was 0.85. The tolerance of the root-mean-square (RMS) wavefront aberrations was defined as the aberration when the normalized signal level decreased to 0.8. Among the three types of aberrations, the influence of the spherical aberration was the most significant. When both the recording and readout beams were aberrated and the signs of the aberrations were in the worst case, the tolerance of the RMS wavefront aberrations was less than half of the Maréchal's criterion. Moreover, when the RMS wavefront aberrations of the recording and readout beams were within the above tolerance, the bit intervals of 0.13 and 0.65 μm in the inplane and vertical directions, respectively, which correspond to the recording density of 91 bit/μm3 (recording capacity of 16 TB for a 120-mm-diameter optical disk having a 300-μm-thick recording layer), were shown to be feasible for confocal detection with an allowable signal-to-noise ratio.

  15. RARγ is required for correct deposition and removal of Suz12 and H2A.Z in embryonic stem cells

    PubMed Central

    Amat, Ramon; Gudas, Lorraine J.

    2012-01-01

    Retinoic acid (RA) induces embryonic stem cell differentiation. The effects of RA are mediated by retinoic acid receptors (RARs) that promote epigenetic changes controlling gene transcription. We show here that RARγ, in the absence of the ligand RA, is required for deposition of the histone variant H2A.Z and the Polycomb protein Suz12 at RA target genes, and that both RARγ and Suz12 exist in a multi-protein complex in the absence of ligand. Addition of RA causes removal of H2A.Z and Suz12 from RARγ target genes when the genes are transcriptionally activated. PMID:20857416

  16. Aberrations of varied line-space grazing incidence gratings in converging light beams

    NASA Technical Reports Server (NTRS)

    Hettrick, M. C.

    1984-01-01

    Analyses of the imaging properties of several designs for varied-line space gratings in converging beams of light in grazing-incidence spectrometers are presented. An explicit model is defined for the case of a plane-reflection grating intercepting light that converges and is reflected to a stigmatic point associated with the zero-order image of the grating. Smooth spatial variation of the grating constant then permits aberration correction. The aberrations are expressed as polynomials in the grating lens coordinates using power series expansions. Application of the model is illustrated in terms of aberrations experienced with the short wavelength spectrometer on the EUVE satellite. Attention is given to straight and parallel in-plane grooves, curved groove in-plane designs and off-plane grooves. Aberrations due to dispersions and misalignment are also considered.

  17. The New Self-Inactivating Lentiviral Vector for Thalassemia Gene Therapy Combining Two HPFH Activating Elements Corrects Human Thalassemic Hematopoietic Stem Cells

    PubMed Central

    Papanikolaou, Eleni; Georgomanoli, Maria; Stamateris, Evangelos; Panetsos, Fottes; Karagiorga, Markisia; Tsaftaridis, Panagiotis; Graphakos, Stelios

    2012-01-01

    Abstract To address how low titer, variable expression, and gene silencing affect gene therapy vectors for hemoglobinopathies, in a previous study we successfully used the HPFH (hereditary persistence of fetal hemoglobin)-2 enhancer in a series of oncoretroviral vectors. On the basis of these data, we generated a novel insulated self-inactivating (SIN) lentiviral vector, termed GGHI, carrying the Aγ-globin gene with the −117 HPFH point mutation and the HPFH-2 enhancer and exhibiting a pancellular pattern of Aγ-globin gene expression in MEL-585 clones. To assess the eventual clinical feasibility of this vector, GGHI was tested on CD34+ hematopoietic stem cells from nonmobilized peripheral blood or bone marrow from 20 patients with β-thalassemia. Our results show that GGHI increased the production of γ-globin by 32.9% as measured by high-performance liquid chromatography (p=0.001), with a mean vector copy number per cell of 1.1 and a mean transduction efficiency of 40.3%. Transduced populations also exhibited a lower rate of apoptosis and resulted in improvement of erythropoiesis with a higher percentage of orthochromatic erythroblasts. This is the first report of a locus control region (LCR)-free SIN insulated lentiviral vector that can be used to efficiently produce the anticipated therapeutic levels of γ-globin protein in the erythroid progeny of primary human thalassemic hematopoietic stem cells in vitro. PMID:21875313

  18. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  19. Meningoencephalitis in two stranded California sea lions (Zalophus californianus) caused by aberrant trematode migration.

    PubMed

    Fauquier, Deborah; Gulland, Frances; Haulena, Martin; Dailey, Murray; Rietcheck, Randall L; Lipscomb, Thomas P

    2004-10-01

    Meningoencephalitis caused by aberrant trematode migration is described in two California sea lions (Zalophus californianus) admitted to a rehabilitation hospital between May and August 2001. Both animals displayed seizure activity and were euthanized due to poor response to therapy. Gross abnormal findings included liver flukes (Zalophotrema hepaticum) in the bile ducts and areas of swelling and necrosis in the cerebrum, cerebellum, and brain stem. Histopathology revealed meningoencephalitis with necrosis, hemorrhage, and many trematode eggs within the brain. In one sea lion, an adult trematode was found on the surface of the cerebrum. These are believed to be the first reported cases of meningoencephalitis caused by aberrant trematode migration in pinnipeds. PMID:15650108

  20. Assessing climate change impacts on the rape stem weevil, Ceutorhynchus napi Gyll., based on bias- and non-bias-corrected regional climate change projections.

    PubMed

    Junk, J; Ulber, B; Vidal, S; Eickermann, M

    2015-11-01

    Agricultural production is directly affected by projected increases in air temperature and changes in precipitation. A multi-model ensemble of regional climate change projections indicated shifts towards higher air temperatures and changing precipitation patterns during the summer and winter seasons up to the year 2100 for the region of Goettingen (Lower Saxony, Germany). A second major controlling factor of the agricultural production is the infestation level by pests. Based on long-term field surveys and meteorological observations, a calibration of an existing model describing the migration of the pest insect Ceutorhynchus napi was possible. To assess the impacts of climate on pests under projected changing environmental conditions, we combined the results of regional climate models with the phenological model to describe the crop invasion of this species. In order to reduce systematic differences between the output of the regional climate models and observational data sets, two different bias correction methods were applied: a linear correction for air temperature and a quantile mapping approach for precipitation. Only the results derived from the bias-corrected output of the regional climate models showed satisfying results. An earlier onset, as well as a prolongation of the possible time window for the immigration of Ceutorhynchus napi, was projected by the majority of the ensemble members.

  1. Assessing climate change impacts on the rape stem weevil, Ceutorhynchus napi Gyll., based on bias- and non-bias-corrected regional climate change projections

    NASA Astrophysics Data System (ADS)

    Junk, J.; Ulber, B.; Vidal, S.; Eickermann, M.

    2015-11-01

    Agricultural production is directly affected by projected increases in air temperature and changes in precipitation. A multi-model ensemble of regional climate change projections indicated shifts towards higher air temperatures and changing precipitation patterns during the summer and winter seasons up to the year 2100 for the region of Goettingen (Lower Saxony, Germany). A second major controlling factor of the agricultural production is the infestation level by pests. Based on long-term field surveys and meteorological observations, a calibration of an existing model describing the migration of the pest insect Ceutorhynchus napi was possible. To assess the impacts of climate on pests under projected changing environmental conditions, we combined the results of regional climate models with the phenological model to describe the crop invasion of this species. In order to reduce systematic differences between the output of the regional climate models and observational data sets, two different bias correction methods were applied: a linear correction for air temperature and a quantile mapping approach for precipitation. Only the results derived from the bias-corrected output of the regional climate models showed satisfying results. An earlier onset, as well as a prolongation of the possible time window for the immigration of Ceutorhynchus napi, was projected by the majority of the ensemble members.

  2. Holographic correction of large telescope primaries by proximal, off-axis beacons.

    PubMed

    Andersen, G; Munch, J; Veitch, P

    1996-02-01

    Compact telescope configurations incorporating a holographic correction of large, low-quality primary collectors are demonstrated. Aberration correction is demonstrated with an off-axis laser beacon located close to the primary. This arrangement results in a compact telescope with minimum obscuration. The reduction of additional off-axis aberrations introduced by the method is also demonstrated.

  3. On the visibility of "heavy" atoms in dark-field STEM

    NASA Astrophysics Data System (ADS)

    Shannon, M. D.; Nellist, P. D.; Nicolosi, V.; Shannon, G. B.; Shmeliov, A.

    2012-07-01

    One of the most useful and apparently straightforward attributes of annular dark-field (ADF) STEM imaging is the ability to image heavy atoms on relatively light substrates using Z-contrast (High-Angle ADF) imaging. From multislice calculations, however, some isolated heavy atoms, e.g. Re, can go undetected in a thin Co matrix in standard aberration-corrected HAADF-STEM imaging of catalyst nanoparticles oriented accurately on a zone-axis [2]. More recently simultaneous Medium-Angle and High-Angle ADF imaging of a few layers of BN has shown experimentally that some adatoms are invisible in MAADF whilst exhibiting very strong contrast in HAADF. Simulations confirm that this can occur for atoms such as sodium. In both situations HOLZ ring imaging can be used to extract additional information.

  4. Psychometric Characteristics of the Aberrant Behavior Checklist.

    ERIC Educational Resources Information Center

    Aman, Michael G.; And Others

    1985-01-01

    Information is presented on the psychometric characteristics of the Aberrant Behavior Checklist, a measure of psychotropic drug effects. Internal consistency and test-retest reliability of the checklist appeared very good. Interrater reliability was generally in the moderate range. In general, validity was established for most Aberrant Behavior…

  5. Harmonic oscillator states in aberration optics

    NASA Technical Reports Server (NTRS)

    Wolf, Kurt Bernardo

    1993-01-01

    The states of the three-dimensional quantum harmonic oscillator classify optical aberrations of axis-symmetric systems due to the isomorphism between the two mathematical structures. Cartesian quanta and angular momentum classifications have their corresponding aberration classifications. The operation of concatenation of optical elements introduces a new operation between harmonic oscillator states.

  6. Aberrant Radial Artery Causing Carpal Tunnel Syndrome

    PubMed Central

    Kokkalis, Zinon T.; Tolis, Konstantinos E.; Megaloikonomos, Panayiotis D.; Panagopoulos, Georgios N.; Igoumenou, Vasilios G.; Mavrogenis, Andreas F.

    2016-01-01

    Anatomical vascular variations are rare causes of carpal tunnel syndrome. An aberrant medial artery is the most common vascular variation, while an aberrant radial artery causing carpal tunnel syndrome is even more rare, with an incidence ranging less than 3%. This article reports a patient with compression of the median nerve at the carpal tunnel by an aberrant superficial branch of the radial artery. An 80- year- old man presented with a 5-year history of right hand carpal tunnel syndrome; Tinel sign, Phalen test and neurophysiological studies were positive. Open carpal tunnel release showed an aberrant superficial branch of the radial artery with its accompanying veins running from radially to medially, almost parallel to the median nerve, ending at the superficial palmar arterial arch. The median nerve was decompressed without ligating the aberrant artery. At the last follow-up, 2 years after diagnosis and treatment the patient is asymptomatic. PMID:27517078

  7. Aberrant Radial Artery Causing Carpal Tunnel Syndrome.

    PubMed

    Kokkalis, Zinon T; Tolis, Konstantinos E; Megaloikonomos, Panayiotis D; Panagopoulos, Georgios N; Igoumenou, Vasilios G; Mavrogenis, Andreas F

    2016-06-01

    Anatomical vascular variations are rare causes of carpal tunnel syndrome. An aberrant medial artery is the most common vascular variation, while an aberrant radial artery causing carpal tunnel syndrome is even more rare, with an incidence ranging less than 3%. This article reports a patient with compression of the median nerve at the carpal tunnel by an aberrant superficial branch of the radial artery. An 80- year- old man presented with a 5-year history of right hand carpal tunnel syndrome; Tinel sign, Phalen test and neurophysiological studies were positive. Open carpal tunnel release showed an aberrant superficial branch of the radial artery with its accompanying veins running from radially to medially, almost parallel to the median nerve, ending at the superficial palmar arterial arch. The median nerve was decompressed without ligating the aberrant artery. At the last follow-up, 2 years after diagnosis and treatment the patient is asymptomatic.

  8. Aberrant Radial Artery Causing Carpal Tunnel Syndrome.

    PubMed

    Kokkalis, Zinon T; Tolis, Konstantinos E; Megaloikonomos, Panayiotis D; Panagopoulos, Georgios N; Igoumenou, Vasilios G; Mavrogenis, Andreas F

    2016-06-01

    Anatomical vascular variations are rare causes of carpal tunnel syndrome. An aberrant medial artery is the most common vascular variation, while an aberrant radial artery causing carpal tunnel syndrome is even more rare, with an incidence ranging less than 3%. This article reports a patient with compression of the median nerve at the carpal tunnel by an aberrant superficial branch of the radial artery. An 80- year- old man presented with a 5-year history of right hand carpal tunnel syndrome; Tinel sign, Phalen test and neurophysiological studies were positive. Open carpal tunnel release showed an aberrant superficial branch of the radial artery with its accompanying veins running from radially to medially, almost parallel to the median nerve, ending at the superficial palmar arterial arch. The median nerve was decompressed without ligating the aberrant artery. At the last follow-up, 2 years after diagnosis and treatment the patient is asymptomatic. PMID:27517078

  9. The BHVI-EyeMapper: Peripheral Refraction and Aberration Profiles

    PubMed Central

    Fedtke, Cathleen; Ehrmann, Klaus; Falk, Darrin; Bakaraju, Ravi C.; Holden, Brien A.

    2014-01-01

    ABSTRACT Purpose The aim of this article was to present the optical design of a new instrument (BHVI-EyeMapper, EM), which is dedicated to rapid peripheral wavefront measurements across the visual field for distance and near, and to compare the peripheral refraction and higher-order aberration profiles obtained in myopic eyes with and without accommodation. Methods Central and peripheral refractive errors (M, J180, and J45) and higher-order aberrations (C[3, 1], C[3, 3], and C[4, 0]) were measured in 26 myopic participants (mean [±SD] age, 20.9 [±2.0] years; mean [±SD] spherical equivalent, −3.00 [±0.90] diopters [D]) corrected for distance. Measurements were performed along the horizontal visual field with (−2.00 to −5.00 D) and without (+1.00 D fogging) accommodation. Changes as a function of accommodation were compared using tilt and curvature coefficients of peripheral refraction and aberration profiles. Results As accommodation increased, the relative peripheral refraction profiles of M and J180 became significantly (p < 0.05) more negative and the profile of M became significantly (p < 0.05) more asymmetric. No significant differences were found for the J45 profiles (p > 0.05). The peripheral aberration profiles of C[3, 1], C[3, 3], and C[4, 0] became significantly (p < 0.05) less asymmetric as accommodation increased, but no differences were found in the curvature. Conclusions The current study showed that significant changes in peripheral refraction and higher-order aberration profiles occurred during accommodation in myopic eyes. With its extended measurement capabilities, that is, permitting rapid peripheral refraction and higher-order aberration measurements up to visual field angles of ±50 degrees for distance and near (up to −5.00 D), the EM is a new advanced instrument that may provide additional insights in the ongoing quest to understand and monitor myopia development. PMID:25105690

  10. Aberrant Wnt Signaling in Leukemia.

    PubMed

    Staal, Frank J T; Famili, Farbod; Garcia Perez, Laura; Pike-Overzet, Karin

    2016-01-01

    The Wnt signaling pathway is essential in the development and homeostasis of blood and immune cells, but its exact role is still controversial and is the subject of intense research. The malignant counterpart of normal hematopoietic cells, leukemic (stem) cells, have hijacked the Wnt pathway for their self-renewal and proliferation. Here we review the multiple ways dysregulated Wnt signaling can contribute to leukemogenesis, both cell autonomously as well as by changes in the microenvironment. PMID:27571104

  11. Aberrant Wnt Signaling in Leukemia

    PubMed Central

    Staal, Frank J. T.; Famili, Farbod; Garcia Perez, Laura; Pike-Overzet, Karin

    2016-01-01

    The Wnt signaling pathway is essential in the development and homeostasis of blood and immune cells, but its exact role is still controversial and is the subject of intense research. The malignant counterpart of normal hematopoietic cells, leukemic (stem) cells, have hijacked the Wnt pathway for their self-renewal and proliferation. Here we review the multiple ways dysregulated Wnt signaling can contribute to leukemogenesis, both cell autonomously as well as by changes in the microenvironment. PMID:27571104

  12. Spherical aberration in on-axis and offset unstable confocal resonators.

    PubMed

    Moyer, R H

    1982-03-15

    An analysis of spherical aberration in on-axis and offset unstable laser resonators is presented. Closed-form analytic expressions of the associated Strehl ratio as a function of cavity dimensions and magnification are derived, and effects of simple phase corrections in the optical system are assumed. PMID:20389813

  13. Repair of left subclavian artery and aberrant right subclavian artery aneurysms.

    PubMed

    Nair, Kannan R; Vasu, Harilal; Jacob, Aju; Velayudhan, Bashi V

    2010-12-01

    Left subclavian artery aneurysm with an aneurysm of the aberrant right subclavian artery is a rare condition with a reported incidence of 0.13% to 1%. We report the successful surgical correction of both conditions in a 34-year-old man.

  14. Statistical distribution of single atoms and clusters of supported Au catalyst analyzed by global high-resolution HAADF-STEM observation with morphological image-processing operation.

    PubMed

    Yamamoto, Yuta; Arai, Shigeo; Esaki, Akihiko; Ohyama, Junya; Satsuma, Atsushi; Tanaka, Nobuo

    2014-06-01

    We have developed a quantitative particle size analytical method at the single atomic level employing electron microscopy and image processing for the investigation of supported metal catalysts. In the present study, a supported gold (Au) catalyst containing sub-nano clusters and individual atoms was globally observed by high-resolution high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) using spherical aberration (Cs)-corrected TEM. To fully extract structural information of the Au clusters and individual atoms from the HAADF-STEM images, a morphological image-processing operation was applied. The resulting mean particle size was in good agreement with particle sizes estimated from average information provided by X-ray absorption fine structure analysis. It is demonstrated that the present HAADF-STEM image analysis gives a quantitative particle size distribution measurement of supported Au clusters and individual atoms.

  15. Aberration-Coreected Electron Microscopy at Brookhaven National Laboratory

    SciTech Connect

    Zhu,Y.; Wall, J.

    2008-04-01

    The last decade witnessed the rapid development and implementation of aberration correction in electron optics, realizing a more-than-70-year-old dream of aberration-free electron microscopy with a spatial resolution below one angstrom [1-9]. With sophisticated aberration correctors, modern electron microscopes now can reveal local structural information unavailable with neutrons and x-rays, such as the local arrangement of atoms, order/disorder, electronic inhomogeneity, bonding states, spin configuration, quantum confinement, and symmetry breaking [10-17]. Aberration correction through multipole-based correctors, as well as the associated improved stability in accelerating voltage, lens supplies, and goniometers in electron microscopes now enables medium-voltage (200-300kV) microscopes to achieve image resolution at or below 0.1nm. Aberration correction not only improves the instrument's spatial resolution but, equally importantly, allows larger objective lens pole-piece gaps to be employed thus realizing the potential of the instrument as a nanoscale property-measurement tool. That is, while retaining high spatial resolution, we can use various sample stages to observe the materials response under various temperature, electric- and magnetic- fields, and atmospheric environments. Such capabilities afford tremendous opportunities to tackle challenging science and technology issues in physics, chemistry, materials science, and biology. The research goal of the electron microscopy group at the Dept. of Condensed Matter Physics and Materials Science and the Center for Functional Nanomaterials, as well as the Institute for Advanced Electron Microscopy, Brookhaven National Laboratory (BNL), is to elucidate the microscopic origin of the physical- and chemical-behavior of materials, and the role of individual, or groups of atoms, especially in their native functional environments. We plan to accomplish this by developing and implementing various quantitative electron

  16. Quantitative analysis of radiation-induced chromosome aberrations.

    PubMed

    Sachs, R K; Levy, D; Hahnfeldt, P; Hlatky, L

    2004-01-01

    We review chromosome aberration modeling and its applications, especially to biodosimetry and to characterizing chromosome geometry. Standard results on aberration formation pathways, randomness, dose-response, proximity effects, transmissibility, kinetics, and relations to other radiobiological endpoints are summarized. We also outline recent work on graph-theoretical descriptions of aberrations, Monte-Carlo computer simulations of aberration spectra, software for quantifying aberration complexity, and systematic links of apparently incomplete with complete or truly incomplete aberrations. PMID:15162028

  17. Refractive and Aberration Outcomes after Customized Photorefractive Keratectomy in Comparison with Customized Femtosecond Laser

    PubMed Central

    Sajjadi, Valleh; Ghoreishi, Mohammad; Jafarzadehpour, Ebrahim

    2015-01-01

    To compare the refractive and visual outcomes and higher order aberrations in patients with low to moderate myopia who underwent customized photorefractive keratectomy (PRK) or femtosecond laser in situ keratomileusis (Femto-LASIK) this research performed. This study includes data of 120 consecutive eyes of 60 patients with myopia between -3.00 D and -7.00 D with or without astigmatism in two surgery groups: PRK and Femto-LASIK. Refractive, visual, and aberration outcomes of the two methods of surgery were compared after 6 months of follow-up. After six months of follow-up, sphere and cylinder were found significantly decreased and there was no statistically significant difference between the two groups. The mean of uncorrected distance visual acuity in LogMar format for the PRK and Femto-LASIK groups was -0.03±0.07 and -0.01±0.08, respectively, which was not significantly different between the two groups. Higher orders and spherical aberrations increased in both groups significantly, while total aberrations decreased in both groups. After surgery, no differences were observed between the two groups in the amount of aberrations. In conclusion, Both PRK and Femto-LASIK are effective and safe in correcting myopia. In this study PRK induced more spherical and higher order aberrations than Femto-LASIK. PMID:27800501

  18. Aberrant repair and fibrosis development in skeletal muscle

    PubMed Central

    2011-01-01

    The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair. PMID:21798099

  19. Polarization Aberrations in Astronomical Telescopes: The Point Spread Function

    NASA Astrophysics Data System (ADS)

    Breckinridge, James B.; Lam, Wai Sze T.; Chipman, Russell A.

    2015-05-01

    and coronagraph applications. (4) Part of the aberration is a polarization-dependent astigmatism, with a magnitude of 22 milliwaves, which enlarges the PSF image. (5) The orthogonally polarized components of unpolarized sources contain different wavefront aberrations, which differ by approximately 32 milliwaves. This implies that a wavefront correction system cannot optimally correct the aberrations for all polarizations simultaneously. (6) The polarization aberrations couple small parts of each polarization component of the light (~10-4) into the orthogonal polarization where these components cause highly distorted secondary, or "ghost" PSF images. (7) The radius of the spatial extent of the 90% encircled energy of these two ghost PSF image is twice as large as the radius of the Airy diffraction pattern. Coronagraphs for terrestrial exoplanet science are expected to image objects 10-10, or 6 orders of magnitude less than the intensity of the instrument-induced "ghost" PSF image, which will interfere with exoplanet measurements. A polarization aberration expansion which approximates the Jones pupil of the example telescope in six polarization terms is presented in the appendix. Individual terms can be associated with particular polarization defects. The dependence of these terms on angles of incidence, numerical aperture, and the Taylor series representation of the Fresnel equations lead to algebraic relations between these parameters and the scaling of the polarization aberrations. These "design rules" applicable to the example telescope are collected in § 5. Currently, exoplanet coronagraph masks are designed and optimized for scalar diffraction in optical systems. Radiation from the "ghost" PSF image leaks around currently designed image plane masks. Here, we show a vector-wave or polarization optimization is recommended. These effects follow from a natural description of the optical system in terms of the Jones matrices associated with each ray path of interest

  20. Sclerocarya birrea (Anacardiaceae) stem-bark extract corrects glycaemia in diabetic rats and acts on beta-cells by enhancing glucose-stimulated insulin secretion.

    PubMed

    Makom Ndifossap, Ivonne Gisèle; Frigerio, Francesca; Casimir, Marina; Ngueguim Tsofack, Florence; Dongo, Etienne; Kamtchouing, Pierre; Dimo, Théophile; Maechler, Pierre

    2010-04-01

    Sclerocarya birrea is a plant widely used as traditional medication for the treatment of diabetes in sub-Saharan regions. However, the mechanism of action is unknown and only hypoglycaemic effects of S. birrea extract (SBE) in diabetic rats have been reported to date. Here, we tested aqueous extracts of S. birrea on insulin-secreting INS-1E cells and isolated rat islets. Following 24 h of treatment at 5 microg/ml, the extract markedly potentiated glucose-stimulated insulin secretion. Neither basal insulin release nor non-nutrient stimulation was affected. The potentiation of the secretory response at stimulatory glucose appeared after 12 h of treatment. No acute effects were observed and, at the effective concentration, SBE was safe regarding cell integrity and differentiation. The mechanism of action of the SBE was related to glucose metabolism as both ATP generation and glucose oxidation were enhanced following the 24-h treatment. In streptozotocin-induced diabetic rats, SBE administration corrected glycaemia and restored plasma insulin levels after 2 weeks of treatment. These data show direct action of S. birrea on insulin-secreting cells and favour further delineation for use of the plant in the management of diabetes.

  1. Wnt Signaling in Cancer Stem Cell Biology.

    PubMed

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-06-27

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer.

  2. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  3. Stomach development, stem cells and disease.

    PubMed

    Kim, Tae-Hee; Shivdasani, Ramesh A

    2016-02-15

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms.

  4. Treatment of foot disease in patients with type 2 diabetes mellitus using human umbilical cord blood mesenchymal stem cells: response and correction of immunological anomalies.

    PubMed

    Li, Xiao-Yan; Zheng, Zhao-Hui; Li, Xue-Yi; Guo, Jian; Zhang, Yan; Li, Hui; Wang, Yang-Wei; Ren, Jun; Wu, Zhen-Biao

    2013-01-01

    This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell (hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. The hUCB-MSCs were directly injected into the quadriceps thigh muscles in patients with foot disease (cell quantity at 2 x 10⁶ per point). Physical attributes, blood cytokines, blood glucose and insulin dosage were evaluated before treatment and 1, 2, 4, 8, and 12 weeks thereafter. The ratios of Treg/Th17, Treg/Th1, and Th17/Th1 cells were measured using flow cytometry and their correlation with various cytokines (FoxP3, IL-17, INF-γ, C-RP, TNF-α, and VEGF) was scrutinized. Levels of blood glucose and insulin dosage were significantly reduced in all 15 patients following hUCB-MSC transplantation. The ratios of CD4⁺CD25(hi)FoxP3⁺ Treg/Th17 and CD4⁺CD25(hi)FoxP3⁺ Treg/Th1 cells were significantly increased 4 weeks after transplantation (p < 0.01), while the ratio of Th17/Th1 cells remained unchanged. Serum levels of VEGF peaked at 4 weeks following transplantation. Levels of C-RP and TNF-α were significantly reduced 4 weeks after transplantation. Intriguingly, the ratios of Treg/Th17 were positively correlated with VEGF levels, and were inversely correlated with plasma IL-6 levels. Our data indicated that immune disorders are associated with the development of type 2 diabetes and its complications. Levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied with improved clinical profiles in diabetic patients. These data favor a role for Treg cells in the onset and progression of T2D.

  5. Transverse chromatic aberration after corneal refractive surgery

    NASA Astrophysics Data System (ADS)

    Anera, R. G.; Jiménez, J. R.; Jiménez del Barco, L.; Hita, E.

    2005-05-01

    An expression has been deduced theoretically from a schematic-eye model, for the transverse or lateral chromatic aberration (TCA) after refractive surgery. The aim was to investigate analytically how chromatic aberration varies after the emmetropization process. These changes in the TCA have been characterized from changes in corneal asphericity. The results indicate that TCA after refractive surgery diminishes as the degree of myopia increases, a trend contrary to that occurring with monochromatic aberrations, such as spherical or coma. These results can explain the fact that the real deterioration of the visual function under photopic conditions detected in those operated on for myopia is less than expected when only monochromatic aberrations are taken into account.

  6. Spherical aberration in electrically thin flat lenses.

    PubMed

    Ruphuy, Miguel; Ramahi, Omar M

    2016-08-01

    We analyze the spherical aberration of a new generation of lenses made of flat electrically thin inhomogeneous media. For such lenses, spherical aberration is analyzed quantitatively and qualitatively, and comparison is made to the classical gradient index rod. Both flat thin and thick lenses are made of gradient index materials, but the physical mechanisms and design equations are different. Using full-wave three-dimensional numerical simulation, we evaluate the spherical aberrations using the Maréchal criterion and show that the thin lens gives significantly better performance than the thick lens (rod). Additionally, based on ray tracing formulation, third-order analysis for longitudinal aberration and optical path difference are presented, showing strong overall performance of thin lenses in comparison to classical rod lenses. PMID:27505651

  7. Pharmacological correction of misfolding of ABC proteins☆

    PubMed Central

    Rudashevskaya, Elena L.; Stockner, Thomas; Trauner, Michael; Freissmuth, Michael; Chiba, Peter

    2014-01-01

    The endoplasmic reticulum (ER) quality control system distinguishes between correctly and incorrectly folded proteins to prevent processing of aberrantly folded conformations along the secretory pathway. Non-synonymous mutations can lead to misfolding of ABC proteins and associated disease phenotypes. Specific phenotypes may at least partially be corrected by small molecules, so-called pharmacological chaperones. Screening for folding correctors is expected to open an avenue for treatment of diseases such as cystic fibrosis and intrahepatic cholestasis. PMID:25027379

  8. Pharmacological correction of misfolding of ABC proteins.

    PubMed

    Rudashevskaya, Elena L; Stockner, Thomas; Trauner, Michael; Freissmuth, Michael; Chiba, Peter

    2014-06-01

    The endoplasmic reticulum (ER) quality control system distinguishes between correctly and incorrectly folded proteins to prevent processing of aberrantly folded conformations along the secretory pathway. Non-synonymous mutations can lead to misfolding of ABC proteins and associated disease phenotypes. Specific phenotypes may at least partially be corrected by small molecules, so-called pharmacological chaperones. Screening for folding correctors is expected to open an avenue for treatment of diseases such as cystic fibrosis and intrahepatic cholestasis. PMID:25027379

  9. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Wu, Honglu; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Bowler, Deborah

    2016-07-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  10. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    NASA Technical Reports Server (NTRS)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    DNA damages induced by space radiation, consisting of protons and high-LET charged particles, can be complex in nature, which are often left unrepaired and cause chromosomal aberrations. Increased level of genomic instability is attributed to tumorigenesis and increased cancer risks. To investigate genomic instability induced by charged particles, human lymphocytes ex vivo, human fibroblasts, and human mammary epithelial cells, as well as mouse bone marrow stem cells isolated from CBA/CaH and C57BL/6 strains were exposed to high energy protons and Fe ions. Metaphase chromosome spreads at different cell divisions after radiation exposure were collected and, chromosome aberrations were analyzed with fluorescence in situ hybridization with whole chromosome-specific probes for human cells. With proton irradiation, levels of chromosome aberrations decreased by about 50% in both lymphocytes and epithelial cells after multiple cell divisions, compared to initial chromosome aberrations at 48 hours post irradiation in both cell types. With Fe ion irradiation, however, the frequency of chromosome aberrations in lymphocytes after multiple cell divisions was significantly lower than that in epithelial cells at comparable cell divisions, while their initial chromosome aberrations were at similar levels. Similar to the human cells, after Fe ion irradiation, the frequency of late chromosome aberrations was similar to that of the early damages for radio-sensitive CBA cells, but different for radio-resistant C57 cells. Our results suggest that relative biological effectiveness (RBE) values are dependent not only on radiation sources, but also on cell types and cell divisions.

  11. Chromosome aberrations in decondensed sperm DNA

    SciTech Connect

    Preston, R.J.

    1982-01-01

    Factors that could influence the chromosomal aberration frequency observed at first cleavage following in vivo exposure of germ cells to chemical mutagens are discussed. The techniques of chromosome aberration analysis following sperm DNA condensation by in vitro fertilization or fusion seem to be viable research areas for providing information of human germ cell exposures. However, the potential sensitivity of the assay needs to be better understood, and factors that can influence this sensitivity require a great deal of further study using animal models.

  12. Corrections stemming from the non-osculating character of the Andoyer variables used in the description of rotation of the elastic Earth

    NASA Astrophysics Data System (ADS)

    Escapa, Alberto

    2011-06-01

    compute the variations of the angular velocity through the approach developed in Getino and Ferrándiz (Celest. Mech. Dyn. Astron. 61:117-180, 1995), but considering the contribution of the convective terms. Specifically, we derive analytical formulas that determine the elastic perturbations of the directional angles of the angular velocity with respect to a non-rotating reference system, and also of its Cartesian components relative to the Tisserand reference system of the Earth. The perturbation of the directional angles of the angular velocity turns out to be different from the evolution law found in Kubo (Celest. Mech. Dyn. Astron. 105:261-274, 2009), where it was stated that the evolution of the angular velocity vector mimics that of the figure axis. We investigate comprehensively the source of this discrepancy, concluding that the difference between our results and those obtained in Ibid. stems from an oversimplification made by Kubo when computing the direct terms. Namely, in his computations Kubo disregarded the motion of the tide raising bodies with respect to a non-rotating reference system when compared with the Earth rotational motion. We demonstrate that, from a numerical perspective, the convective part provides the principal contribution to the variation of the directional angles and of length of day. In the case of the x and y components in the Tisserand system, the convective contribution is of the same order of magnitude as the direct one. Finally, we show that the approximation employed in Kubo ( Ibid.) leads to significant numerical differences at the level of a hundred micro-arcsecond.

  13. Analysis of electron beam damage of exfoliated MoS2 sheets and quantitative HAADF-STEM imaging

    PubMed Central

    Garcia, A.; Raya, A.M.; Mariscal, M.M.; Esparza, R.; Herrera, M.; Molina, S.I.; Scavello, G.; Galindo, P.L.; Jose-Yacaman, M.; Ponce, A.

    2014-01-01

    In this work we examined MoS2 sheets by aberration-corrected scanning transmission electron microscopy (STEM) at three different energies: 80, 120 and 200 kV. Structural damage of the MoS2 sheets has been controlled at 80 kV according a theoretical calculation based on the inelastic scattering of the electrons involved in the interaction electron-matter. The threshold energy for the MoS2 material has been found and experimentally verified in the microscope. At energies higher than the energy threshold we show surface and edge defects produced by the electron beam irradiation. Quantitative analysis at atomic level in the images obtained at 80 kV has been performed using the experimental images and via STEM simulations using SICSTEM software to determine the exact number of MoS2 layers. PMID:24929924

  14. Analysis of electron beam damage of exfoliated MoS₂ sheets and quantitative HAADF-STEM imaging.

    PubMed

    Garcia, Alejandra; Raya, Andres M; Mariscal, Marcelo M; Esparza, Rodrigo; Herrera, Miriam; Molina, Sergio I; Scavello, Giovanni; Galindo, Pedro L; Jose-Yacaman, Miguel; Ponce, Arturo

    2014-11-01

    In this work we examined MoS₂ sheets by aberration-corrected scanning transmission electron microscopy (STEM) at three different energies: 80, 120 and 200 kV. Structural damage of the MoS₂ sheets has been controlled at 80 kV according a theoretical calculation based on the inelastic scattering of the electrons involved in the interaction electron-matter. The threshold energy for the MoS₂ material has been found and experimentally verified in the microscope. At energies higher than the energy threshold we show surface and edge defects produced by the electron beam irradiation. Quantitative analysis at atomic level in the images obtained at 80 kV has been performed using the experimental images and via STEM simulations using SICSTEM software to determine the exact number of MoS2₂ layers.

  15. An optical tomography PSF almost insensitive to aberrations: the benefit of a spatial incoherent illumination (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xiao, Peng; Fink, Mathias; Boccara, A. Claude

    2016-03-01

    An aberrated imaging system PSF is broadened; this broadening is responsible of the blurring of the images. A lot of effort has been carried out to correct the effects of aberrations on OCT images for eye examination or biological samples. We have worked on quantifying the effect of geometrical aberrations on Full-Field OCT images and found that there is mostly no loss of resolution but a decrease of the signal level. This is obviously why we use these signals as metric to correct the wavefront distortion. Moreover we found that this absence of blurring, which is due to the fact that we record the dot product of a diffraction limited reference signal and the distorted sample signal, is specific to the use of an incoherent illumination and did not show up with OCT approaches that use spatially coherent sources. More precisely the loss in signal is roughly proportional to the square root of the Strehl ratio: for example, a Strehl ratio of 1/9, which is considered to give a low quality image, would only be 1/3 in Full-Field OCT while keeping the sharpness of the image. Using both an USAF resolution target and a transmissive SLM we have demonstrated this unique feature of sharpness conservation. It was also confirmed by using biological samples. We think that we can thus restrict the aberration corrections in eye examination to the main aberrations (e.g. focus and astigmatism) that will increase the speed of the correction.

  16. Measuring aberrations in the rat brain by coherence-gated wavefront sensing using a Linnik interferometer.

    PubMed

    Wang, Jinyu; Léger, Jean-François; Binding, Jonas; Boccara, A Claude; Gigan, Sylvain; Bourdieu, Laurent

    2012-10-01

    Aberrations limit the resolution, signal intensity and achievable imaging depth in microscopy. Coherence-gated wavefront sensing (CGWS) allows the fast measurement of aberrations in scattering samples and therefore the implementation of adaptive corrections. However, CGWS has been demonstrated so far only in weakly scattering samples. We designed a new CGWS scheme based on a Linnik interferometer and a SLED light source, which is able to compensate dispersion automatically and can be implemented on any microscope. In the highly scattering rat brain tissue, where multiply scattered photons falling within the temporal gate of the CGWS can no longer be neglected, we have measured known defocus and spherical aberrations up to a depth of 400 µm. PMID:23082292

  17. Measuring aberrations in the rat brain by coherence-gated wavefront sensing using a Linnik interferometer

    PubMed Central

    Wang, Jinyu; Léger, Jean-François; Binding, Jonas; Boccara, A. Claude; Gigan, Sylvain; Bourdieu, Laurent

    2012-01-01

    Aberrations limit the resolution, signal intensity and achievable imaging depth in microscopy. Coherence-gated wavefront sensing (CGWS) allows the fast measurement of aberrations in scattering samples and therefore the implementation of adaptive corrections. However, CGWS has been demonstrated so far only in weakly scattering samples. We designed a new CGWS scheme based on a Linnik interferometer and a SLED light source, which is able to compensate dispersion automatically and can be implemented on any microscope. In the highly scattering rat brain tissue, where multiply scattered photons falling within the temporal gate of the CGWS can no longer be neglected, we have measured known defocus and spherical aberrations up to a depth of 400 µm. PMID:23082292

  18. Measuring aberrations in the rat brain by coherence-gated wavefront sensing using a Linnik interferometer.

    PubMed

    Wang, Jinyu; Léger, Jean-François; Binding, Jonas; Boccara, A Claude; Gigan, Sylvain; Bourdieu, Laurent

    2012-10-01

    Aberrations limit the resolution, signal intensity and achievable imaging depth in microscopy. Coherence-gated wavefront sensing (CGWS) allows the fast measurement of aberrations in scattering samples and therefore the implementation of adaptive corrections. However, CGWS has been demonstrated so far only in weakly scattering samples. We designed a new CGWS scheme based on a Linnik interferometer and a SLED light source, which is able to compensate dispersion automatically and can be implemented on any microscope. In the highly scattering rat brain tissue, where multiply scattered photons falling within the temporal gate of the CGWS can no longer be neglected, we have measured known defocus and spherical aberrations up to a depth of 400 µm.

  19. Segment aberration effects on contrast.

    PubMed

    Crossfield, Ian J; Troy, Mitchell

    2007-07-20

    High-contrast imaging, particularly the direct detection of extrasolar planets, is a major science driver for the next generation of telescopes. This science requires the suppression of scattered starlight at extremely high levels and that telescopes be correctly designed today to meet these stringent requirements in the future. The challenge increases in systems with complicated aperture geometries such as obscured, segmented telescopes. Such systems can also require intensive modeling and simulation efforts in order to understand the trade-offs between different optical parameters. The feasibility and development of a contrast prediction tool for use in the design and systems engineering of these telescopes is described. The performance of a particular starlight suppression system on a large segmented telescope is described analytically. These analytical results and the results of a contrast predictor are then compared with the results of a full wave-optics simulation. PMID:17609697

  20. Aberration in proper motions for Galactic stars

    NASA Astrophysics Data System (ADS)

    Liu, J.-C.; Xie, Y.; Zhu, Z.

    2014-12-01

    Accelerations of both the solar system barycenter (SSB) and stars in the MilkyWay cause a systematic observational effect on the stellar proper motions, which was first studied by J. Kovalevsky (2003). This paper intends to extend that work and aims to estimate the magnitude and significance of the aberration in proper motions of stars, especially in the region near the Galactic center (GC). We adopt two models for the Galactic rotation curve to evaluate the aberrational effect on the Galactic plane. We show that the effect of aberration in proper motions depends on the galactocentric distance of stars; it is dominated by the acceleration of stars in the central region of the Galaxy. Then we investigate the applicability of the theoretical expressions: if the orbital period of stars is only a fraction of the light time from the star to the SSB, the expression with approximation proposed by Kovalevsky is not appropriate. With a more suitable formulation, we found that the aberration has no effect on the determination of the stellar orbits on the celestial sphere. In the future this aberrational effect under consideration should be considered with high-accurate astrometry, particularly in constructing the Gaia celestial reference system realized by Galactic stars.

  1. Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia

    PubMed Central

    Ceaser, Alan E.; Barch, Deanna M.

    2016-01-01

    A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive control that involves updating, interference control, and simple maintenance. The current study included a sample of 22 patients with schizophrenia and 20 healthy controls and used a slow event-related fMRI design. We predicted that (1) aberrant salience symptoms would be greater for patient's, (2) patients would demonstrate increased errors during interference control trials, given that patients may be inappropriately assigning salience to distracters, and (3) striatal activity during those errors would be correlated with aberrant salience symptoms. We found a trend toward a significant difference between patients and controls on aberrant salience symptoms, and a significant difference between groups on select task conditions. During interference control trials, patients were more likely to inappropriately encode distracters. For patients, both prefrontal and striatal activity was significantly greater when patients inappropriately identified the distracter as correct compared to activity during distracter rejection. During updating, patient prefrontal and striatal activity was significantly lower for incorrect than correct updating trials. Finally, as predicted, for patients the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the striatal region. These relationships may have implications for treatments that improve cognitive function and reduce symptom expression. PMID:26869912

  2. Redox regulation in cancer stem cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processe...

  3. Wide field-of-view fluorescence image deconvolution with aberration-estimation from Fourier ptychography

    PubMed Central

    Chung, Jaebum; Kim, Jinho; Ou, Xiaoze; Horstmeyer, Roarke; Yang, Changhuei

    2016-01-01

    This paper presents a method to simultaneously acquire an aberration-corrected, wide field-of-view fluorescence image and a high-resolution coherent bright-field image using a computational microscopy method. First, the procedure applies Fourier ptychographic microscopy (FPM) to retrieve the amplitude and phase of a sample, at a resolution that significantly exceeds the cutoff spatial frequency of the microscope objective lens. At the same time, redundancy within the set of acquired FPM bright-field images offers a means to estimate microscope aberrations. Second, the procedure acquires an aberrated fluorescence image, and computationally improves its resolution through deconvolution with the estimated aberration map. An experimental demonstration successfully improves the bright-field resolution of fixed, stained and fluorescently tagged HeLa cells by a factor of 4.9, and reduces the error caused by aberrations in a fluorescence image by up to 31%, over a field of view of 6.2 mm by 9.3 mm. For optimal deconvolution, we show the fluorescence image needs to have a signal-to-noise ratio of at least ~18. PMID:26977345

  4. Wide field-of-view fluorescence image deconvolution with aberration-estimation from Fourier ptychography.

    PubMed

    Chung, Jaebum; Kim, Jinho; Ou, Xiaoze; Horstmeyer, Roarke; Yang, Changhuei

    2016-02-01

    This paper presents a method to simultaneously acquire an aberration-corrected, wide field-of-view fluorescence image and a high-resolution coherent bright-field image using a computational microscopy method. First, the procedure applies Fourier ptychographic microscopy (FPM) to retrieve the amplitude and phase of a sample, at a resolution that significantly exceeds the cutoff spatial frequency of the microscope objective lens. At the same time, redundancy within the set of acquired FPM bright-field images offers a means to estimate microscope aberrations. Second, the procedure acquires an aberrated fluorescence image, and computationally improves its resolution through deconvolution with the estimated aberration map. An experimental demonstration successfully improves the bright-field resolution of fixed, stained and fluorescently tagged HeLa cells by a factor of 4.9, and reduces the error caused by aberrations in a fluorescence image by up to 31%, over a field of view of 6.2 mm by 9.3 mm. For optimal deconvolution, we show the fluorescence image needs to have a signal-to-noise ratio of at least ~18. PMID:26977345

  5. Comparison between two different methods to obtain the wavefront aberration function

    NASA Astrophysics Data System (ADS)

    Cruz Félix, Angel S.; Ibarra, Jorge; López, Estela; Rosales, Marco A.; Tepichín, Eduardo

    2010-08-01

    The analysis and measurement of the wavefront aberration function are very important tools that allow us to evaluate the performance of any specified optical system. This technology has been adopted in visual optics for the analysis of optical aberrations in the human eye, before and after being subjected to laser refractive surgery. We have been working in the characterization and evaluation of the objective performance of human eyes that have been subjected to two different surface ablation techniques known as ASA and PASA1. However, optical aberrations in the human eye are time-dependent2 and, hence, difficult to analyze. In order to obtain a static profile from the post-operatory wavefront aberration function we applied these ablation techniques directly over hard contact lenses. In this work we show the comparison between two different methods to obtain the wavefront aberration function from a reference refractive surface, in order to generalize this method and being able to fully characterize hard contact lenses which have been subjected to different ablation techniques typically used in refractive surgery for vision correction. For the first method we used a Shack-Hartmann wavefront sensor, and in the second method we used a Mach-Zehnder type interferometer. We show the preliminary results of this characterization.

  6. Computation of astigmatic and trefoil figure errors and misalignments for two-mirror telescopes using nodal-aberration theory.

    PubMed

    Ju, Guohao; Yan, Changxiang; Gu, Zhiyuan; Ma, Hongcai

    2016-05-01

    In active optics systems, one concern is how to quantitatively separate the effects of astigmatic and trefoil figure errors and misalignments that couple together in determining the total aberration fields when wavefront measurements are available at only a few field points. In this paper, we first quantitatively describe the impact of mount-induced trefoil deformation on the net aberration fields by proposing a modified theoretical formulation for the field-dependent aberration behavior of freeform surfaces based on the framework of nodal aberration theory. This formulation explicitly expresses the quantitative relationships between the magnitude of freeform surfaces and the induced aberration components where the freeform surfaces can be located away from the aperture stop and decentered from the optical axis. On this basis, and in combination with the mathematical presentation of nodal aberration theory for the effects of misalignments, we present the analytic expressions for the aberration fields of two-mirror telescopes in the presence of astigmatic primary mirror figure errors, mount-induced trefoil deformations on both mirrors, and misalignments. We quantitatively separate these effects using the analytical expressions with wavefront measurements at a few field points and pointing errors. Valuable insights are provided on how to separate these coupled effects in the computation process. Monte Carlo simulations are conducted to demonstrate the correctness and accuracy of the analytic method presented in this paper. PMID:27140345

  7. Computation of astigmatic and trefoil figure errors and misalignments for two-mirror telescopes using nodal-aberration theory.

    PubMed

    Ju, Guohao; Yan, Changxiang; Gu, Zhiyuan; Ma, Hongcai

    2016-05-01

    In active optics systems, one concern is how to quantitatively separate the effects of astigmatic and trefoil figure errors and misalignments that couple together in determining the total aberration fields when wavefront measurements are available at only a few field points. In this paper, we first quantitatively describe the impact of mount-induced trefoil deformation on the net aberration fields by proposing a modified theoretical formulation for the field-dependent aberration behavior of freeform surfaces based on the framework of nodal aberration theory. This formulation explicitly expresses the quantitative relationships between the magnitude of freeform surfaces and the induced aberration components where the freeform surfaces can be located away from the aperture stop and decentered from the optical axis. On this basis, and in combination with the mathematical presentation of nodal aberration theory for the effects of misalignments, we present the analytic expressions for the aberration fields of two-mirror telescopes in the presence of astigmatic primary mirror figure errors, mount-induced trefoil deformations on both mirrors, and misalignments. We quantitatively separate these effects using the analytical expressions with wavefront measurements at a few field points and pointing errors. Valuable insights are provided on how to separate these coupled effects in the computation process. Monte Carlo simulations are conducted to demonstrate the correctness and accuracy of the analytic method presented in this paper.

  8. Psychometric characteristics of the aberrant behavior checklist.

    PubMed

    Aman, M G; Singh, N N; Stewart, A W; Field, C J

    1985-03-01

    Information was presented on the psychometric characteristics of the Aberrant Behavior Checklist. The internal consistency and test-retest reliability of the Checklist appeared to be very good. Interrater reliability tended to vary across raters and subscales and ranged from mediocre to good but was generally in the moderate range and acceptable for research purposes. Validity was assessed by comparing Checklist scores for residents presenting with attributes thought to reflect varying degrees of social adaptation. Validity was also evaluated by comparing Aberrant Behavior Checklist scores with ratings on adaptive behavior scales and with objective observations of behavior. In general, validity was established for most Aberrant Behavior Checklist subscales. Preliminary data from drug investigations suggested that the Checklist may provide a useful adjunct for the assessment of psychotropic drug effects.

  9. Chromosome aberrations as bioindicators of environmental genotoxicity.

    PubMed

    Ibrulj, Slavica; Haverić, Sanin; Haverić, Anja

    2007-11-01

    Due to the exposure to various potentially genotoxic xenobiotics, derived from recent war activities such as NATO air strikes with antitank ammunition containing depleted uranium, we have evaluated chromosome aberrations in 84 peripheral blood samples from three local populations. One population sample included 30 individuals who lived in the Sarajevo area during and after the war (exposed to potential genotoxins), second population was presented with 26 employees of the tank repair facility in Hadzići (target of NATO air strikes), and 28 inhabitants of Posusje (not exposed to war-related activities) were treated as sample of control population. The mean of chromosome aberration frequencies for the population from Hadzići was significantly higher than the frequencies for the two other populations. Point bi-serial coefficient analysis did not reveal any relationship between the frequencies of chromosome aberrations and smoking habits or gender. Results suggest that depleted uranium could be a risk factor for human health.

  10. An aberrant precision account of autism

    PubMed Central

    Lawson, Rebecca P.; Rees, Geraint; Friston, Karl J.

    2014-01-01

    Autism is a neurodevelopmental disorder characterized by problems with social-communication, restricted interests and repetitive behavior. A recent and thought-provoking article presented a normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation—namely, predictive coding—many features of autistic perception can be attributed to aberrant precision (or beliefs about precision) within the context of hierarchical message passing in the brain (Friston et al., 2013). Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings—that speak directly or indirectly to neurobiological mechanisms—are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs. PMID:24860482

  11. The Politics of Political Correctness.

    ERIC Educational Resources Information Center

    Minsky, Leonard

    1992-01-01

    This article reacts to President Bush's entry into the dispute over "political correctness" on college campuses. The paper summarizes discussions of students, faculty, and others in the Washington, D.C. area which concluded that this seeming defense of free speech is actually an attack on affirmative action and multiculturalism stemming from the…

  12. Seidel aberrations of an inflated membrane.

    PubMed

    Vaughan, H

    1980-09-15

    The Seidel aberrations of a shallow reflecting bowl are examined. In particular the bowl is formed by pressurizing a prestretched polymer membrane over the end of a cylindrical pressure vessel. Precise values for each of the five aberrations are given in terms of the bowl depth, radius, and amount of prestretch in the membrane for the case of an object at infinity and aperture stop in contact with the mirror. The analysis neglects terms of order (4)compared to unity where = bowl depth/bowl radius.

  13. [Corneal higher order aberrations and their changes with aging].

    PubMed

    Cermáková, S; Skorkovská, S

    2010-12-01

    Cornea is the most important refractive medium of the eye and affects its total aberration state. This paper deals with corneal higher order aberrations in healthy humans and evaluates their changes with aging and corneal curvature. The influence of the corneal anterior and posterior surfaces on aberrations of the whole cornea was also investigated. The examination was performed with a Scheimpflug camera which enables to examine the anterior and posterior corneal surface separately. The results show that higher order aberrations of the whole cornea are influenced mainly by the anterior surface aberrations. The main corneal higher order aberration is the Z (4,0) spherical aberration which has a positive value and increases with age. Also, 3rd order aberration values are of importance, especially coma which also increases with age. As a consequence, the root-mean-square of the 3rd and 4th order aberrations in elderly people has a higher value.

  14. Multinodal fifth-order optical aberrations of optical systems without rotational symmetry: spherical aberration.

    PubMed

    Thompson, Kevin P

    2009-05-01

    Building off an earlier work on multinodal third-order aberrations [J. Opt. Soc. Am. A22, 1389 (2005)], this is the first in a series of papers that derives and illustrates the characteristic multinodal geometry for each of the fifth-order aberrations. Part I (as this paper will be referred to) will present the spherical aberration family: specifically, W(060), W(240M) and W(242), and W(080) (fifth-order spherical, oblique spherical, and seventh-order spherical). Nodal aberration theory is proving to be very effective as both an optical design tool for fully unobscured off-axis telescopes and as an analysis method, particularly in the context of the response of any imaging optical systems to misalignment. It is important to recognize that this multinodal approach to aberration theory is not restricted to small perturbations. The remaining papers in this series will result in a complete presentation of the intrinsic characteristic multinodal properties of each of the fifth-order aberrations. As such, this series provides a definitive theory of the optical aberrations of (nonanamorphic) imaging systems with a circular aperture stop. PMID:19412225

  15. Aberrations of diffracted wave fields. II. Diffraction gratings.

    PubMed

    Mahajan, V N

    2000-12-01

    The Rayleigh-Sommerfeld theory is applied to diffraction of a spherical wave by a grating. The grating equation is obtained from the aberration-free diffraction pattern, and its aberrations are shown to be the same as the conventional aberrations obtained by using Fermat's principle. These aberrations are shown to be not associated with the diffraction process. Moreover, it is shown that the irradiance distribution of a certain diffraction order is the Fraunhofer diffraction pattern of the grating aperture as a whole aberrated by the aberration of that order. PMID:11140481

  16. Aberration averaging using point spread function for scanning projection systems

    NASA Astrophysics Data System (ADS)

    Ooki, Hiroshi; Noda, Tomoya; Matsumoto, Koichi

    2000-07-01

    Scanning projection system plays a leading part in current DUV optical lithography. It is frequently pointed out that the mechanically induced distortion and field curvature degrade image quality after scanning. On the other hand, the aberration of the projection lens is averaged along the scanning direction. This averaging effect reduces the residual aberration significantly. The aberration averaging based on the point spread function and phase retrieval technique in order to estimate the effective wavefront aberration after scanning is described in this paper. Our averaging method is tested using specified wavefront aberration, and its accuracy is discussed based on the measured wavefront aberration of recent Nikon projection lens.

  17. Electroweak Corrections

    NASA Astrophysics Data System (ADS)

    Barbieri, Riccardo

    2016-10-01

    The test of the electroweak corrections has played a major role in providing evidence for the gauge and the Higgs sectors of the Standard Model. At the same time the consideration of the electroweak corrections has given significant indirect information on the masses of the top and the Higgs boson before their discoveries and important orientation/constraints on the searches for new physics, still highly valuable in the present situation. The progression of these contributions is reviewed.

  18. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  19. Whole transcriptome characterization of aberrant splicing events induced by lentiviral vector integrations

    PubMed Central

    Cesana, Daniela; Sgualdino, Jacopo; Rudilosso, Laura; Merella, Stefania; Naldini, Luigi; Montini, Eugenio

    2012-01-01

    Gamma-retroviral/lentiviral vectors (γRV/LV) with self-inactivating (SIN) long terminal repeats (LTRs) and internal moderate cellular promoters pose a reduced risk of insertional mutagenesis when compared with vectors with active LTRs. Yet, in a recent LV-based clinical trial for β-thalassemia, vector integration within the HMGA2 gene induced the formation of an aberrantly spliced mRNA form that appeared to cause clonal dominance. Using a method that we developed, cDNA linear amplification-mediated PCR, in combination with high-throughput sequencing, we conducted a whole transcriptome analysis of chimeric LV-cellular fusion transcripts in transduced human lymphoblastoid cells and primary hematopoietic stem/progenitor cells. We observed a surprising abundance of read-through transcription originating outside and inside the provirus and identified the vector sequences contributing to the aberrant splicing process. We found that SIN LV has a sharply reduced propensity to engage in aberrant splicing compared with that of vectors carrying active LTRs. Moreover, by recoding the identified vector splice sites, we reduced residual read-through transcription and demonstrated an effective strategy for improving vectors. Characterization of the mechanisms and genetic features underlying vector-induced aberrant splicing will enable the generation of safer vectors, with low impact on the cellular transcriptome. PMID:22523064

  20. Aberration features in directional dark matter detection

    SciTech Connect

    Bozorgnia, Nassim; Gelmini, Graciela B.; Gondolo, Paolo E-mail: gelmini@physics.ucla.edu

    2012-08-01

    The motion of the Earth around the Sun causes an annual change in the magnitude and direction of the arrival velocity of dark matter particles on Earth, in a way analogous to aberration of stellar light. In directional detectors, aberration of weakly interacting massive particles (WIMPs) modulates the pattern of nuclear recoil directions in a way that depends on the orbital velocity of the Earth and the local galactic distribution of WIMP velocities. Knowing the former, WIMP aberration can give information on the latter, besides being a curious way of confirming the revolution of the Earth and the extraterrestrial provenance of WIMPs. While observing the full aberration pattern requires extremely large exposures, we claim that the annual variation of the mean recoil direction or of the event counts over specific solid angles may be detectable with moderately large exposures. For example, integrated counts over Galactic hemispheres separated by planes perpendicular to Earth's orbit would modulate annually, resulting in Galactic Hemisphere Annual Modulations (GHAM) with amplitudes larger than the usual non-directional annual modulation.

  1. Anti-forensics of chromatic aberration

    NASA Astrophysics Data System (ADS)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  2. Designing refractive beam shapers via aberration theory

    NASA Astrophysics Data System (ADS)

    Laskin, Alexander; Shealy, David

    2014-10-01

    In this paper, we use aberration theory to design a refractive laser beam shaper in the configuration of two-aspheric lenses, whose analytical equations are known, but rather complicated. Specifically, we use results from third order aberration theory to obtain the parameters of the refracting laser beam shaper from the transverse aberration, which are then used as a starting point for further optimization by using optical design software. This approach was developed during the beginning of the twentieth century, works well for systems with a low numerical aperture, and allows one to define the following parameters of an optical system: radii of curvature, indices of refraction, thicknesses or air gaps, and conic constants of second order aspheric surfaces. We shall consider surfaces of the second-order spherical and conic sections and shall consider the example of designing of a two-lens beam shaper of the Keplerian 1-to-1 telescopic design providing a theoretical flat phase front and a flat-top irradiance profile of the output beam, where the ray mapping function from the input aperture to the output aperture is known from the literature. Explicit expression for third order longitudinal aberration and the Seidel coefficients are expressed in terms beam waist and input beam geometrical parameter, indices, lens radii and conic constants.

  3. Impact of retrotransposons in pluripotent stem cells.

    PubMed

    Tanaka, Yoshiaki; Chung, Leeyup; Park, In-Hyun

    2012-12-01

    Retrotransposons, which constitute approximately 40% of the human genome, have the capacity to 'jump' across the genome. Their mobility contributes to oncogenesis, evolution, and genomic plasticity of the host genome. Induced pluripotent stem cells as well as embryonic stem cells are more susceptible than differentiated cells to genomic aberrations including insertion, deletion and duplication. Recent studies have revealed specific behaviors of retrotransposons in pluripotent cells. Here, we review recent progress in understanding retrotransposons and provide a perspective on the relationship between retrotransposons and genomic variation in pluripotent stem cells. PMID:23135636

  4. Atomic-level imaging of Mo-V-O complex oxide phase intergrowth, grain boundaries, and defects using HAADF-STEM.

    PubMed

    Pyrz, William D; Blom, Douglas A; Sadakane, Masahiro; Kodato, Katsunori; Ueda, Wataru; Vogt, Thomas; Buttrey, Douglas J

    2010-04-01

    In this work, we structurally characterize defects, grain boundaries, and intergrowth phases observed in various Mo-V-O materials using aberration-corrected high-angle annular dark-field (HAADF) imaging within a scanning transmission electron microscope (STEM). Atomic-level imaging of these preparations clearly shows domains of the orthorhombic M1-type phase intergrown with the trigonal phase. Idealized models based on HAADF imaging indicate that atomic-scale registry at the domain boundaries can be seamless with several possible trigonal and M1-type unit cell orientation relationships. The alignment of two trigonal domains separated by an M1-type domain or vice versa can be predicted by identifying the number of rows/columns of parallel symmetry operators. Intergrowths of the M1 catalyst with the M2 phase or with the Mo(5)O(14)-type phase have not been observed. The resolution enhancements provided by aberration-correction have provided new insights to the understanding of phase equilibria of complex Mo-V-O materials. This study exemplifies the utility of STEM for the characterization of local structure at crystalline phase boundaries.

  5. Liquid Crystal based adaptive optics system to compensate both low and high order aberrations in a model eye

    NASA Astrophysics Data System (ADS)

    Mu, Quanquan; Cao, Zhaoliang; Li, Dayu; Hu, Lifa; Xuan, Li

    2007-02-01

    Based on a simple eye model system, a high resolution adaptive optics retina imaging system was built to demonstrate the availability of using liquid crystal devices as a wave-front corrector for both low and high order aberrations. Myopia glass was used to introduce large low order aberrations. A fiber bundle was used to simulate the retina. After correction, its image at different diopters became very clear. We can get a root mean square (RMS) correction precision of lower than 0.049λ (λ=0.63μm) for over to 10 diopters and the modulation transfer function (MTF) retains 511p/mm, which is nearly the diffraction limited resolution for a 2.7mm pupil diameter. The closed loop bandwidth was nearly 4 Hz, which is capable to track most of the aberration dynamics in a real eye.

  6. High-resolution chemical analysis by STEM-EELS of nanosized oxide particles in a mechanically-alloyed FeCrAl intermetallic

    SciTech Connect

    Morris, D.G. Muñoz-Morris, M.A.

    2015-05-15

    The chemical composition of nanosized oxides has been analysed in a mechanically-alloyed (MA) iron–chromium–aluminium intermetallic containing yttria additions using an aberration-corrected, high-resolution scanning transmission electron microscope (STEM). The oxide particles are seen to contain yttrium and oxygen only, but very little of the matrix metallic elements, while the matrix in the immediate vicinity shows a very low iron content. Possible reasons for the change of matrix composition outside the particle-matrix interface are discussed. - Highlights: • High-resolution chemical analysis of oxide particles was performed using STEM-EELS. • Oxide particles contain Y and O but essentially no elements from the Fe–Cr–Al matrix. • The matrix immediately outside the particles appears to be depleted in Fe. • Diffusion of Y during particle growth possibly transports vacancies to the interface.

  7. Laser-induced retinal damage threshold measurements with wavefront correction.

    PubMed

    Lund, Brian J; Lund, David J; Esdall, Peter R

    2008-01-01

    An adaptive optics (AO) system was incorporated into a laser retinal exposure setup in order to correct for refractive error and higher-order aberrations of the nonhuman primate (NHP) eye during an in vivo retinal ED(50) measurement. Using this system, the ED(50) for a 100-ms, 532-nm small spot size exposure was measured to be 1.05 mJ total intraocular energy (TIE), a reduction of 22% from the value measured without aberration correction. The ED(50) for a 3.5-ns, 532-nm exposure was measured to be 0.51 microJ TIE, the lowest ED(50) reported for a ns-duration exposure. This is a reduction of 37% from the value measured without aberration correction and is a factor of only 2.6 higher than the maximum permissible exposure (MPE) for a 3.5-ns, visible wavelength small spot size exposure. The trend of in vitro measurements using retinal explants suggests that the in vivo ED(50) for small spot-size exposures could potentially be one order of magnitude smaller than the previously reported in vivo ED(50). Distortion of the incident laser beam by ocular aberrations cannot fully explain the discrepancy between the in vivo measurements with no aberration correction and the in vitro results.

  8. Implementation of a Shack-Hartmann wavefront sensor for the measurement of embryo-induced aberrations using fluorescent microscopy

    NASA Astrophysics Data System (ADS)

    Azucena, Oscar; Kubby, Joel; Crest, Justin; Cao, Jian; Sullivan, William; Kner, Peter; Gavel, Donald; Dillon, Daren; Olivier, Scot

    2009-02-01

    Adaptive optics (AO) improves the quality of astronomical imaging systems by using real time measurement of the turbulent medium in the optical path using a guide star (natural or artificial) as a point source reference beacon. AO has also been applied to vision science to improve the current view of the human eye. This paper will address our current research focused on the improvement of fluorescent microscopy for biological imaging utilizing current AO technology. A Shack-Hartmann wavefront sensor (SHWS) was used to measure the aberration introduced by a Drosophila Melanogaster embryo with an implanted 1 micron fluorescent bead that serves as a point source reference beacon. The measurements show an average peak-to-valley and root-mean-square (RMS) wavefront error of 0.77 micrometers and 0.15 micrometers, respectively. The Zernike coefficients have been measured for these aberrations which indicate that the correction of the first 14 Zernike coefficients should be sufficient to correct the aberrations we have obtained. These results support the utilization of SHWS for biological imaging applications and that a MEMS deformable mirror with 1 micron of stroke and 100 actuators will be sufficient to correct these aberrations. The design, assembly and initial results for the use of a MEMS deformable mirror, SHWS and implanted fluorescent reference beacon for wavefront correction will also be discussed.

  9. Differentiated Effects of Sensory Activities as Abolishing Operations via Non-Contingent Reinforcement on Academic and Aberrant Behavior

    ERIC Educational Resources Information Center

    Mancil, G. Richmond; Haydon, Todd; Boman, Marty

    2016-01-01

    The purpose of the study was to evaluate the effectiveness of sensory activities used as antecedent interventions on the percentage correct on academic tasks and rate of aberrant behavior in three elementary aged children with Autism Spectrum Disorders (ASD). Study activities were conducted in an after school program for children with ASD where…

  10. TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.

    PubMed

    Matsuda, Taito; Murao, Naoya; Katano, Yuki; Juliandi, Berry; Kohyama, Jun; Akira, Shizuo; Kawai, Taro; Nakashima, Kinichi

    2015-01-01

    Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity. PMID:25751136

  11. TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.

    PubMed

    Matsuda, Taito; Murao, Naoya; Katano, Yuki; Juliandi, Berry; Kohyama, Jun; Akira, Shizuo; Kawai, Taro; Nakashima, Kinichi

    2015-03-09

    Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity.

  12. Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality

    PubMed Central

    Alvarez, Silvia; Díaz, Marcos; Flach, Johanna; Rodriguez-Acebes, Sara; López-Contreras, Andrés J.; Martínez, Dolores; Cañamero, Marta; Fernández-Capetillo, Oscar; Isern, Joan; Passegué, Emmanuelle; Méndez, Juan

    2015-01-01

    Replicative stress during embryonic development influences ageing and predisposition to disease in adults. A protective mechanism against replicative stress is provided by the licensing of thousands of origins in G1 that are not necessarily activated in the subsequent S-phase. These ‘dormant' origins provide a backup in the presence of stalled forks and may confer flexibility to the replication program in specific cell types during differentiation, a role that has remained unexplored. Here we show, using a mouse strain with hypomorphic expression of the origin licensing factor mini-chromosome maintenance (MCM)3 that limiting origin licensing in vivo affects the functionality of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. Mcm3-deficient erythroblasts display aberrant DNA replication patterns and fail to complete maturation, causing lethal anemia. Our results indicate that hematopoietic progenitors are particularly sensitive to replication stress, and full origin licensing ensures their correct differentiation and functionality. PMID:26456157

  13. Jitter Correction

    NASA Technical Reports Server (NTRS)

    Waegell, Mordecai J.; Palacios, David M.

    2011-01-01

    Jitter_Correct.m is a MATLAB function that automatically measures and corrects inter-frame jitter in an image sequence to a user-specified precision. In addition, the algorithm dynamically adjusts the image sample size to increase the accuracy of the measurement. The Jitter_Correct.m function takes an image sequence with unknown frame-to-frame jitter and computes the translations of each frame (column and row, in pixels) relative to a chosen reference frame with sub-pixel accuracy. The translations are measured using a Cross Correlation Fourier transformation method in which the relative phase of the two transformed images is fit to a plane. The measured translations are then used to correct the inter-frame jitter of the image sequence. The function also dynamically expands the image sample size over which the cross-correlation is measured to increase the accuracy of the measurement. This increases the robustness of the measurement to variable magnitudes of inter-frame jitter

  14. A challenging case due to uncommon aberrancies.

    PubMed

    Waleed, Mohammad; Raza, Ali; Minhaj, Tariq; Houghton, Timothy

    2015-09-24

    A 71-year-old man was referred to a rapid access chest pain clinic by his general practitioner. He presented with a 6-month history of twice weekly central chest pain lasting 2-3 min with walking and exertion, relieved with rest or co-codamol tablets. After initial investigations and a positive myoview scan, he was listed for an elective coronary angiogram. Unfortunately, the procedure was abandoned due to unclear course of the guide wire and a possible aberrant aortic course. Further non-invasive tests were arranged to clarify the anatomy of the vessels. After getting a clear idea of the aberrancies, coronary angiogram was replanned, and the patient underwent successful angiography with angioplasty to one of the coronary arteries, without any complications.

  15. Chromosome aberrations among the Yanomamma Indians.

    PubMed

    Bloom, A D; Neel, J V; Choi, K W; Iida, S; Chagnon, N

    1970-07-01

    The chromosomes of leucocytes cultured from the peripheral blood of 49 primitive Yanomama Indians of Venezuela were studied to determine the types and frequencies of aberrations in a human population not exposed to the same exogenous agents as civilized man. In all but one instance, 100 cells per individual were scored. In 13 cases, we found one or more cells with multiple complex breaks and rearrangements, represented by tetracentric, tricentric, and numerous dicentric chromosomes. From the standpoint of chromosomal damage, these cells are among the most abnormal cells yet described in vivo in man, and were not seen in the controls. There was also a higher than expected frequency of cells with an isolated structural aberration in both Indians and controls. This may be the result of a 24- to 48-hour delay in the initiation of culture. The cause of the more extensive damage to some cells remains to be determined.

  16. LSST Telescope Alignment Plan Based on Nodal Aberration Theory

    NASA Astrophysics Data System (ADS)

    Sebag, J.; Gressler, W.; Schmid, T.; Rolland, J. P.; Thompson, K. P.

    2012-04-01

    The optical alignment of the Large Synoptic Survey Telescope (LSST) is potentially challenging, due to its fast three-mirror optical design and its large 3.5° field of view (FOV). It is highly advantageous to align the three-mirror optical system prior to the integration of the complex science camera on the telescope, which corrects the FOV via three refractive elements and includes the operational wavefront sensors. A telescope alignment method based on nodal aberration theory (NAT) is presented here to address this challenge. Without the science camera installed on the telescope, the on-axis imaging performance of the telescope is diffraction-limited, but the field of view is not corrected. The nodal properties of the three-mirror telescope design have been analyzed and an alignment approach has been developed using the intrinsically linear nodal behavior, which is linked via sensitivities to the misalignment parameters. Since mirror figure errors will exist in any real application, a methodology to introduce primary-mirror figure errors into the analysis has been developed and is also presented.

  17. Chromosomal aberrations in oral solitary fibrous tumor.

    PubMed

    Manor, Esther; Bodner, Lipa

    2007-04-15

    The results of cytogenetic analysis of a solitary fibrous tumor (SFT) of the oral cavity in a 43-year-old man is reported. The abnormal cells carried a complex translocation with the karyotype 46,XY [15 cells]/46,XYt(1;17;18)(p13;q11.2;q21)[5 cells]. This is the first case reporting chromosomal aberrations in an oral SFT.

  18. Types of Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  19. Aberrant phenotypes in Kikuchi’s disease

    PubMed Central

    Wei, Xue-Jing; Zhou, Xiao-Ge; Xie, Jian-Lan; Zheng, Xiao-Dan; Zheng, Yuan-Yuan

    2014-01-01

    Initial reports emphasized the immunophenotypic similarities between benign and malignant T cell populations, while some previous studies indicating that aberrant T-cell antigen loss is a good marker for detecting malignant T-cell proliferation. Recently, we found a very interesting and thought-provoking phenomenon: In benign disease-28 of 38 (73.7%) cases of Kikuchi’s disease also showed aberrant phenotypes with loss of pan-T cell antigens, which makes the differential diagnosis between Kikuchi’s disease and T cell lymphoma more challenging. In our study, 38 cases of Kikuchi’s disease and 30 cases of reactive lymphoid hyperplasia (RLH) were studied by EliVision immunohistochemical staining. As well as TCR gene rearrangement using PCR was negative in 10 tested cases of the Kikuchi’s disease. Among these cases, the most common antigen deficiency was CD5 (22 cases), then CD7 (11 cases), CD2 (8 cases) and CD3 (2 cases). Compared with proliferative and xanthomatous types of Kikuchi’s disease, antigens tended to be lost in necrotizing type. Based on follow-up data, a correlation was not found between the occurrence of aberrant phenotypes and prognosis. In RLH, obvious pan-T cell antigen loss was also not found. In conclusion, this is the first study to demonstrate distinct patterns of antigen loss in Kikuchi’s disease, suggesting that T cell antigen loss is not reliable as an auxiliary diagnostic standard for T cell lymphoma. PMID:25337197

  20. Misalignment-induced nodal aberration fields in two-mirror astronomical telescopes.

    PubMed

    Schmid, Tobias; Thompson, Kevin P; Rolland, Jannick P

    2010-06-01

    We present the effects of misalignments on the field dependence of the third-order aberration fields of traditional, two-mirror astronomical telescopes in the context of nodal aberration theory, which we believe is the most general and extensible framework for describing and improving on-station performance. While many of the advantages of nodal aberration theory, compared to other, often power series expansion-based descriptions of misalignment effects on aberrations, become particularly important when analyzing telescopes with more than two mirrors, or in the presence of figure errors; this paper aims to provide and demonstrate the fundamental concepts needed to fully describe the state of correction of misaligned two-mirror telescopes. Importantly, it is shown that the assumption that perfect performance on axis ensures a fully aligned telescope is false, and we demonstrate that if Ritchey-Chrétien telescopes are aligned for zero coma on axis as the sole criterion, formidable misalignments will likely remain, leading to image quality degradation, particularly beyond midfield caused by astigmatism with binodal field dependence (i.e., astigmatism goes to zero at two points in the field).

  1. Uniparental disomy of the entire X chromosome in Turner syndrome patient-specific induced pluripotent stem cells

    PubMed Central

    Luo, Yumei; Zhu, Detu; Du, Rong; Gong, Yu; Xie, Chun; Xu, Xiangye; Fan, Yong; Yu, Bolan; Sun, Xiaofang; Chen, Yaoyong

    2015-01-01

    The human induced pluripotent stem cell (iPSC) technique promises to provide an unlimited, reliable source of genetically matched pluripotent cells for personalized therapy and disease modeling. Recently, it is observed that cells with ring chromosomes 13 or 17 autonomously correct the defects via compensatory uniparental disomy during cellular reprogramming to iPSCs. This breakthrough finding suggests a potential therapeutic approach to repair large-scale chromosomal aberrations. However, due to the scarceness of ring chromosome samples, the reproducibility of this approach in different individuals is not carefully evaluated yet. Moreover, the underlying mechanism and the applicability to other types of chromosomal aberrations remain unknown. Here we generated iPSCs from four 45,X chorionic villous fibroblast lines and found that only one reprogrammed line acquired 46,XX karyotype via uniparental disomy of the entire X chromosome. The karyotype correction was reproducible in the same cell line by either retroviral or episomal reprogramming. The karyotype-corrected iPSCs were subject to X chromosome inactivation and obtained better colony morphology and higher proliferation rate than other uncorrected ones. Further transcriptomic comparison among the fibroblast lines identified a distinct expression pattern of cell cycle regulators in the uncorrectable ones. These findings demonstrate that the iPSC technique holds the potential to correct X monosomy, but the correction rate is very low, probably due to differential regulation of cell cycle genes between individuals. Our data strongly suggest that more systematic investigations are needed before defining the iPSC technique as a novel means of chromosome therapy. PMID:27462421

  2. Chromatic variation of aberration: the role of induced aberrations and raytrace direction

    NASA Astrophysics Data System (ADS)

    Berner, A.; Nobis, T.; Shafer, D.; Gross, H.

    2015-09-01

    The design and optimization process of an optical system contains several first order steps. The definition of the appropriate lens type and the fixation of the raytrace direction are some of them. The latter can be understood as a hidden assumption rather than an aware design step. This is usually followed by the determination of the paraxial lens layout calculated for the primary wavelength. It is obvious, that for this primary wavelength the paraxial calculations are independent of raytrace direction. Today, most of the lens designs are specified not to work only for one wavelength, but in a certain wavelength range. Considering such rays of other wavelengths, one can observe that depending on the direction there will already occur differences in the first order chromatic aberrations and additionally in the chromatic variation of the third-order aberrations. The reason for this effect are induced aberrations emerging from one surface to the following surfaces by perturbed ray heights and ray angles. It can be shown, that the total amount of surface-resolved first order chromatic aberrations and the chromatic variation of the five primary aberrations can be split into an intrinsic part and an induced part. The intrinsic part is independent of the raytrace direction whereas the induced part is not.

  3. Development of high-resolution cathodoluminescence system for STEM and application to plasmonic nanostructures.

    PubMed

    Yamamoto, Naoki

    2016-08-01

    A high-resolution cathodoluminescence (CL) system for scanning transmission electron microscope (STEM) has been developed by employing a field emission gun and a spherical aberration corrector, which realizes a probe size of 1 nm even at an accelerating voltage of 80 kV and beam current of the order of 1 nA. Angle resolved measurement of light emission from a sample in the STEM is possible by combining a parabolic mirror and position-controlled pinhole. CL spectra are successively acquired by a highly sensitive charge-coupled device while scanning the incident electron beam or pinhole, which enables various detection modes, i.e. (i) angle resolved spectral pattern, (ii) beam scan spectral image and (iii) photon map. In order to calibrate the acquired spectrum, the correction function is created from the comparison between the observed and theoretical spectra of the transition radiation. Furthermore, the modification of polarization by the parabolic mirror is discussed. Some examples of the applications of the STEM-CL system to plasmonics are presented to demonstrate the unique measurement features of the CL system, i.e. (i) multipole modes in silver nanoparticles, (ii) surface plasmon polariton modes in a 2D plasmonic crystal and (iii) localized surface plasmon modes in a gold bow tie nano-antenna.

  4. Development of high-resolution cathodoluminescence system for STEM and application to plasmonic nanostructures.

    PubMed

    Yamamoto, Naoki

    2016-08-01

    A high-resolution cathodoluminescence (CL) system for scanning transmission electron microscope (STEM) has been developed by employing a field emission gun and a spherical aberration corrector, which realizes a probe size of 1 nm even at an accelerating voltage of 80 kV and beam current of the order of 1 nA. Angle resolved measurement of light emission from a sample in the STEM is possible by combining a parabolic mirror and position-controlled pinhole. CL spectra are successively acquired by a highly sensitive charge-coupled device while scanning the incident electron beam or pinhole, which enables various detection modes, i.e. (i) angle resolved spectral pattern, (ii) beam scan spectral image and (iii) photon map. In order to calibrate the acquired spectrum, the correction function is created from the comparison between the observed and theoretical spectra of the transition radiation. Furthermore, the modification of polarization by the parabolic mirror is discussed. Some examples of the applications of the STEM-CL system to plasmonics are presented to demonstrate the unique measurement features of the CL system, i.e. (i) multipole modes in silver nanoparticles, (ii) surface plasmon polariton modes in a 2D plasmonic crystal and (iii) localized surface plasmon modes in a gold bow tie nano-antenna. PMID:27473259

  5. Review: Aberrant EVI1 expression in acute myeloid leukaemia.

    PubMed

    Hinai, Adil A; Valk, Peter J M

    2016-03-01

    Deregulated expression of the ecotropic virus integration site 1 (EVI1) gene is the molecular hallmark of therapy-resistant myeloid malignancies bearing chromosomal inv(3)(q21q26·2) or t(3;3)(q21;q26·2) [hereafter referred to as inv(3)/t(3;3)] abnormalities. EVI1 is a haematopoietic stemness and transcription factor with chromatin remodelling activity. Interestingly, the EVI1 gene also shows overexpression in 6-11% of adult acute myeloid leukaemia (AML) cases that do not carry any 3q aberrations. Deregulated expression of EVI1 is strongly associated with monosomy 7 and 11q23 abnormalities, which are known to be associated with poor response to treatment. However, EVI1 overexpression has been revealed as an important independent adverse prognostic marker in adult AML and defines distinct risk categories in 11q23-rearranged AML. Recently, important progress has been made in the delineation of the mechanism by which EVI1 becomes deregulated in inv(3)/t(3;3) as well as the cooperating mutations in this specific subset of AML with dismal prognosis.

  6. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    SciTech Connect

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  7. Freeform mirror polishing for compensation on non-symmetry system aberrations of remote sensing instrument

    NASA Astrophysics Data System (ADS)

    Kuo, Ching-Hsiang; Yu, Zong-Ru; Ho, Cheng-Fang; Hsu, Wei-Yao; Chen, Fong-Zhi

    2013-09-01

    Cassegrain optical systems are widely used in remote sensing instrument. Cassegrain telescope is composed of a primary mirror (M1), a secondary mirror (M2), and a set of correction lenses. The system aberrations of telescope could be corrected and balanced by M1 and M2. In the event of deformation of telescope assembly, the non-symmetry aberrations will be induced to the optical system and reduce the optical performance. The non-symmetry aberrations can be measured after completing M1 and M2 assembly and alignment processes. Compensating this identified error to M1 or M2 can improve the optical performance of the telescope system. The error compensation on M2 is more efficient due to its smaller aperture and quickly assembly and de-assembly processes. In this study, we map the system wavefront error caused by deformation of mirror supporting and gravity onto the designed aspheric surface of M2. The surface of M2 becomes a freeform from aspheric. The polishing process combines the techniques of conventional lapping and CNC polishing. We apply the conventional spherical lapping process to quick remove the sub-surface damage (SSD) layer and to get the accurate radius of best fit sphere of the designed aspheric surface with fine surface texture simultaneously. The polishing and metrology processes were performed by using Zeeko IRP1000 polisher and QED ASI. A Φ 150 mm mirror with freeform surface was completed.

  8. STEM Sell

    ERIC Educational Resources Information Center

    Pantic, Zorica

    2007-01-01

    Between 1994 and 2003, employment in science, technology, engineering and math (STEM) fields grew by a remarkable 23 percent, compared with 17 percent in non-STEM fields, according to federal data. The Bureau of Labor Statistics predicts continued strong growth in STEM job openings through 2014, with emphasis on life sciences, environmental…

  9. Wavefront aberrations of x-ray dynamical diffraction beams.

    PubMed

    Liao, Keliang; Hong, Youli; Sheng, Weifan

    2014-10-01

    The effects of dynamical diffraction in x-ray diffractive optics with large numerical aperture render the wavefront aberrations difficult to describe using the aberration polynomials, yet knowledge of them plays an important role in a vast variety of scientific problems ranging from optical testing to adaptive optics. Although the diffraction theory of optical aberrations was established decades ago, its application in the area of x-ray dynamical diffraction theory (DDT) is still lacking. Here, we conduct a theoretical study on the aberration properties of x-ray dynamical diffraction beams. By treating the modulus of the complex envelope as the amplitude weight function in the orthogonalization procedure, we generalize the nonrecursive matrix method for the determination of orthonormal aberration polynomials, wherein Zernike DDT and Legendre DDT polynomials are proposed. As an example, we investigate the aberration evolution inside a tilted multilayer Laue lens. The corresponding Legendre DDT polynomials are obtained numerically, which represent balanced aberrations yielding minimum variance of the classical aberrations of an anamorphic optical system. The balancing of classical aberrations and their standard deviations are discussed. We also present the Strehl ratio of the primary and secondary balanced aberrations.

  10. Chromosomal aberrations in ISS crew members

    NASA Astrophysics Data System (ADS)

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  11. Predicting aberrant CpG island methylation

    PubMed Central

    Feltus, F. A.; Lee, E. K.; Costello, J. F.; Plass, C.; Vertino, P. M.

    2003-01-01

    Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss of tumor suppressor function in human cancer. Profiling of CpG island methylation indicates that some genes are more frequently methylated than others, and that each tumor type is associated with a unique set of methylated genes. However, little is known about why certain genes succumb to this aberrant event. To address this question, we used Restriction Landmark Genome Scanning to analyze the susceptibility of 1,749 unselected CpG islands to de novo methylation driven by overexpression of DNA cytosine-5-methyltransferase 1 (DNMT1). We found that although the overall incidence of CpG island methylation was increased in cells overexpressing DNMT1, not all loci were equally affected. The majority of CpG islands (69.9%) were resistant to de novo methylation, regardless of DNMT1 overexpression. In contrast, we identified a subset of methylation-prone CpG islands (3.8%) that were consistently hypermethylated in multiple DNMT1 overexpressing clones. Methylation-prone and methylation-resistant CpG islands were not significantly different with respect to size, C+G content, CpG frequency, chromosomal location, or promoter association. We used DNA pattern recognition and supervised learning techniques to derive a classification function based on the frequency of seven novel sequence patterns that was capable of discriminating methylation-prone from methylation-resistant CpG islands with 82% accuracy. The data indicate that CpG islands differ in their intrinsic susceptibility to de novo methylation, and suggest that the propensity for a CpG island to become aberrantly methylated can be predicted based on its sequence context. PMID:14519846

  12. Aberrations in Fresnel Lenses and Mirrors

    NASA Technical Reports Server (NTRS)

    Gregory, Don

    1999-01-01

    The NASA/MSFC Shooting Star program revealed a number of technical problems that must be solved before solar thermal propulsion can become a reality. The fundamental problem of interest here is the collection of solar energy. This is the first step in the propulsion process and indeed the most important. Everything else depends on the efficiency and focusing ability of the collection lens or mirror. An initial model of Fresnel lens behavior using a wave optics approach has been completed and the results were encouraging enough to warrant an experimental investigation. This experimental investigation confirmed some of the effects predicted and produced invaluable photographic evidence of coherence based diffraction and aberration.

  13. Aberrant splicing and drug resistance in AML.

    PubMed

    de Necochea-Campion, Rosalia; Shouse, Geoffrey P; Zhou, Qi; Mirshahidi, Saied; Chen, Chien-Shing

    2016-01-01

    The advent of next-generation sequencing technologies has unveiled a new window into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent mutations in spliceosome machinery and genome-wide aberrant splicing events have been recognized as a prominent component of this disease. This review will focus on how these factors influence drug resistance through altered splicing of tumor suppressor and oncogenes and dysregulation of the apoptotic signaling network. A better understanding of these factors in disease progression is necessary to design appropriate therapeutic strategies recognizing specific alternatively spliced or mutated oncogenic targets. PMID:27613060

  14. Aberration-free volumetric high-speed imaging of in vivo retina

    PubMed Central

    Hillmann, Dierck; Spahr, Hendrik; Hain, Carola; Sudkamp, Helge; Franke, Gesa; Pfäffle, Clara; Winter, Christian; Hüttmann, Gereon

    2016-01-01

    Certain topics in research and advancements in medical diagnostics may benefit from improved temporal and spatial resolution during non-invasive optical imaging of living tissue. However, so far no imaging technique can generate entirely diffraction-limited tomographic volumes with a single data acquisition, if the target moves or changes rapidly, such as the human retina. Additionally, the presence of aberrations may represent further difficulties. We show that a simple interferometric setup–based on parallelized optical coherence tomography–acquires volumetric data with 10 billion voxels per second, exceeding previous imaging speeds by an order of magnitude. This allows us to computationally obtain and correct defocus and aberrations resulting in entirely diffraction-limited volumes. As demonstration, we imaged living human retina with clearly visible nerve fiber layer, small capillary networks, and photoreceptor cells. Furthermore, the technique can also obtain phase-sensitive volumes of other scattering structures at unprecedented acquisition speeds. PMID:27762314

  15. Cancer Genes Hypermethylated in Human Embryonic Stem Cells

    PubMed Central

    Calvanese, Vincenzo; Horrillo, Angelica; Hmadcha, Abdelkrim; Suarez-Álvarez, Beatriz; Fernandez, Agustín F.; Lara, Ester; Casado, Sara; Menendez, Pablo; Bueno, Clara; Garcia-Castro, Javier; Rubio, Ruth; Lapunzina, Pablo; Alaminos, Miguel; Borghese, Lodovica; Terstegge, Stefanie; Harrison, Neil J.; Moore, Harry D.; Brüstle, Oliver; Lopez-Larrea, Carlos; Andrews, Peter W.; Soria, Bernat; Esteller, Manel; Fraga, Mario F.

    2008-01-01

    Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation. PMID:18820729

  16. Shadow images for in-line holography in a STEM instrument.

    PubMed

    Wang, S Y; Cowley, J M

    1995-02-01

    In a dedicated STEM instrument equipped with a field emission gun, shadow images are easily obtained and have many uses. They are very sensitive to misalignment of the instrument and astigmatism, and therefore can be used for rapid and accurate alignment of the microscope. For crystalline materials, the shadow image contains both the bright-field and dark-field images. It is a summation of the transmitted and diffracted beams, and is basically a kind of Gabor's in-line hologram. Under small or medium defocus, shadow images of a thin, well-orientated crystalline specimen take the characteristic form of Ronchigrams, which offer a unique means to calibrate the microscope operation parameters, such as the spherical aberration coefficient Cs and defocus settings of the objective lens, with high accuracy. With the calibrated values of Cs and delta, a transfer function of the objective lens may be generated. In the stage of numerical reconstruction, by adapting this transfer function to the experimentally recorded hologram the lens aberration introduced in forming the hologram may be corrected and an improved resolution may be achieved for electron microscope images.

  17. A Monte-Carlo Model for the Formation of Radiation-induced Chromosomal Aberrations

    NASA Technical Reports Server (NTRS)

    Ponomarev, Artem L.; Cornforth, Michael N.; Loucas, Brad D.; Cucinotta, Francis A.

    2009-01-01

    multi-centrics were also recorded. Conclusion: High-LET DNA damage affects the frequencies of chromosomal aberrations. The ratio of rings to dicentrics is correct for the genomic size cut-offs corresponding to available experimental data. The present work predicts a relative abundance of small rings following irradiation by heavy ions.

  18. When things go wrong: correcting the scientific record

    PubMed Central

    Pulverer, Bernd

    2015-01-01

    A reliable scientific literature is crucial for an efficient research process. Peer review remains a highly successful quality assurance mechanism, but it does not always prevent data and image aberrations and the publication of flawed data. Journals need to be in a position to detect such problems and take proportionate action. Publishers should apply consistent policies to correcting the published literature and adopt versioning. The scientific community ought to encourage corrections. PMID:26467018

  19. Aberration measurement from specific photolithographic images: a different approach.

    PubMed

    Nomura, H; Tawarayama, K; Kohno, T

    2000-03-01

    Techniques for measurement of higher-order aberrations of a projection optical system in photolithographic exposure tools have been established. Even-type and odd-type aberrations are independently obtained from printed grating patterns on a wafer by three-beam interference under highly coherent illumination. Even-type aberrations, i.e., spherical aberration and astigmatism, are derived from the best focus positions of vertical, horizontal, and oblique grating patterns by an optical microscope. Odd-type aberrations, i.e., coma and three-foil, are obtained by detection of relative shifts of a fine grating pattern to a large pattern by an overlay inspection tool. Quantitative diagnosis of lens aberrations with a krypton fluoride (KrF) excimer laser scanner is demonstrated.

  20. Lymphocyte chromosomal aberration assay in radiation biodosimetry

    PubMed Central

    Agrawala, Paban K.; Adhikari, J. S.; Chaudhury, N. K.

    2010-01-01

    Exposure to ionizing radiations, whether medical, occupational or accidental, leads to deleterious biological consequences like mortality or carcinogenesis. It is considered that no dose of ionizing radiation exposure is safe. However, once the accurate absorbed dose is estimated, one can be given appropriate medical care and the severe consequences can be minimized. Though several accurate physical dose estimation modalities exist, it is essential to estimate the absorbed dose in biological system taking into account the individual variation in radiation response, so as to plan suitable medical care. Over the last several decades, lots of efforts have been taken to design a rapid and easy biological dosimeter requiring minimum invasive procedures. The metaphase chromosomal aberration assay in human lymphocytes, though is labor intensive and requires skilled individuals, still remains the gold standard for radiation biodosimetry. The current review aims at discussing the human lymphocyte metaphase chromosomal aberration assay and recent developments involving the application of molecular cytogenetic approaches and other technological advancements to make the assay more authentic and simple to use even in the events of mass radiation casualties. PMID:21829315

  1. Relationships between chromosome structure and chromosomal aberrations

    NASA Astrophysics Data System (ADS)

    Eidelman, Yuri; Andreev, Sergey

    An interphase nucleus of human lymphocyte was simulated by the novel Monte Carlo tech-nique. The main features of interphase chromosome structure and packaging were taken into account: different levels of chromatin organisation; nonrandom localisation of chromosomes within a nucleus; chromosome loci dynamics. All chromosomes in a nucleus were modelled as polymer globules. A dynamic pattern of intra/interchromosomal contacts was simulated. The detailed information about chromosomal contacts, such as distribution of intrachromoso-mal contacts over the length of each chromosome and dependence of contact probability on genomic separation between chromosome loci, were calculated and compared to the new exper-imental data obtained by the Hi-C technique. Types and frequencies of simple and complex radiation-induced chromosomal exchange aberrations (CA) induced by X-rays were predicted with taking formation and decay of chromosomal contacts into account. Distance dependence of exchange formation probability was calculated directly. mFISH data for human lymphocytes were analysed. The calculated frequencies of simple CA agreed with the experimental data. Complex CA were underestimated despite the dense packaging of chromosome territories within a nucleus. Possible influence of chromosome-nucleus structural organisation on the frequency and spectrum of radiation-induced chromosome aberrations is discussed.

  2. A CORRECTION.

    PubMed

    Johnson, D

    1940-03-22

    IN a recently published volume on "The Origin of Submarine Canyons" the writer inadvertently credited to A. C. Veatch an excerpt from a submarine chart actually contoured by P. A. Smith, of the U. S. Coast and Geodetic Survey. The chart in question is Chart IVB of Special Paper No. 7 of the Geological Society of America entitled "Atlantic Submarine Valleys of the United States and the Congo Submarine Valley, by A. C. Veatch and P. A. Smith," and the excerpt appears as Plate III of the volume fist cited above. In view of the heavy labor involved in contouring the charts accompanying the paper by Veatch and Smith and the beauty of the finished product, it would be unfair to Mr. Smith to permit the error to go uncorrected. Excerpts from two other charts are correctly ascribed to Dr. Veatch. PMID:17839404

  3. A CORRECTION.

    PubMed

    Johnson, D

    1940-03-22

    IN a recently published volume on "The Origin of Submarine Canyons" the writer inadvertently credited to A. C. Veatch an excerpt from a submarine chart actually contoured by P. A. Smith, of the U. S. Coast and Geodetic Survey. The chart in question is Chart IVB of Special Paper No. 7 of the Geological Society of America entitled "Atlantic Submarine Valleys of the United States and the Congo Submarine Valley, by A. C. Veatch and P. A. Smith," and the excerpt appears as Plate III of the volume fist cited above. In view of the heavy labor involved in contouring the charts accompanying the paper by Veatch and Smith and the beauty of the finished product, it would be unfair to Mr. Smith to permit the error to go uncorrected. Excerpts from two other charts are correctly ascribed to Dr. Veatch.

  4. Aberration influenced generation of rotating two-lobe light fields

    NASA Astrophysics Data System (ADS)

    Kotova, S. P.; Losevsky, N. N.; Prokopova, D. V.; Samagin, S. A.; Volostnikov, V. G.; Vorontsov, E. N.

    2016-08-01

    The influence of aberrations on light fields with a rotating intensity distribution is considered. Light fields were generated with the phase masks developed using the theory of spiral beam optics. The effects of basic aberrations, such as spherical aberration, astigmatism and coma are studied. The experimental implementation of the fields was achieved with the assistance of a liquid crystal spatial light modulator HOLOEYE HEO-1080P, operating in reflection mode. The results of mathematical modelling and experiments have been qualitatively compared.

  5. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal

    PubMed Central

    Zhao, Zhen; Zuber, Johannes; Diaz-Flores, Ernesto; Lintault, Laura; Kogan, Scott C.; Shannon, Kevin; Lowe, Scott W.

    2010-01-01

    The p53 tumor suppressor limits proliferation in response to cellular stress through several mechanisms. Here, we test whether the recently described ability of p53 to limit stem cell self-renewal suppresses tumorigenesis in acute myeloid leukemia (AML), an aggressive cancer in which p53 mutations are associated with drug resistance and adverse outcome. Our approach combined mosaic mouse models, Cre-lox technology, and in vivo RNAi to disable p53 and simultaneously activate endogenous KrasG12D—a common AML lesion that promotes proliferation but not self-renewal. We show that p53 inactivation strongly cooperates with oncogenic KrasG12D to induce aggressive AML, while both lesions on their own induce T-cell malignancies with long latency. This synergy is based on a pivotal role of p53 in limiting aberrant self-renewal of myeloid progenitor cells, such that loss of p53 counters the deleterious effects of oncogenic Kras on these cells and enables them to self-renew indefinitely. Consequently, myeloid progenitor cells expressing oncogenic Kras and lacking p53 become leukemia-initiating cells, resembling cancer stem cells capable of maintaining AML in vivo. Our results establish an efficient new strategy for interrogating oncogene cooperation, and provide strong evidence that the ability of p53 to limit aberrant self-renewal contributes to its tumor suppressor activity. PMID:20595231

  6. [A case of central nervous system myelomatosis with complex chromosome aberrations].

    PubMed

    Bang, Hae In; Yoo, Jin Young; Kim, Kyoung Ha; Park, Rojin; Shin, Jeong Won; Choi, Tae Youn; Lee, Sang Cheol; Park, Hee Sook; Won, Jong Ho

    2010-08-01

    Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later, the patient expired.

  7. Aberration design of zoom lens systems using thick lens modules.

    PubMed

    Zhang, Jinkai; Chen, Xiaobo; Xi, Juntong; Wu, Zhuoqi

    2014-12-20

    A systematic approach for the aberration design of a zoom lens system using a thick lens module is presented. Each component is treated as a thick lens module at the beginning of the design. A thick lens module refers to a thick lens component with a real lens structure, like lens materials, lens curvatures, lens thicknesses, and lens interval distances. All nine third-order aberrations of a thick lens component are considered during the design. The relationship of component aberrations in different zoom positions can be approximated from the aberration shift. After minimizing the aberrations of the zoom lens system, the nine third-order aberrations of every lens component can be determined. Then the thick lens structure of every lens component can be determined after optimization according to their first-order properties and third-order aberration targets. After a third optimization for minimum practical third-order aberrations of a zoom lens system, the aberration design using the thick lens module is complete, which provides a practical zoom lens system with thick lens structures. A double-sided telecentric zoom lens system is designed using the thick lens module in this paper, which shows that this method is practical for zoom lens design.

  8. Transverse ray aberrations of Wolter type 1 telescopes

    NASA Technical Reports Server (NTRS)

    Saha, Timo T.

    1986-01-01

    Transverse ray aberration expansions are derived for Wolter type 1 telescopes. The analysis gives third order aberration terms, most of the fifth order terms and two seventh order terms as functions of system parameters and entrance aperture coordinates. The third order distortion is negligible and, therefore, this term is omitted in the expansions. The spot diagrams derived from exact ray tracing and aberration expansions agree well. The importance of fifth and seventh order terms is discussed. The derived aberration expansions are also valid for Wolter type 2 telescopes.

  9. Aberrant glycosylation associated with enzymes as cancer biomarkers

    PubMed Central

    2011-01-01

    Background One of the new roles for enzymes in personalized medicine builds on a rational approach to cancer biomarker discovery using enzyme-associated aberrant glycosylation. A hallmark of cancer, aberrant glycosylation is associated with differential expressions of enzymes such as glycosyltransferase and glycosidases. The aberrant expressions of the enzymes in turn cause cancer cells to produce glycoproteins with specific cancer-associated aberrations in glycan structures. Content In this review we provide examples of cancer biomarker discovery using aberrant glycosylation in three areas. First, changes in glycosylation machinery such as glycosyltransferases/glycosidases could be used as cancer biomarkers. Second, most of the clinically useful cancer biomarkers are glycoproteins. Discovery of specific cancer-associated aberrations in glycan structures of these existing biomarkers could improve their cancer specificity, such as the discovery of AFP-L3, fucosylated glycoforms of AFP. Third, cancer-associated aberrations in glycan structures provide a compelling rationale for discovering new biomarkers using glycomic and glycoproteomic technologies. Summary As a hallmark of cancer, aberrant glycosylation allows for the rational design of biomarker discovery efforts. But more important, we need to translate these biomarkers from discovery to clinical diagnostics using good strategies, such as the lessons learned from translating the biomarkers discovered using proteomic technologies to OVA 1, the first FDA-cleared In Vitro Diagnostic Multivariate Index Assay (IVDMIA). These lessons, providing important guidance in current efforts in biomarker discovery and translation, are applicable to the discovery of aberrant glycosylation associated with enzymes as cancer biomarkers as well. PMID:21906357

  10. Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer.

    PubMed

    Zhao, Ronghua; Casson, Alan G

    2008-09-01

    Squamous cell carcinoma of the esophagus is one of the ten most frequent malignancies worldwide, characterized by a striking geographic variation in incidence. In North America and Europe, there has recently been a marked change in the epidemiology of this disease, where incidence rates for primary esophageal adenocarcinoma have increased in excess of any other human solid tumor. Although the reasons for this are largely unknown, several molecular genetic alterations have been associated with esophageal tumor progression. In recent years, epigenetic aberrations have been increasingly recognized as an important alternative mechanism of carcinogenesis and it is anticipated that substantial progress in the treatment of esophageal malignancy will likely only be made with a clearer understanding of esophageal tumor biology. Whereas genetic mutations, deletions, or allelic losses are fixed and irreversible, epigenetic abnormalities can potentially be corrected without interfering with the fundamental sequence of the target gene. Our current understanding of epigenetics in esophageal cancer, and the potential for targeted epigenetic therapy, will be the subject of this review.

  11. Overlapped Fourier coding for optical aberration removal

    PubMed Central

    Horstmeyer, Roarke; Ou, Xiaoze; Chung, Jaebum; Zheng, Guoan; Yang, Changhuei

    2014-01-01

    We present an imaging procedure that simultaneously optimizes a camera’s resolution and retrieves a sample’s phase over a sequence of snapshots. The technique, termed overlapped Fourier coding (OFC), first digitally pans a small aperture across a camera’s pupil plane with a spatial light modulator. At each aperture location, a unique image is acquired. The OFC algorithm then fuses these low-resolution images into a full-resolution estimate of the complex optical field incident upon the detector. Simultaneously, the algorithm utilizes redundancies within the acquired dataset to computationally estimate and remove unknown optical aberrations and system misalignments via simulated annealing. The result is an imaging system that can computationally overcome its optical imperfections to offer enhanced resolution, at the expense of taking multiple snapshots over time. PMID:25321982

  12. Patterns of Chromosomal Aberrations in Solid Tumors.

    PubMed

    Grade, Marian; Difilippantonio, Michael J; Camps, Jordi

    2015-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  13. Aberrant pancreatic ductal organisation: a case report.

    PubMed

    Goel, Shivi; Rustagi, Shaifaly Madan; Saha, Susmita; Mehta, Vandana; Suri, Rajesh Kumar; Rath, Gayatri

    2015-07-01

    Anomalous pancreatic ductal system has always enthralled the anatomists, surgeons, gastroenterologists and radiologists alike. With the growing use of MRCP, ERCP and endoscopic and surgical procedures, the knowledge of anatomical aberrations of pancreaticobiliary tract becomes extremely important. Moreover, the anomalous pancreatic duct morphology may be responsible for atypical gastrointestinal complains. We report an exceptionally rare case of two accessory ventral pancreatic ducts opening separately into the common bile duct proximal to the hepato pancreatic ampulla. Concomitant occurrence of an ectopic major duodenal papilla, 3.8 cm distal to the pyloric end of stomach was also seen. Moreover, the accessory pancreatic duct and the minor duodenal papilla were absent. Clinical implications and embryological description of these rare anomalies are discussed. Awareness of such rare morphological variants can go a long way in assisting effective patient management.

  14. Patterns of Chromosomal Aberrations in Solid Tumors

    PubMed Central

    Grade, Marian; Difilippantonio, Michael J.

    2016-01-01

    Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID:26376875

  15. Structural aberrations in group A Staphylococcus bacteriophages.

    PubMed Central

    Ackermann, H W; Berthiaume, L; Sonea, S; Kasatiya, S S

    1976-01-01

    Six related Staphylococcus phages spontaneously produced various abnormal head and tail structures: (i) giant capsids which were tailed and apparently contained nucleic acid; (ii) regular and irregular smooth polyheads; (iii) heads and polyheads with wavy outlines; (iv) mottled heads and polyheads; (v) abnormally long and short tails; and (vi) "double capsids" connected by a small bridge. Some of these structures are rare, or have not yet been reported. The frequency os specific aberrant particles varied from one phage to another. Length distribution of smooth irregular polyheads and of abnormal tails indicated that these structures assemble at random from protein synthesized in excess. These phages represent an interesting model for genetic and morphogentic studies. Images PMID:131865

  16. Aberrant diagnoses by individual surgical pathologists.

    PubMed

    Wakely, S L; Baxendine-Jones, J A; Gallagher, P J; Mullee, M; Pickering, R

    1998-01-01

    Methods of auditing the performance of histopathologists, such as external and internal quality assurance, clinicopathological conferences, and "double-reporting" of microscopic slides, show significant diagnostic errors in at least 1.2% of reports. Although some of these are in well-recognized areas of difficulty, such as melanoma or lymphoma, most errors are in common biopsy specimens. We have developed a method that compares diagnostic patterns of individual histopathologists. This aims to identify specific diagnoses that a pathologist makes more or less frequently than other colleagues and enables the individual to reflect on his or her own histologic expertise in reporting on specific biopsy results. The bottom line diagnoses of transurethral resection of prostate specimens; rectal, gastric, and bladder biopsy samples; and endometrial curettages were analyzed retrospectively. Analyses were performed on diagnoses made by at least 15 pathologists on each specimen type and expressed as a standardized ratio (SR) with 95% confidence intervals (CI). An SR of 1.0 indicated a pattern of diagnosis matching the combined pattern of other colleagues. An SR <1.0 indicated relative "underdiagnosis" and an SR >1.0 indicated relative "overdiagnosis." Diagnostic rates of individual pathologists whose CIs did not straddle the value of 1.0 were considered aberrant, although not necessarily incorrect. The 47 of 226 (20.8%) aberrant SRs included four pathologists' diagnoses of prostatic carcinoma, three each of endometrial, rectal, and bladder carcinoma, and one of gastric malignancy. This method, which could easily be automated and used regionally or nationally, should provide pathologists with a profile of their diagnostic patterns in comparison with their peers.

  17. Congenital Aberrant Tearing: A Re-Look

    PubMed Central

    Miller, Marilyn T.; Strömland, Kerstin; Ventura, Liana

    2008-01-01

    Purpose Congenital aberrant tearing is characterized by tearing when eating (“crocodile tears”), lack of emotional tearing, or both. Most reported cases are associated with Duane syndrome. In our previous studies we observed aberrant tearing in individuals with thalidomide embryopathy and Möbius sequence. This report summarizes the literature on the subject and adds 3 new studies that give information on this unusual condition. Methods Twenty-eight individuals with Möbius sequence were interviewed about tearing symptoms at a support group meeting in Italy. In Sweden 30 adults primarily from the original thalidomide series were reexamined. In this latter study, a Schirmer test was done at baseline and repeated 5 minutes after eating. Twenty families in Brazil who have children with Möbius sequence were questioned about tearing symptoms and exposure to misoprostol during pregnancy. Results In the 28 Italian individuals, either “crocodile tears” or lack of emotional tearing was noted in 7 cases. In the thalidomide study, 10 of 30 patients had tearing when eating and 7 had no emotional tearing. Low Schirmer scores or increased tearing after eating was noted in a few asymptomatic individuals. Among the 20 Brazilian children with Möbius sequence, 10 had some tearing abnormality. Conclusion Congenital anomalous lacrimation is rare but usually associated with Duane syndrome or abduction deficits, as in Möbius sequence and, less frequently, facial nerve palsy. Studies implicate an early insult in development at 4 to 6 weeks. At that time the facial nerve, sixth nerve, and lacrimal nucleus are in close proximity in the embryo. PMID:19277226

  18. Three-dimensional motion correction using speckle and phase for in vivo computed optical interferometric tomography

    PubMed Central

    Shemonski, Nathan D.; Ahn, Shawn S.; Liu, Yuan-Zhi; South, Fredrick A.; Carney, P. Scott; Boppart, Stephen A.

    2014-01-01

    Over the years, many computed optical interferometric techniques have been developed to perform high-resolution volumetric tomography. By utilizing the phase and amplitude information provided with interferometric detection, post-acquisition corrections for defocus and optical aberrations can be performed. The introduction of the phase, though, can dramatically increase the sensitivity to motion (most prominently along the optical axis). In this paper, we present two algorithms which, together, can correct for motion in all three dimensions with enough accuracy for defocus and aberration correction in computed optical interferometric tomography. The first algorithm utilizes phase differences within the acquired data to correct for motion along the optical axis. The second algorithm utilizes the addition of a speckle tracking system using temporally- and spatially-coherent illumination to measure motion orthogonal to the optical axis. The use of coherent illumination allows for high-contrast speckle patterns even when imaging apparently uniform samples or when highly aberrated beams cannot be avoided. PMID:25574426

  19. Characterization of conductive nanobiomaterials derived from viral assemblies by low-voltage STEM imaging and Raman scattering

    NASA Astrophysics Data System (ADS)

    Plascencia-Villa, Germán; Carreño-Fuentes, Liliana; Bahena, Daniel; José-Yacamán, Miguel; Palomares, Laura A.; Ramírez, Octavio T.

    2014-09-01

    New technologies require the development of novel nanomaterials that need to be fully characterized to achieve their potential. High-resolution low-voltage scanning transmission electron microscopy (STEM) has proven to be a very powerful technique in nanotechnology, but its use for the characterization of nanobiomaterials has been limited. Rotavirus VP6 self-assembles into nanotubular assemblies that possess an intrinsic affinity for Au ions. This property was exploited to produce hybrid nanobiomaterials by the in situ functionalization of recombinant VP6 nanotubes with gold nanoparticles. In this work, Raman spectroscopy and advanced analytical electron microscopy imaging with spherical aberration-corrected (Cs) STEM and nanodiffraction at low-voltage doses were employed to characterize nanobiomaterials. STEM imaging revealed the precise structure and arrangement of the protein templates, as well as the nanostructure and atomic arrangement of gold nanoparticles with high spatial sub-Angstrom resolution and avoided radiation damage. The imaging was coupled with backscattered electron imaging, ultra-high resolution scanning electron microscopy and x-ray spectroscopy. The hybrid nanobiomaterials that were obtained showed unique properties as bioelectronic conductive devices and showed enhanced Raman scattering by their precise arrangement into superlattices, displaying the utility of viral assemblies as functional integrative self-assembled nanomaterials for novel applications.

  20. Optical aberrations measurement with a low cost optometric instrument

    NASA Astrophysics Data System (ADS)

    Furlan, Walter D.; Muñoz-Escrivá, L.; Pons, A.; Martínez-Corral, M.

    2002-08-01

    A simple experimental method for measuring optical aberrations of a single lens is proposed. The technique is based on the use of an optometric instrument employed for the assessment of the refractive state of the eye: the retinoscope. Experimental results for spherical aberration and astigmatism are obtained.

  1. Using Brief Assessments to Evaluate Aberrant Behavior Maintained by Attention.

    ERIC Educational Resources Information Center

    O'Reilly, Mark F.; Lancioni, Giulio E.; King, Lisa; Lally, Grainne; Dhomhnaill, Orla Nic

    2000-01-01

    Functional assessments were conducted for two Irish individuals with severe disabilities and aberrant behavior. A modified attention condition was introduced, which involved both parents interacting with a third person. Aberrant behavior occurred only in the modified attention condition. Successful treatment consisted of delivery of attention on a…

  2. Aberration analysis calculations for synchrotron radiation beamline design

    SciTech Connect

    McKinney, W.R.; Howells, M.; Padmore, H.A.

    1997-09-01

    The application of ray deviation calculations based on aberration coefficients for a single optical surface for the design of beamline optical systems is reviewed. A systematic development is presented which allows insight into which aberration may be causing the rays to deviate from perfect focus. A new development allowing analytical calculation of line shape is presented.

  3. Modified Matching Ronchi Test to Visualize Lens Aberrations

    ERIC Educational Resources Information Center

    Hassani, Kh; Ziafi, H. Hooshmand

    2011-01-01

    We introduce a modification to the matching Ronchi test to visualize lens aberrations with simple and inexpensive equipment available in educational optics labs. This method can help instructors and students to observe and estimate lens aberrations in real time. It is also a semi-quantitative tool for primary tests in research labs. In this work…

  4. Reactive Oxygen Species in Normal and Tumor Stem Cells

    PubMed Central

    Zhou, Daohong; Shao, Lijian; Spitz, Douglas R.

    2014-01-01

    Reactive oxygen species (ROS) play an important role in determining the fate of normal stem cells. Low levels of ROS are required for stem cells to maintain quiescence and self-renewal. Increases in ROS production cause stem cell proliferation/differentiation, senescence, and apoptosis in a dose-dependent manner, leading to their exhaustion. Therefore, the production of ROS in stem cells is tightly regulated to ensure that they have the ability to maintain tissue homeostasis and repair damaged tissues for the life span of an organism. In this chapter, we discuss how the production of ROS in normal stem cells is regulated by various intrinsic and extrinsic factors and how the fate of these cells is altered by the dysregulation of ROS production under various pathological conditions. In addition, the implications of the aberrant production of ROS by tumor stem cells for tumor progression and treatment are also discussed. PMID:24974178

  5. Exoplanet detection with simultaneous spectral differential imaging: effects of out-of-pupil-plane optical aberrations

    SciTech Connect

    Marois, C; Phillion, D W; Macintosh, B

    2006-05-02

    Imaging faint companions (exoplanets and brown dwarfs) around nearby stars is currently limited by speckle noise. To efficiently attenuate this noise, a technique called simultaneous spectral differential imaging (SSDI) can be used. This technique consists of acquiring simultaneously images of the field of view in several adjacent narrow bands and in combining these images to suppress speckles. Simulations predict that SSDI can achieve, with the acquisition of three wavelengths, speckle noise attenuation of several thousands. These simulations are usually performed using the Fraunhofer approximation, i.e. considering that all aberrations are located in the pupil plane. We have performed wavefront propagation simulations to evaluate how out-of-pupil-plane aberrations affect SSDI speckle noise attenuation performance. The Talbot formalism is used to give a physical insight of the problem; results are confirmed using a proper wavefront propagation algorithm. We will show that near-focal-plane aberrations can significantly reduce SSDI speckle noise attenuation performance at several {lambda}/D separation. It is also shown that the Talbot effect correctly predicts the PSF chromaticity. Both differential atmospheric refraction effects and the use of a coronagraph will be discussed.

  6. Multiphoton imaging microscopy at deeper layers with adaptive optics control of spherical aberration.

    PubMed

    Bueno, Juan M; Skorsetz, Martin; Palacios, Raquel; Gualda, Emilio J; Artal, Pablo

    2014-01-01

    Despite the inherent confocality and optical sectioning capabilities of multiphoton microscopy, three-dimensional (3-D) imaging of thick samples is limited by the specimen-induced aberrations. The combination of immersion objectives and sensorless adaptive optics (AO) techniques has been suggested to overcome this difficulty. However, a complex plane-by-plane correction of aberrations is required, and its performance depends on a set of image-based merit functions. We propose here an alternative approach to increase penetration depth in 3-D multiphoton microscopy imaging. It is based on the manipulation of the spherical aberration (SA) of the incident beam with an AO device while performing fast tomographic multiphoton imaging. When inducing SA, the image quality at best focus is reduced; however, better quality images are obtained from deeper planes within the sample. This is a compromise that enables registration of improved 3-D multiphoton images using nonimmersion objectives. Examples on ocular tissues and nonbiological samples providing different types of nonlinear signal are presented. The implementation of this technique in a future clinical instrument might provide a better visualization of corneal structures in living eyes.

  7. Genomic instability, driver genes and cell selection: Projections from cancer to stem cells.

    PubMed

    Ben-David, Uri

    2015-04-01

    Cancer cells and stem cells share many traits, including a tendency towards genomic instability. Human cancers exhibit tumor-specific genomic aberrations, which often affect their malignancy and drug response. During their culture propagation, human pluripotent stem cells (hPSCs) also acquire characteristic genomic aberrations, which may have significant impact on their molecular and cellular phenotypes. These aberrations vary in size from single nucleotide alterations to copy number alterations to whole chromosome gains. A prominent challenge in both cancer and stem cell research is to identify "driver aberrations" that confer a selection advantage, and "driver genes" that underlie the recurrence of these aberrations. Following principles that are already well-established in cancer research, candidate driver genes have also been suggested in hPSCs. Experimental validation of the functional role of such candidates can uncover whether these are bona fide driver genes. The identification of driver genes may bring us closer to a mechanistic understanding of the genomic instability of stem cells. Guided by terminologies and methodologies commonly applied in cancer research, such understanding may have important ramifications for both stem cell and cancer biology. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.

  8. Chaos in ocular aberration dynamics of the human eye

    PubMed Central

    Hampson, Karen M.; Mallen, Edward A. H.

    2012-01-01

    Since the characterization of the eye’s monochromatic aberration fluctuations in 2001, the power spectrum has remained the most widely used method for analyzing their dynamics. However, the power spectrum does not capture the complexities of the fluctuations. We measured the monochromatic aberration dynamics of six subjects using a Shack-Hartmann sensor sampling at 21 Hz. We characterized the dynamics using techniques from chaos theory. We found that the attractor embedding dimension for all aberrations, for all subjects, was equal to three. The embedding lag averaged across aberrations and subjects was 0.31 ± 0.07 s. The Lyapunov exponent of the rms wavefront error was positive for each subject, with an average value of 0.44 ± 0.15 µm/s. This indicates that the aberration dynamics are chaotic. Implications for future modeling are discussed. PMID:22567581

  9. Minimum change in spherical aberration that can be perceived

    PubMed Central

    Manzanera, Silvestre; Artal, Pablo

    2016-01-01

    It is important to know the visual sensitivity to optical blur from both a basic science perspective and a practical point of view. Of particular interest is the sensitivity to blur induced by spherical aberration because it is being used to increase depth of focus as a component of a presbyopic solution. Using a flicker detection-based procedure implemented on an adaptive optics visual simulator, we measured the spherical aberration thresholds that produce just-noticeable differences in perceived image quality. The thresholds were measured for positive and negative values of spherical aberration, for best focus and + 0.5 D and + 1.0 D of defocus. At best focus, the SA thresholds were 0.20 ± 0.01 µm and −0.17 ± 0.03 µm for positive and negative spherical aberration respectively (referred to a 6-mm pupil). These experimental values may be useful in setting spherical aberration permissible levels in different ophthalmic techniques.

  10. De Novo Prediction of Stem Cell Identity using Single-Cell Transcriptome Data.

    PubMed

    Grün, Dominic; Muraro, Mauro J; Boisset, Jean-Charles; Wiebrands, Kay; Lyubimova, Anna; Dharmadhikari, Gitanjali; van den Born, Maaike; van Es, Johan; Jansen, Erik; Clevers, Hans; de Koning, Eelco J P; van Oudenaarden, Alexander

    2016-08-01

    Adult mitotic tissues like the intestine, skin, and blood undergo constant turnover throughout the life of an organism. Knowing the identity of the stem cell is crucial to understanding tissue homeostasis and its aberrations upon disease. Here we present a computational method for the derivation of a lineage tree from single-cell transcriptome data. By exploiting the tree topology and the transcriptome composition, we establish StemID, an algorithm for identifying stem cells among all detectable cell types within a population. We demonstrate that StemID recovers two known adult stem cell populations, Lgr5+ cells in the small intestine and hematopoietic stem cells in the bone marrow. We apply StemID to predict candidate multipotent cell populations in the human pancreas, a tissue with largely uncharacterized turnover dynamics. We hope that StemID will accelerate the search for novel stem cells by providing concrete markers for biological follow-up and validation. PMID:27345837

  11. De Novo Prediction of Stem Cell Identity using Single-Cell Transcriptome Data.

    PubMed

    Grün, Dominic; Muraro, Mauro J; Boisset, Jean-Charles; Wiebrands, Kay; Lyubimova, Anna; Dharmadhikari, Gitanjali; van den Born, Maaike; van Es, Johan; Jansen, Erik; Clevers, Hans; de Koning, Eelco J P; van Oudenaarden, Alexander

    2016-08-01

    Adult mitotic tissues like the intestine, skin, and blood undergo constant turnover throughout the life of an organism. Knowing the identity of the stem cell is crucial to understanding tissue homeostasis and its aberrations upon disease. Here we present a computational method for the derivation of a lineage tree from single-cell transcriptome data. By exploiting the tree topology and the transcriptome composition, we establish StemID, an algorithm for identifying stem cells among all detectable cell types within a population. We demonstrate that StemID recovers two known adult stem cell populations, Lgr5+ cells in the small intestine and hematopoietic stem cells in the bone marrow. We apply StemID to predict candidate multipotent cell populations in the human pancreas, a tissue with largely uncharacterized turnover dynamics. We hope that StemID will accelerate the search for novel stem cells by providing concrete markers for biological follow-up and validation.

  12. The RNA–Methyltransferase Misu (NSun2) Poises Epidermal Stem Cells to Differentiate

    PubMed Central

    Blanco, Sandra; Kurowski, Agata; Nichols, Jennifer; Watt, Fiona M.; Benitah, Salvador Aznar; Frye, Michaela

    2011-01-01

    Homeostasis of most adult tissues is maintained by balancing stem cell self-renewal and differentiation, but whether post-transcriptional mechanisms can regulate this process is unknown. Here, we identify that an RNA methyltransferase (Misu/Nsun2) is required to balance stem cell self-renewal and differentiation in skin. In the epidermis, this methyltransferase is found in a defined sub-population of hair follicle stem cells poised to undergo lineage commitment, and its depletion results in enhanced quiescence and aberrant stem cell differentiation. Our results reveal that post-transcriptional RNA methylation can play a previously unappreciated role in controlling stem cell fate. PMID:22144916

  13. Chromatic aberration and the roles of double-opponent and color-luminance neurons in color vision.

    PubMed

    Vladusich, Tony

    2007-03-01

    How does the visual cortex encode color? I summarize a theory in which cortical double-opponent color neurons perform a role in color constancy and a complementary set of color-luminance neurons function to selectively correct for color fringes induced by chromatic aberration in the eye. The theory may help to resolve an ongoing debate concerning the functional properties of cortical receptive fields involved in color coding.

  14. STEM Education

    PubMed Central

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-01-01

    Improving science, technology, engineering, and mathematics (STEM) education, especially for traditionally disadvantaged groups, is widely recognized as pivotal to the U.S.’s long-term economic growth and security. In this article, we review and discuss current research on STEM education in the U.S., drawing on recent research in sociology and related fields. The reviewed literature shows that different social factors affect the two major components of STEM education attainment: (1) attainment of education in general, and (2) attainment of STEM education relative to non-STEM education conditional on educational attainment. Cognitive and social psychological characteristics matter for both major components, as do structural influences at the neighborhood, school, and broader cultural levels. However, while commonly used measures of socioeconomic status (SES) predict the attainment of general education, social psychological factors are more important influences on participation and achievement in STEM versus non-STEM education. Domestically, disparities by family SES, race, and gender persist in STEM education. Internationally, American students lag behind those in some countries with less economic resources. Explanations for group disparities within the U.S. and the mediocre international ranking of US student performance require more research, a task that is best accomplished through interdisciplinary approaches. PMID:26778893

  15. Multidetector computed tomographic angiography of aberrant subclavian arteries.

    PubMed

    Türkvatan, Aysel; Büyükbayraktar, Fatma Gül; Olçer, Tülay; Cumhur, Turhan

    2009-02-01

    The purpose of this study was to evaluate the utility of 16-slice multidetector computed tomographic (MDCT) angiography for identifying anatomic features of aberrant subclavian arteries. Seventeen patients with aberrant subclavian arteries were assessed by MDCT angiography. The aortic arch position, the presence of a Kommerell's diverticulum, aneurysm, vascular compression of trachea and oesophagus and associated cardiovascular abnormalities were evaluated. MDCT findings were confirmed by surgery in eight patients but in the other nine patients no further evaluation or management was warranted as the aberrant subclavian artery had no significant clinical consequence. Eleven patients had an aberrant right subclavian artery arising from the left aortic arch and six patients had an aberrant left subclavian artery arising from the right aortic arch. Kommerell's diverticulum was identified in three patients with an aberrant right subclavian artery and in five patients with an aberrant left subclavian artery. In two patients it was aneurysmal. Oesophageal compression was detected in eight patients, and tracheal compression was identified in only one paediatric patient. An aberrant subclavian artery was associated with complex congenital heart disease in one patient, intracardiac defects in two patients, aortic coarctation in two patients, patent ductus arteriosus in two patients and an aberrant vertebral artery in one patient. In conclusion, MDCT angiography is superior to digital subtraction angiography for the assessment of aberrant subclavian arteries since digital subtraction angiography has only a poor ability to visualize adjacent structures completely and is invasive in nature. MDCT angiography or magnetic resonance angiography are the current standard in the initial evaluation of thoracic vascular anomalies.

  16. Tilt correction for intracavity mirror of laser with an unstable resonator

    NASA Astrophysics Data System (ADS)

    Zhang, Xiang; Xu, Bing; Yang, Wei

    2005-12-01

    The influence on outcoupled mode by introducing intracavity tilt-perturbation in confocal unstable resonator is analyzed. The intracavity mode properties and Zernike-aberration coefficient of intrcavity mirror's maladjustment are calculated theoretically. The experimental results about the relations of intracavity mirror maladjustment and the properties of mode aberration are presented by adopting Hartmann-Shack wavefront sensor. The results show that the intracavity perturbation of the concave mirror has more remarkable effect on outcoupled beam-quality than that of the convex mirror. For large Fresnel-number resonator, the tilt angle of intracavity mirror has a close linear relationship with extracavity Zernike tilt coefficient. The ratio of tilt aberration coefficient approaches to the magnification of unstable resonator if equivalent perturbation is applied to concave mirror and convex mirror respectively. Furthermore, astigmatism and defocus aberration also increase with the augment of tilt aberration of beam mode. So intracavity phase-corrected elements used in unstable resonator should be close to the concave mirror. Based these results, a set of automatic control system of intracavity tilt aberration is established and the aberration-corrected results are presented and analyzed in detail.

  17. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons.

    PubMed

    LeGates, Tara A; Altimus, Cara M; Wang, Hui; Lee, Hey-Kyoung; Yang, Sunggu; Zhao, Haiqing; Kirkwood, Alfredo; Weber, E Todd; Hattar, Samer

    2012-11-22

    The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

  18. Measurement of non-common path static aberrations in an interferometric camera by phase diversity

    NASA Astrophysics Data System (ADS)

    Yan, Zhaojun; Herbst, Thomas M.; Yang, Pengqian; Bizenberger, Peter; Zhang, Xianyu; Conrad, Albert R.; Bertram, Thomas; Kuerster, Martin; Rix, Hans-Walter; Li, Xinyang; Rao, Changhui

    2012-10-01

    LINC-NIRVANA (LN) is a near-infrared image-plane beam combiner with advanced, multi-conjugated adaptive optics for the Large Binocular Telescope. Non-common path aberrations (NCPAs) between the near-infrared science camera and the wave-front sensor (WFS) are unseen by the WFS and therefore are not corrected in closed loop. This would prevent LN from achieving its ultimate performance. We use a modified phase diversity technique to measure the internal optical static aberrations and hence the NCPAs. Phase diversity is a methodology for estimating wave-front aberrations by solving an unconstrained optimization problem from multiple images whose pupil phases differ from one another by a known amount. We conduct computer simulations of the reconstruction of aberrations of an optical system with the phase diversity method. In the reconstruction, we fit the wave-front to Zernike polynomials to reduce the number of variables. The limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm is very well suited to phase diversity (PD) due to its good performance in solving large scale optimization problems. The main constraint for the implementation of PD for LN is that we cannot add extra components to the internal interferometric camera imaging system to obtain infocus and defocus images. In this paper, we introduce a new method, namely shifting the focal plane source, not the detector, to overcome this constraint. Some experiments were done to test and verify this method and the results are presented and discussed. The study shows that the method is very flexible and the paper gives practical guidelines for the application of phase diversity methods to characterize adaptive optics systems.

  19. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons.

    PubMed

    LeGates, Tara A; Altimus, Cara M; Wang, Hui; Lee, Hey-Kyoung; Yang, Sunggu; Zhao, Haiqing; Kirkwood, Alfredo; Weber, E Todd; Hattar, Samer

    2012-11-22

    The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells. PMID:23151476

  20. Mesenchymal stem cells in multiple sclerosis - translation to clinical trials.

    PubMed

    Dulamea, A

    2015-01-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters. The author reviews the data about experimental studies and clinical trials using mesenchymal stem cells for the treatment of multiple sclerosis.

  1. Stem Cell Basics

    MedlinePlus

    ... stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before ... two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells . ...

  2. Learn About Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... ISSCR Get Involved Media © 2015 International Society for Stem Cell Research Terms of Use Disclaimer Privacy Policy

  3. The biology of cancer stem cells.

    PubMed

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies.

  4. Control of the epithelial stem cell epigenome: the shaping of epithelial stem cell identity.

    PubMed

    Iglesias-Bartolome, Ramiro; Callejas-Valera, Juan Luis; Gutkind, J Silvio

    2013-04-01

    The squamous epithelium covering the skin and oral mucosa relies on epithelial stem cells for tissue renewal. Dynamic changes in DNA methylation, histone methylation and acetylation, and higher order chromatin structure are required to preserve their self-renewal capacity while orchestrating the timely execution of cell differentiation programs. This complex network of epigenetic modifications shapes the epithelial stem cell identity and fate. Pathological alterations can be perceived by aberrant chromatin sensors, such as the INK4/ARF locus, which initiate tumor suppressive cell senescence programs, and can often result in epithelial stem cell exhaustion. Unveiling the mechanisms controlling the epigenome in epithelial stem cells may help protect against the loss of their tissue regenerative capacity, thereby preventing premature aging without increasing cancer risk. PMID:23434069

  5. High Resolution STEM-EELS Study of Silver Nanoparticles Exposed to Light and Humic Substances.

    PubMed

    Römer, Isabella; Wang, Zhi Wei; Merrifield, Ruth C; Palmer, Richard E; Lead, Jamie

    2016-03-01

    Nanoparticles (NPs) are defined as particles with at least one dimension between 1 and 100 nm or with properties that differ from their bulk material, which possess unique properties. The extensive use of NPs means that discharge to the environment is likely increasing, but fate, behavior, and effects under environmentally relevant conditions are insufficiently studied. This paper focuses on the transformations of silver nanoparticles (AgNPs) under simulated but realistic environmental conditions. High resolution aberration-corrected scanning transmission electron microscopy (HAADF STEM) coupled with electron energy loss spectroscopy (EELS) and UV-vis were used within a multimethod approach to study morphology, surface chemistry transformations, and corona formation. Although loss, most likely by dissolution, was observed, there was no direct evidence of oxidation from the STEM-EELS. However, in the presence of fulvic acid (FA), a 1.3 nm oxygen-containing corona was observed around the AgNPs in water; modeled data based on the HAADF signal at near atomic resolution suggest this was an FA corona was formed and was not silver oxide, which was coherent (i.e., fully coated in FA), where observed. The corona further colloidally stabilized the NPs for periods of weeks to months, dependent on the solution conditions. PMID:26792384

  6. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study

    PubMed Central

    Klusmann, Jan-Henning; Reinhardt, Dirk; Zimmermann, Martin; Kremens, Bernhard; Vormoor, Josef; Dworzak, Michael; Creutzig, Ursula; Klingebiel, Thomas

    2012-01-01

    Background The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. Design and Methods HLA-typed patients with high-risk acute myeloid leukemia, who achieved first complete remission (n=247), were included in this analysis. All patients received double induction and consolidation. Based on the availability of a matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n=61) or chemotherapy-only (i.e. intensification and maintenance therapy; n=186). The main analysis was done on an intention-to-treat basis according to this allocation. Results Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49±6% versus 45±4%, Plog rank=0.44) or overall survival (68±6% versus 57±4%, Plog rank=0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% versus 31.8%, PFischer<0.01). These results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72±8% versus 60±4%, PMantel-Byar 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94±6% versus 52±7%, Plog-rank=0.01; n=18 versus 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58±8% versus 55±5%, Plog-rank=0.66). Conclusions Our analyses defined a genetic subgroup of children with high-risk acute myeloid leukemia who benefited from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For

  7. Using graph theory to describe and model chromosome aberrations.

    PubMed

    Sachs, Rainer K; Arsuaga, Javier; Vázquez, Mariel; Hlatky, Lynn; Hahnfeldt, Philip

    2002-11-01

    A comprehensive description of chromosome aberrations is introduced that is suitable for all cytogenetic protocols (e.g. solid staining, banding, FISH, mFISH, SKY, bar coding) and for mathematical analyses. "Aberration multigraphs" systematically characterize and interrelate three basic aberration elements: (1) the initial configuration of chromosome breaks; (2) the exchange process, whose cycle structure helps to describe aberration complexity; and (3) the final configuration of rearranged chromosomes, which determines the observed pattern but may contain cryptic misrejoinings in addition. New aberration classification methods and a far-reaching generalization of mPAINT descriptors, applicable to any protocol, emerge. The difficult problem of trying to infer actual exchange processes from cytogenetically observed final patterns is analyzed using computer algorithms, adaptations of known theorems on cubic graphs, and some new graph-theoretical constructs. Results include the following: (1) For a painting protocol, unambiguously inferring the occurrence of a high-order cycle requires a corresponding number of different colors; (2) cycle structure can be computed by a simple trick directly from mPAINT descriptors if the initial configuration has no more than one break per homologue pair; and (3) higher-order cycles are more frequent than the obligate cycle structure specifies. Aberration multigraphs are a powerful new way to describe, classify and quantitatively analyze radiation-induced chromosome aberrations. They pinpoint (but do not eliminate) the problem that, with present cytogenetic techniques, one observed pattern corresponds to many possible initial configurations and exchange processes. PMID:12385633

  8. The Mechanisms of Aberrant Protein Aggregation

    NASA Astrophysics Data System (ADS)

    Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

    2012-02-01

    We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

  9. Epigenetic aberrations and therapeutic implications in gliomas.

    PubMed

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  10. Aneurysm of an Aberrant Right Subclavian Artery

    PubMed Central

    Gordini, Veliano; Collice, Massimo; Fedriga, Emanuele; Moreo, Antonella; Morello, Marco; Porrini, Annamaria; Donatelli, Francesco

    1991-01-01

    A 53-year-old man was admitted for treatment of an aberrant right subclavian artery aneurysm that had been diagnosed 5 years earlier and had recently begun to enlarge. The aneurysm, which involved the right subclavian artery from its origin, measured 47 mm in diameter and about 10 cm in length. Because of the lesion's size and friability, a 2-stage operation was performed. In the 1st stage, the right subclavian and right vertebral arteries were revascularized with double bypass grafts via a right cervical approach. In the 2nd stage, the patient was repositioned and a left thoracotomy incision was made. With the aid of left-heart bypass, the aorta was cross-clamped proximal and distal to the lesion, and the aneurysmal orifice was closed with a Dacron patch. The patient was discharged from the hospital on the 17th postoperative day and remains asymptomatic 24 months later. We recommend the 2-stage technique for similar cases because it prevents limb ischemia and reduces the risk of hemorrhagic and embolic complications. (Texas Heart Institute Journal 1991;18:76-9) Images PMID:15227513

  11. Atom-column distinction by Kikuchi pattern observed by an aberration-corrected convergent electron probe.

    PubMed

    Saitoh, Koh; Tatara, Yoshihide; Tanaka, Nobuo

    2010-01-01

    Kikuchi patterns of an MgO crystal at the [110] incidence have been taken by a sub-angstrom electron beam focused on the single atom-column. A significant change in intensity has been observed in the 111 band; that is, the contrast in the central and side bands is reversed depending on the illuminated atom-column. The contrast reversal in the 111 band has been reproduced by multislice simulation using the frozen-phonon approach. The beam-position dependence of the 111 band intensity can be interpreted by electron channelling and the reciprocity theorem. The anomalous Kikuchi pattern can be a probe for identifying the illuminated atom-column, which is useful for column-by-column electron energy-loss spectroscopy and X-ray emission spectroscopy.

  12. Development of a monochromator for aberration-corrected scanning transmission electron microscopy.

    PubMed

    Mukai, Masaki; Okunishi, Eiji; Ashino, Masanori; Omoto, Kazuya; Fukuda, Tomohisa; Ikeda, Akihiro; Somehara, Kazunori; Kaneyama, Toshikatsu; Saitoh, Tomohiro; Hirayama, Tsukasa; Ikuhara, Yuichi

    2015-06-01

    In this article, we report the development of a new 200-kV analytical electron microscope equipped with a monochromator with an integrated double Wien-filter system. It enables us to study the electronic structures of materials in detail using electron energy-loss spectroscopy (EELS) analysis at an atomic scale. A highly monochromated and isotropically round electron probe is produced on the specimen plane. The ultimate energy resolutions with 0.1-s acquisition times are measured to be 36 meV at 200 kV and 30 meV at 60 kV. In an EELS mapping experiment performed on SrTiO3 with a monochromated electron probe whose energy resolution is 146 meV, an elemental map exhibits atomic resolution.

  13. Radiation-induced transmissable chromosomal instability in haemopoietic stem cells

    NASA Astrophysics Data System (ADS)

    Kadhim, M. A.; Wright, E. G.

    Heritable radiation-induced genetic alterations have long been assumed to be ``fixed'' within the first cell division. However, there is a growing body of evidence that a considerable fraction of cells surviving radiation exposure appear normal, but a variety of mutational changes arise in their progeny due to a transmissible genomic instability. In our investigations of G-banded metaphases, non-clonal cytogenetic aberrations, predominantly chromatid-type aberrations, have been observed in the clonal descendants of murine and human haemopoietic stem cells surviving low doses (~1 track per cell) of alpha-particle irradiations. The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of chromosomal aberrations in its clonal progeny many cell divisions later. Recent studies have demonstrated that the instability phenotype persists in vivo and that the expression of chromosomal instability has a strong dependence on the genetic characteristics of the irradiated cell. At the time when cytogenetic aberrations are detected, an increased incidence of hprt mutations and apoptotic cells have been observed in the clonal descendants of alpha-irradiated murine haemopoietic stem cells. Thus, delayed chromosomal abnormalities, delayed cell death by apoptosis and late-arising specific gene mutations may reflect diverse consequences of radiation-induced genomic instability. The relationship, if any, between these effects is not established. Current studies suggest that expression of these delayed heritable effects is determined by the type of radiation exposure, type of cell and a variety of genetic factors.

  14. [Right aortic arch, Kommerell's diverticulum and aberrant left subclavian artery].

    PubMed

    Simón-Yarza, I; Viteri-Ramírez, G; Etxano, J; Roblero, P Slon; Ferreira, M; Alemañ, G Bastarrika

    2011-01-01

    The right aberrant subclavian artery or "arteria lusoria" is the most common anatomical variant of the embryonic development of the aorta and its branches, with a presence in 0.5-2% of the population. Less frequently, a right aortic arch with aberrant left subclavian artery may be present. These anatomical variations should be included in the differential diagnosis of superior mediastinal widening seen on chest radiographs. In this report, we present a right aortic arch with left aberrant subclavian artery dilated at its origin (Kommerell's diverticulum) as a cause of superior mediastinal widening detected incidentally on a chest radiograph.

  15. Electrostatic mirror objective with eliminated spherical and axial chromatic aberrations.

    PubMed

    Bimurzaev, Seitkerim B; Serikbaeva, Gulnur S; Yakushev, Evgeniy M

    2003-01-01

    Computational formulae for the coefficients of the third-order spherical aberration and the second-order axial chromatic aberration are presented for an axially symmetric electrostatic electron mirror. A technique for eliminating the high-order derivatives of the potential axial distribution in mirror systems from the integrands is described. Conditions for elimination of spherical and axial chromatic aberrations, either separately or simultaneously, are found for a three-electrode axially symmetric mirror composed of coaxial cylinders of the same diameter. A principal scheme of the transmission electron microscope, where an electrostatic electron mirror serves as its objective, is presented. PMID:14599097

  16. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-01-01

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies. PMID:26580604

  17. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain.

    PubMed

    Seymour, Tracy; Twigger, Alecia-Jane; Kakulas, Foteini

    2015-11-13

    Pluripotent stem cells (PSCs) attracted considerable interest with the successful isolation of embryonic stem cells (ESCs) from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs) OCT4 (octamer-binding transcription factor 4), SOX2 (sex determining region Y-box 2), and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC), which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.

  18. 77 FR 72199 - Technical Corrections; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ...) is correcting a final rule that was published in the Federal Register on July 6, 2012 (77 FR 39899), and effective on August 6, 2012. That final rule amended the NRC regulations to make technical... COMMISSION 10 CFR Part 171 RIN 3150-AJ16 Technical Corrections; Correction AGENCY: Nuclear...

  19. Performance of a phase-conjugate-engine implementing a finite-bit phase correction

    SciTech Connect

    Baker, K; Stappaerts, E; Wilks, S; Young, P; Gavel, D; Tucker, J; Silva, D; Olivier, S

    2003-10-23

    This article examines the achievable Strehl ratio when a finite-bit correction to an aberrated wave-front is implemented. The phase-conjugate-engine (PCE) used to measure the aberrated wavefront consists of a quadrature interferometric wave-front sensor, a liquid-crystal spatial-light-modulator and computer hardware/software to calculate and apply the correction. A finite-bit approximation to the conjugate phase is calculated and applied to the spatial light modulator to remove the aberrations from the optical beam. The experimentally determined Strehl ratio of the corrected beam is compared with analytical expressions for the expected Strehl ratio and shown to be in good agreement with those predictions.

  20. Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance.

    PubMed

    Palle, Komaraiah; Mani, Chinnadurai; Tripathi, Kaushlendra; Athar, Mohammad

    2015-01-01

    The canonical hedgehog (HH) pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1), smoothened (SMO)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1), GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. However, dysregulation or mutations in HH signaling leads to genomic instability (GI) and various cancers, for example, germline mutation in PTCH1 lead to Gorlin syndrome, a condition where patients develop numerous basal cell carcinomas and rarely rhabdomyosarcoma (RMS). Activating mutations in SMO have also been recognized in sporadic cases of medulloblastoma and SMO is overexpressed in many other cancers. Recently, studies in several human cancers have shown that GLI1 expression is independent from HH ligand and canonical intracellular signaling through PTCH and SMO. In fact, this aberrantly regulated GLI1 has been linked to several non-canonical oncogenic growth signals such as Kirsten rat sarcoma viral oncogene homolog (KRAS), avian myelocytomatosis virus oncogene cellular homolog (C-MYC), transforming growth factor β (TGFβ), wingless-type MMTV integration site family (WNT) and β-catenin. Recent studies from our lab and other independent studies demonstrate that aberrantly expressed GLI1 influences the integrity of several DNA damage response and repair signals, and if altered, these networks can contribute to GI and impact tumor response to chemo- and radiation therapies. Furthermore, the ineffectiveness of SMO inhibitors in clinical studies argues for the development of GLI1-specific inhibitors in order to develop effective therapeutic modalities to treat these tumors. In this review, we focus on summarizing current understanding of the molecular, biochemical and cellular basis for