FIR Light Microscopy Module Set Up

NASA Image and Video Library

2009-11-09

ISS021-E-022457 (9 Nov. 2009) --- NASA astronaut Nicole Stott, Expedition 21 flight engineer, uses a communication system while installing the Light Microscopy Module (LMM) Spindle Bracket Assembly in the Fluids Integrated Rack (FIR) in the Destiny laboratory of the International Space Station. Canadian Space Agency astronaut Robert Thirsk (out of frame) assisted Stott.

GRC-2013-C-01423

NASA Image and Video Library

2009-04-22

University of Florida, Professor and Director of Interdisciplinary Center for Biotechnology Research Interacting with the Fluids Integration Rack, FIR, Light Microscopy Module, LMM, Ground Integration Unit, GIU, Hardware

GRC-2013-C-01422

NASA Image and Video Library

2009-04-22

University of Florida, Professor and Director of Interdisciplinary Center for Biotechnology Research Interacting with the Fluids Integration Rack, FIR, Light Microscopy Module, LMM, Ground Integration Unit, GIU, Hardware

Light Microscopy Module Fan Disturbance Characterized Through Microgravity Emissions Laboratory Testing

NASA Technical Reports Server (NTRS)

McNelis, Anne M.; Motil, Susan M.

2003-01-01

A Light Microscopy Module (LMM) is being engineered, designed, and developed at the NASA Glenn Research Center. The LMM is planned as a remotely controllable on-orbit microscope subrack facility, allowing flexible scheduling and control of physical science and biological science experiments within Glenn s Fluids Integrated Rack on the International Space Station. The LMM concept is a modified commercial research imaging light microscope with powerful laser-diagnostic hardware and interfaces, creating a one-of-a-kind, state-of-the-art microscopic research facility. The microscope will house several different objectives, corresponding to magnifications of 10, 40, 50, 63, and 100. Features of the LMM include high-resolution color video microscopy, brightfield, darkfield, phase contrast, differential interference contrast, spectrophotometry, and confocal microscopy combined in a single configuration. Also, laser tweezers are integrated with the diagnostics as a sample manipulation technique. As part of the development phase of the LMM, it was necessary to quantify the microgravity disturbances generated by the control box fan. Isolating the fan was deemed necessary to reduce the fan speed harmonic amplitudes and to eliminate any broadband disturbances across the 60- to 70-Hz and 160- to 170-Hz frequency ranges. The accelerations generated by a control box fan component of the LMM were measured in the Microgravity Emissions Laboratory (MEL). The MEL is a low-frequency measurement system developed to simulate and verify the on-orbit International Space Station (ISS) microgravity environment. The accelerations generated by various operating components of the ISS, if too large, could hinder the science performed onboard by disturbing the microgravity environment. The MEL facility gives customers a test-verified way of measuring their compliance with ISS limitations on vibratory disturbance levels. The facility is unique in that inertial forces in 6 degrees of freedom can be characterized simultaneously for an operating test article. Vibratory disturbance levels are measured for engineering or flight-level hardware following development from component to subassembly through the rack-level configuration. The MEL can measure accelerations as small as 10-7g, the accuracy needed to confirm compliance with ISS requirements.

Burbank conducts PACE Session

NASA Image and Video Library

2011-12-01

ISS030-E-007417 (1 Dec. 2011) --- In the International Space Station?s Destiny laboratory, NASA astronaut Dan Burbank, Expedition 30 commander, conducts a session with the Preliminary Advanced Colloids Experiment (PACE) at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). PACE is designed to investigate the capability of conducting high magnification colloid experiments with the LMM for determining the minimum size particles which can be resolved with it.

Ford poses at the FIR/LMM/ACE in the U.S. Laboratory

NASA Image and Video Library

2013-02-21

ISS034-E-056144 (21 Feb. 2013) --- Inside the U.S. Laboratory (Destiny) aboard the Earth-orbiting International Space Statio, NASA astronaut Kevin Ford, Expedition 34 commander, is seen with the Fluids Integration Rack (FIR)/Light Microscopy Module (LMM)/Advanced Colloids Experiment (ACE). ACE samples, which produce microscopic images of materials containing small colloidal particles, are scheduled for arrival on SpaceX-2 in the first week of March.

Burbank conducts PACE Session

NASA Image and Video Library

2011-12-01

ISS030-E-007418 (1 Dec. 2011) --- In the International Space Station’s Destiny laboratory, NASA astronaut Dan Burbank, Expedition 30 commander, conducts a session with the Preliminary Advanced Colloids Experiment (PACE) at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). PACE is designed to investigate the capability of conducting high magnification colloid experiments with the LMM for determining the minimum size particles which can be resolved with it.

Burbank conducts PACE Session

NASA Image and Video Library

2011-12-01

ISS030-E-007419 (1 Dec. 2011) --- In the International Space Station’s Destiny laboratory, NASA astronaut Dan Burbank, Expedition 30 commander, conducts a session with the Preliminary Advanced Colloids Experiment (PACE) at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). PACE is designed to investigate the capability of conducting high magnification colloid experiments with the LMM for determining the minimum size particles which can be resolved with it.

GRC-2015-C-00903

NASA Image and Video Library

2011-03-15

NASA (Zin Technologies) engineer prepares Advanced Colloid Experiment Heated-2 samples that will be analyzed aboard the International Space Station using the zero-gravity Light Microscopy Module, LMM in the Fluids Integrated Rack, FIR

Nespoli services the FCF in the US Lab

NASA Image and Video Library

2011-04-21

ISS027-E-014888 (21 April 2011) --- European Space Agency astronaut Paolo Nespoli, Expedition 27 flight engineer, works with the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

Nespoli services the FCF in the US Lab

NASA Image and Video Library

2011-04-21

ISS027-E-014895 (21 April 2011) --- European Space Agency astronaut Paolo Nespoli, Expedition 27 flight engineer, works with the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

Nespoli services the FCF in the US Lab

NASA Image and Video Library

2011-04-21

ISS027-E-014894 (21 April 2011) --- European Space Agency astronaut Paolo Nespoli, Expedition 27 flight engineer, works with the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

FIR

NASA Image and Video Library

2013-09-16

ISS037-E-001115 (16 Sept. 2013) ---NASA astronaut Karen Nyberg, Expedition 37 flight engineer, works with test samples housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station’s Destiny laboratory.

Observation Platform for Dynamic Biomedical and Biotechnology Experiments Using the International Space Station (ISS) Light Microscopy Module (LMM)

NASA Technical Reports Server (NTRS)

Kurk, Michael A. (Andy)

2015-01-01

Techshot, Inc., has developed an observation platform for the LMM on the ISS that will enable biomedical and biotechnology experiments. The LMM Dynamic Stage consists of an electronics module and the first two of a planned suite of experiment modules. Specimens and reagent solutions can be injected into a small, hollow microscope slide-the heart of the innovation-via a combination of small reservoirs, pumps, and valves. A life science experiment module allows investigators to load up to two different fluids for on-orbit, real-time image cytometry. Fluids can be changed to initiate a process, fix biological samples, or retrieve suspended cells. A colloid science experiment module conducts microparticle and nanoparticle tests for investigation of colloid self-assembly phenomena. This module includes a hollow glass slide and heating elements for the creation of a thermal gradient from one end of the slide to the other. The electronics module supports both experiment modules and contains a unique illuminator/condenser for bright and dark field and phase contrast illumination, power supplies for two piezoelectric pumps, and controller boards for pumps and valves. This observation platform safely contains internal fluids and will greatly accelerate the research and development (R&D) cycle of numerous experiments, products, and services aboard the ISS.

Light Microscopy Module: International Space Station Premier Automated Microscope

NASA Technical Reports Server (NTRS)

Sicker, Ronald J.; Foster, William M.; Motil, Brian J.; Meyer, William V.; Chiaramonte, Francis P.; Abbott-Hearn, Amber; Atherton, Arthur; Beltram, Alexander; Bodzioney, Christopher; Brinkman, John;

Light Microscopy Module: On-Orbit Microscope Planned for the Fluids Integrated Rack on the International Space Station

NASA Technical Reports Server (NTRS)

Motil, Susan M.

2002-01-01

The Light Microscopy Module (LMM) is planned as a remotely controllable, automated, on-orbit facility, allowing flexible scheduling and control of physical science and biological science experiments within the Fluids Integrated Rack (FIR) on the International Space Station. Initially four fluid physics experiments in the FIR will use the LMM the Constrained Vapor Bubble, the Physics of Hard Spheres Experiment-2, Physics of Colloids in Space-2, and Low Volume Fraction Entropically Driven Colloidal Assembly. The first experiment will investigate heat conductance in microgravity as a function of liquid volume and heat flow rate to determine, in detail, the transport process characteristics in a curved liquid film. The other three experiments will investigate various complementary aspects of the nucleation, growth, structure, and properties of colloidal crystals in microgravity and the effects of micromanipulation upon their properties.

Preliminary Advanced Colloids Experiment

NASA Image and Video Library

2011-09-29

ISS029-E-011867 (29 Sept. 2011) --- NASA astronaut Mike Fossum, Expedition 29 commander, works with the Light Microscopy Module (LMM) control box in the Destiny laboratory of the International Space Station in preparation for another session with the Preliminary Advanced Colloids Experiment (PACE) hardware.

Hopkins in U.S. Lab with FIR/FCF

NASA Image and Video Library

2013-10-15

ISS037-E-013951 (14 Oct. 2013) --- NASA astronaut Michael Hopkins, Expedition 37 flight engineer, works at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF) located in the Destiny laboratory of the International Space Station.

iss038e055240

NASA Image and Video Library

2014-02-24

ISS038-E-055240 (24 Feb. 2014) --- In the International Space Station's Destiny laboratory, NASA astronaut Mike Hopkins, Expedition 38 flight engineer, sets up the Advanced Colloids Experiment (ACE) housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack. ACE studies microscopic particles suspended in a liquid.

Advanced Colloids Experiment (ACE) Science Overview

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ronald J.; Chiaramonte, Francis P.; Luna, Unique J.; Chaiken, Paul M.; Hollingsworth, Andrew; Secanna, Stefano; Weitz, David; Lu, Peter; Yodh, Arjun;

FIR sample change

NASA Image and Video Library

2011-10-11

ISS029-E-025108 (11 Oct. 2011) --- NASA astronaut Mike Fossum, Expedition 29 commander, works on the Fluids Integrated Rack/Fluids and Combustion Facility (FIR/FCF), conducting another session with the Preliminary Advanced Colloids Experiment (PACE). Fossum is working at the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

Advanced Plant Experiment, APEX-4

NASA Image and Video Library

2017-03-10

Advanced Plant Experiment, APEX-4, support in the Telescience Support Center at NASA Glenn. APEX-4 continues a highly successful investigation into the effects of microgravity on the development of roots and cells on plant seedlings. After four days of growth, the petri plate will be inserted into the Fluids Integrated Rack (FIR) Light Microscopy Module (LMM) facility for detailed imaging.

Microgravity Emissions Laboratory Testing of the Light Microscopy Module Control Box Fan

NASA Technical Reports Server (NTRS)

McNelis, Anne M.; Samorezov, Sergey; Haecker, Anthony H.

2003-01-01

The Microgravity Emissions Laboratory (MEL) was developed at the NASA Glenn Research Center for the characterization, simulation, and verification of the International Space Station (ISS) microgravity environment. This Glenn lab was developed in support of the Fluids and Combustion Facility (FCF). The MEL is a six-degrees-of-freedom inertial measurement system that can characterize the inertial response forces (emissions) of components, subrack payloads, or rack-level payloads down to 10 7g. The inertial force output data generated from the steady-state or transient operations of the test article are used with finite element analysis, statistical energy analysis, and other analysis tools to predict the on-orbit environment at specific science or rack interface locations. Customers of the MEL have used benefits in isolation performance testing in defining available attenuation during the engineering hardware design phase of their experiment s development. The Light Microscopy Module (LMM) Control Box (LCB) fan was tested in the MEL in June and July of 2002. The LMM is planned as a remotely controllable on-orbit microscope subrack facility that will be accommodated in an FCF Fluids Integrated Rack on the ISS. The disturbances measured in the MEL test resulted from operation of the air-circulation fan within the LCB. The objectives of the testing were (1) to identify an isolator to be added to the LCB fan assembly to reduce fan-speed harmonics and (2) to identify the fan-disturbance forcing functions for use in rack-response analysis of the LMM and Fluids Integrated Rack facility. This report describes the MEL, the testing process, and the results from ground-based MEL LCB fan testing.

InSPACE-3 experiment

NASA Image and Video Library

2013-08-18

ISS036-E-033948 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Advanced Colloids Experiment-1 (ACE-1)

NASA Image and Video Library

2013-07-22

ISS036-E-023770 (22 July 2013) --- NASA astronaut Chris Cassidy, Expedition 36 flight engineer, conducts science work with the ongoing experiment Advanced Colloids Experiment-1 (ACE-1) inside the Fluids Integrated Rack. The experiment observes colloids, microscopic particles evenly dispersed throughout materials, with the potential for manufacturing improved materials and products on Earth. Cassidy is working at the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035770 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035767 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035780 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

In the International Space Stations Destiny laboratory,NASA astronaut Karen Nyberg,Expedition 36 flight engineer,speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019760 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019830 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

Light Microsopy Module, International Space Station Premier Automated Microscope

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ronald J.; Chiaramonte, Francis P.; Brown, Daniel F.; O'Toole, Martin A.; Foster, William M.; Motil, Brian J.; Abbot-Hearn, Amber Ashley; Atherton, Arthur Johnson; Beltram, Alexander;

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019783 (24 June 2013) --- In the International Space Station’s Destiny laboratory, a fisheye lens attached to an electronic still camera was used to capture this image of NASA astronaut Karen Nyberg, Expedition 36 flight engineer, as she conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

High Temperature Protonic Conductors

NASA Technical Reports Server (NTRS)

Dynys, Fred; Berger, Marie-Helen; Sayir, Ali

2007-01-01

High Temperature Protonic Conductors (HTPC) with the perovskite structure are envisioned for electrochemical membrane applications such as H2 separation, H2 sensors and fuel cells. Successive membrane commercialization is dependent upon addressing issues with H2 permeation rate and environmental stability with CO2 and H2O. HTPC membranes are conventionally fabricated by solid-state sintering. Grain boundaries and the presence of intergranular second phases reduce the proton mobility by orders of magnitude than the bulk crystalline grain. To enhanced protonic mobility, alternative processing routes were evaluated. A laser melt modulation (LMM) process was utilized to fabricate bulk samples, while pulsed laser deposition (PLD) was utilized to fabricate thin film membranes . Sr3Ca(1+x)Nb(2-x)O9 and SrCe(1-x)Y(x)O3 bulk samples were fabricated by LMM. Thin film BaCe(0.85)Y(0.15)O3 membranes were fabricated by PLD on porous substrates. Electron microscopy with chemical mapping was done to characterize the resultant microstructures. High temperature protonic conduction was measured by impedance spectroscopy in wet air or H2 environments. The results demonstrate the advantage of thin film membranes to thick membranes but also reveal the negative impact of defects or nanoscale domains on protonic conductivity.

Physics of Hard Sphere Experiment: Scattering, Rheology and Microscopy Study of Colloidal Particles

NASA Technical Reports Server (NTRS)

Cheng, Z.-D.; Zhu, J.; Phan, S.-E.; Russel, W. B.; Chaikin, P. M.; Meyer, W. V.

2002-01-01

The Physics of Hard Sphere Experiment has two incarnations: the first as a scattering and rheology experiment on STS-83 and STS-94 and the second as a microscopy experiment to be performed in the future on LMM on the space station. Here we describe some of the quantitative and qualitative results from previous flights on the dynamics of crystallization in microgravity and especially the observed interaction of growing crystallites in the coexistance regime. To clarify rheological measurements we also present ground based experiments on the low shear rate viscosity and diffusion coefficient of several hard sphere experiments at high volume fraction. We also show how these experiments will be performed with confocal microscopy and laser tweezers in our lab and as preparation for the phAse II experiments on LMM. One of the main aims of the microscopy study will be the control of colloidal samples using an array of applied fields with an eye toward colloidal architectures. Temperature gradients, electric field gradients, laser tweezers and a variety of switchable imposed surface patterns are used toward this control.

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy.

PubMed

Persechino, Flavia; De Carvalho, Nathalie; Ciardo, Silvana; De Pace, Barbara; Casari, Alice; Chester, Johanna; Kaleci, Shaniko; Stanganelli, Ignazio; Longo, Caterina; Farnetani, Francesca; Pellacani, Giovanni

2018-03-01

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already-described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Axial arrangement of the myosin rod in vertebrate thick filaments: immunoelectron microscopy with a monoclonal antibody to light meromyosin

PubMed Central

1985-01-01

A monoclonal antibody, MF20, which has been shown previously to bind the myosin heavy chain of vertebrate striated muscle, has been proven to bind the light meromyosin (LMM) fragment by solid phase radioimmune assay with alpha-chymotryptic digests of purified myosin. Epitope mapping by electron microscopy of rotary-shadowed, myosin-antibody complexes has localized the antibody binding site to LMM at a point approximately 92 nm from the C-terminus of the myosin heavy chain. Since this epitope in native thick filaments is accessible to monoclonal antibodies, we used this antibody as a high affinity ligand to analyze the packing of LMM along the backbone of the thick filament. By immunofluorescence microscopy, MF20 was shown to bind along the entire A-band of chicken pectoralis myofibrils, although the epitope accessibility was greater near the ends than at the center of the A- bands. Thin-section, transmission electron microscopy of myofibrils decorated with MF20 revealed 50 regularly spaced, cross-striations in each half A-band, with a repeat distance of approximately 13 nm. These were numbered consecutively, 1-50, from the A-band to the last stripe, approximately 68 nm from the filament tips. These same striations could be visualized by negative staining of native thick filaments labeled with MF20. All 50 striations were of a consecutive, uninterrupted repeat which approximated the 14-15-nm axial translation of cross- bridges. Each half M-region contained five MF20 striations (approximately 13 nm apart) with a distance between stripes 1 and 1', on each half of the bare zone, of approximately 18 nm. This is compatible with a packing model with full, antiparallel overlap of the myosin rods in the bare zone region. Differences in the spacings measured with negatively stained myofilaments and thin-sectioned myofibrils have been shown to arise from specimen shrinkage in the fixed and embedded preparations. These observations provide strong support for Huxley's original proposal for myosin packing in thick filaments of vertebrate muscle (Huxley, H. E., 1963, J. Mol. Biol., 7:281-308) and, for the first time, directly demonstrate that the 14-15- nm axial translation of LMM in the thick filament backbone corresponds to the cross-bridge repeat detected with x-ray diffraction of living muscle. PMID:3897243

Light Microscopy Module: An On-Orbit Microscope Planned for the Fluids and Combustion Facility on the International Space Station

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Motil, Susan M.; Snead, John H.; Griffin, DeVon W.

2001-01-01

The Light Microscopy Module (LMM) is planned as a fully remotely controllable on-orbit microscope subrack facility, allowing flexible scheduling and control of fluids and biology experiments within NASA Glenn Research Center's Fluids and Combustion Facility on the International Space Station. Within the Fluids and Combustion Facility, four fluids physics experiments will utilize an instrument built around a light microscope. These experiments are the Constrained Vapor Bubble experiment (Peter C. Wayner of Rensselaer Polytechnic Institute), the Physics of Hard Spheres Experiment-2 (Paul M. Chaikin of Princeton University), the Physics of Colloids in Space-2 experiment (David A. Weitz of Harvard University), and the Low Volume Fraction Colloidal Assembly experiment (Arjun G. Yodh of the University of Pennsylvania). The first experiment investigates heat conductance in microgravity as a function of liquid volume and heat flow rate to determine, in detail, the transport process characteristics in a curved liquid film. The other three experiments investigate various complementary aspects of the nucleation, growth, structure, and properties of colloidal crystals in microgravity and the effects of micromanipulation upon their properties. Key diagnostic capabilities for meeting the science requirements of the four experiments include video microscopy to observe sample features including basic structures and dynamics, interferometry to measure vapor bubble thin film thickness, laser tweezers for colloidal particle manipulation and patterning, confocal microscopy to provide enhanced three-dimensional visualization of colloidal structures, and spectrophotometry to measure colloidal crystal photonic properties.

Study of the effect of thiols on the vasodilatory potency of S-nitrosothiols by using a modified aortic ring assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giustarini, Daniela, E-mail: giustarini@unisi.it; Tsikas, Dimitrios, E-mail: tsikas.dimitros@mh-hannover.de; Rossi, Ranieri, E-mail: ranieri@unisi.it

2011-10-15

Both low-molecular-mass thiols (LMM-SH) and protein thiols (P-SH) can modulate the biological activity of S-nitrosothiols (RSNO) via S-transnitrosation reactions. It has been difficult to evaluate the entity of this effect in blood circulation by in vitro assays with isolated aorta rings so far, because media rich in proteins cannot be used due to the foaming as a consequence of the needed gas bubbling. We have modified the original apparatus for organ bioassay in order to minimize foaming and to increase analytical performance. By using this modified bioassay we investigated the vasodilatory potency of various endogenous RSNOs in the presence ofmore » physiologically relevant concentrations of albumin and LMM-SH. Our results show that the sulfhydryl group of the cysteine moiety of albumin and LMM-SH has a dramatic effect on the vasodilatory potency of RSNO. Considering the equilibrium constants for S-transnitrosation reactions and the concentration of P-SH and LMM-SH we measured in healthy humans (aged 18-85 years), we infer that the age-dependency of hematic levels of LMM-SH may have a considerable impact in RSNO-mediated vasodilation. S-Nitrosoproteins such as S-nitrosoalbumin may constitute a relatively silent and constant amount of circulating RSNO. On the other hand, LMM-SH may mediate and control the biological actions of S-nitrosoproteins via S-transnitrosation reactions, by forming more potent nitric oxide-releasing LMM-S-nitrosothiols. Lifestyle habits, status of health and individual age are proven factors that, in turn, may influence the concentration of these compounds. These aspects should be taken into consideration when testing the vasodilatory effects of RSNO in pre-clinical studies. - Highlights: > A modification of the organ chamber apparatus for aortic ring bioassays is proposed. > The new apparatus can work in the presence of albumin at physiological concentrations. > Potency of RSNOs was studied in the presence of albumin and low molecular mass -SH. > Plasma thiol levels decrease with age. > Potency of RSNOs varies in dependence of age and more in general of plasma thiol status.« less

Low-bandgap, monolithic, multi-bandgap, optoelectronic devices

DOEpatents

Wanlass, Mark W.; Carapella, Jeffrey J.

2016-01-05

Low bandgap, monolithic, multi-bandgap, optoelectronic devices (10), including PV converters, photodetectors, and LED's, have lattice-matched (LM), double-heterostructure (DH), low-bandgap GaInAs(P) subcells (22, 24) including those that are lattice-mismatched (LMM) to InP, grown on an InP substrate (26) by use of at least one graded lattice constant transition layer (20) of InAsP positioned somewhere between the InP substrate (26) and the LMM subcell(s) (22, 24). These devices are monofacial (10) or bifacial (80) and include monolithic, integrated, modules (MIMs) (190) with a plurality of voltage-matched subcell circuits (262, 264, 266, 270, 272) as well as other variations and embodiments.

Low-bandgap, monolithic, multi-bandgap, optoelectronic devices

DOEpatents

Wanlass, Mark W.; Carapella, Jeffrey J.

2014-07-08

Low bandgap, monolithic, multi-bandgap, optoelectronic devices (10), including PV converters, photodetectors, and LED's, have lattice-matched (LM), double-heterostructure (DH), low-bandgap GaInAs(P) subcells (22, 24) including those that are lattice-mismatched (LMM) to InP, grown on an InP substrate (26) by use of at least one graded lattice constant transition layer (20) of InAsP positioned somewhere between the InP substrate (26) and the LMM subcell(s) (22, 24). These devices are monofacial (10) or bifacial (80) and include monolithic, integrated, modules (MIMs) (190) with a plurality of voltage-matched subcell circuits (262, 264, 266, 270, 272) as well as other variations and embodiments.

Low-bandgap, monolithic, multi-bandgap, optoelectronic devices

DOEpatents

Wanlass, Mark W.; Carapella, Jeffrey J.

2016-03-22

Low bandgap, monolithic, multi-bandgap, optoelectronic devices (10), including PV converters, photodetectors, and LED's, have lattice-matched (LM), double-heterostructure (DH), low-bandgap GaInAs(P) subcells (22, 24) including those that are lattice-mismatched (LMM) to InP, grown on an InP substrate (26) by use of at least one graded lattice constant transition layer (20) of InAsP positioned somewhere between the InP substrate (26) and the LMM subcell(s) (22, 24). These devices are monofacial (10) or bifacial (80) and include monolithic, integrated, modules (MIMs) (190) with a plurality of voltage-matched subcell circuits (262, 264, 266, 270, 272) as well as other variations and embodiments.

Molecular mechanism for adhesion in humid conditions - lessons from spider glue

NASA Astrophysics Data System (ADS)

Amarpuri, Gaurav; Singla, Saranshu; Dhopatkar, Nishad; Blackledge, Todd; Dhinojwal, Ali

Adhesion in humid conditions is a fundamental challenge for both natural and synthetic adhesives. Water lubricates the interface between the adhesive and the substrate resulting in an interfacial failure at high humidity. Yet, glue from most spider species fail cohesively at high humidity, and the spider species from wet habitat show an increase in adhesion with humidity. We use tensile testing, microscopy and surface sensitive spectroscopy techniques to probe the mechanism of spider glue adhesion under high humidity. Humidity responsive structural changes in the glue structure are observed both at the interface and in bulk. However, the humidity responsiveness is lost after washing the water soluble low molecular weight molecules (LMM) from the glue. Many natural systems display a functional response to their environment, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic LMM that respond to humidity in a unique way. We therefore anticipate that manipulation of polymer-LMM interaction can provide a simple mechanism to design humidity responsive smart adhesives. We acknowledge support from National Science Foundation Grant IOS-1257719.

Light Microscopy Microscope Experiment

NASA Image and Video Library

2016-02-04

Ground testing for the first confocal Light Microscopy Microscope (LMM) Experiment. Procter and Gamble is working with NASA Glenn scientists to prepare for a study that examines product stabilizers in a microgravity environment. The particles in the tube glow orange because they have been fluorescently tagged with a dye that reacts to green laser lights to allow construction of a 3D image point by point. The experiment, which will be sent to the ISS later this year, will help P&G develop improved product stabilizers to extend shelf life and develop more environmentally friendly packaging.

Epidemiology of Lentigo Maligna and Lentigo Maligna Melanoma in the Netherlands, 1989-2013.

PubMed

Greveling, Karin; Wakkee, Marlies; Nijsten, Tamar; van den Bos, Renate R; Hollestein, Loes M

2016-10-01

Lentigo maligna (LM) is considered a precursor to LM melanoma (LMM). We assessed trends in LM and LMM incidence rates between 1989 and 2013 in the Netherlands, and estimated the risk of an LMM after LM. Data on newly diagnosed LM and LMM were obtained from the Netherlands Cancer Registry and PALGA: Dutch Pathology Registry. Age-standardized incidence rates (European standardized rate), estimated annual percentage changes, and the cumulative incidence of LMM after LM were calculated. Between 1989 and 2013, 10,545 patients were diagnosed with a primary LM and 2,898 with a primary LMM in the Netherlands. The age-standardized incidence rate for LM increased from 0.72 to 3.84 per 100,000 person-years, and for LMM from 0.24 to 1.19 between 1989 and 2013. LM incidence increased from 2002 to 2013 with 6.8% annually, before an even steeper rise in LMM incidence from 2007 to 2013 (estimated annual percentage change: 12.4%). The cumulative incidence of LMM after a primary LM after 25-year follow-up was 2.0% for males and 2.6% for females. The increased incidence of LM and LMM in the Netherlands seems, besides increased awareness and increased histological confirmation of LM, to reflect a true increase. The absolute risk of an LMM (at any location) after a histologically confirmed LM was low (2.0-2.6%). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

THE COMPARISON OF THE LUMBAR MULTIFIDUS MUSCLES FUNCTION BETWEEN GYMNASTIC ATHLETES WITH SWAY-BACK POSTURE AND NORMAL POSTURE.

PubMed

Mahdavie, Elnaz; Rezasoltani, Asghar; Simorgh, Leila

2017-08-01

The prevalence of sway back posture (SBP) is very high among elite gymnasts. This posture may be partly due to the improper function of lumbar multifidus muscles (LMM) as lumbar stabilizers muscles. The aim of this study was to compare the thicknesses of LMM measured at rest and during the contraction elicited during an arm lift between elite gymnasts with SBP and normal posture. Observational, descriptive, comparative. The participants consist of twenty gymnasts between the ages of 17 and 30 who had trained in gymnastics for more than ten years. They were assigned to two groups: SBP (n=10) and control (n=10). Posture analysis with grid paper and plumb line was performed for all subjects. The thickness of LMM on dominant side of spinal column was measured by a real-time ultrasound at five lumbar levels. The thickness of the LMM was measured both at rest and during the contraction elicited during an arm lift. The variation between the LMM thickness between the muscle at rest and muscle at the peak of contraction was regarded as LMM muscle function. The thickness of LMM was less in SBP group than the control group at all lumbar segments. The variation in LMM thickness between the state of rest and muscle contraction was significantly less in athletes with SBP than controls when compared at all levels of the lumbar spine (p < 0.05). The function of LMM may be disturbed in athletes with SBP as demonstrated by decreased thicknesses of LMM found in gymnasts with SBP. Additionally, the thickness of the LMM as a strong antigravity and stabilizing muscle group was decreased during arm raising in gymnasts with SBP. 3a.

Role of Pseudomonas aeruginosa low-molecular-mass penicillin-binding proteins in AmpC expression, β-lactam resistance, and peptidoglycan structure.

PubMed

Ropy, Alaa; Cabot, Gabriel; Sánchez-Diener, Irina; Aguilera, Cristian; Moya, Bartolome; Ayala, Juan A; Oliver, Antonio

2015-07-01

This study aimed to characterize the role of Pseudomonas aeruginosa low-molecular-mass penicillin-binding proteins (LMM PBPs), namely, PBP4 (DacB), PBP5 (DacC), and PBP7 (PbpG), in peptidoglycan composition, β-lactam resistance, and ampC regulation. For this purpose, we constructed all single and multiple mutants of dacB, dacC, pbpG, and ampC from the wild-type P. aeruginosa PAO1 strain. Peptidoglycan composition was determined by high-performance liquid chromatography (HPLC), ampC expression by reverse transcription-PCR (RT-PCR), PBP patterns by a Bocillin FL-binding test, and antimicrobial susceptibility by MIC testing for a panel of β-lactams. Microscopy and growth rate analyses revealed no apparent major morphological changes for any of the mutants compared to the wild-type PAO1 strain. Of the single mutants, only dacC mutation led to significantly increased pentapeptide levels, showing that PBP5 is the major dd-carboxypeptidase in P. aeruginosa. Moreover, our results indicate that PBP4 and PBP7 play a significant role as dd-carboxypeptidase only if PBP5 is absent, and their dd-endopeptidase activity is also inferred. As expected, the inactivation of PBP4 led to a significant increase in ampC expression (around 50-fold), but, remarkably, the sequential inactivation of the three LMM PBPs produced a much greater increase (1,000-fold), which correlated with peptidoglycan pentapeptide levels. Finally, the β-lactam susceptibility profiles of the LMM PBP mutants correlated well with the ampC expression data. However, the inactivation of ampC in these mutants also evidenced a role of LMM PBPs, especially PBP5, in intrinsic β-lactam resistance. In summary, in addition to assessing the effect of P. aeruginosa LMM PBPs on peptidoglycan structure for the first time, we obtained results that represent a step forward in understanding the impact of these PBPs on β-lactam resistance, apparently driven by the interplay between their roles in AmpC induction, β-lactam trapping, and dd-carboxypeptidase/β-lactamase activity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Precision Mechanical Measurement Using the Levitation Mass Method (LMM)

NASA Astrophysics Data System (ADS)

Fujii, Yusaku; Jin, Tao; Maru, Koichi

2010-12-01

The present status and the future prospects of a method for precision mass and force measurement, the levitation mass method (LMM), are reviewed. The LMM has been proposed and improved by the authors. In the LMM, the inertial force of a mass levitated using a pneumatic linear bearing is used as the reference force applied to the objects under test, such as force transducers, materials or structures. The inertial force of the levitated mass is measured using an optical interferometer. The three typical applications of the LMM, i.e. the dynamic force calibration, the micro force material tester and the space scale, are reviewed in this paper.

Correlation between lumbar dysfunction and fat infiltration in lumbar multifidus muscles in patients with low back pain.

PubMed

Hildebrandt, Markus; Fankhauser, Gabriela; Meichtry, André; Luomajoki, Hannu

2017-01-10

Lumbar multifidus muscles (LMM) are important for spinal motion and stability. Low back pain (LBP) is often associated with fat infiltration in LMM. An increasing fat infiltration of LMM may lead to lumbar dysfunction. The purpose of this study was to investigate whether there is a correlation between the severity of lumbar dysfunction and the severity of fat infiltration of LMM. In a cross-sectional study, 42 patients with acute or chronic LBP were recruited. Their MRI findings were visually rated and graded using three criteria for fat accumulation in LMM: Grade 0 (0-10%), Grade 1 (10-50%) and Grade 2 (>50%). Lumbar sagittal range of motion, dynamic upright and seated posture control, sagittal movement control, body awareness and self-assessed functional disability were measured to determine the patients' low back dysfunction. The main result of this study was that increased severity of fat infiltration in the lumbar multifidus muscles correlated significantly with decreased range of motion of lumbar flexion (p = 0.032). No significant correlation was found between the severity of fat infiltration in LMM and impaired movement control, posture control, body awareness or self-assessed functional disability. This is the first study investigating the relationship between the severity of fat infiltration in LMM and the severity of lumbar dysfunction. The results of this study will contribute to the understanding of the mechanisms leading to fat infiltration of LMM and its relation to spinal function. Further studies should investigate whether specific treatment strategies are effective in reducing or preventing fat infiltration of LMM.

Light meromyosin paracrystal formation.

PubMed

Chowrashi, P K; Pepe, F A

1977-07-01

STUDIES OF PARACRYSTAL FORMATION BY COLUMN PURIFIED LIGHT MEROMYOSIN (LMM) PREPARED IN A VARIETY OF WAYS LED TO THE FOLLOWING CONCLUSIONS: (a) different portions of the myosin rod may be coded for different stagger relationships. This was concluded from observations that paracrystals with different axial repeat periodicities could be obtained either with LMM framents of different lengths prepared with the same enzyme, or with LMM fragments of identical lengths but prepared with different enzymes. (b) Paracrystals with a 14-nm axial repeat periodicity are most likely formed by the aggregation of sheets with a 44-nm axial repeat within the sheets which are staggered by 14 nm. All of the axial repeat patterns expected from one sheet or aggregates of more than one sheet, on this basis, were observed in the same electron micrograph. (c) C-protein binding probably occurs preferentially to LMM molecules related in some specific way. This was concluded from the observation that the same axial repeat pattern was obtained in paracrystals formed from different LMM preparations in the presence of C-protein, regardless of differences in the axial repeat obtained in the absence of C-protein. (d) Nucleic acid is responsible for the 43-nm axial repeat patterns observed in paracrystals formed by the ethanol-resistant fraction of LMM. In the absence of nuclei acid, paracrystals with a 14nm axial repeat are obtained. (e) The 43-nm axial repeat pattern observed with the ethanol-resistant fraction of LMM is different for LMM preparations obtained by trypsin and papain digestions.

Implication of Sarcopenia and Sarcopenic Obesity on Lung Function in Healthy Elderly: Using Korean National Health and Nutrition Examination Survey.

PubMed

Moon, Ji Hyun; Kong, Mi Hee; Kim, Hyeon Ju

2015-11-01

Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index ≥ 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age.

Evaluation of Learning Money Matters (LMM). Final Report

ERIC Educational Resources Information Center

Spielhofer, Thomas; Kerr, David; Gardiner, Clare

2009-01-01

This report presents the final findings of research carried out by the National Foundation for Educational Research (NFER), as part of an independent evaluation on behalf of pfeg, of the Learning Money Matters (LMM) initiative. LMM provides help, support and advice for secondary schools in delivering personal finance education (PFE) to their…

78 FR 22414 - Amendment of Class E Airspace; Reno, NV

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... Marker (LMM) and the Middle Marker (MM) has made this action necessary for the safety and management of... is necessary due to the decommissioning of the LMM and MM navigation aids. The Airport Reference Point is used to describe the airspace instead of the LMM and the MM navigational aids. There is no...

Overview of recent trends in diagnosis and management of leptomeningeal multiple myeloma.

PubMed

Yellu, Mahender R; Engel, Jessica M; Ghose, Abhimanyu; Onitilo, Adedayo A

2016-03-01

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population. Copyright © 2014 John Wiley & Sons, Ltd.

Longitudinal data analyses using linear mixed models in SPSS: concepts, procedures and illustrations.

PubMed

Shek, Daniel T L; Ma, Cecilia M S

2011-01-05

Although different methods are available for the analyses of longitudinal data, analyses based on generalized linear models (GLM) are criticized as violating the assumption of independence of observations. Alternatively, linear mixed models (LMM) are commonly used to understand changes in human behavior over time. In this paper, the basic concepts surrounding LMM (or hierarchical linear models) are outlined. Although SPSS is a statistical analyses package commonly used by researchers, documentation on LMM procedures in SPSS is not thorough or user friendly. With reference to this limitation, the related procedures for performing analyses based on LMM in SPSS are described. To demonstrate the application of LMM analyses in SPSS, findings based on six waves of data collected in the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong are presented.

Longitudinal Data Analyses Using Linear Mixed Models in SPSS: Concepts, Procedures and Illustrations

PubMed Central

Shek, Daniel T. L.; Ma, Cecilia M. S.

2011-01-01

Although different methods are available for the analyses of longitudinal data, analyses based on generalized linear models (GLM) are criticized as violating the assumption of independence of observations. Alternatively, linear mixed models (LMM) are commonly used to understand changes in human behavior over time. In this paper, the basic concepts surrounding LMM (or hierarchical linear models) are outlined. Although SPSS is a statistical analyses package commonly used by researchers, documentation on LMM procedures in SPSS is not thorough or user friendly. With reference to this limitation, the related procedures for performing analyses based on LMM in SPSS are described. To demonstrate the application of LMM analyses in SPSS, findings based on six waves of data collected in the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong are presented. PMID:21218263

Enzyme Mini-Test for Field Identification of Leishmania Isolates from U.S. Military Personnel.

DTIC Science & Technology

1986-05-15

Panama Dominques L2 539 NWC LBP Man - Panama Carillo 530 NWC LBP Man - Panama Schoonmaker 063 NWC LBG Man - Peru Terborgh/Muco 294 NWC LBB Man - Brazil...NWC LMA-G Man - Panama Castro 140 NWC LMM-P Man - Peru UTA 381 NWC LMM-P Man - Panama Peters 453 NWC LMM-P Man - Dominican Republic - 457 NWC LMM-P...LV24 547 OWC LMJ Man R. Beach Kenya LRC-L137 551 OWC LMJ Rodent R. Beach Kenya NLB095 552 OWC LMJ Sandfly R. Beach Kenya NLBI44 558 OWC LMJ Man

78 FR 5153 - Proposed Amendment of Class E Airspace; Reno, NV

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... Compass Locator at the Instrument Landing System Middle Marker (LMM) and the Middle Marker (MM) has made... necessary due to the decommissioning of the LMM and the MM navigation aids. The Airport Reference Point (ARP) would be used to describe the airspace instead of the LMM and the MM navigational aids. There would be...

Risk factors for lentigo maligna melanoma compared with superficial spreading melanoma: a case-control study in Australia.

PubMed

Kvaskoff, Marina; Siskind, Victor; Green, Adèle C

2012-02-01

To investigate risk factors for lentigo maligna melanoma (LMM) compared with superficial spreading melanoma (SSM). Population-based case-control study in Queensland, Australia. General community. Population-based sample of 49 patients with LMM and 141 with SSM (in situ or invasive) aged 14 to 86 years at diagnosis in 1979 and 1980 and 232 control subjects. Response rates were 97.1% in cases and 91.8% in controls. Risks of both subtypes in relation to phenotypic and environmental factors, estimated by multinomial logistic regression. The number of solar lentigines was the strongest determinant for LMM (odds ratio [OR], 15.93; P < .001 for trend) and significantly weaker for SSM (4.61; P < .001 for trend; P = .04 for homogeneity). Skin cancer history was significantly associated with LMM (OR, 2.84) but not with SSM (1.33; P = .07 for homogeneity). In contrast, the number of nevi was the strongest determinant for SSM (OR, 23.22; P < .001 for trend) while significantly weaker for LMM (3.60; P = .02 for trend; P < .001 for homogeneity). Multiple lifetime sunburns almost tripled the risk for SSM, whereas no association was detected with LMM (P = .04 for homogeneity). Shared risk factors for both subtypes were the number of solar keratoses (P < .001 for trend for both) and sun-sensitive complexion (ie, light eye/hair colors, sunburn propensity, and freckling) (2-fold to 5-fold increased risks). A propensity to lentigines is a stronger predictor of LMM, whereas high nevus propensity is a stronger predictor of SSM. Skin cancer history appears to determine LMM risk only, whereas the number of lifetime sunburns determines SSM only. Prevention strategies could be tailored differently given these distinctive points of difference.

78 FR 34417 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... directed to LMM3. The Exchange System operates as follows: LMM3 is entitled to the greater of: (i) pro-rata... (30) Incoming Directed Order: Sell 2 contracts @ 1.00 directed to LMM3. The Exchange System operates... prepared summaries, set forth in sections A, B, and C below, of the most significant aspects of such...

The importance of subfragment 2 and C-terminus of myosin heavy chain for thick filament assembly in skeletal muscle cells.

PubMed

Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Muroya, Susumu; Chikuni, Koichi; Hattori, Akihito; Nishimura, Takanori

2015-04-01

In skeletal muscle cells, myofibrillar proteins are highly organized into sarcomeres in which thick filaments interdigitate with thin filaments to generate contractile force. The size of thick filaments, which consist mainly of myosin molecules, is strictly controlled. However, little is known about the mechanisms by which myosin molecules assemble into thick filaments. Here, we assessed the ability of each domain of myosin heavy chain (Myh) to form thick filaments. We showed that exogenously expressed subfragment 2 (S2) + light meromyosin (LMM) of Myh was efficiently incorporated into thick filaments in muscle cells, although neither solely expressed S2 nor LMM targeted to thick filaments properly. In nonmuscle COS7 cells, S2+LMM formed more enlarged filaments/speckles than LMM. These results suggest that Myh filament formation is induced by S2 accompanying LMM. We further examined the effects of Myh C-terminus on thick filament assembly. C-terminal deletion mutants were incorporated not into entire thick filaments but rather into restricted regions of thick filaments. Our findings suggest that the elongation of myosin filaments to form thick filaments is regulated by S2 as well as C-terminus of LMM. © 2014 Japanese Society of Animal Science.

Diagnosis of the "large medial meniscus" of the knee on MR imaging.

PubMed

Samoto, Nobuhiko; Kozuma, Masakazu; Tokuhisa, Toshio; Kobayashi, Kunio

2006-11-01

Although several quantitative magnetic resonance (MR) diagnostic criteria for discoid lateral meniscus (DLM) have been described, there are no criteria by which to estimate the size of the medial meniscus. We define a medial meniscus that exceeds the normal size as a "large medial meniscus" (LMM), and the purpose of this study is to establish the quantitative MR diagnostic criteria for LMM. The MR imaging findings of 96 knees with arthroscopically confirmed intact semilunar lateral meniscus (SLM), 18 knees with intact DLM, 105 knees with intact semilunar medial meniscus (SMM) and 4 knees with torn LMM were analyzed. The following three quantitative parameters were measured: (a) meniscal width (MW): the minimum MW on the coronal slice; (b) ratio of the meniscus to the tibia (RMT): the ratio of minimum MW to maximum tibial width on the coronal slice; (c) continuity of the anterior and posterior horns (CAPH): the number of consecutive 5-mm-thick sagittal slices showing continuity between the anterior horn and the posterior horn of the meniscus on sagittal slices. Using logistic discriminant analysis between intact SLM and DLM groups and using descriptive statistics of intact SLM and SMM groups, the cutoff values used to discriminate LMM from SMM were calculated by MW and RMT. Moreover, the efficacy of these cutoff values and three slices of the cutoff values for CAPH were estimated in the medial meniscus group. "MW> or =11 mm" and "RMT> or =15%" were determined to be effective diagnostic criteria for LMM, while three of four cases in the torn LMM group were true positives and specificity was 99% in both criteria. When "CAPH> or =3 slices" was used as a criterion, three of four torn LMM cases were true positives and specificity was 93%.

The Biocontrol Efficacy of Streptomyces pratensis LMM15 on Botrytis cinerea in Tomato

PubMed Central

Lian, Qinggui; Zhang, Jing; Gan, Liang; Ma, Qing; Zong, Zhaofeng

2017-01-01

LMM15, an actinomycete with broad spectrum antifungal activity, was isolated from a diseased tomato leaf using the baiting technique. A phylogenetic tree analysis based on similarity percentage of 16S rDNA sequences showed that the bacterium was 97.0% affiliated with the species Streptomyces pratensis. This strain was therefore coded as S. pratensis LMM15. The ferment filtrate of LMM15 had ability to inhibit mycelia growth of Botrytis cinerea and reduce lesion expansion of gray mold on detached leaves and fruits. In greenhouse experiments, both the fresh and dry weights of tomato seedlings were significantly increased with the increased concentrations of total chlorophyll. The incidence of tomato gray mold decreased by 46.35%; this was associated with the increase of proline content and malondialdehyde (MDA) and the changes in defense-related enzymes on tomato leaves when the strain was sprayed on the tomato leaves 24 h prior to inoculation with pathogens. This study showed that the strain S. pratensis LMM15 could be a potential agent for controlling tomato gray mold. PMID:29318156

Rolling, slip and traction measurements on low modulus materials

NASA Technical Reports Server (NTRS)

Tevaarwerk, J. L.

1985-01-01

Traction and wear tests were performed on six low modulus materials (LMM). Three different traction tests were performed to determine the suitability of the material for use as traction rollers. These were the rolling, slip and endurance traction tests. For each material the combination LMM on LMM and LMM on steel were evaluated. Rolling traction test were conducted to determine the load - velocity limits, the rolling traction coefficient of the materials and to establish the type of failures that would result when loading beyond the limit. It was found that in general a simple constant rolling traction coefficient was enough to describe the results of all the test. The slip traction tests revealed that the peak traction coefficients were considerably higher than for lubricated traction contacts. The endurance traction tests were performed to establish the durability of the LMM under conditions of prolonged traction. Wear measurements were performed during and after the test. Energetic wear rates were determined from the wear measurements conducted in the endurance traction tests. These values show that the roller wear is not severe when reasonable levels of traction are transmitted.

Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

PubMed Central

McCormick, Sean P.; Moore, Michael J.; Lindahl, Paul A.

2015-01-01

Liquid chromatography was used with an on-line inductively coupled plasma mass spectrometer to detect low-molecular-mass (LMM) transition metal complexes in mitochondria isolated from fermenting yeast cells, human Jurkat cells, and mouse brain and liver. These complexes constituted 20 – 40% of total mitochondrial Mn, Fe, Zn, and Cu ions. The major LMM Mn complex in yeast mitochondria had a mass of ca. 1100 Da and a concentration of ~ 2 μM. Mammalian mitochondria contained a second Mn species with a mass of ca. 2000 Da at a comparable concentration. The major Fe complex in mitochondria isolated from exponentially growing yeast cells had a mass of ca. 580 Da; the concentration of Fe580 in mitochondria was ca. 100 μM. When mitochondria were isolated from fermenting cells in post-exponential phase, the mass of the dominant LMM Fe complex was ca. 1100 Da. Upon incubation, the intensity of Fe1100 declined and Fe580 increased, suggesting that the two are interrelated. Mammalian mitochondria contained Fe580 and 2 other Fe species (Fe2000 and Fe1100) at concentrations of ca. 50 μM each. The dominant LMM Zn species in mitochondria had a mass of ca. 1200 Da and a concentration of ca. 110 μM. Mammalian mitochondria contained a second major LMM Zn species at 1500 Da. The dominant LMM Cu species in yeast mitochondria had a mass of ca. 5000 Da and a concentration in yeast mitochondria of ca. 16 μM; Cu5000 was not observed in mammalian mitochondria. The dominant Co species in mitochondria, Co1200, had a concentration of 20 nM and was probably a cobalamin. Mammalian but not yeast mitochondria contained a LMM Mo species, Mo730, at ca. 1 μM concentration. Increasing Mn, Fe, Cu, and Zn concentrations 10 fold in the medium increased the concentration of the same element in the corresponding isolated mitochondria. Treatment with metal chelators confirmed that these LMM species were labile. The dominant S species at 1100 Da was not free GSH or GSSG. PMID:26018429

The effect of spaceflight on the gravity-sensing auxin gradient of roots: GFP reporter gene microscopy on orbit

PubMed Central

Ferl, Robert J; Paul, Anna-Lisa

2016-01-01

Our primary aim was to determine whether gravity has a direct role in establishing the auxin-mediated gravity-sensing system in primary roots. Major plant architectures have long been thought to be guided by gravity, including the directional growth of the primary root via auxin gradients that are then disturbed when roots deviate from the vertical as a gravity sensor. However, experiments on the International Space Station (ISS) now allow physical clarity with regard to any assumptions regarding the role of gravity in establishing fundamental root auxin distributions. We examined the spaceflight green fluorescent protein (GFP)-reporter gene expression in roots of transgenic lines of Arabidopsis thaliana: pDR5r::GFP, pTAA1::TAA1–GFP, pSCR::SCR–GFP to monitor auxin and pARR5::GFP to monitor cytokinin. Plants on the ISS were imaged live with the Light Microscopy Module (LMM), and compared with control plants imaged on the ground. Preserved spaceflight and ground control plants were examined post flight with confocal microscopy. Plants on orbit, growing in the absence of any physical reference to the terrestrial gravity vector, displayed typically “vertical” distribution of auxin in the primary root. This confirms that the establishment of the auxin-gradient system, the primary guide for gravity signaling in the root, is gravity independent. The cytokinin distribution in the root tip differs between spaceflight and the ground controls, suggesting spaceflight-induced features of root growth may be cytokinin related. The distribution of auxin in the gravity-sensing portion of the root is not dependent on gravity. Spaceflight appears benign to auxin and its role in the development of the primary root tip, whereas spaceflight may influence cytokinin-associated processes. PMID:28725721

On the reconciliation of missing heritability for genome-wide association studies

PubMed Central

Chen, Guo-Bo

2016-01-01

The definition of heritability has been unique and clear, but its estimation and estimates vary across studies. Linear mixed model (LMM) and Haseman–Elston (HE) regression analyses are commonly used for estimating heritability from genome-wide association data. This study provides an analytical resolution that can be used to reconcile the differences between LMM and HE in the estimation of heritability given the genetic architecture, which is responsible for these differences. The genetic architecture was classified into three forms via thought experiments: (i) coupling genetic architecture that the quantitative trait loci (QTLs) in the linkage disequilibrium (LD) had a positive covariance; (ii) repulsion genetic architecture that the QTLs in the LD had a negative covariance; (iii) and neutral genetic architecture that the QTLs in the LD had a covariance with a summation of zero. The neutral genetic architecture is so far most embraced, whereas the coupling and the repulsion genetic architecture have not been well investigated. For a quantitative trait under the coupling genetic architecture, HE overestimated the heritability and LMM underestimated the heritability; under the repulsion genetic architecture, HE underestimated but LMM overestimated the heritability for a quantitative trait. These two methods gave identical results under the neutral genetic architecture. A general analytical result for the statistic estimated under HE is given regardless of genetic architecture. In contrast, the performance of LMM remained elusive, such as further depended on the ratio between the sample size and the number of markers, but LMM converged to HE with increased sample size. PMID:27436266

The cellular source for APOBEC3G's incorporation into HIV-1

PubMed Central

2011-01-01

Background Human APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity. Viral incorporation of hA3G is an essential step for its antiviral activity. Although the mechanism underlying hA3G virion encapsidation has been investigated extensively, the cellular source of viral hA3G remains unclear. Results Previous studies have shown that hA3G forms low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of the mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation. Conclusions Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G. PMID:21211018

Evidence for age-associated cognitive decline from Internet game scores.

PubMed

Geyer, Jason; Insel, Philip; Farzin, Faraz; Sternberg, Daniel; Hardy, Joseph L; Scanlon, Michael; Mungas, Dan; Kramer, Joel; Mackin, R Scott; Weiner, Michael W

2015-06-01

Lumosity's Memory Match (LMM) is an online game requiring visual working memory. Change in LMM scores may be associated with individual differences in age-related changes in working memory. Effects of age and time on LMM learning and forgetting rates were estimated using data from 1890 game sessions for users aged 40 to 79 years. There were significant effects of age on baseline LMM scores (β = -.31, standard error or SE = .02, P < .0001) and lower learning rates (β = -.0066, SE = .0008, P < .0001). A sample size of 202 subjects/arm was estimated for a 1-year study for subjects in the lower quartile of game performance. Online memory games have the potential to identify age-related decline in cognition and to identify subjects at risk for cognitive decline with smaller sample sizes and lower cost than traditional recruitment methods.

Dynamical Structure of Madden-Julian Oscillation over Malay Peninsula

NASA Astrophysics Data System (ADS)

Djamil, Y. S.; Koh, T. Y.; Chandimala, J.; Teo, C. K.

2014-12-01

Madden-Julian Oscillation (MJO) is the dominant weather event in the intraseasonal time scale over Malay Peninsula region. The MJO signals are represented by the first two modes of radiosonde records extracted using Extended Empirical Orthogonal Function (EEOF) analyses which we label as Local Multivariate MJO (LMM). LMM is able to capture the spatio-temporal profile of MJO along the global tropics in all seasons. With the help of LMM, we clarify the dynamical and thermodynamical structure of the MJO over Malay Peninsula, including the unique "boomerang-shaped" feature in the time-height temperature profile identified in previous literature.

Changes in composition of spider orb web sticky droplets with starvation and web removal, and synthesis of sticky droplet compounds

PubMed Central

Townley, Mark A.; Tillinghast, Edward K.; Neefus, Christopher D.

2006-01-01

Summary The sticky spiral of araneoid spider orb webs consists of silk fibers coated with adhesive droplets. The droplets contain a variety of low-molecular-mass compounds (LMM). Within a species, a fairly consistent ratio of LMM is often observed, but substantial variability can exist. To gain insight into factors influencing LMM composition, spiders of three araneid species were starved and LMM from their webs were analyzed for changes in composition. To determine if these changes were consistent with the spider’s ability to synthesize the different organic LMM, synthetic capacities were estimated following the feeding of radiolabeled metabolites. Some changes in droplet composition were broadly consistent with differing synthetic capacities: molar percentages of less readily synthesized compounds (e.g., choline, isethionate, n-acetyltaurine) typically declined with starvation, at least during a portion of the imposed fast, while more readily synthesized compounds (e.g., GABamide, glycine) tended to increase. Most striking was the apparent partial substitution of n-acetylputrescine by the more readily synthesized GABamide in fasting Argiope trifasciata. However, departures from expected compositional shifts demonstrated that synthetic capacity alone does not adequately predict sticky droplet compositional shifts with starvation. Moreover, feeding controls exhibited some changes in composition similar to starving spiders. As the webs of both feeding and starving spiders were removed for chemical analysis and could not be recycled, the loss of LMM contained in these webs likely contributed to similarities between treatments. In addition, feeding spiders molted, oviposited, and/or built heavier webs. The added metabolic demands of these activities may have contributed to changes in composition similar to those resulting from starvation. PMID:16574806

Changes in composition of spider orb web sticky droplets with starvation and web removal, and synthesis of sticky droplet compounds.

PubMed

Townley, Mark A; Tillinghast, Edward K; Neefus, Christopher D

2006-04-01

The sticky spiral of araneoid spider orb webs consists of silk fibers coated with adhesive droplets. The droplets contain a variety of low-molecular-mass compounds (LMM). Within a species, a fairly consistent ratio of LMM is often observed, but substantial variability can exist. To gain insight into factors influencing LMM composition, spiders of three araneid species were starved and LMM from their webs were analyzed for changes in composition. To determine if these changes were consistent with the spider's ability to synthesize the different organic LMM, synthetic capacities were estimated following the feeding of radiolabeled metabolites. Some changes in droplet composition were broadly consistent with differing synthetic capacities: molar percentages of less readily synthesized compounds (e.g. choline, isethionate, N-acetyltaurine) typically declined with starvation, at least during a portion of the imposed fast, while more readily synthesized compounds (e.g. GABamide, glycine) tended to increase. Most striking was the apparent partial substitution of N-acetylputrescine by the more readily synthesized GABamide in fasting Argiope trifasciata. However, departures from expected compositional shifts demonstrated that synthetic capacity alone does not adequately predict sticky droplet compositional shifts with starvation. Moreover, feeding controls exhibited some changes in composition similar to starving spiders. As the webs of both feeding and starving spiders were removed for chemical analysis and could not be recycled, the loss of LMM contained in these webs likely contributed to similarities between treatments. In addition, feeding spiders molted, oviposited and/or built heavier webs. The added metabolic demands of these activities may have contributed to changes in composition similar to those resulting from starvation.

Low muscle mass is associated with metabolic syndrome only in nonobese young adults: the Korea National Health and Nutrition Examination Survey 2008-2010.

PubMed

Kim, Byung Chul; Kim, Mee Kyoung; Han, Kyungdo; Lee, Sae-Young; Lee, Seung-Hwan; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Merchant, Anwar T; Yim, Hyeon Woo; Lee, Won-Chul; Park, Yong Gyu; Park, Yong-Moon

2015-12-01

Little is known about the relationship between body composition and metabolic risk factors in young adults. We hypothesized that low muscle mass (LMM) is associated with metabolic syndrome (MetS) and its components in young adults and that the associations vary by obesity. A cross-sectional analysis was conducted using the Korea National Health and Nutrition Examination Survey data. In total, 5300 young adults aged 19 to 39 years were evaluated. Low muscle mass was defined as an appendicular skeletal muscle mass/weight less than 1 SD below the mean for each participant's corresponding sex and age group. Obesity was defined as a body mass index greater than or equal to 25 kg/m2. The prevalence of LMM was higher in obese than nonobese participants (37.6% vs. 9.6%). In the nonobese participants, the prevalence of MetS, high waist circumference, high triglycerides, and high blood pressure was significantly greater in the LMM group than in the high muscle mass group. In the nonobese group, compared with high muscle mass participants, those with LMM had odds ratios for MetS of 3.6 (95% confidence interval, 1.48-8.76; P < .001) and 3.6 (95% confidence interval, 1.48-8.71; P < .001) in men and women, respectively, after adjusting for confounding factors. However, no significant association of LMM with MetS or its components was found in obese participants. In conclusion, our results suggest that young adults with LMM may have a high risk of MetS, especially when they are nonobese. Interventions aimed at increasing muscle mass at younger ages may have the potential to reduce MetS. Published by Elsevier Inc.

Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.

PubMed

Lloyd-Jones, Luke R; Robinson, Matthew R; Yang, Jian; Visscher, Peter M

2018-04-01

Genome-wide association studies (GWAS) have identified thousands of loci that are robustly associated with complex diseases. The use of linear mixed model (LMM) methodology for GWAS is becoming more prevalent due to its ability to control for population structure and cryptic relatedness and to increase power. The odds ratio (OR) is a common measure of the association of a disease with an exposure ( e.g. , a genetic variant) and is readably available from logistic regression. However, when the LMM is applied to all-or-none traits it provides estimates of genetic effects on the observed 0-1 scale, a different scale to that in logistic regression. This limits the comparability of results across studies, for example in a meta-analysis, and makes the interpretation of the magnitude of an effect from an LMM GWAS difficult. In this study, we derived transformations from the genetic effects estimated under the LMM to the OR that only rely on summary statistics. To test the proposed transformations, we used real genotypes from two large, publicly available data sets to simulate all-or-none phenotypes for a set of scenarios that differ in underlying model, disease prevalence, and heritability. Furthermore, we applied these transformations to GWAS summary statistics for type 2 diabetes generated from 108,042 individuals in the UK Biobank. In both simulation and real-data application, we observed very high concordance between the transformed OR from the LMM and either the simulated truth or estimates from logistic regression. The transformations derived and validated in this study improve the comparability of results from prospective and already performed LMM GWAS on complex diseases by providing a reliable transformation to a common comparative scale for the genetic effects. Copyright © 2018 by the Genetics Society of America.

The Roles of APOBEC3G Complexes in the Incorporation of APOBEC3G into HIV-1

PubMed Central

Zhang, Quan; Liu, Zhenlong; Jia, Pingping; Zhou, Jinming; Guo, Fei; You, Xuefu; Yu, Liyan; Zhao, Lixun; Jiang, Jiandong; Cen, Shan

2013-01-01

Background The incorporation of human APOBEC3G (hA3G) into HIV is required for exerting its antiviral activity, therefore the mechanism underlying hA3G virion encapsidation has been investigated extensively. hA3G was shown to form low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. The function of different forms of hA3G in its viral incorporation remains unclear. Methodology/Principal Findings In this study, we investigated the subcellular distribution and lipid raft association of hA3G using subcellular fractionation, membrane floatation assay and pulse-chase radiolabeling experiments respectively, and studied the correlation between the ability of hA3G to form the different complex and its viral incorporation. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation. Conclusions/Significance Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G. PMID:24098356

Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development

PubMed Central

Liao, Yongxiang; Bai, Que; Xu, Peizhou; Wu, Tingkai; Guo, Daiming; Peng, Yongbin; Zhang, Hongyu; Deng, Xiaoshu; Chen, Xiaoqiong; Luo, Ming; Ali, Asif; Wang, Wenming; Wu, Xianjun

2018-01-01

Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA) synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 (lmm9150), exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H2O2. Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610) in lmm9150. Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150. Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150. Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance. PMID:29643863

Johnson square procedure for lentigo maligna and lentigo maligna melanoma.

PubMed

Patel, A N; Perkins, W; Leach, I H; Varma, S

2014-07-01

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) can be difficult to manage surgically. Predetermined margins can be inadequate because of subclinical spread, or can affect function when margins are adjacent to the eye or mouth. To describe our 5-year experience in Nottingham of using the staged square procedure (Johnson square) in excising difficult facial LM and LMM. The square procedure is a staged technique useful for ill-defined lesions and for lesions that have a high recurrence rate due to subclinical spread. It uses paraffin wax-embedded peripheral vertical sections for margin control, ensuring complete clearance as the surgical margins are usually examined at distances of 2-5 mm from the periphery of the lesion. We treated 21 patients with LM or LMM with the staged square procedure over a 5-year period. Of the 21 patients, 10 needed only one stage of surgery, 6 needed two stages, 3 needed three stages and 2 needed four stages. To date, there has been only one recurrence, which was of an extensive lesion that crossed the medial canthus, making margin control impossible because of the anatomical limitations. The staged square procedure is an effective treatment for LM and LMM. It attempts to conserve tissue while ensuring a higher clearance rate. This offers favourable cosmetic outcomes and better prognosis, especially for facial LM and LMM. © 2014 British Association of Dermatologists.

Mutation in Rice Abscisic Acid2 Results in Cell Death, Enhanced Disease-Resistance, Altered Seed Dormancy and Development.

PubMed

Liao, Yongxiang; Bai, Que; Xu, Peizhou; Wu, Tingkai; Guo, Daiming; Peng, Yongbin; Zhang, Hongyu; Deng, Xiaoshu; Chen, Xiaoqiong; Luo, Ming; Ali, Asif; Wang, Wenming; Wu, Xianjun

2018-01-01

Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA) synthesis pathway is not reported. In the present study, we identified a rice mutant, lesion mimic mutant 9150 ( lmm9150 ), exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H 2 O 2 . Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610) in lmm9150 . Knock-out of OsABA2 through CRISPR/Cas9 led to phenotypes similar to those of lmm9150 . Consistent with the function of OsABA2 in ABA biosynthesis, ABA level in the lmm9150 mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of lmm9150 . Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

Different mechanisms lead to the angiogenic process induced by three adenocarcinoma cell lines.

PubMed

Davel, Lilia E; Rimmaudo, Laura; Español, Alejandro; de la Torre, Eulalia; Jasnis, María Adela; Ribeiro, María Laura; Gotoh, Tomomi; de Lustig, Eugenia Sacerdote; Sales, María Elena

2004-01-01

Neoangiogenesis is essential for tumor and metastasis growth, but this complex process does not follow the same activation pathway, at least in tumor cell lines originated from different murine mammary adenocarcinomas. LMM3 cells were the most potent to stimulate new blood vessel formation. This response was significantly reduced by preincubating cells with indomethacin and NS-398, non-selective cyclooxygenase (COX) and COX-2 selective inhibitors, respectively. COX-1 and COX-2 isoenzymes were both highly expressed in LMM3 cells, and we observed that indomethacin was more effective than NS-398 to inhibit prostaglandin E2 (PGE2) synthesis. In addition, nitric oxide synthase (NOS) inhibitors, Nomega monomethyl L-arginine and aminoguanidine, also reduced LMM3-induced angiogenesis and nitric oxide (NO) synthesis as well. NOS2 > NOS3 proteins and arginase II isoform were detected in LMM3 cells by Western blot. The latter enzyme was also involved in the LMM3 neovascular response, since the arginase inhibitor, Nomega hydroxy L-arginine reduced the angiogenic cascade. On the other hand, parental LM3 cells were able to stimulate neovascularization via COX-1 and arginase products since only indomethacin and Nomega hydroxy L-arginine, which diminished PGE2 and urea synthesis, respectively, also reduced angiogenesis. In turn, LM2 cells angiogenic response could be due in fact to PGE2-induced VEGF liberation that stimulated neoangiogenesis at very low levels of NO.

Linear mixed model for heritability estimation that explicitly addresses environmental variation.

PubMed

Heckerman, David; Gurdasani, Deepti; Kadie, Carl; Pomilla, Cristina; Carstensen, Tommy; Martin, Hilary; Ekoru, Kenneth; Nsubuga, Rebecca N; Ssenyomo, Gerald; Kamali, Anatoli; Kaleebu, Pontiano; Widmer, Christian; Sandhu, Manjinder S

2016-07-05

The linear mixed model (LMM) is now routinely used to estimate heritability. Unfortunately, as we demonstrate, LMM estimates of heritability can be inflated when using a standard model. To help reduce this inflation, we used a more general LMM with two random effects-one based on genomic variants and one based on easily measured spatial location as a proxy for environmental effects. We investigated this approach with simulated data and with data from a Uganda cohort of 4,778 individuals for 34 phenotypes including anthropometric indices, blood factors, glycemic control, blood pressure, lipid tests, and liver function tests. For the genomic random effect, we used identity-by-descent estimates from accurately phased genome-wide data. For the environmental random effect, we constructed a covariance matrix based on a Gaussian radial basis function. Across the simulated and Ugandan data, narrow-sense heritability estimates were lower using the more general model. Thus, our approach addresses, in part, the issue of "missing heritability" in the sense that much of the heritability previously thought to be missing was fictional. Software is available at https://github.com/MicrosoftGenomics/FaST-LMM.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rimmaudo, Laura Elizabeth; Torre, Eulalia de la; Sacerdote de Lustig, Eugenia

Angiogenesis is a process of new blood vessel development from pre-existing vasculature and it plays an essential role in tumor growth and metastases. Here, we investigate the expression of muscarinic acetylcholine receptors (mAchR) and their participation in tumor cell proliferation and angiogenesis ability. Saturation binding assays with the tritiated muscarinic antagonist quinuclidinyl benzilate indicate that LMM3 cells derived from a murine mammary adenocarcinoma express a single class of functional mAchR. Competition binding assays with selective muscarinic antagonists indicate a predominance of M{sub 3} receptor subtype. The muscarinic agonist carbachol (CARB) stimulates LMM3 cell proliferation in a concentration dependent manner. Themore » maximal effect induced by 10{sup -9} M CARB was totally blunted by atropine and by the selective M{sub 3} and M{sub 1} antagonists, para-fluoro hexahydro sila-difenidol (pf-HHSiD) and pirenzepine, respectively. In addition, pf-HHSiD completely blocked in vivo CARB-induced neovascular formation and vascular endothelial growth factor-A in LMM3 tumor cells. We can conclude that mAchR expressed in LMM3 mammary tumor cells positively regulate proliferation and angiogenesis required for tumor progression.« less

Small organic solutes in sticky droplets from orb webs of the spider Zygiella atrica (Araneae; Araneidae): β-alaninamide is a novel and abundant component.

PubMed

Townley, Mark A; Pu, Qinglin; Zercher, Charles K; Neefus, Christopher D; Tillinghast, Edward K

2012-10-01

In northeastern North America, Zygiella atrica often build their orb webs near the ocean. We analyzed individual field-built Z. atrica webs to determine if organic low-molecular-mass solutes (LMM) in their sticky droplets showed any unusual features not previously seen in orb webs of other species living in less salty environments. While two of the three most abundant organic LMM (putrescine (butane-1,4-diamine) and GABamide (4-aminobutanamide)) are already well-known from webs of inland spiders, the third major LMM, β-alaninamide (3-aminopropanamide), a homolog of GABamide, has not been detected in sticky droplets from any other araneoid spiders (27 species). It remains to be established, however, whether or not use of β-alaninamide is related to proximity to saltwater. We observed variability in organic LMM composition in Z. atrica webs that appeared to be influenced more by an undetermined factor associated with different collecting locations and/or collection dates than by different genders or instars. Shifts in composition when adult females were transferred from the field to the laboratory were also observed. Structural similarities and inverse correlations among β-alaninamide, GABamide, and N-acetylputrescine suggest that they may form a series of LMM fulfilling essentially the same, as yet unknown, role in the webs of those species in which they occur. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

On summary measure analysis of linear trend repeated measures data: performance comparison with two competing methods.

PubMed

Vossoughi, Mehrdad; Ayatollahi, S M T; Towhidi, Mina; Ketabchi, Farzaneh

2012-03-22

The summary measure approach (SMA) is sometimes the only applicable tool for the analysis of repeated measurements in medical research, especially when the number of measurements is relatively large. This study aimed to describe techniques based on summary measures for the analysis of linear trend repeated measures data and then to compare performances of SMA, linear mixed model (LMM), and unstructured multivariate approach (UMA). Practical guidelines based on the least squares regression slope and mean of response over time for each subject were provided to test time, group, and interaction effects. Through Monte Carlo simulation studies, the efficacy of SMA vs. LMM and traditional UMA, under different types of covariance structures, was illustrated. All the methods were also employed to analyze two real data examples. Based on the simulation and example results, it was found that the SMA completely dominated the traditional UMA and performed convincingly close to the best-fitting LMM in testing all the effects. However, the LMM was not often robust and led to non-sensible results when the covariance structure for errors was misspecified. The results emphasized discarding the UMA which often yielded extremely conservative inferences as to such data. It was shown that summary measure is a simple, safe and powerful approach in which the loss of efficiency compared to the best-fitting LMM was generally negligible. The SMA is recommended as the first choice to reliably analyze the linear trend data with a moderate to large number of measurements and/or small to moderate sample sizes.

78 FR 55126 - Order Exempting Broker-Dealers Participating in NYSE Arca, Inc.'s Lead Market Maker Incentive...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70303] Order Exempting Broker-Dealers... Exchange Act of 1934 and Rule 11d1-2 Thereunder September 3, 2013. On June 6, 2013, the Securities and... LMMs and ``LMM Payments'' that would be funded from the Exchange's general revenues if the LMM meets or...

78 FR 68108 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

... for Low-Volume Issues November 6, 2013. Pursuant to Section 19(b)(1) \\1\\ of the Securities Exchange... 100,000 1,500 The Exchange introduced the current lowest-volume LMM rights fee tier on October 1, 2013...-volume LMM rights fee tier, beginning November 1, 2013 the fee for the next highest tier would apply...

Characterization of rice lesion mimic mutants of 93-11 for a better understanding of general host defense response to both rice blast and sheath blight diseases

USDA-ARS?s Scientific Manuscript database

Rice lesion mimic mutants (LMM) exhibit necrotic lesions resembling programmed cell death (PCD). PCD is one of the significant hallmarks of disease resistance genes mediated defense responses. LMM can be used to study the mechanisms of plant disease resistance. In the present study, a total of 133 ...

Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.

PubMed

Rier, Hánah N; Jager, Agnes; Sleijfer, Stefan; van Rosmalen, Joost; Kock, Marc C J M; Levin, Mark-David

2017-02-01

Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). A skeletal muscle index (SMI) in cm 2 /m 2 and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm 2 /m 2 ), sarcopenic obesity (LMM and BMI ≥30 kg/m 2 ) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT. The prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34-3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14-2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA. LMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Construction and performance of combustion beamline at NSRL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Xuewei; Wei, Shen; Du, Liangliang

2016-07-27

An undulator-based VUV beamline BL03U is constructed at the National Synchrotron Radiation Laboratory. Optical design and performance test results are presented in this paper. The monochromator is a Czerny–Turner configuration with a toroidal collimating mirror, two plane gratings, and a toroidal focusing mirror. Plane gratings with line densities of 200 and 400 l/mm are used to cover the photon energy range of 5–21 eV. A gas absorption spectrum is used to evaluate the beamline performance. The photon energy resolving power (E/ΔE) of the beamline is approximately 3900 at 7.3 eV for the 200 l/mm grating and 4200 at 14.6 eVmore » for the 400 l/mm grating. The photon flux is approximately 5×10{sup 12} photons/s/300 mA at energy of 10 eV.« less

The frequency of low muscle mass and its overlap with low bone mineral density and lipodystrophy in individuals with HIV--a pilot study using DXA total body composition analysis.

PubMed

Buehring, Bjoern; Kirchner, Elizabeth; Sun, Zhiyuan; Calabrese, Leonard

2012-01-01

As a result of the advances in antiretroviral therapy, the life span of human immunodeficiency virus (HIV)-infected patients has increased dramatically. Attendant to these effects are signs of premature aging with notable changes in the musculoskeletal system. Although changes in bone and fat distribution have been studied extensively, far less is known about changes in muscle. This study examined the extent of low muscle mass (LMM) and its relationship with low bone mineral density (BMD) and lipodystrophy (LD) in HIV-positive males. As such, HIV-positive males on therapy or treatment naive underwent dual-energy X-ray absorptiometry total body composition measurements. Appendicular lean mass/(height)2 and lowest 20% of residuals from regression analysis were used to define LMM. BMD criteria defined osteopenia/osteoporosis, and the percent central fat/percent lower extremity ratio defined LD. Several potential risk factors were assessed through chart review. Sixty-six males (57 with treatment and 9 treatment naive) volunteered. Treated individuals were older than naive (44 vs 34 yr) and had HIV longer (108 vs 14 mo). When definitions for sarcopenia (SP) in elderly individuals were applied, the prevalence of LMM was 21.9% and 18.8% depending on the definition used. Low BMD was present in 68.2% of participants. LD with a cutoff of 1.5 and 1.961 was present in 54.7% and 42.2% of participants, respectively. LMM and LD were negatively associated. In conclusion, this study shows that LMM is common in males with HIV and that SP affecting muscle function could be present in a substantial number of individuals. Future research needs to examine what impact decreased muscle mass and function has on morbidity, physical function, and quality of life in individuals with HIV. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Large Regional Differences in Serological Follow-Up of Q Fever Patients in The Netherlands

PubMed Central

Morroy, Gabriëlla; Wielders, Cornelia C. H.; Kruisbergen, Mandy J. B.; van der Hoek, Wim; Marcelis, Jan H.; Wegdam-Blans, Marjolijn C. A.; Wijkmans, Clementine J.; Schneeberger, Peter M.

2013-01-01

Background During the Dutch Q fever epidemic more than 4,000 Q fever cases were notified. This provided logistical challenges for the organisation of serological follow-up, which is considered mandatory for early detection of chronic infection. The aim of this study was to investigate the proportion of acute Q fever patients that received serological follow-up, and to identify regional differences in follow-up rates and contributing factors, such as knowledge of medical practitioners. Methods Serological datasets of Q fever patients diagnosed between 2007 and 2009 (N = 3,198) were obtained from three Laboratories of Medical Microbiology (LMM) in the province of Noord-Brabant. One LMM offered an active follow-up service by approaching patients; the other two only tested on physician's request. The medical microbiologist in charge of each LMM was interviewed. In December 2011, 240 general practices and 112 medical specialists received questionnaires on their knowledge and practices regarding the serological follow-up of Q fever patients. Results Ninety-five percent (2,226/2,346) of the Q fever patients diagnosed at the LMM with a follow-up service received at least one serological follow-up within 15 months of diagnosis. For those diagnosed at a LMM without this service, this was 25% (218/852) (OR 54, 95% CI 43–67). Although 80% (162/203) of all medical practitioners with Q fever patients reported informing patients of the importance of serological follow-up, 33% (67/203) never requested it. Conclusions Regional differences in follow-up are substantial and range from 25% to 95%. In areas with a low follow-up rate the proportion of missed chronic Q fever is potentially higher than in areas with a high follow-up rate. Medical practitioners lack knowledge regarding the need, timing and implementation of serological follow-up, which contributes to patients receiving incorrect or no follow-up. Therefore, this information should be incorporated in national guidelines and patient information forms. PMID:23577152

Flexibility of myosin attachment to surfaces influences F-actin motion.

PubMed Central

Winkelmann, D A; Bourdieu, L; Ott, A; Kinose, F; Libchaber, A

1995-01-01

We have analyzed the dependence of actin filament sliding movement on the mode of myosin attachment to surfaces. Monoclonal antibodies (mAbs) that bind to three distinct sites were used to tether myosin to nitrocellulose-coated glass. One antibody reacts with an epitope on the regulatory light chain (LC2) located at the head-rod junction. The other two react with sites in the rod domain, one in the S2 region near the S2-LMM hinge, and the other at the C terminus of the myosin rod. This method of attachment provides a means of controlling the flexibility and density of myosin on the surface. Fast skeletal muscle myosin monomers were bound to the surfaces through the specific interaction with these mAbs, and the sliding movement of fluorescently labeled actin filaments was analyzed by video microscopy. Each of these antibodies produced stable myosin-coated surfaces that supported uniform motion of actin over the course of several hours. Attachment of myosin through the anti-S2 and anti-LMM mAbs yielded significantly higher velocities (10 microns/s at 30 degrees C) than attachment through anti-LC2 (4-5 microns/s at 30 degrees C). For each antibody, we observed a characteristic value of the myosin density for the onset of F-actin motion and a second critical density for velocity saturation. The specific mode of attachment influences the velocity of actin filaments and the characteristic surface density needed to support movement. Images FIGURE 1 FIGURE 4 FIGURE 8 PMID:7544167

Efficient Bayesian mixed model analysis increases association power in large cohorts

PubMed Central

Loh, Po-Ru; Tucker, George; Bulik-Sullivan, Brendan K; Vilhjálmsson, Bjarni J; Finucane, Hilary K; Salem, Rany M; Chasman, Daniel I; Ridker, Paul M; Neale, Benjamin M; Berger, Bonnie; Patterson, Nick; Price, Alkes L

2014-01-01

Linear mixed models are a powerful statistical tool for identifying genetic associations and avoiding confounding. However, existing methods are computationally intractable in large cohorts, and may not optimize power. All existing methods require time cost O(MN2) (where N = #samples and M = #SNPs) and implicitly assume an infinitesimal genetic architecture in which effect sizes are normally distributed, which can limit power. Here, we present a far more efficient mixed model association method, BOLT-LMM, which requires only a small number of O(MN)-time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes. We applied BOLT-LMM to nine quantitative traits in 23,294 samples from the Women’s Genome Health Study (WGHS) and observed significant increases in power, consistent with simulations. Theory and simulations show that the boost in power increases with cohort size, making BOLT-LMM appealing for GWAS in large cohorts. PMID:25642633

Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

NASA Technical Reports Server (NTRS)

Guinart-Ramirez, Y.; Cooley, V. M.; Love, J. E.

2016-01-01

International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy capability will allow for optical sectioning of biological tissues to determine microanatomical localization of biomarkers. Furthermore, NASA's geneLAB effort addresses integration of genomic, epigenomic, transcriptomic, proteomic and metabolomic datasets, by applying an innovative open source science platform for multi-investigator high throughput utilization of the ISS. In sum, the expanding ISS capability for analysis of biomolecules is enabling innovative research in a broad spectrum of areas such as cellular and molecular biology, biotechnology, tissue engineering, biomedicine, and Omics, providing manifold benefits for humanity.

Interest rates in quantum finance: the Wilson expansion and Hamiltonian.

PubMed

Baaquie, Belal E

2009-10-01

Interest rate instruments form a major component of the capital markets. The Libor market model (LMM) is the finance industry standard interest rate model for both Libor and Euribor, which are the most important interest rates. The quantum finance formulation of the Libor market model is given in this paper and leads to a key generalization: all the Libors, for different future times, are imperfectly correlated. A key difference between a forward interest rate model and the LMM lies in the fact that the LMM is calibrated directly from the observed market interest rates. The short distance Wilson expansion [Phys. Rev. 179, 1499 (1969)] of a Gaussian quantum field is shown to provide the generalization of Ito calculus; in particular, the Wilson expansion of the Gaussian quantum field A(t,x) driving the Libors yields a derivation of the Libor drift term that incorporates imperfect correlations of the different Libors. The logarithm of Libor phi(t,x) is defined and provides an efficient and compact representation of the quantum field theory of the Libor market model. The Lagrangian and Feynman path integrals of the Libor market model of interest rates are obtained, as well as a derivation given by its Hamiltonian. The Hamiltonian formulation of the martingale condition provides an exact solution for the nonlinear drift of the Libor market model. The quantum finance formulation of the LMM is shown to reduce to the industry standard Bruce-Gatarek-Musiela-Jamshidian model when the forward interest rates are taken to be exactly correlated.

Factors Influencing Intraocular Pressure Changes after Laser In Situ Keratomileusis with Flaps Created by Femtosecond Laser or Mechanical Microkeratome.

PubMed

Lin, Meng-Yin; Chang, David C K; Shen, Yun-Dun; Lin, Yen-Kuang; Lin, Chang-Ping; Wang, I-Jong

2016-01-01

The aim of this study is to describe factors that influence the measured intraocular pressure (IOP) change and to develop a predictive model after myopic laser in situ keratomileusis (LASIK) with a femtosecond (FS) laser or a microkeratome (MK). We retrospectively reviewed preoperative, intraoperative, and 12-month postoperative medical records in 2485 eyes of 1309 patients who underwent LASIK with an FS laser or an MK for myopia and myopic astigmatism. Data were extracted, such as preoperative age, sex, IOP, manifest spherical equivalent (MSE), central corneal keratometry (CCK), central corneal thickness (CCT), and intended flap thickness and postoperative IOP (postIOP) at 1, 6 and 12 months. Linear mixed model (LMM) and multivariate linear regression (MLR) method were used for data analysis. In both models, the preoperative CCT and ablation depth had significant effects on predicting IOP changes in the FS and MK groups. The intended flap thickness was a significant predictor only in the FS laser group (P < .0001 in both models). In the FS group, LMM and MLR could respectively explain 47.00% and 18.91% of the variation of postoperative IOP underestimation (R2 = 0.47 and R(2) = 0.1891). In the MK group, LMM and MLR could explain 37.79% and 19.13% of the variation of IOP underestimation (R(2) = 0.3779 and 0.1913 respectively). The best-fit model for prediction of IOP changes was the LMM in LASIK with an FS laser.

Factors Influencing Intraocular Pressure Changes after Laser In Situ Keratomileusis with Flaps Created by Femtosecond Laser or Mechanical Microkeratome

PubMed Central

Lin, Meng-Yin; Chang, David C. K.; Shen, Yun-Dun; Lin, Yen-Kuang; Lin, Chang-Ping; Wang, I-Jong

2016-01-01

The aim of this study is to describe factors that influence the measured intraocular pressure (IOP) change and to develop a predictive model after myopic laser in situ keratomileusis (LASIK) with a femtosecond (FS) laser or a microkeratome (MK). We retrospectively reviewed preoperative, intraoperative, and 12-month postoperative medical records in 2485 eyes of 1309 patients who underwent LASIK with an FS laser or an MK for myopia and myopic astigmatism. Data were extracted, such as preoperative age, sex, IOP, manifest spherical equivalent (MSE), central corneal keratometry (CCK), central corneal thickness (CCT), and intended flap thickness and postoperative IOP (postIOP) at 1, 6 and 12 months. Linear mixed model (LMM) and multivariate linear regression (MLR) method were used for data analysis. In both models, the preoperative CCT and ablation depth had significant effects on predicting IOP changes in the FS and MK groups. The intended flap thickness was a significant predictor only in the FS laser group (P < .0001 in both models). In the FS group, LMM and MLR could respectively explain 47.00% and 18.91% of the variation of postoperative IOP underestimation (R2 = 0.47 and R2 = 0.1891). In the MK group, LMM and MLR could explain 37.79% and 19.13% of the variation of IOP underestimation (R2 = 0.3779 and 0.1913 respectively). The best-fit model for prediction of IOP changes was the LMM in LASIK with an FS laser. PMID:26824754

Is Media Multitasking Good for Cybersecurity? Exploring the Relationship Between Media Multitasking and Everyday Cognitive Failures on Self-Reported Risky Cybersecurity Behaviors.

PubMed

Hadlington, Lee; Murphy, Karen

2018-03-01

The current study focused on how engaging in media multitasking (MMT) and the experience of everyday cognitive failures impact on the individual's engagement in risky cybersecurity behaviors (RCsB). In total, 144 participants (32 males, 112 females) completed an online survey. The age range for participants was 18 to 43 years (M = 20.63, SD = 4.04). Participants completed three scales which included an inventory of weekly MMT, a measure of everyday cognitive failures, and RCsB. There was a significant difference between heavy media multitaskers (HMM), average media multitaskers (AMM), and light media multitaskers (LMM) in terms of RCsB, with HMM demonstrating more frequent risky behaviors than LMM or AMM. The HMM group also reported more cognitive failures in everyday life than the LMM group. A regression analysis showed that everyday cognitive failures and MMT acted as significant predictors for RCsB. These results expand our current understanding of the relationship between human factors and cybersecurity behaviors, which are useful to inform the design of training and intervention packages to mitigate RCsB.

The weighted function method: A handy tool for flood frequency analysis or just a curiosity?

NASA Astrophysics Data System (ADS)

Bogdanowicz, Ewa; Kochanek, Krzysztof; Strupczewski, Witold G.

2018-04-01

The idea of the Weighted Function (WF) method for estimation of Pearson type 3 (Pe3) distribution introduced by Ma in 1984 has been revised and successfully applied for shifted inverse Gaussian (IGa3) distribution. Also the conditions of WF applicability to a shifted distribution have been formulated. The accuracy of WF flood quantiles for both Pe3 and IGa3 distributions was assessed by Monte Caro simulations under the true and false distribution assumption versus the maximum likelihood (MLM), moment (MOM) and L-moments (LMM) methods. Three datasets of annual peak flows of Polish catchments serve the case studies to compare the results of the WF, MOM, MLM and LMM performance for the real flood data. For the hundred-year flood the WF method revealed the explicit superiority only over the MLM surpassing the MOM and especially LMM both for the true and false distributional assumption with respect to relative bias and relative mean root square error values. Generally, the WF method performs well and for hydrological sample size and constitutes good alternative for the estimation of the flood upper quantiles.

Bivariate random-effects meta-analysis models for diagnostic test accuracy studies using arcsine-based transformations.

PubMed

Negeri, Zelalem F; Shaikh, Mateen; Beyene, Joseph

2018-05-11

Diagnostic or screening tests are widely used in medical fields to classify patients according to their disease status. Several statistical models for meta-analysis of diagnostic test accuracy studies have been developed to synthesize test sensitivity and specificity of a diagnostic test of interest. Because of the correlation between test sensitivity and specificity, modeling the two measures using a bivariate model is recommended. In this paper, we extend the current standard bivariate linear mixed model (LMM) by proposing two variance-stabilizing transformations: the arcsine square root and the Freeman-Tukey double arcsine transformation. We compared the performance of the proposed methods with the standard method through simulations using several performance measures. The simulation results showed that our proposed methods performed better than the standard LMM in terms of bias, root mean square error, and coverage probability in most of the scenarios, even when data were generated assuming the standard LMM. We also illustrated the methods using two real data sets. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Motility assays using myosin attached to surfaces through specific binding to monoclonal antibodies.

PubMed Central

Winkelmann, D. A.; Bourdieu, L.; Kinose, F.; Libchaber, A.

1995-01-01

We have analyzed the dependence of actin filament movement on the mode of myosin attachment to surfaces. Monoclonal antibodies that bind to three distinct sites were used to tether myosin to nitrocellulose-coated glass. One antibody reacts with an epitope on the regulatory light chain located at the head-rod junction. The other two react with sites in the rod domain, one in the S2 region near the S2-LMM hinge, and the other at the C terminus of the myosin rod. These monoclonal antibodies were used to provide increasing flexibility in the mode of attachment. Fast skeletal muscle myosin monomers were bound to the surfaces through the specific interaction with these monoclonal antibodies and the sliding movement of fluorescently labeled actin filaments analyzed by video microscopy. Each of these antibodies produced stable, myosin-coated surfaces that supported uniform movement of actin over the course of several hours. Attachment of myosin through the anti-S2 and anti-LMM monoclonal antibodies yielded a maximum velocity of 10 microns/s at 30 degrees C, whereas attachment through anti-LC2 produced a lower velocity of 4-5 microns/s. Each antibody showed a characteristic minimum myosin density below which sliding movement was no longer supported and an exponential dependence of actin filament velocity on myosin surface density below Vmax. Maximum sliding velocity was achieved over a range of myosin surface densities. Thus, the specific mode of attachment can influence the characteristic velocity of actin filament movement and the surface density needed to support movement. These data are being used to analyze the dynamics of sliding filament assays and evaluate estimates of the average number of motor molecules per unit length of actin required to support movement. PMID:7787107

The Current Performance of the Wide Range (90-2500 eV) Soft X-ray Beamline at the Australian Synchrotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowie, B. C. C.; Tadich, A.; Thomsen, L.

2010-06-23

The Soft X-ray beamline at the Australian synchrotron has been constructed around a collimated light Plane Grating Monochromator taking light from an Elliptically Polarized Undulator (EPU). The beamline covers a wide photon energy range between 90 to 2500 eV, using two gratings of 250 l/mm and 1200 l/mm. At present the output from the monochromator is directed into one branchline with a dedicated UHV endstation. The measured performance of the beamline in flux and resolution is shown to be very close to that of theoretical calculations.

Resistance Exercise Impacts Lean Muscle Mass in Women with Polycystic Ovary Syndrome.

PubMed

Kogure, Gislaine Satyko; Miranda-Furtado, Cristiana Libardi; Silva, Rafael Costa; Melo, Anderson Sanches; Ferriani, Rui Alberto; De Sá, Marcos Felipe Silva; Dos Reis, Rosana Maria

2016-04-01

This study investigated the effects of progressive resistance training (PRT) on lean muscle mass (LMM) in women with or without polycystic ovary syndrome (PCOS) and its effects on metabolic factors and concentrations of related steroid hormones. This was a nonrandomized, therapeutic, open, single-arm study. All in all, 45 sedentary women with PCOS and 52 without (non-PCOS), 18-37 yr of age, with body mass indexes (BMI) of 18-39.9 kg·m(-2) of all races and social status, performed PRT three times a week for 4 months. Before and after PRT, the concentrations of hormones and metabolic factors and waist circumference were measured. LMM and total body fat percentage were determined using dual-energy x-ray absorptiometry. Clinical characteristics, LMM, and fasting glucose were adjusted for confounding covariables and compared using general linear mixed models. Each patient's menstrual history was taken before study enrollment and after PRT. PRT resulted in reduced plasma testosterone and fasting glucose levels. After PRT, the androstenedione concentration increased and the sex hormone-binding globulin concentration decreased in women with PCOS. The waist circumference was reduced (P < 0.01) and the muscle mass index, lean mass (LM)/height2, increased in women with PCOS (P = 0.04). Women with PCOS showed increased muscle mass indexes of appendicular LM/height2 (P = 0.03) and LM/height2 (P < 0.01) compared with the baseline. Total LM and trunk LM were elevated in women with PCOS (P = 0.01) at the baseline and after PRT. To our knowledge, this is the first report to show that resistance exercise alone can improve hyperandrogenism, reproductive function, and body composition by decreasing visceral fat and increasing LMM, but it has no metabolic impact on women with PCOS.

Thermal Conductivity of Polyimide/Carbon Nanofiller Blends

NASA Technical Reports Server (NTRS)

Delozier, D. M.; Watson, K. A.; Ghose, S.; Working, D. C.; Connell, J. W.; Smith, J. G.; Sun, Y. P.; Lin, Y.

2006-01-01

Ultem(TM) was mixed with three different carbon-based nanofillers in efforts to increase the thermal conductivity of the polymer. After initial mixing, the nanocomposites were extruded or processed via the Laboratory Mixing Molder (LMM) process. High resolution scanning electron microscopy (HRSEM) revealed significant alignment of the nanofillers in the extruded samples. Thermal conductivity measurements were made both in the direction and perpendicular to the direction of alignment of nanofillers as well as for unaligned samples. It was found that the largest improvement in thermal conductivity was achieved in the case of aligned samples when the measurement was performed in the direction of alignment. Unaligned samples also showed a significant improvement in thermal conductivity and may be useful in applications when it is not possible to align the nanofiller. However the improvements in thermal conductivity did not approach those expected based on a rule of mixtures. This is likely due to poor phonon transfer through the matrix.

Origin of Si(LMM) Auger Electron Emission from Silicon and Si-Alloys by keV Ar+ Ion Bombardment

NASA Astrophysics Data System (ADS)

Iwami, Motohiro; Kim, Su Chol; Kataoka, Yoshihide; Imura, Takeshi; Hiraki, Akio; Fujimoto, Fuminori

1980-09-01

Si(LMM) Auger electrons emitted from specimens of pure silicon and several Si-alloys (Ni-Si, Pd-Si and Cu-Si) under keV Ar+ ion bombardment, were examined. In the Auger spectra from all specimens studied there were four peaks at energies of 92, 86, 76 and 66 eV. The Auger signal intensity varied considerably with both the incident angle and the energy of the primary ion beam. It is proposed that the Auger electrons are emitted from silicon atoms (or ions) just beneath the specimen surface but free from the bulk network.

Modeling of LMM-MVV Auger-Auger Coincidence Spectra From Solids

NASA Astrophysics Data System (ADS)

Sundaramoorthy, R.; Weiss, A. H.; Hulbert, S. L.; Bartynski, R. A.

2006-03-01

Atoms that are highly excited due to the presence of a hole in an inner shell often relax via an Auger transition. This auto-ionizing process results in a final state with two or more holes from an Auger cascade. We present results of the direct measurements of the second and third Auger decays in this sequence. We have measured the Mn MVV Auger spectra from a single-crystal sample of MnO in time coincidence with Auger electrons emitted from prior Mn LMM Auger decays and find these to be much wider than the MVV spectrum measured in time coincidence with M core photoelectron emission. We present a model which attributes the increased energy width of the MVV transitions that follow LMM decays to the rearrangement of ``not so innocent'' bystander hole(s) in the valence band. The energetics of the Auger cascade process are modeled mathematically in terms of correlation integral(s) and convolution integral(s) over the valence band density of states. Comparisons with recent Auger-Auger coincidence studies of Ag and Pd will be made. Acknowledgements: Welch Foundation, NSF DMR98-12628, NSF DMR98-01681, and DOE DE-AC02-98CH10886.

Complex Sentence Comprehension and Working Memory in Children With Specific Language Impairment

PubMed Central

Montgomery, James W.; Evans, Julia L.

2015-01-01

Purpose This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method Twenty-four children with SLI, 18 age-matched (CA) children, and 16 language- and memory-matched (LMM) children completed a nonword repetition task (PSTM), the competing language processing task (CLPT; resource capacity/allocation), and a sentence comprehension task comprising complex and simple sentences. Results (1) The SLI group performed worse than the CA group on each memory task; (2) all 3 groups showed comparable simple sentence comprehension, but for complex sentences, the SLI and LMM groups performed worse than the CA group; (3) for the SLI group, (a) CLPT correlated with complex sentence comprehension, and (b) nonword repetition correlated with simple sentence comprehension; (4) for CA children, neither memory variable correlated with either sentence type; and (5) for LMM children, only CLPT correlated with complex sentences. Conclusions Comprehension of both complex and simple grammar by school-age children with SLI is a mentally demanding activity, requiring significant working memory resources. PMID:18723601

Further Improvements to Linear Mixed Models for Genome-Wide Association Studies

PubMed Central

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-01-01

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science. PMID:25387525

Is Media Multitasking Good for Cybersecurity? Exploring the Relationship Between Media Multitasking and Everyday Cognitive Failures on Self-Reported Risky Cybersecurity Behaviors

PubMed Central

Murphy, Karen

2018-01-01

Abstract The current study focused on how engaging in media multitasking (MMT) and the experience of everyday cognitive failures impact on the individual's engagement in risky cybersecurity behaviors (RCsB). In total, 144 participants (32 males, 112 females) completed an online survey. The age range for participants was 18 to 43 years (M = 20.63, SD = 4.04). Participants completed three scales which included an inventory of weekly MMT, a measure of everyday cognitive failures, and RCsB. There was a significant difference between heavy media multitaskers (HMM), average media multitaskers (AMM), and light media multitaskers (LMM) in terms of RCsB, with HMM demonstrating more frequent risky behaviors than LMM or AMM. The HMM group also reported more cognitive failures in everyday life than the LMM group. A regression analysis showed that everyday cognitive failures and MMT acted as significant predictors for RCsB. These results expand our current understanding of the relationship between human factors and cybersecurity behaviors, which are useful to inform the design of training and intervention packages to mitigate RCsB. PMID:29638157

An efficient empirical Bayes method for genomewide association studies.

PubMed

Wang, Q; Wei, J; Pan, Y; Xu, S

2016-08-01

Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits. © 2015 Blackwell Verlag GmbH.

Further Improvements to Linear Mixed Models for Genome-Wide Association Studies

NASA Astrophysics Data System (ADS)

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-11-01

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science.

Further improvements to linear mixed models for genome-wide association studies.

PubMed

Widmer, Christian; Lippert, Christoph; Weissbrod, Omer; Fusi, Nicolo; Kadie, Carl; Davidson, Robert; Listgarten, Jennifer; Heckerman, David

2014-11-12

We examine improvements to the linear mixed model (LMM) that better correct for population structure and family relatedness in genome-wide association studies (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which encodes the pairwise similarity between every two individuals in a cohort. These similarities are estimated from single nucleotide polymorphisms (SNPs) or other genetic variants. Traditionally, all available SNPs are used to estimate the GSM. In empirical studies across a wide range of synthetic and real data, we find that modifications to this approach improve GWAS performance as measured by type I error control and power. Specifically, when only population structure is present, a GSM constructed from SNPs that well predict the phenotype in combination with principal components as covariates controls type I error and yields more power than the traditional LMM. In any setting, with or without population structure or family relatedness, a GSM consisting of a mixture of two component GSMs, one constructed from all SNPs and another constructed from SNPs that well predict the phenotype again controls type I error and yields more power than the traditional LMM. Software implementing these improvements and the experimental comparisons are available at http://microsoft.com/science.

Estimation of apparent rate coefficients for radionuclides interacting with marine sediments from Novaya Zemlya.

PubMed

Børretzen, P; Salbu, B

2000-10-30

To assess the impact of radionuclides entering the marine environment from dumped nuclear waste, information on the physico-chemical forms of radionuclides and their mobility in seawater-sediment systems is essential. Due to interactions with sediment components, sediments may act as a sink, reducing the mobility of radionuclides in seawater. Due to remobilisation, however, contaminated sediments may also act as a potential source of radionuclides to the water phase. In the present work, time-dependent interactions of low molecular mass (LMM, i.e. species < 10 kDa) radionuclides with sediments from the Stepovogo Fjord, Novaya Zemlya and their influence on the distribution coefficients (Kd values) have been studied in tracer experiments using 109Cd2+ and 60Co2+ as gamma tracers. Sorption of the LMM tracers occurred rapidly and the estimated equilibrium Kd(eq)-values for 109Cd and 60Co were 500 and 20000 ml/g, respectively. Remobilisation of 109Cd and 60Co from contaminated sediment fractions as a function of contact time was studied using sequential extraction procedures. Due to redistribution, the reversibly bound fraction of the gamma tracers decreased with time, while the irreversibly (or slowly reversibly) associated fraction of the gamma tracers increased. Two different three-compartment models, one consecutive and one parallel, were applied to describe the time-dependent interaction of the LMM tracers with operationally defined reversible and irreversible (or slowly reversible) sediment fractions. The interactions between these fractions were described using first order differential equations. By fitting the models to the experimental data, apparent rate constants were obtained using numerical optimisation software. The model optimisations showed that the interactions of LMM 60Co were well described by the consecutive model, while the parallel model was more suitable to describe the interactions of LMM 109Cd with the sediments, when the squared sum of residuals were compared. The rate of sorption of the irreversibly (or slowly reversibly) associated fraction was greater than the rate of desorption of the reversibly bound fractions (i.e. k3 > k2) for both radionuclides. Thus, the Novaya Zemlya sediment are supposed to act as a sink for the radionuclides under oxic conditions, and transport to the water phase should mainly be attributed to resuspended particles.

Spatial Differentiation of Arable Land and Permanent Grasslands to Improve a Regional Land Management Model for Nutrient Balancing

NASA Astrophysics Data System (ADS)

Gómez Giménez, M.; Della Peruta, R.; de Jong, R.; Keller, A.; Schaepman, M. E.

2015-12-01

Agroecosystems play an important role providing economic and ecosystem services, which directly impact society. Inappropriate land use and unsustainable agricultural management with associated nutrient cycles can jeopardize important soil functions such as food production, livestock feeding and conservation of biodiversity. The objective of this study was to integrate remotely sensed land cover information into a regional Land Management Model (LMM) to improve the assessment of spatial explicit nutrient balances for agroecosystems. Remotely sensed data as well as an optimized parameter set contributed to feed the LMM providing a better spatial allocation of agricultural data aggregated at farm level. The integration of land use information in the land allocation process relied predominantly on three factors: i) spatial resolution, ii) classification accuracy and iii) parcels definition. The best-input parameter combination resulted in two different land cover classifications with overall accuracies of 98%, improving the LMM performance by 16% as compared to using non-spatially explicit input. Firstly, the use of spatial explicit information improved the spatial allocation output resulting in a pattern that better followed parcel boundaries (Figure 1). Second, the high classification accuracies ensured consistency between the datasets used. Third, the use of a suitable spatial unit to define the parcels boundaries influenced the model in terms of computational time and the amount of farmland allocated. We conclude that the combined use of remote sensing (RS) data with the LMM has the potential to provide highly accurate information of spatial explicit nutrient balances that are crucial for policy options concerning sustainable management of agricultural soils. Figure 1. Details of the spatial pattern obtained: a) Using only the farm census data, b) using also land use information. Framed in black in the left image (a), examples of artifacts that disappeared when using land use information (right image, b). Colors represent different ownership.

Determination of Zn-citrate in human milk by CIM monolithic chromatography with atomic and mass spectrometry detection.

PubMed

Milačič, Radmila; Ajlec, Dejan; Zuliani, Tea; Žigon, Dušan; Ščančar, Janez

2012-11-15

In human milk zinc (Zn) is bound to proteins and low molecular mass (LMM) ligands. Numerous investigations demonstrated that Zn bioavailability in human milk is for infant much higher than in cow's milk. It was presumed that in the LMM human milk fraction highly bioavailable Zn-citrate prevails. However, literature data are controversial regarding the amount of Zn-citrate in human milk since analytical procedures reported were not quantitative. So, complex investigation was carried out to develop analytical method for quantitative determination of this biologically important molecule. Studies were performed within the pH range 5-7 by the use of synthetic solutions of Zn-citrate prepared in HEPES, MOPS and MES buffers. Zn-citrate was separated on weak anion-exchange convective interaction media (CIM) diethylaminoethyl (DEAE) monolithic chromatographic column using NH(4)NO(3) as an eluent. Separated Zn species were determined by flame atomic absorption spectrometry (FAAS) or inductively coupled plasma mass spectrometry (ICP-MS). Quantitative separation of Zn-citrate complexes ([Zn(Cit)](-) and [Zn(Cit)(2)](4-); column recoveries 94-102%) and good repeatability and reproducibility of results with relative standard deviation (RSD±3.0%) were obtained. In fractions under the chromatographic peaks Zn-binding ligand was identified by electrospray ionization tandem mass spectrometry (ESI-MS-MS). Limits of detection (LOD) for determination of Zn-citrate species by CIM DEAE-FAAS and CIM DEAE-ICP-MS were 0.01 μg Zn mL(-1) and 0.0005 μg Zn mL(-1), respectively. Both techniques were sensitive enough for quantification of Zn-citrate in human milk. Results demonstrated that about 23% of total Zn was present in the LMM milk fraction and that LMM-Zn corresponded to Zn-citrate. The developed speciation method represents a reliable analytical tool for investigation of the percentage and the amount of Zn-citrate in human milk. Copyright © 2012 Elsevier B.V. All rights reserved.

A review of statistical estimators for risk-adjusted length of stay: analysis of the Australian and new Zealand Intensive Care Adult Patient Data-Base, 2008-2009.

PubMed

Moran, John L; Solomon, Patricia J

2012-05-16

For the analysis of length-of-stay (LOS) data, which is characteristically right-skewed, a number of statistical estimators have been proposed as alternatives to the traditional ordinary least squares (OLS) regression with log dependent variable. Using a cohort of patients identified in the Australian and New Zealand Intensive Care Society Adult Patient Database, 2008-2009, 12 different methods were used for estimation of intensive care (ICU) length of stay. These encompassed risk-adjusted regression analysis of firstly: log LOS using OLS, linear mixed model [LMM], treatment effects, skew-normal and skew-t models; and secondly: unmodified (raw) LOS via OLS, generalised linear models [GLMs] with log-link and 4 different distributions [Poisson, gamma, negative binomial and inverse-Gaussian], extended estimating equations [EEE] and a finite mixture model including a gamma distribution. A fixed covariate list and ICU-site clustering with robust variance were utilised for model fitting with split-sample determination (80%) and validation (20%) data sets, and model simulation was undertaken to establish over-fitting (Copas test). Indices of model specification using Bayesian information criterion [BIC: lower values preferred] and residual analysis as well as predictive performance (R2, concordance correlation coefficient (CCC), mean absolute error [MAE]) were established for each estimator. The data-set consisted of 111663 patients from 131 ICUs; with mean(SD) age 60.6(18.8) years, 43.0% were female, 40.7% were mechanically ventilated and ICU mortality was 7.8%. ICU length-of-stay was 3.4(5.1) (median 1.8, range (0.17-60)) days and demonstrated marked kurtosis and right skew (29.4 and 4.4 respectively). BIC showed considerable spread, from a maximum of 509801 (OLS-raw scale) to a minimum of 210286 (LMM). R2 ranged from 0.22 (LMM) to 0.17 and the CCC from 0.334 (LMM) to 0.149, with MAE 2.2-2.4. Superior residual behaviour was established for the log-scale estimators. There was a general tendency for over-prediction (negative residuals) and for over-fitting, the exception being the GLM negative binomial estimator. The mean-variance function was best approximated by a quadratic function, consistent with log-scale estimation; the link function was estimated (EEE) as 0.152(0.019, 0.285), consistent with a fractional-root function. For ICU length of stay, log-scale estimation, in particular the LMM, appeared to be the most consistently performing estimator(s). Neither the GLM variants nor the skew-regression estimators dominated.

Modulated-alignment dual-axis (MAD) confocal microscopy for deep optical sectioning in tissues

PubMed Central

Leigh, Steven Y.; Chen, Ye; Liu, Jonathan T.C.

2014-01-01

A strategy is presented to enable optical-sectioning microscopy with improved contrast and imaging depth using low-power (0.5 - 1 mW) diode laser illumination. This technology combines the inherent strengths of focal-modulation microscopy and dual-axis confocal (DAC) microscopy for rejecting out-of-focus and multiply scattered background light in tissues. The DAC architecture is unique in that it utilizes an intersecting pair of illumination and collection beams to improve the spatial-filtering and optical-sectioning performance of confocal microscopy while focal modulation selectively ‘labels’ in-focus signals via amplitude modulation. Simulations indicate that modulating the spatial alignment of dual-axis beams at a frequency f generates signals from the focal volume of the microscope that are modulated at 2f with minimal modulation of background signals, thus providing nearly an order-of-magnitude improvement in optical-sectioning contrast compared to DAC microscopy alone. Experiments show that 2f lock-in detection enhances contrast and imaging depth within scattering phantoms and fresh tissues. PMID:24940534

A compact multichannel spectrometer for Thomson scatteringa)

NASA Astrophysics Data System (ADS)

Schoenbeck, N. L.; Schlossberg, D. J.; Dowd, A. S.; Fonck, R. J.; Winz, G. R.

2012-10-01

The availability of high-efficiency volume phase holographic (VPH) gratings and intensified CCD (ICCD) cameras have motivated a simplified, compact spectrometer for Thomson scattering detection. Measurements of Te < 100 eV are achieved by a 2971 l/mm VPH grating and measurements Te > 100 eV by a 2072 l/mm VPH grating. The spectrometer uses a fast-gated (˜2 ns) ICCD camera for detection. A Gen III image intensifier provides ˜45% quantum efficiency in the visible region. The total read noise of the image is reduced by on-chip binning of the CCD to match the 8 spatial channels and the 10 spectral bins on the camera. Three spectrometers provide a minimum of 12 spatial channels and 12 channels for background subtraction.

The distribution of a phage-related insertion sequence element in the cyanobacterium, Microcystis aeruginosa.

PubMed

Kuno, Sotaro; Yoshida, Takashi; Kamikawa, Ryoma; Hosoda, Naohiko; Sako, Yoshihiko

2010-01-01

The cyanophage Ma-LMM01, specifically-infecting Microcystis aeruginosa, has an insertion sequence (IS) element that we named IS607-cp showing high nucleotide similarity to a counterpart in the genome of the cyanobacterium Cyanothece sp. We tested 21 strains of M. aeruginosa for the presence of IS607-cp using PCR and detected the element in strains NIES90, NIES112, NIES604, and RM6. Thermal asymmetric interlaced PCR (TAIL-PCR) revealed each of these strains has multiple copies of IS607-cp. Some of the ISs were classified into three types based on their inserted positions; IS607-cp-1 is common in strains NIES90, NIES112 and NIES604, whereas IS607-cp-2 and IS607-cp-3 are specific to strains NIES90 and RM6, respectively. This multiplicity may reflect the replicative transposition of IS607-cp. The sequence of IS607-cp in Ma-LMM01 showed robust affinity to those found in M. aeruginosa and Cyanothece spp. in a phylogenetic tree inferred from counterparts of various bacteria. This suggests the transfer of IS607-cp between the cyanobacterium and its cyanophage. We discuss the potential role of Ma-LMM01-related phages as donors of IS elements that may mediate the transfer of IS607-cp; and thereby partially contribute to the genome plasticity of M. aeruginosa.

Wide-field imaging through scattering media by scattered light fluorescence microscopy

NASA Astrophysics Data System (ADS)

Zhou, Yulan; Li, Xun

2017-08-01

To obtain images through scattering media, scattered light fluorescence (SLF) microscopy that utilizes the optical memory effect has been developed. However, the small field of view (FOV) of SLF microscopy limits its application. In this paper, we have introduced a re-modulation method to achieve wide-field imaging through scattering media by SLF microscopy. In the re-modulation method, to raster scan the focus across the object plane, the incident wavefront is re-modulated via a spatial light modulator (SLM) in the updated phase compensation calculated using the optimized iterative algorithm. Compared with the conventional optical memory effect method, the re-modulation method can greatly increase the FOV of a SLF microscope. With the phase compensation theoretically calculated, the process of updating the phase compensation of a high speed SLM is fast. The re-modulation method does not increase the imaging time. The re-modulation method is, therefore, expected to make SLF microscopy have much wider applications in biology, medicine and physiology.

Multiple myeloma invasion of the central nervous system.

PubMed

Marjanović, Slobodan; Mijusković, Zoran; Stamatović, Dragana; Madjaru, Lavinika; Ralić, Tijana; Trimcev, Jovana; Stojanović, Jelica; Radović, Vesna

2012-02-01

Multiple myeloma (MM) is characterized by the presence of neoplastic proliferating plasma cells. The tumor is generally restricted to the bone marrow. The most common complications include renal insufficiency, hypercalcemia, anemia and reccurent infections. The spectrum of MM neurological complications is diverse, however, involvement of MM in the cerebrospinal fluid (CSF) and leptomeningeal infiltration are rare considered. In about 1% of the cases, the disease affects the central nervous system (CNS) and presents itself in the form of localized intraparenchymal lesions, solitary cerebral plasmocytoma or CNS myelomatosis (LMM). We presented the clinical course of a 55-year-old man with MM and LMM proven by malignant plasma cells in the CSF, hospitalized with the pain in the thoracic spine. His medical history was uneventful. There had been no evidence of mental or neurological impairment prior to the seizures. Physical examination showed no abnormalities. After a complete staging, the diagnosis of MM type biclonal gammopathia IgG lambda and free lambda light chains in the stage III was confirmed. The treatment started with systemic chemotherapy (with vincristine, doxorubicin plus high-dose dexamethasone--VAD protocol), radiotherapy and bisphosphonate. The patient developed weakness, nausea, febrility, dispnea, bilateral bronchopneumonia, acute renal insufficiency, confusions, headaches and soon thereafter sensomotor aphasias and right hemiparesis. The patient was treated with the adequate therapy including one hemodyalisis. His neurological status was deteriorated, so Multislice Computed Tomography (MSCT) of the head was performed and the findings were normal. Analysis of CSF showed pleocytosis, 26 elements/mL and increased concentrations of proteins. Cytological analysis revealed an increased number of plasma cells (29%). Electrophoretic analysis of proteins disclosed the existance of monoclonal components in the serum, urine and CSF. Immunofixation electrophoretic and quantitative nephelometric tests confirmed Biclonal multiple myeloma of IgG lambda and light chain lambda isotypes. Analysis of neurothropic viruses with ELISA methods was negative. Once the presence of LMM was confirmed, the patient received intrathecal chemotherapy with methotrexate, cytosine arabinoside, dexamethasone three times a week, and systemic high doses of dexamethasone iv like a single agent without craniospinale irradiations. Despite the treatment, the patient died one month after the diagnosis. Autopsy was not performed. Presented patient, as well as most other patients with MM progressing to CN Sinfiltration was in the stage III. In addition to the detailed clinical examination, and all investigations required for MM diagnosis and staging of the disease, we introduced the additional CSF examination and calculation of kappa lambda ratio, that helped us make an early diagnosis and prognosis of MM with LMM. Although LMM had a low prevalence, it could be more frequent than expected especially in patients with high risk. CSF examination with positive plasma cells and abnormal morphology remains the hallmark for diag nosing CNS infiltration.

Prediction of gene expression with cis-SNPs using mixed models and regularization methods.

PubMed

Zeng, Ping; Zhou, Xiang; Huang, Shuiping

2017-05-11

It has been shown that gene expression in human tissues is heritable, thus predicting gene expression using only SNPs becomes possible. The prediction of gene expression can offer important implications on the genetic architecture of individual functional associated SNPs and further interpretations of the molecular basis underlying human diseases. We compared three types of methods for predicting gene expression using only cis-SNPs, including the polygenic model, i.e. linear mixed model (LMM), two sparse models, i.e. Lasso and elastic net (ENET), and the hybrid of LMM and sparse model, i.e. Bayesian sparse linear mixed model (BSLMM). The three kinds of prediction methods have very different assumptions of underlying genetic architectures. These methods were evaluated using simulations under various scenarios, and were applied to the Geuvadis gene expression data. The simulations showed that these four prediction methods (i.e. Lasso, ENET, LMM and BSLMM) behaved best when their respective modeling assumptions were satisfied, but BSLMM had a robust performance across a range of scenarios. According to R 2 of these models in the Geuvadis data, the four methods performed quite similarly. We did not observe any clustering or enrichment of predictive genes (defined as genes with R 2  ≥ 0.05) across the chromosomes, and also did not see there was any clear relationship between the proportion of the predictive genes and the proportion of genes in each chromosome. However, an interesting finding in the Geuvadis data was that highly predictive genes (e.g. R 2  ≥ 0.30) may have sparse genetic architectures since Lasso, ENET and BSLMM outperformed LMM for these genes; and this observation was validated in another gene expression data. We further showed that the predictive genes were enriched in approximately independent LD blocks. Gene expression can be predicted with only cis-SNPs using well-developed prediction models and these predictive genes were enriched in some approximately independent LD blocks. The prediction of gene expression can shed some light on the functional interpretation for identified SNPs in GWASs.

The use of multiple imputation for the accurate measurements of individual feed intake by electronic feeders.

PubMed

Jiao, S; Tiezzi, F; Huang, Y; Gray, K A; Maltecca, C

2016-02-01

Obtaining accurate individual feed intake records is the key first step in achieving genetic progress toward more efficient nutrient utilization in pigs. Feed intake records collected by electronic feeding systems contain errors (erroneous and abnormal values exceeding certain cutoff criteria), which are due to feeder malfunction or animal-feeder interaction. In this study, we examined the use of a novel data-editing strategy involving multiple imputation to minimize the impact of errors and missing values on the quality of feed intake data collected by an electronic feeding system. Accuracy of feed intake data adjustment obtained from the conventional linear mixed model (LMM) approach was compared with 2 alternative implementations of multiple imputation by chained equation, denoted as MI (multiple imputation) and MICE (multiple imputation by chained equation). The 3 methods were compared under 3 scenarios, where 5, 10, and 20% feed intake error rates were simulated. Each of the scenarios was replicated 5 times. Accuracy of the alternative error adjustment was measured as the correlation between the true daily feed intake (DFI; daily feed intake in the testing period) or true ADFI (the mean DFI across testing period) and the adjusted DFI or adjusted ADFI. In the editing process, error cutoff criteria are used to define if a feed intake visit contains errors. To investigate the possibility that the error cutoff criteria may affect any of the 3 methods, the simulation was repeated with 2 alternative error cutoff values. Multiple imputation methods outperformed the LMM approach in all scenarios with mean accuracies of 96.7, 93.5, and 90.2% obtained with MI and 96.8, 94.4, and 90.1% obtained with MICE compared with 91.0, 82.6, and 68.7% using LMM for DFI. Similar results were obtained for ADFI. Furthermore, multiple imputation methods consistently performed better than LMM regardless of the cutoff criteria applied to define errors. In conclusion, multiple imputation is proposed as a more accurate and flexible method for error adjustments in feed intake data collected by electronic feeders.

Warped linear mixed models for the genetic analysis of transformed phenotypes

PubMed Central

Fusi, Nicolo; Lippert, Christoph; Lawrence, Neil D.; Stegle, Oliver

2014-01-01

Linear mixed models (LMMs) are a powerful and established tool for studying genotype–phenotype relationships. A limitation of the LMM is that the model assumes Gaussian distributed residuals, a requirement that rarely holds in practice. Violations of this assumption can lead to false conclusions and loss in power. To mitigate this problem, it is common practice to pre-process the phenotypic values to make them as Gaussian as possible, for instance by applying logarithmic or other nonlinear transformations. Unfortunately, different phenotypes require different transformations, and choosing an appropriate transformation is challenging and subjective. Here we present an extension of the LMM that estimates an optimal transformation from the observed data. In simulations and applications to real data from human, mouse and yeast, we show that using transformations inferred by our model increases power in genome-wide association studies and increases the accuracy of heritability estimation and phenotype prediction. PMID:25234577

Warped linear mixed models for the genetic analysis of transformed phenotypes.

PubMed

Fusi, Nicolo; Lippert, Christoph; Lawrence, Neil D; Stegle, Oliver

2014-09-19

Linear mixed models (LMMs) are a powerful and established tool for studying genotype-phenotype relationships. A limitation of the LMM is that the model assumes Gaussian distributed residuals, a requirement that rarely holds in practice. Violations of this assumption can lead to false conclusions and loss in power. To mitigate this problem, it is common practice to pre-process the phenotypic values to make them as Gaussian as possible, for instance by applying logarithmic or other nonlinear transformations. Unfortunately, different phenotypes require different transformations, and choosing an appropriate transformation is challenging and subjective. Here we present an extension of the LMM that estimates an optimal transformation from the observed data. In simulations and applications to real data from human, mouse and yeast, we show that using transformations inferred by our model increases power in genome-wide association studies and increases the accuracy of heritability estimation and phenotype prediction.

Global Asymptotic Behavior of Iterative Implicit Schemes

NASA Technical Reports Server (NTRS)

Yee, H. C.; Sweby, P. K.

1994-01-01

The global asymptotic nonlinear behavior of some standard iterative procedures in solving nonlinear systems of algebraic equations arising from four implicit linear multistep methods (LMMs) in discretizing three models of 2 x 2 systems of first-order autonomous nonlinear ordinary differential equations (ODEs) is analyzed using the theory of dynamical systems. The iterative procedures include simple iteration and full and modified Newton iterations. The results are compared with standard Runge-Kutta explicit methods, a noniterative implicit procedure, and the Newton method of solving the steady part of the ODEs. Studies showed that aside from exhibiting spurious asymptotes, all of the four implicit LMMs can change the type and stability of the steady states of the differential equations (DEs). They also exhibit a drastic distortion but less shrinkage of the basin of attraction of the true solution than standard nonLMM explicit methods. The simple iteration procedure exhibits behavior which is similar to standard nonLMM explicit methods except that spurious steady-state numerical solutions cannot occur. The numerical basins of attraction of the noniterative implicit procedure mimic more closely the basins of attraction of the DEs and are more efficient than the three iterative implicit procedures for the four implicit LMMs. Contrary to popular belief, the initial data using the Newton method of solving the steady part of the DEs may not have to be close to the exact steady state for convergence. These results can be used as an explanation for possible causes and cures of slow convergence and nonconvergence of steady-state numerical solutions when using an implicit LMM time-dependent approach in computational fluid dynamics.

Comparison of gene-based rare variant association mapping methods for quantitative traits in a bovine population with complex familial relationships.

PubMed

Zhang, Qianqian; Guldbrandtsen, Bernt; Calus, Mario P L; Lund, Mogens Sandø; Sahana, Goutam

2016-08-17

There is growing interest in the role of rare variants in the variation of complex traits due to increasing evidence that rare variants are associated with quantitative traits. However, association methods that are commonly used for mapping common variants are not effective to map rare variants. Besides, livestock populations have large half-sib families and the occurrence of rare variants may be confounded with family structure, which makes it difficult to disentangle their effects from family mean effects. We compared the power of methods that are commonly applied in human genetics to map rare variants in cattle using whole-genome sequence data and simulated phenotypes. We also studied the power of mapping rare variants using linear mixed models (LMM), which are the method of choice to account for both family relationships and population structure in cattle. We observed that the power of the LMM approach was low for mapping a rare variant (defined as those that have frequencies lower than 0.01) with a moderate effect (5 to 8 % of phenotypic variance explained by multiple rare variants that vary from 5 to 21 in number) contributing to a QTL with a sample size of 1000. In contrast, across the scenarios studied, statistical methods that are specialized for mapping rare variants increased power regardless of whether multiple rare variants or a single rare variant underlie a QTL. Different methods for combining rare variants in the test single nucleotide polymorphism set resulted in similar power irrespective of the proportion of total genetic variance explained by the QTL. However, when the QTL variance is very small (only 0.1 % of the total genetic variance), these specialized methods for mapping rare variants and LMM generally had no power to map the variants within a gene with sample sizes of 1000 or 5000. We observed that the methods that combine multiple rare variants within a gene into a meta-variant generally had greater power to map rare variants compared to LMM. Therefore, it is recommended to use rare variant association mapping methods to map rare genetic variants that affect quantitative traits in livestock, such as bovine populations.

Microstructural Evaluation of Porous Nutritional Sustainment Module Extrudates and Infusates

DTIC Science & Technology

1989-07-01

TECHNICAL REPORT NATICK/TR-89/034 fi- MICROSTRUCTURAL EVALUATION OF POROUS NUTRITIONAL SUSTAINMENT MODULE EXTRUDATES AND INFUSATES BY SAMUEL...Nutritional Sustainment Module Extrudates and Infusates 12. PERSONAL AUTHOR(S) Samuel Cohen, Charles Voyle, Richard Harniman, Robyn Rufner, Ann...4ICR0STRUCTUREy EXTRUDATES , PYCNGMETRY; MICROSCOPY; tNFUSATES; SCANNING ELECTRON MICROSCOPY (CEM)>’ NUTRITIONAL SUSTAINING MODULE (NSM)j

Flipping interferometry and its application for quantitative phase microscopy in a micro-channel.

PubMed

Roitshtain, Darina; Turko, Nir A; Javidi, Bahram; Shaked, Natan T

2016-05-15

We present a portable, off-axis interferometric module for quantitative phase microscopy of live cells, positioned at the exit port of a coherently illuminated inverted microscope. The module creates on the digital camera an interference pattern between the image of the sample and its flipped version. The proposed simplified module is based on a retro-reflector modification in an external Michelson interferometer. The module does not contain any lenses, pinholes, or gratings and its alignment is straightforward. Still, it allows full control of the off-axis angle and does not suffer from ghost images. As experimentally demonstrated, the module is useful for quantitative phase microscopy of live cells rapidly flowing in a micro-channel.

CVB: the Constrained Vapor Bubble Capillary Experiment on the International Space Station MARANGONI FLOW REGION

NASA Technical Reports Server (NTRS)

Wayner, Peter C., Jr.; Kundan, Akshay; Plawsky, Joel

2014-01-01

The Constrained Vapor Bubble (CVB) is a wickless, grooved heat pipe and we report on a full- scale fluids experiment flown on the International Space Station (ISS). The CVB system consists of a relatively simple setup a quartz cuvette with sharp corners partially filled with either pentane or an ideal mixture of pentane and isohexane as the working fluids. Along with temperature and pressure measurements, the two-dimensional thickness profile of the menisci formed at the corners of the quartz cuvette was determined using the Light Microscopy Module (LMM). Even with the large, millimeter dimensions of the CVB, interfacial forces dominate in these exceedingly small Bond Number systems. The experiments were carried out at various power inputs. Although conceptually simple, the transport processes were found to be very complex with many different regions. At the heated end of the CVB, due to a high temperature gradient, we observed Marangoni flow at some power inputs. This region from the heated end to the central drop region is defined as a Marangoni dominated region. We present a simple analysis based on interfacial phenomena using only measurements from the ISS experiments that lead to a predictive equation for the thickness of the film near the heated end of the CVB. The average pressure gradient for flow in the film is assumed due to the measured capillary pressure at the two ends of the liquid film and that the pressure stress gradient due to cohesion self adjusts to a constant value over a distance L. The boundary conditions are the no slip condition at the wall interface and an interfacial shear stress at the liquid- vapor interface due to the Marangoni stress, which is due to the high temperature gradient. Although the heated end is extremely complex, since it includes three- dimensional variations in radiation, conduction, evaporation, condensation, fluid flow and interfacial forces, we find that using the above simplifying assumptions, a simple successful model can be developed.

Microscopy imaging system and method employing stimulated raman spectroscopy as a contrast mechanism

DOEpatents

Xie, Xiaoliang Sunney [Lexington, MA; Freudiger, Christian [Boston, MA; Min, Wei [Cambridge, MA

2011-09-27

A microscopy imaging system includes a first light source for providing a first train of pulses at a first center optical frequency .omega..sub.1, a second light source for providing a second train of pulses at a second center optical frequency .omega..sub.2, a modulator system, an optical detector, and a processor. The modulator system is for modulating a beam property of the second train of pulses at a modulation frequency f of at least 100 kHz. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of the first train of pulses from the common focal volume by blocking the second train of pulses being modulated. The processor is for detecting, a modulation at the modulation frequency f, of the integrated intensity of the optical frequency components of the first train of pulses to provide a pixel of an image for the microscopy imaging system.

Prevalence, patterns and predictors of substance use among Latino migrant men in a new receiving community.

PubMed

Kissinger, Patricia; Althoff, Meghan; Burton, Nicole; Schmidt, Norine; Hembling, John; Salinas, Oscar; Shedlin, Michele

2013-12-15

The purpose of this study was to evaluate the prevalence, patterns and predictors (individual, social, cultural, and environmental) of illicit drug use and binge drinking in a cohort of Latino migrant men (LMM) in a new receiving community. A cohort of LMM in New Orleans (n=125) was assembled in 2007 using respondent driven sampling and interviewed quarterly for 18 months regarding past month substance use and other potential covariates. Baseline frequencies were weighted using RDSAT and longitudinal analyses included generalized estimating equations (GEE) and the Cochran-Armitage test for trends. At baseline, substance use behaviors were: drug use 15.0% (range 7.3-25.0%) and binge drinking 58.3% (range 43.6-74.6%). All three of these behaviors decreased over follow-up (P<0.01). Baseline alcohol dependence and drug problem were 11.8% (range 5.6-24.3%) and 0.08% (range 0.00-2.7%) and both remained the same over time. Baseline rate of chlamydia was 9% (range 0.00-22.4%); all men tested negative for gonorrhea, HIV, and syphilis. For both binge drinking and drug use, having sex with a female sex worker was associated with increased risk, whereas belonging to a club or organization was associated with less risk. Additional factors associated with increased drug use were: having a friend in New Orleans upon arrival, symptoms of depression, and working in construction. An additional factor associated with less binge drinking was having family in New Orleans upon arrival. Among LMM, substance use is influenced by social and environmental factors. Interventions increase community connectedness may help decrease usage. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

GWAS with longitudinal phenotypes: performance of approximate procedures

PubMed Central

Sikorska, Karolina; Montazeri, Nahid Mostafavi; Uitterlinden, André; Rivadeneira, Fernando; Eilers, Paul HC; Lesaffre, Emmanuel

2015-01-01

Analysis of genome-wide association studies with longitudinal data using standard procedures, such as linear mixed model (LMM) fitting, leads to discouragingly long computation times. There is a need to speed up the computations significantly. In our previous work (Sikorska et al: Fast linear mixed model computations for genome-wide association studies with longitudinal data. Stat Med 2012; 32.1: 165–180), we proposed the conditional two-step (CTS) approach as a fast method providing an approximation to the P-value for the longitudinal single-nucleotide polymorphism (SNP) effect. In the first step a reduced conditional LMM is fit, omitting all the SNP terms. In the second step, the estimated random slopes are regressed on SNPs. The CTS has been applied to the bone mineral density data from the Rotterdam Study and proved to work very well even in unbalanced situations. In another article (Sikorska et al: GWAS on your notebook: fast semi-parallel linear and logistic regression for genome-wide association studies. BMC Bioinformatics 2013; 14: 166), we suggested semi-parallel computations, greatly speeding up fitting many linear regressions. Combining CTS with fast linear regression reduces the computation time from several weeks to a few minutes on a single computer. Here, we explore further the properties of the CTS both analytically and by simulations. We investigate the performance of our proposal in comparison with a related but different approach, the two-step procedure. It is analytically shown that for the balanced case, under mild assumptions, the P-value provided by the CTS is the same as from the LMM. For unbalanced data and in realistic situations, simulations show that the CTS method does not inflate the type I error rate and implies only a minimal loss of power. PMID:25712081

Sarcopenia according to the european working group on sarcopenia in older people (EWGSOP) versus Dynapenia as a risk factor for disability in the elderly.

PubMed

da Silva Alexandre, T; de Oliveira Duarte, Y A; Ferreira Santos, J L; Wong, R; Lebrão, M L

2014-05-01

Sarcopenia, defined as low muscle mass (LMM), and dynapenia have been associated with adverse outcomes in elderly. Contrast the association of sarcopenia versus dynapenia with incidence of disability. A four-year prospective study (2006-2010). São Paulo, Brazil. 478 individuals aged 60 and older from the Saúde, Bem-Estar e Envelhecimento (SABE) study who were non-disabled at baseline. Sarcopenia, measured according to the European Working Group on Sarcopenia in Older People (EWGSOP), includes: LMM assessed by skeletal muscle mass index ≤8.90kg/m2 (men) and ≤6.37kg/m2 (women); low muscle strength (LMS) assessed by handgrip strength <30kg (men) and <20kg (women); and low physical performance (LPP) assessed by gait speed ≤0.8m/s. Diagnosis of sarcopenia required LMM plus LMS or LPP. Dynapenia was defined as handgrip strength <30kg (men) and <20kg (women). Covariates included socio-demographic and behavioral variables, medical conditions, hospitalization, depressive symptoms, cognition, perception of vision, hearing and body mass index. Disability in mobility or instrumental activities of daily living (IADL) or disability in activities of daily living (ADL) and IADL. The incidence density of mobility or IADL disability was 43.4/1000 person/year and 22.6/1000 person/year for IADL and ADL disability. There was no significant difference in incidence density according sarcopenia or dynapenia status. After controlling for all covariates, sarcopenia was associated with mobility or IADL disability (relative risk ratio = 2.23, 95%Confidence Interval: 1.03-4.85). Dynapenia was not associated with disability. Sarcopenia according to the EWGSOP definition can be used in clinical practice as a screening tool for early functional decline (mobility or IADL disability).

Prevalence, patterns and predictors of substance use among Latino migrant men in a new receiving community

PubMed Central

Kissinger, Patricia; Althoff, Meghan; Burton, Nicole; Schmidt, Norine; Hembling, John; Salinas, Oscar; Shedlin, Michele

2014-01-01

Background The purpose of this study was to evaluate the prevalence, patterns and predictors (individual, social, cultural, and environmental) of illicit drug use and binge drinking in a cohort of Latino migrant men (LMM) in a new receiving community. Methods A cohort of LMM in New Orleans (n = 125) was assembled in 2007 using respondent driven sampling and interviewed quarterly for 18 months regarding past month substance use and other potential covariates. Baseline frequencies were weighted using RDSAT and longitudinal analyses included generalized estimating equations (GEE) and the Cochran–Armitage test for trends. Results At baseline, substance use behaviors were: drug use 15.0% (range 7.3–25.0%) and binge drinking 58.3% (range 43.6–74.6%). All three of these behaviors decreased over follow-up (P < 0.01). Baseline alcohol dependence and drug problem were 11.8% (range 5.6–24.3%) and 0.08% (range 0.00–2.7%) and both remained the same over time. Baseline rate of chlamydia was 9% (range 0.00–22.4%); all men tested negative for gonorrhea, HIV, and syphilis. For both binge drinking and drug use, having sex with a female sex worker was associated with increased risk, whereas belonging to a club or organization was associated with less risk. Additional factors associated with increased drug use were: having a friend in New Orleans upon arrival, symptoms of depression, and working in construction. An additional factor associated with less binge drinking was having family in New Orleans upon arrival. Conclusion Among LMM, substance use is influenced by social and environmental factors. Interventions increase community connectedness may help decrease usage. PMID:24099968

CERAMIC: Case-Control Association Testing in Samples with Related Individuals, Based on Retrospective Mixed Model Analysis with Adjustment for Covariates

PubMed Central

Zhong, Sheng; McPeek, Mary Sara

2016-01-01

We consider the problem of genetic association testing of a binary trait in a sample that contains related individuals, where we adjust for relevant covariates and allow for missing data. We propose CERAMIC, an estimating equation approach that can be viewed as a hybrid of logistic regression and linear mixed-effects model (LMM) approaches. CERAMIC extends the recently proposed CARAT method to allow samples with related individuals and to incorporate partially missing data. In simulations, we show that CERAMIC outperforms existing LMM and generalized LMM approaches, maintaining high power and correct type 1 error across a wider range of scenarios. CERAMIC results in a particularly large power increase over existing methods when the sample includes related individuals with some missing data (e.g., when some individuals with phenotype and covariate information have missing genotype), because CERAMIC is able to make use of the relationship information to incorporate partially missing data in the analysis while correcting for dependence. Because CERAMIC is based on a retrospective analysis, it is robust to misspecification of the phenotype model, resulting in better control of type 1 error and higher power than that of prospective methods, such as GMMAT, when the phenotype model is misspecified. CERAMIC is computationally efficient for genomewide analysis in samples of related individuals of almost any configuration, including small families, unrelated individuals and even large, complex pedigrees. We apply CERAMIC to data on type 2 diabetes (T2D) from the Framingham Heart Study. In a genome scan, 9 of the 10 smallest CERAMIC p-values occur in or near either known T2D susceptibility loci or plausible candidates, verifying that CERAMIC is able to home in on the important loci in a genome scan. PMID:27695091

Numerical modeling of two-photon focal modulation microscopy with a sinusoidal phase filter.

PubMed

Chen, Rui; Shen, Shuhao; Chen, Nanguang

2018-05-01

A spatiotemporal phase modulator (STPM) is theoretically investigated using the vectorial diffraction theory. The STPM is equivalent to a time-dependent phase-only pupil filter that alternates between a homogeneous filter and a stripe-shaped filter with a sinusoidal phase distribution. It is found that two-photon focal modulation microscopy (TPFMM) using this STPM can significantly suppress the background contribution from out-of-focus ballistic excitation and achieve almost the same resolution as two-photon microscopy. The modulation depth is also evaluated and a compromise exists between the signal-to-background ratio and signal-to-noise ratio. The theoretical investigations provide important insights into future implementations of TPFMM and its potential to further extend the penetration depth of nonlinear microscopy in imaging multiple-scattering biological tissues. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Variation in nitrogen use efficiencies on Dutch dairy farms.

PubMed

Daatselaar, Co Hg; Reijs, Joan R; Oenema, Jouke; Doornewaard, Gerben J; Aarts, H Frans M

2015-12-01

On dairy farms, the input of nutrients including nitrogen is higher than the output in products such as milk and meat. This causes losses of nitrogen to the environment. One of the indicators for the losses of nitrogen is the nitrogen use efficiency. In the Dutch Minerals Policy Monitoring Program (LMM), many data on nutrients of a few hundred farms are collected which can be processed by the instrument Annual Nutrient Cycle Assessment (ANCA, in Dutch: Kringloopwijzer) in order to provide nitrogen use efficiencies. After dividing the dairy farms (available in the LMM program) according to soil type and in different classes for milk production ha(-1) , it is shown that considerable differences in nitrogen use efficiency exist between farms on the same soil type and with the same level of milk production ha(-1) . This offers opportunities for improvement of the nitrogen use efficiency on many dairy farms. Benchmarking will be a useful first step in this process. © 2015 Society of Chemical Industry.

High-resolution photoluminescence electro-modulation microscopy by scanning lock-in

NASA Astrophysics Data System (ADS)

Koopman, W.; Muccini, M.; Toffanin, S.

2018-04-01

Morphological inhomogeneities and structural defects in organic semiconductors crucially determine the charge accumulation and lateral transport in organic thin-film transistors. Photoluminescence Electro-Modulation (PLEM) microscopy is a laser-scanning microscopy technique that relies on the modulation of the thin-film fluorescence in the presence of charge-carriers to image the spatial distribution of charges within the active organic semiconductor. Here, we present a lock-in scheme based on a scanning beam approach for increasing the PLEM microscopy resolution and contrast. The charge density in the device is modulated by a sinusoidal electrical signal, phase-locked to the scanning beam of the excitation laser. The lock-in detection scheme is achieved by acquiring a series of images with different phases between the beam scan and the electrical modulation. Application of high resolution PLEM to an organic transistor in accumulation mode demonstrates its potential to image local variations in the charge accumulation. A diffraction-limited precision of sub-300 nm and a signal to noise ratio of 21.4 dB could be achieved.

Nonlinear Focal Modulation Microscopy.

PubMed

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M; Toussaint, Kimani C; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-11

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ∼60  nm (∼λ/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Nonlinear Focal Modulation Microscopy

NASA Astrophysics Data System (ADS)

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M.; Toussaint, Kimani C.; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-01

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ˜60 nm (˜λ /10 ). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Atomic force microscopy captures length phenotypes in single proteins

PubMed Central

Carrion-Vazquez, Mariano; Marszalek, Piotr E.; Oberhauser, Andres F.; Fernandez, Julio M.

1999-01-01

We use single-protein atomic force microscopy techniques to detect length phenotypes in an Ig module. To gain amino acid resolution, we amplify the mechanical features of a single module by engineering polyproteins composed of up to 12 identical repeats. We show that on mechanical unfolding, mutant polyproteins containing five extra glycine residues added to the folded core of the module extend 20 Å per module farther than the wild-type polyproteins. By contrast, similar insertions near the N or C termini have no effect. Hence, our atomic force microscopy measurements readily discriminate the location of the insert and measure its size with a resolution similar to that of NMR and x-ray crystallography. PMID:10500169

Low skeletal muscle mass index is associated with function and nutritional status in residents in a Turkish nursing home.

PubMed

Tufan, Asli; Bahat, Gulistan; Ozkaya, Hilal; Taşcıoğlu, Didem; Tufan, Fatih; Saka, Bülent; Akin, Sibel; Karan, Mehmet Akif

2016-09-01

To determine the prevalence of low muscle mass (LMM) and the relationship between LMM with functional and nutritional status as defined using the LMM evaluation method of European Working Group on Sarcopenia in Older People (EWGSOP) criteria among male residents in a nursing home. Male residents aged >60 years of a nursing home located in Turkey were included in our study. Their body mass index (BMI) kg/m 2 , skeletal muscle mass (SMM-kg) and skeletal muscle mass index (SMMI-kg/m 2 ) were calculated. The participants were regarded as having low SMMI if they had SMMI <9.2 kg/m 2 according to our population specific cut-off point. Functional status was evaluated with Katz activities of daily living (ADL) and Lawton Instrumental Activities of Daily Living (IADL). Nutritional assessment was performed using the Mini Nutritional Assessment (MNA). The number of drugs taken and chronic diseases were recorded. One hundred fifty-seven male residents were enrolled into the study. Their mean age was 73.1 ± 6.7 years with mean ADL score of 8.9 ± 2.0 and IADL score of 8.7 ± 4.6. One hundred twelve (71%) residents were aged >70 years. Thirty-five men (23%) had low SMMI in group aged >60 years, and twenty-eight subjects (25%) in the group aged >70 years. MNA scores were significantly lower in residents with low SMMI compared with having normal SMMI (17.1 ± 3.4 versus 19.6 ± 2.5, p = 0.005). BMI was significantly lower in the residents with low SMMI compared with normal SMMI (19.6 ± 2.7 versus 27.1 ± 4.1, p< 0.001). ADL scores were significantly different between residents with low SMMI and normal SMMI in those aged >70 years (8.1 ± 2.6 versus 9.1 ± 1.6, p = 0.014). In regression analyses, the only factor associated with better functional status was the lower age (p = 0.04) while the only factor associated with better nutrition was higher SMMI (p = 0.01). Low SMMI detected by LMM evaluation method of EWGSOP criteria is prevalent among male nursing home residents. There is association of low SMMI with nutritional status and probably with functional status within the nursing home setting using the EWGSOP criteria with Turkish normative reference cut-off value.

Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the Superficial Zone of the Human Articular Cartilage and Changes in Surface Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.

PubMed

Kiyan, Wataru; Ito, Akira; Nakagawa, Yasuaki; Mukai, Shogo; Mori, Koji; Arai, Tatsuo; Uchino, Eiichiro; Okuno, Yasushi; Kuroki, Hiroshi

2017-08-01

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (R q ), average collagen content (A 1 ) and collagen orientation (A 12 ) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (R c ) had a significant coefficient of determination with R q and A 12 (R LMMm 2 =0.79); however, R c did not correlate with A 1 . Concerning the collagen characteristic in the superficial zone, R c was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Spatial Assessment of Model Errors from Four Regression Techniques

Treesearch

Lianjun Zhang; Jeffrey H. Gove; Jeffrey H. Gove

2005-01-01

Fomst modelers have attempted to account for the spatial autocorrelations among trees in growth and yield models by applying alternative regression techniques such as linear mixed models (LMM), generalized additive models (GAM), and geographicalIy weighted regression (GWR). However, the model errors are commonly assessed using average errors across the entire study...

Model Selection with the Linear Mixed Model for Longitudinal Data

ERIC Educational Resources Information Center

Ryoo, Ji Hoon

2011-01-01

Model building or model selection with linear mixed models (LMMs) is complicated by the presence of both fixed effects and random effects. The fixed effects structure and random effects structure are codependent, so selection of one influences the other. Most presentations of LMM in psychology and education are based on a multilevel or…

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... proposed MQP would be a program designed to promote market quality in certain securities listed on NASDAQ... contain the specific quantitative listing requirements for listing on the Global Select, Global Market... pilot (for comparative purposes), volume metrics, NBBO bid/ask spread differentials, LMM participation...

Personal Finance Education: Effective Practice Guide for Schools

ERIC Educational Resources Information Center

Spielhofer, Thomas; Kerr, David; Gardiner, Clare

2010-01-01

This document provides guidance on effective practice in delivering personal finance education in secondary schools. It is based on the findings from research carried out by NFER (the National Foundation for Educational Research) on behalf of pfeg (Personal Finance Education Group) as part of an evaluation of Learning Money Matters (LMM). This…

Reliability of environmental sampling culture results using the negative binomial intraclass correlation coefficient.

PubMed

Aly, Sharif S; Zhao, Jianyang; Li, Ben; Jiang, Jiming

2014-01-01

The Intraclass Correlation Coefficient (ICC) is commonly used to estimate the similarity between quantitative measures obtained from different sources. Overdispersed data is traditionally transformed so that linear mixed model (LMM) based ICC can be estimated. A common transformation used is the natural logarithm. The reliability of environmental sampling of fecal slurry on freestall pens has been estimated for Mycobacterium avium subsp. paratuberculosis using the natural logarithm transformed culture results. Recently, the negative binomial ICC was defined based on a generalized linear mixed model for negative binomial distributed data. The current study reports on the negative binomial ICC estimate which includes fixed effects using culture results of environmental samples. Simulations using a wide variety of inputs and negative binomial distribution parameters (r; p) showed better performance of the new negative binomial ICC compared to the ICC based on LMM even when negative binomial data was logarithm, and square root transformed. A second comparison that targeted a wider range of ICC values showed that the mean of estimated ICC closely approximated the true ICC.

The infrared imaging spectrograph (IRIS) for TMT: volume phase holographic grating performance testing and discussion

NASA Astrophysics Data System (ADS)

Chen, Shaojie; Meyer, Elliot; Wright, Shelley A.; Moore, Anna M.; Larkin, James E.; Maire, Jerome; Mieda, Etsuko; Simard, Luc

2014-07-01

Maximizing the grating efficiency is a key goal for the first light instrument IRIS (Infrared Imaging Spectrograph) currently being designed to sample the diffraction limit of the TMT (Thirty Meter Telescope). Volume Phase Holographic (VPH) gratings have been shown to offer extremely high efficiencies that approach 100% for high line frequencies (i.e., 600 to 6000l/mm), which has been applicable for astronomical optical spectrographs. However, VPH gratings have been less exploited in the near-infrared, particularly for gratings that have lower line frequencies. Given their potential to offer high throughputs and low scattered light, VPH gratings are being explored for IRIS as a potential dispersing element in the spectrograph. Our team has procured near-infrared gratings from two separate vendors. We have two gratings with the specifications needed for IRIS current design: 1.51-1.82μm (H-band) to produce a spectral resolution of 4000 and 1.19-1.37μm (J-band) to produce a spectral resolution of 8000. The center wavelengths for each grating are 1.629μm and 1.27μm, and the groove densities are 177l/mm and 440l/mm for H-band R=4000 and J-band R=8000, respectively. We directly measure the efficiencies in the lab and find that the peak efficiencies of these two types of gratings are quite good with a peak efficiency of ~88% at the Bragg angle in both TM and TE modes at H-band, and 90.23% in TM mode, 79.91% in TE mode at J-band for the best vendor. We determine the drop in efficiency off the Bragg angle, with a 20-23% decrease in efficiency at H-band when 2.5° deviation from the Bragg angle, and 25%-28% decrease at J-band when 5° deviation from the Bragg angle.

The impact of regional climate change on malaria risk due to greenhouse forcing and land-use changes in tropical Africa.

PubMed

Ermert, Volker; Fink, Andreas H; Morse, Andrew P; Paeth, Heiko

2012-01-01

Climate change will probably alter the spread and transmission intensity of malaria in Africa. In this study, we assessed potential changes in the malaria transmission via an integrated weather-disease model. We simulated mosquito biting rates using the Liverpool Malaria Model (LMM). The input data for the LMM were bias-corrected temperature and precipitation data from the regional model (REMO) on a 0.5° latitude-longitude grid. A Plasmodium falciparum infection model expands the LMM simulations to incorporate information on the infection rate among children. Malaria projections were carried out with this integrated weather-disease model for 2001 to 2050 according to two climate scenarios that include the effect of anthropogenic land-use and land-cover changes on climate. Model-based estimates for the present climate (1960 to 2000) are consistent with observed data for the spread of malaria in Africa. In the model domain, the regions where malaria is epidemic are located in the Sahel as well as in various highland territories. A decreased spread of malaria over most parts of tropical Africa is projected because of simulated increased surface temperatures and a significant reduction in annual rainfall. However, the likelihood of malaria epidemics is projected to increase in the southern part of the Sahel. In most of East Africa, the intensity of malaria transmission is expected to increase. Projections indicate that highland areas that were formerly unsuitable for malaria will become epidemic, whereas in the lower-altitude regions of the East African highlands, epidemic risk will decrease. We project that climate changes driven by greenhouse-gas and land-use changes will significantly affect the spread of malaria in tropical Africa well before 2050. The geographic distribution of areas where malaria is epidemic might have to be significantly altered in the coming decades.

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...-Regulatory Organizations; NYSE Arca, Inc.; Notice of Designation of Longer Period for Commission Action on Proceedings To Determine Whether To Approve or Disapprove Proposed Rule Change Proposing a Pilot Program To... change to create and implement, on a pilot basis, a Lead Market Maker (``LMM'') Issuer Incentive Program...

Marginal and Random Intercepts Models for Longitudinal Binary Data with Examples from Criminology

ERIC Educational Resources Information Center

Long, Jeffrey D.; Loeber, Rolf; Farrington, David P.

2009-01-01

Two models for the analysis of longitudinal binary data are discussed: the marginal model and the random intercepts model. In contrast to the linear mixed model (LMM), the two models for binary data are not subsumed under a single hierarchical model. The marginal model provides group-level information whereas the random intercepts model provides…

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... contracts for Market Makers \\3\\ registered on the Exchange. \\3\\ Market Makers may be registered as a Lead Market Maker or as a Registered Market Maker. See Exchange Rule 600(b). Market Makers registered on the...) Registered Market Maker (``RMM''); (ii) Lead Market Maker (``LMM''); (iii) Directed Order Lead Market Maker...

Diatomaceous Fungal and Bacterial Building Blocks for Material Synthesis

DTIC Science & Technology

2008-04-08

Thalassiosira-templated metallic microshells. Thalassiosira, only 1mM rhodamine 6G (d) lmM, (e) I piM ,(f 100 nM R6G. 4 concentrations gave detectable...hybridized with a 27-mer 7 oligonucleotide containing a 7-mer TAG GAA TAG TTA TA AT OTT ATT AGO complementary region 2, which produces TAIOATCCTTA TACAATAATCC

Analysis of higher order harmonics with holographic reflection gratings

NASA Astrophysics Data System (ADS)

Mas-Abellan, P.; Madrigal, R.; Fimia, A.

2017-05-01

Silver halide emulsions have been considered one of the most energetic sensitive materials for holographic applications. Nonlinear recording effects on holographic reflection gratings recorded on silver halide emulsions have been studied by different authors obtaining excellent experimental results. In this communication specifically we focused our investigation on the effects of refractive index modulation, trying to get high levels of overmodulation that will produce high order harmonics. We studied the influence of the overmodulation and its effects on the transmission spectra for a wide exposure range by use of 9 μm thickness films of ultrafine grain emulsion BB640, exposed to single collimated beams using a red He-Ne laser (wavelength 632.8 nm) with Denisyuk configuration obtaining a spatial frequency of 4990 l/mm recorded on the emulsion. The experimental results show that high overmodulation levels of refractive index produce second order harmonics with high diffraction efficiency (higher than 75%) and a narrow grating bandwidth (12.5 nm). Results also show that overmodulation produce diffraction spectra deformation of the second order harmonic, transforming the spectrum from sinusoidal to approximation of square shape due to very high overmodulation. Increasing the levels of overmodulation of refractive index, we have obtained higher order harmonics, obtaining third order harmonic with diffraction efficiency (up to 23%) and narrowing grating bandwidth (5 nm). This study is the first step to develop a new easy technique to obtain narrow spectral filters based on the use of high index modulation reflection gratings.

Effects of pupil filter patterns in line-scan focal modulation microscopy

NASA Astrophysics Data System (ADS)

Shen, Shuhao; Pant, Shilpa; Chen, Rui; Chen, Nanguang

2018-03-01

Line-scan focal modulation microscopy (LSFMM) is an emerging imaging technique that affords high imaging speed and good optical sectioning at the same time. We present a systematic investigation into optimal design of the pupil filter for LSFMM in an attempt to achieve the best performance in terms of spatial resolutions, optical sectioning, and modulation depth. Scalar diffraction theory was used to compute light propagation and distribution in the system and theoretical predictions on system performance, which were then compared with experimental results.

Photoacoustic microscopy of single cells employing an intensity-modulated diode laser

NASA Astrophysics Data System (ADS)

Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Dasa, Manoj Kumar; Klar, Thomas A.; Berer, Thomas

2018-02-01

In this work, we employ frequency-domain photoacoustic microscopy to obtain photoacoustic images of labeled and unlabeled cells. The photoacoustic microscope is based on an intensity-modulated diode laser in combination with a focused piezo-composite transducer and allows imaging of labeled cells without severe photo-bleaching. We demonstrate that frequency-domain photoacoustic microscopy realized with a diode laser is capable of recording photoacoustic images of single cells with sub-µm resolution. As examples, we present images of undyed human red blood cells, stained human epithelial cells, and stained yeast cells.

Effects of Lecture Method Supplemented with Music and Computer Animation on Senior Secondary School Students' Academic Achievement in Electrochemistry

ERIC Educational Resources Information Center

Akpoghol, T. V.; Ezeudu, F. O.; Adzape, J. N.; Otor, E. E.

2016-01-01

The study investigated the effects of Lecture Method Supplemented with Music (LMM) and Computer Animation (LMC) on senior secondary school students' academic achievement in electrochemistry in Makurdi metropolis. Six research questions and six hypotheses guided the study. The design of the study was quasi experimental, specifically the pre-test,…

Relative Effect of Lecture Method Supplemented with Music and Computer Animation on Senior Secondary School Students' Retention in Electrochemistry

ERIC Educational Resources Information Center

Akpoghol, T. V.; Ezeudu, F. O.; Adzape, J. N.; Otor, E. E.

2016-01-01

The study investigated the effects of Lecture Method Supplemented with Music (LMM) and Computer Animation (LMC) on senior secondary school students' retention in electrochemistry in Makurdi metropolis. Three research questions and three hypotheses guided the study. The design of the study was quasi experimental, specifically the pre-test,…

Parental and Early Childhood Influences on Adolescent Obesity: A Longitudinal Study

ERIC Educational Resources Information Center

Chivers, Paola; Parker, Helen; Bulsara, Max; Beilin, Lawrence; Hands, Beth

2012-01-01

The influence of parental and early childhood factors on adolescent obesity was investigated using a longitudinal model of body mass index (BMI) from birth to 14 years. Trajectories of BMI using linear mixed model (LMM) analysis were used to investigate the influence of early parental and childhood factors on BMI at 14 years in the Raine birth…

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...). Currently, Section 1(b) of the Fee Schedule, which relates to the marketing fee, states that an LMM will... Schedule, fn. 6; NASDAQ OMX Phlx, LLC (``Phlx'') Pricing Schedule, section on Payment for Order Flow Fee... encourage greater order flow to be sent to the Exchange. This increased order flow would benefit all market...

WIYN bench upgrade: a revitalized spectrograph

NASA Astrophysics Data System (ADS)

Bershady, M.; Barden, S.; Blanche, P.-A.; Blanco, D.; Corson, C.; Crawford, S.; Glaspey, J.; Habraken, S.; Jacoby, G.; Keyes, J.; Knezek, P.; Lemaire, P.; Liang, M.; McDougall, E.; Poczulp, G.; Sawyer, D.; Westfall, K.; Willmarth, D.

2008-07-01

We describe the redesign and upgrade of the versatile fiber-fed Bench Spectrograph on the WIYN 3.5m telescope. The spectrograph is fed by either the Hydra multi-object positioner or integral-field units (IFUs) at two other ports, and can be configured with an adjustable camera-collimator angle to use low-order and echelle gratings. The upgrade, including a new collimator, charge-coupled device (CCD) and modern controller, and volume-phase holographic gratings (VPHG), has high performance-to-cost ratio by combining new technology with a system reconfiguration that optimizes throughput while utilizing as much of the existing instrument as possible. A faster, all-refractive collimator enhances throughput by 60%, nearly eliminates the slit-function due to vignetting, and improves image quality to maintain instrumental resolution. Two VPH gratings deliver twice the diffraction efficiency of existing surface-relief gratings: A 740 l/mm grating (float-glass and post-polished) used in 1st and 2nd-order, and a large 3300 l/mm grating (spectral resolution comparable to the R2 echelle). The combination of collimator, high-quantum efficiency (QE) CCD, and VPH gratings yields throughput gain-factors of up to 3.5.

Stimulated Raman scattering microscopy by Nyquist modulation of a two-branch ultrafast fiber source.

PubMed

Riek, Claudius; Kocher, Claudius; Zirak, Peyman; Kölbl, Christoph; Fimpel, Peter; Leitenstorfer, Alfred; Zumbusch, Andreas; Brida, Daniele

2016-08-15

A highly stable setup for stimulated Raman scattering (SRS) microscopy is presented. It is based on a two-branch femtosecond Er:fiber laser operating at a 40 MHz repetition rate. One of the outputs is directly modulated at the Nyquist frequency with an integrated electro-optic modulator (EOM). This compact source combines a jitter-free pulse synchronization with a broad tunability and allows for shot-noise limited SRS detection. The performance of the SRS microscope is illustrated with measurements on samples from material science and cell biology.

Label-free super-resolution with coherent nonlinear structured-illumination microscopy

NASA Astrophysics Data System (ADS)

Huttunen, Mikko J.; Abbas, Aazad; Upham, Jeremy; Boyd, Robert W.

2017-08-01

Structured-illumination microscopy enables up to a two-fold lateral resolution improvement by spatially modulating the intensity profile of the illumination beam. We propose a novel way to generalize the concept of structured illumination to nonlinear widefield modalities by spatially modulating, instead of field intensities, the phase of the incident field while interferometrically measuring the complex-valued scattered field. We numerically demonstrate that for second-order and third-order processes an almost four- and six-fold increase in lateral resolution is achievable, respectively. This procedure overcomes the conventional Abbe diffraction limit and provides new possibilities for label-free super-resolution microscopy.

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2010-01-05

... electronic matching algorithm from CBOE Rule 6.45B shall apply to SAL executions (e.g., pro-rata, price-time... entitlement when the pro-rata algorithm is in effect for SAL in selected Hybrid 3.0 classes as part of a pilot... what it would have been under the pre-pilot allocation algorithm. The Exchange will reduce the DPM/LMM...

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

...,000.\\3\\ ETP issuers also pay a graduated Annual Fee based on the number of shares of the ETP that are..., and the ETP therefore trades without an LMM assigned to it. The Exchange operates under the price-time... may be higher for certain ETPs with low volume and low shares outstanding because there are fewer...

The potential effects of climate change on malaria in tropical Africa using regionalised climate projections

NASA Astrophysics Data System (ADS)

Ermert, V.; Fink, A. H.; Paeth, H.; Morse, A. P.

2012-04-01

The projected climate change will probably alter the range and transmission potential of malaria in Africa. The potential impacts of climate change on the malaria distribution is assessed for tropical Africa. Bias-corrected regional climate projections with a horizontal resolution of 0.5° are used from the Regional Model (REMO), which include land use and land cover changes. The malaria models employed are the 2010 version of the Liverpool Malaria Model (LMM2010), the Garki model, the Plasmodium falciparum infection model from Smith et al. (2005) (S2005), and the Malaria Seasonality Model (MSM) from the Mapping Malaria Risk in Africa project. The results of the models are compared with data from the Malaria Atlas Project (MAP) and novel validation procedures for the LMM2010 and MSM lend more credence to their results. For climate scenarios A1B and B1 and for 2001-2050, REMO projects an overall drying and warming trend in the African malaria belt, that is largely imposed by the man-made degradation of vegetation. As a result, the malaria projections show a decreased malaria spread in West Africa. The northern Sahel is no more suitable for malaria in the projections. More unstable malaria transmission and shorter malaria seasons are expected for various areas farther south. An increase in the malaria epidemic risk is found for more densely populated areas in the southern part of the Sahel. In East Africa, higher temperatures and nearly unchanged precipitation patterns lead to longer transmission seasons and an increase in the area of highland malaria. For altitudes up to 2000 m the malaria transmission stabilises and the epidemic risk is reduced but for higher altitudes the risk of malaria epidemics is increased. The results of the more complex and simple malaria models are similar to each other. However, a different response to the warming of highlands is found for the LMM2010 and MSM. This shows the requirement of a multi model uncertainty analysis for the projection of the future malaria spread.

On continuous and discontinuous approaches for modeling groundwater flow in heterogeneous media using the Numerical Manifold Method: Model development and comparison

NASA Astrophysics Data System (ADS)

Hu, Mengsu; Wang, Yuan; Rutqvist, Jonny

2015-06-01

One major challenge in modeling groundwater flow within heterogeneous geological media is that of modeling arbitrarily oriented or intersected boundaries and inner material interfaces. The Numerical Manifold Method (NMM) has recently emerged as a promising method for such modeling, in its ability to handle boundaries, its flexibility in constructing physical cover functions (continuous or with gradient jump), its meshing efficiency with a fixed mathematical mesh (covers), its convenience for enhancing approximation precision, and its integration precision, achieved by simplex integration. In this paper, we report on developing and comparing two new approaches for boundary constraints using the NMM, namely a continuous approach with jump functions and a discontinuous approach with Lagrange multipliers. In the discontinuous Lagrange multiplier method (LMM), the material interfaces are regarded as discontinuities which divide mathematical covers into different physical covers. We define and derive stringent forms of Lagrange multipliers to link the divided physical covers, thus satisfying the continuity requirement of the refraction law. In the continuous Jump Function Method (JFM), the material interfaces are regarded as inner interfaces contained within physical covers. We briefly define jump terms to represent the discontinuity of the head gradient across an interface to satisfy the refraction law. We then make a theoretical comparison between the two approaches in terms of global degrees of freedom, treatment of multiple material interfaces, treatment of small area, treatment of moving interfaces, the feasibility of coupling with mechanical analysis and applicability to other numerical methods. The newly derived boundary-constraint approaches are coded into a NMM model for groundwater flow analysis, and tested for precision and efficiency on different simulation examples. We first test the LMM for a Dirichlet boundary and then test both LMM and JFM for an idealized heterogeneous model, comparing the numerical results with analytical solutions. Then we test both approaches for a heterogeneous model and compare the results of hydraulic head and specific discharge. We show that both approaches are suitable for modeling material boundaries, considering high accuracy for the boundary constraints, the capability to deal with arbitrarily oriented or complexly intersected boundaries, and their efficiency using a fixed mathematical mesh.

A Hypertrophic Cardiomyopathy-associated MYBPC3 Mutation Common in Populations of South Asian Descent Causes Contractile Dysfunction*

PubMed Central

Kuster, Diederik W. D.; Govindan, Suresh; Springer, Tzvia I.; Martin, Jody L.; Finley, Natosha L.; Sadayappan, Sakthivel

2015-01-01

Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). A recently discovered HCM-associated 25-base pair deletion in MYBPC3 is inherited in millions worldwide. Although this mutation causes changes in the C10 domain of cMyBP-C (cMyBP-CC10mut), which binds to the light meromyosin (LMM) region of the myosin heavy chain, the underlying molecular mechanism causing HCM is unknown. In this study, adenoviral expression of cMyBP-CC10mut in cultured adult rat cardiomyocytes was used to investigate protein localization and evaluate contractile function and Ca2+ transients, compared with wild-type cMyBP-C expression (cMyBP-CWT) and controls. Forty-eight hours after infection, 44% of cMyBP-CWT and 36% of cMyBP-CC10mut protein levels were determined in total lysates, confirming equal expression. Immunofluorescence experiments showed little or no localization of cMyBP-CC10mut to the C-zone, whereas cMyBP-CWT mostly showed C-zone staining, suggesting that cMyBP-CC10mut could not properly integrate in the C-zone of the sarcomere. Subcellular fractionation confirmed that most cMyBP-CC10mut resided in the soluble fraction, with reduced presence in the myofilament fraction. Also, cMyBP-CC10mut displayed significantly reduced fractional shortening, sarcomere shortening, and relaxation velocities, apparently caused by defects in sarcomere function, because Ca2+ transients were unaffected. Co-sedimentation and protein cross-linking assays confirmed that C10mut causes the loss of C10 domain interaction with myosin LMM. Protein homology modeling studies showed significant structural perturbation in cMyBP-CC10mut, providing a potential structural basis for the alteration in its mode of interaction with myosin LMM. Therefore, expression of cMyBP-CC10mut protein is sufficient to cause contractile dysfunction in vitro. PMID:25583989

Collective Modes and Structural Modulation in Ni-Mn-Ga(Co) Martensite Thin Films Probed by Femtosecond Spectroscopy and Scanning Tunneling Microscopy.

PubMed

Schubert, M; Schaefer, H; Mayer, J; Laptev, A; Hettich, M; Merklein, M; He, C; Rummel, C; Ristow, O; Großmann, M; Luo, Y; Gusev, V; Samwer, K; Fonin, M; Dekorsy, T; Demsar, J

2015-08-14

The origin of the martensitic transition in the magnetic shape memory alloy Ni-Mn-Ga has been widely discussed. While several studies suggest it is electronically driven, the adaptive martensite model reproduced the peculiar nonharmonic lattice modulation. We used femtosecond spectroscopy to probe the temperature and doping dependence of collective modes, and scanning tunneling microscopy revealed the corresponding static modulations. We show that the martensitic phase can be described by a complex charge-density wave tuned by magnetic ordering and strong electron-lattice coupling.

Collective Modes and Structural Modulation in Ni-Mn-Ga(Co) Martensite Thin Films Probed by Femtosecond Spectroscopy and Scanning Tunneling Microscopy

NASA Astrophysics Data System (ADS)

Schubert, M.; Schaefer, H.; Mayer, J.; Laptev, A.; Hettich, M.; Merklein, M.; He, C.; Rummel, C.; Ristow, O.; Großmann, M.; Luo, Y.; Gusev, V.; Samwer, K.; Fonin, M.; Dekorsy, T.; Demsar, J.

2015-08-01

The origin of the martensitic transition in the magnetic shape memory alloy Ni-Mn-Ga has been widely discussed. While several studies suggest it is electronically driven, the adaptive martensite model reproduced the peculiar nonharmonic lattice modulation. We used femtosecond spectroscopy to probe the temperature and doping dependence of collective modes, and scanning tunneling microscopy revealed the corresponding static modulations. We show that the martensitic phase can be described by a complex charge-density wave tuned by magnetic ordering and strong electron-lattice coupling.

The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles.

PubMed

Lässer, Cecilia; Théry, Clotilde; Buzás, Edit I; Mathivanan, Suresh; Zhao, Weian; Gho, Yong Song; Lötvall, Jan

2016-01-01

The International Society for Extracellular Vesicles (ISEV) has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs). This course, "Basics of Extracellular Vesicles," uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field covering the nomenclature and history of EVs. Module 2 focuses on the biogenesis and uptake mechanisms of EVs, as well as their RNA, protein and lipid cargo. Module 3 covers the collection and processing of cell culture media and body fluids such as blood, breast milk, cerebrospinal fluid and urine prior to isolation of EVs. Modules 4 and 5 present different isolation methods and characterisation techniques utilised in the EV field. Here, differential ultracentrifugation, size-exclusion chromatography, density gradient centrifugation, kit-based precipitation, electron microscopy, cryo-electron microscopy, flow cytometry, atomic-force microscopy and nanoparticle-tracking analysis are covered. This first massive open online course (MOOC) on EVs was launched on 15 August 2016 at the platform "Coursera" and is free of charge.

Drive-amplitude-modulation atomic force microscopy: From vacuum to liquids

PubMed Central

Jaafar, Miriam; Cuenca, Mariano; Melcher, John; Raman, Arvind

2012-01-01

Summary We introduce drive-amplitude-modulation atomic force microscopy as a dynamic mode with outstanding performance in all environments from vacuum to liquids. As with frequency modulation, the new mode follows a feedback scheme with two nested loops: The first keeps the cantilever oscillation amplitude constant by regulating the driving force, and the second uses the driving force as the feedback variable for topography. Additionally, a phase-locked loop can be used as a parallel feedback allowing separation of the conservative and nonconservative interactions. We describe the basis of this mode and present some examples of its performance in three different environments. Drive-amplutide modulation is a very stable, intuitive and easy to use mode that is free of the feedback instability associated with the noncontact-to-contact transition that occurs in the frequency-modulation mode. PMID:22563531

Implementation of spatial overlap modulation nonlinear optical microscopy using an electro-optic deflector

PubMed Central

Isobe, Keisuke; Kawano, Hiroyuki; Kumagai, Akiko; Miyawaki, Atsushi; Midorikawa, Katsumi

2013-01-01

A spatial overlap modulation (SPOM) technique is a nonlinear optical microscopy technique which enhances the three-dimensional spatial resolution and rejects the out-of-focus background limiting the imaging depth inside a highly scattering sample. Here, we report on the implementation of SPOM in which beam pointing modulation is achieved by an electro-optic deflector. The modulation and demodulation frequencies are enhanced to 200 kHz and 400 kHz, respectively, resulting in a 200-fold enhancement compared with the previously reported system. The resolution enhancement and suppression of the out-of-focus background are demonstrated by sum-frequency-generation imaging of pounded granulated sugar and deep imaging of fluorescent beads in a tissue-like phantom, respectively. PMID:24156055

Advanced SLMs for microscopy

NASA Astrophysics Data System (ADS)

Linnenberger, A.

2018-02-01

Wavefront shaping devices such as deformable mirrors, liquid crystal spatial light modulators (SLMs), and active lenses are of considerable interest in microscopy for aberration correction, volumetric imaging, and programmable excitation. Liquid crystal SLMs are high resolution phase modulators capable of creating complex phase profiles to reshape, or redirect light within a three-dimensional (3D) volume. Recent advances in Meadowlark Optics (MLO) SLMs reduce losses by increasing fill factor from 83.4% to 96%, and improving resolution from 512 x 512 pixels to 1920 x 1152 pixels while maintaining a liquid crystal response time of 300 Hz at 1064 nm. This paper summarizes new SLM capabilities, and benefits for microscopy.

Correcting for population structure and kinship using the linear mixed model: theory and extensions.

PubMed

Hoffman, Gabriel E

2013-01-01

Population structure and kinship are widespread confounding factors in genome-wide association studies (GWAS). It has been standard practice to include principal components of the genotypes in a regression model in order to account for population structure. More recently, the linear mixed model (LMM) has emerged as a powerful method for simultaneously accounting for population structure and kinship. The statistical theory underlying the differences in empirical performance between modeling principal components as fixed versus random effects has not been thoroughly examined. We undertake an analysis to formalize the relationship between these widely used methods and elucidate the statistical properties of each. Moreover, we introduce a new statistic, effective degrees of freedom, that serves as a metric of model complexity and a novel low rank linear mixed model (LRLMM) to learn the dimensionality of the correction for population structure and kinship, and we assess its performance through simulations. A comparison of the results of LRLMM and a standard LMM analysis applied to GWAS data from the Multi-Ethnic Study of Atherosclerosis (MESA) illustrates how our theoretical results translate into empirical properties of the mixed model. Finally, the analysis demonstrates the ability of the LRLMM to substantially boost the strength of an association for HDL cholesterol in Europeans.

Optimal allocation of resources for suppressing epidemic spreading on networks

NASA Astrophysics Data System (ADS)

Chen, Hanshuang; Li, Guofeng; Zhang, Haifeng; Hou, Zhonghuai

2017-07-01

Efficient allocation of limited medical resources is crucial for controlling epidemic spreading on networks. Based on the susceptible-infected-susceptible model, we solve the optimization problem of how best to allocate the limited resources so as to minimize prevalence, providing that the curing rate of each node is positively correlated to its medical resource. By quenched mean-field theory and heterogeneous mean-field (HMF) theory, we prove that an epidemic outbreak will be suppressed to the greatest extent if the curing rate of each node is directly proportional to its degree, under which the effective infection rate λ has a maximal threshold λcopt=1 / , where is the average degree of the underlying network. For a weak infection region (λ ≳λcopt ), we combine perturbation theory with the Lagrange multiplier method (LMM) to derive the analytical expression of optimal allocation of the curing rates and the corresponding minimized prevalence. For a general infection region (λ >λcopt ), the high-dimensional optimization problem is converted into numerically solving low-dimensional nonlinear equations by the HMF theory and LMM. Counterintuitively, in the strong infection region the low-degree nodes should be allocated more medical resources than the high-degree nodes to minimize prevalence. Finally, we use simulated annealing to validate the theoretical results.

Marginal and Random Intercepts Models for Longitudinal Binary Data With Examples From Criminology.

PubMed

Long, Jeffrey D; Loeber, Rolf; Farrington, David P

2009-01-01

Two models for the analysis of longitudinal binary data are discussed: the marginal model and the random intercepts model. In contrast to the linear mixed model (LMM), the two models for binary data are not subsumed under a single hierarchical model. The marginal model provides group-level information whereas the random intercepts model provides individual-level information including information about heterogeneity of growth. It is shown how a type of numerical averaging can be used with the random intercepts model to obtain group-level information, thus approximating individual and marginal aspects of the LMM. The types of inferences associated with each model are illustrated with longitudinal criminal offending data based on N = 506 males followed over a 22-year period. Violent offending indexed by official records and self-report were analyzed, with the marginal model estimated using generalized estimating equations and the random intercepts model estimated using maximum likelihood. The results show that the numerical averaging based on the random intercepts can produce prediction curves almost identical to those obtained directly from the marginal model parameter estimates. The results provide a basis for contrasting the models and the estimation procedures and key features are discussed to aid in selecting a method for empirical analysis.

Testing a Low Molecular Mass Fraction of a Mushroom (Lentinus edodes) Extract Formulated as an Oral Rinse in a Cohort of Volunteers

PubMed Central

Signoretto, Caterina; Burlacchini, Gloria; Marchi, Anna; Grillenzoni, Marcello; Cavalleri, Giacomo; Ciric, Lena; Lingström, Peter; Pezzati, Elisabetta; Daglia, Maria; Zaura, Egija; Pratten, Jonathan; Spratt, David A.; Wilson, Michael; Canepari, Pietro

2011-01-01

Although foods are considered enhancing factors for dental caries and periodontitis, laboratory researches indicate that several foods and beverages contain components endowed with antimicrobial and antiplaque activities. A low molecular mass (LMM) fraction of an aqueous mushroom extract has been found to exert these activities in in vitro experiments against potential oral pathogens. We therefore conducted a clinical trial in which we tested an LMM fraction of shiitake mushroom extract formulated in a mouthrinse in 30 young volunteers, comparing the results with those obtained in two identical cohorts, one of which received water (placebo) and the other Listerine. Plaque index, gingival index and bacterial counts in plaque samples were determined in all volunteers over the 11 days of the clinical trial. Statistically significant differences (P < 0.05) were obtained for the plaque index on day 12 in subjects treated with mushroom versus placebo, while for the gingival index significant differences were found for both mushroom versus placebo and mushroom versus Listerine. Decreases in total bacterial counts and in counts of specific oral pathogens were observed for both mushroom extract and Listerine in comparison with placebo. The data suggest that a mushroom extract may prove beneficial in controlling dental caries and/or gingivitis/periodontitis. PMID:21912481

Simultaneous multicolor imaging of wide-field epi-fluorescence microscopy with four-bucket detection

PubMed Central

Park, Kwan Seob; Kim, Dong Uk; Lee, Jooran; Kim, Geon Hee; Chang, Ki Soo

2016-01-01

We demonstrate simultaneous imaging of multiple fluorophores using wide-field epi-fluorescence microscopy with a monochrome camera. The intensities of the three lasers are modulated by a sinusoidal waveform in order to excite each fluorophore with the same modulation frequency and a different time-delay. Then, the modulated fluorescence emissions are simultaneously detected by a camera operating at four times the excitation frequency. We show that two different fluorescence beads having crosstalk can be clearly separated using digital processing based on the phase information. In addition, multiple organelles within multi-stained single cells are shown with the phase mapping method, demonstrating an improved dynamic range and contrast compared to the conventional fluorescence image. These findings suggest that wide-field epi-fluorescence microscopy with four-bucket detection could be utilized for high-contrast multicolor imaging applications such as drug delivery and fluorescence in situ hybridization. PMID:27375944

Improvement of axial excitation confinement in temporal focusing-based multiphoton microscopy via spatially modulated illumination

NASA Astrophysics Data System (ADS)

Chang, Chia-Yuan; Chen, Shean-Jen

2017-02-01

Conventional temporal focusing-based multiphoton excitation microscopy (TFMPEM) can offer widefield optical sectioning with an axial excitation confinement (AEC) of a few microns. Herein, a developed TFMPEM with a digital micromirror device (DMD), acting as the blazed grating for light spatial dispersion and simultaneous patterned illumination, has been extended to implement spatially modulated illumination at structured frequency and orientation. By implementing the spatially modulated illumination, the beam coverage at the back-focal aperture of the objective lens can be increased. As a result, the AEC can be condensed from 3.0 μm to 1.5 μm in full width at half maximum for a 2-fold enhancement. Furthermore, by using HiLo microscopy with two structured illuminations at the same spatial frequency but different orientation, biotissue images according to the structured illumination with condensed AEC is obviously superior in contrast and scattering suppression.

Systems and methods for selective detection and imaging in coherent Raman microscopy by spectral excitation shaping

DOEpatents

Xie, Xiaoliang Sunney; Freudiger, Christian; Min, Wei

2016-03-15

A microscopy imaging system is disclosed that includes a light source system, a spectral shaper, a modulator system, an optics system, an optical detector and a processor. The light source system is for providing a first train of pulses and a second train of pulses. The spectral shaper is for spectrally modifying an optical property of at least some frequency components of the broadband range of frequency components such that the broadband range of frequency components is shaped producing a shaped first train of pulses to specifically probe a spectral feature of interest from a sample, and to reduce information from features that are not of interest from the sample. The modulator system is for modulating a property of at least one of the shaped first train of pulses and the second train of pulses at a modulation frequency. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of a train of pulses of interest transmitted or reflected through the common focal volume. The processor is for detecting a modulation at the modulation frequency of the integrated intensity of substantially all of the optical frequency components of the train of pulses of interest due to the non-linear interaction of the shaped first train of pulses with the second train of pulses as modulated in the common focal volume, and for providing an output signal for a pixel of an image for the microscopy imaging system.

Thermal Images of Seeds Obtained at Different Depths by Photoacoustic Microscopy (PAM)

NASA Astrophysics Data System (ADS)

Domínguez-Pacheco, A.; Hernández-Aguilar, C.; Cruz-Orea, A.

2015-06-01

The objective of the present study was to obtain thermal images of a broccoli seed ( Brassica oleracea) by photoacoustic microscopy, at different modulation frequencies of the incident light beam ((0.5, 1, 5, and 20) Hz). The thermal images obtained in the amplitude of the photoacoustic signal vary with each applied frequency. In the lowest light frequency modulation, there is greater thermal wave penetration in the sample. Likewise, the photoacoustic signal is modified according to the structural characteristics of the sample and the modulation frequency of the incident light. Different structural components could be seen by photothermal techniques, as shown in the present study.

Traveling interface modulations and anisotropic front propagation in ammonia oxidation over Rh(110)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rafti, Matías; Institut für Physikalische Chemie und Elektrochemie, Leibniz-Universität Hannover, Callinstr. 3-3a, D-30167 Hannover; Borkenhagen, Benjamin

The bistable NH{sub 3} + O{sub 2} reaction over a Rh(110) surface was explored in the pressure range 10{sup −6}–10{sup −3} mbar and in the temperature range 300–900 K using photoemission electron microscopy and low energy electron microscopy as spatially resolving methods. We observed a history dependent anisotropy in front propagation, traveling interface modulations, transitions with secondary reaction fronts, and stationary island structures.

Interpretation of frequency modulation atomic force microscopy in terms of fractional calculus

NASA Astrophysics Data System (ADS)

Sader, John E.; Jarvis, Suzanne P.

2004-07-01

It is widely recognized that small amplitude frequency modulation atomic force microscopy probes the derivative of the interaction force between tip and sample. For large amplitudes, however, such a physical connection is currently lacking, although it has been observed that the frequency shift presents a quantity intermediate to the interaction force and energy for certain force laws. Here we prove that these observations are a universal property of large amplitude frequency modulation atomic force microscopy, by establishing that the frequency shift is proportional to the half-fractional integral of the force, regardless of the force law. This finding indicates that frequency modulation atomic force microscopy can be interpreted as a fractional differential operator, where the order of the derivative/integral is dictated by the oscillation amplitude. We also establish that the measured frequency shift varies systematically from a probe of the force gradient for small oscillation amplitudes, through to the measurement of a quantity intermediate to the force and energy (the half-fractional integral of the force) for large oscillation amplitudes. This has significant implications to measurement sensitivity, since integrating the force will smooth its behavior, while differentiating it will enhance variations. This highlights the importance in choice of oscillation amplitude when wishing to optimize the sensitivity of force spectroscopy measurements to short-range interactions and consequently imaging with the highest possible resolution.

The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles

PubMed Central

Lässer, Cecilia; Théry, Clotilde; Buzás, Edit I.; Mathivanan, Suresh; Zhao, Weian; Gho, Yong Song; Lötvall, Jan

2016-01-01

The International Society for Extracellular Vesicles (ISEV) has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs). This course, “Basics of Extracellular Vesicles,” uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field covering the nomenclature and history of EVs. Module 2 focuses on the biogenesis and uptake mechanisms of EVs, as well as their RNA, protein and lipid cargo. Module 3 covers the collection and processing of cell culture media and body fluids such as blood, breast milk, cerebrospinal fluid and urine prior to isolation of EVs. Modules 4 and 5 present different isolation methods and characterisation techniques utilised in the EV field. Here, differential ultracentrifugation, size-exclusion chromatography, density gradient centrifugation, kit-based precipitation, electron microscopy, cryo-electron microscopy, flow cytometry, atomic-force microscopy and nanoparticle-tracking analysis are covered. This first massive open online course (MOOC) on EVs was launched on 15 August 2016 at the platform “Coursera” and is free of charge. PMID:27989272

Comparison of Cornea Module and DermaInspect for noninvasive imaging of ocular surface pathologies

NASA Astrophysics Data System (ADS)

Steven, Philipp; Müller, Maya; Koop, Norbert; Rose, Christian; Hüttmann, Gereon

2009-11-01

Minimally invasive imaging of ocular surface pathologies aims at securing clinical diagnosis without actual tissue probing. For this matter, confocal microscopy (Cornea Module) is in daily use in ophthalmic practice. Multiphoton microscopy is a new optical technique that enables high-resolution imaging and functional analysis of living tissues based on tissue autofluorescence. This study was set up to compare the potential of a multiphoton microscope (DermaInspect) to the Cornea Module. Ocular surface pathologies such as pterygia, papillomae, and nevi were investigated in vivo using the Cornea Module and imaged immediately after excision by DermaInspect. Two excitation wavelengths, fluorescence lifetime imaging and second-harmonic generation (SHG), were used to discriminate different tissue structures. Images were compared with the histopathological assessment of the samples. At wavelengths of 730 nm, multiphoton microscopy exclusively revealed cellular structures. Collagen fibrils were specifically demonstrated by second-harmonic generation. Measurements of fluorescent lifetimes enabled the highly specific detection of goblet cells, erythrocytes, and nevus-cell clusters. At the settings used, DermaInspect reaches higher resolutions than the Cornea Module and obtains additional structural information. The parallel detection of multiphoton excited autofluorescence and confocal imaging could expand the possibilities of minimally invasive investigation of the ocular surface toward functional analysis at higher resolutions.

Marshburn configures FIR/LMM ACE hardware, in the U.S. Laboratory

NASA Image and Video Library

2013-02-21

ISS034-E-051798 (21 Feb. 2013) --- NASA astronaut Tom Marshburn, Expedition 34 flight engineer, configures one of the experiment racks in the U.S. lab called Destiny aboard the International Space Station in Earth orbit. ACE produces microscopic images of materials which contain small colloidal particles, and it examines flow characteristics and the evolution and ordering effects within these colloidal materials in 1-G and micro-G environments.

Excimer Laser Research

DTIC Science & Technology

1976-10-01

X> X ^^ X X E o lmm X X X X X > J Ä2 NX x xs 10 n N(P) X...to the cell through a stainless steel valve. The crystals and sample cylinder were repeatedly allowed to outgas at room temperature (under vacuum... 350 (1975). 3. J.J. Ewing and C.A. Brau, Appl. Phys. Lett. 27, 557(1975). 4. J.J. Ewing and C.A. Brau, Phys. Rev. A12, 129(1975). 5

Slotted Waveguide and Antenna Study for HPM and RF Applications

DTIC Science & Technology

2017-07-25

parallel metal plates separated by lmm, depending on the particular characteristics of the case (waveguide dimensions, SEY (secondary e lectron yield...waveguide antenna, shown in Figure 23, was studied . A new feed ing network based on a composite right-hand/left-hand (CRLH) waveguide structure was...approach is based on the assumption that the external coupling between the array elements is negligible, which is acceptable in the case of the

Atomic force microscopy reveals the mechanical design of a modular protein

PubMed Central

Li, Hongbin; Oberhauser, Andres F.; Fowler, Susan B.; Clarke, Jane; Fernandez, Julio M.

2000-01-01

Tandem modular proteins underlie the elasticity of natural adhesives, cell adhesion proteins, and muscle proteins. The fundamental unit of elastic proteins is their individually folded modules. Here, we use protein engineering to construct multimodular proteins composed of Ig modules of different mechanical strength. We examine the mechanical properties of the resulting tandem modular proteins by using single protein atomic force microscopy. We show that by combining modules of known mechanical strength, we can generate proteins with novel elastic properties. Our experiments reveal the simple mechanical design of modular proteins and open the way for the engineering of elastic proteins with defined mechanical properties, which can be used in tissue and fiber engineering. PMID:10823913

Atomic force microscopy reveals the mechanical design of a modular protein.

PubMed

Li, H; Oberhauser, A F; Fowler, S B; Clarke, J; Fernandez, J M

2000-06-06

Tandem modular proteins underlie the elasticity of natural adhesives, cell adhesion proteins, and muscle proteins. The fundamental unit of elastic proteins is their individually folded modules. Here, we use protein engineering to construct multimodular proteins composed of Ig modules of different mechanical strength. We examine the mechanical properties of the resulting tandem modular proteins by using single protein atomic force microscopy. We show that by combining modules of known mechanical strength, we can generate proteins with novel elastic properties. Our experiments reveal the simple mechanical design of modular proteins and open the way for the engineering of elastic proteins with defined mechanical properties, which can be used in tissue and fiber engineering.

Maintenance on the Advanced Colloids Experiment Module

NASA Image and Video Library

2018-04-16

iss055e035366 (April 16, 2018) --- NASA astronaut Ricky Arnold performs maintenance on the Advanced Colloids Experiment Module located inside the Light Microscopy Module which is a modified commercial, highly flexible, state-of-the-art light imaging microscope facility that provides researchers with powerful diagnostic hardware and software in microgravity.

Magnetic force microscopy with frequency-modulated capacitive tip-sample distance control

NASA Astrophysics Data System (ADS)

Zhao, X.; Schwenk, J.; Mandru, A. O.; Penedo, M.; Baćani, M.; Marioni, M. A.; Hug, H. J.

2018-01-01

In a step towards routinely achieving 10 nm spatial resolution with magnetic force microscopy, we have developed a robust method for active tip-sample distance control based on frequency modulation of the cantilever oscillation. It allows us to keep a well-defined tip-sample distance of the order of 10 nm within better than +/- 0.4 nm precision throughout the measurement even in the presence of energy dissipative processes, and is adequate for single-passage non-contact operation in vacuum. The cantilever is excited mechanically in a phase-locked loop to oscillate at constant amplitude on its first flexural resonance mode. This frequency is modulated by an electrostatic force gradient generated by tip-sample bias oscillating from a few hundred Hz up to a few kHz. The sum of the side bands’ amplitudes is a proxy for the tip-sample distance and can be used for tip-sample distance control. This method can also be extended to other scanning probe microscopy techniques.

Carrier Density Modulation in Ge Heterostructure by Ferroelectric Switching

DOE PAGES

Ponath, Patrick; Fredrickson, Kurt; Posadas, Agham B.; ...

2015-01-14

The development of nonvolatile logic through direct coupling of spontaneous ferroelectric polarization with semiconductor charge carriers is nontrivial, with many issues, including epitaxial ferroelectric growth, demonstration of ferroelectric switching, and measurable semiconductor modulation. Here we report a true ferroelectric field effect carrier density modulation in an underlying Ge(001) substrate by switching of the ferroelectric polarization in the epitaxial c-axis-oriented BaTiO3 (BTO) grown by molecular beam epitaxy (MBE) on Ge. Using density functional theory, we demonstrate that switching of BTO polarization results in a large electric potential change in Ge. Aberration-corrected electron microscopy confirms the interface sharpness, and BTO tetragonality. Electron-energy-lossmore » spectroscopy (EELS) indicates the absence of any low permittivity interlayer at the interface with Ge. Using piezoelectric force microscopy (PFM), we confirm the presence of fully switchable, stable ferroelectric polarization in BTO that appears to be single domain. Using microwave impedance microscopy (MIM), we clearly demonstrate a ferroelectric field effect.« less

Image restoration approach to address reduced modulation contrast in structured illumination microscopy

PubMed Central

Patwary, Nurmohammed; Doblas, Ana; Preza, Chrysanthe

2018-01-01

The performance of structured illumination microscopy (SIM) is hampered in many biological applications due to the inability to modulate the light when imaging deep into the sample. This is in part because sample-induced aberration reduces the modulation contrast of the structured pattern. In this paper, we present an image restoration approach suitable for processing raw incoherent-grid-projection SIM data with a low fringe contrast. Restoration results from simulated and experimental ApoTome SIM data show results with improved signal-to-noise ratio (SNR) and optical sectioning compared to the results obtained from existing methods, such as 2D demodulation and 3D SIM deconvolution. Our proposed method provides satisfactory results (quantified by the achieved SNR and normalized mean square error) even when the modulation contrast of the illumination pattern is as low as 7%. PMID:29675307

Comprehensive study of unexpected microscope condensers formed in sample arrangements commonly used in optical microscopy.

PubMed

Desai, Darshan B; Aldawsari, Mabkhoot Mudith S; Alharbi, Bandar Mohammed H; Sen, Sanchari; Grave de Peralta, Luis

2015-09-01

We show that various setups for optical microscopy which are commonly used in biomedical laboratories behave like efficient microscope condensers that are responsible for observed subwavelength resolution. We present a series of experiments and simulations that reveal how inclined illumination from such unexpected condensers occurs when the sample is perpendicularly illuminated by a microscope's built-in white-light source. In addition, we demonstrate an inexpensive add-on optical module that serves as an efficient and lightweight microscope condenser. Using such add-on optical module in combination with a low-numerical-aperture objective lens and Fourier plane imaging microscopy technique, we demonstrate detection of photonic crystals with a period nearly eight times smaller than the Rayleigh resolution limit.

Auger electron diffraction study of the initial stage of Ge heteroepitaxy on Si(001)

NASA Astrophysics Data System (ADS)

Sasaki, M.; Abukawa, T.; Yeom, H. W.; Yamada, M.; Suzuki, S.; Sato, S.; Kono, S.

1994-12-01

The initial stage of pure and surfactant (Sb)-assisted Ge growth on a Si(001) surface has been studied by Auger electron diffraction (AED) and X-ray photoelectron diffraction (XPD). A single-domain Si(001)2 × 1 substrate was used to avoid the ambiguity arising from the usual double-domain substrate. For the pure Ge growth, 1 monolayer of Ge was deposited onto the room temperature substrate followed by annealing at 350°C-600°C, which appeared to have (1 × 2) periodicity by LEED. Ge LMM AED patterns were measured to find that a substantial amount of Ge atoms diffuse to the bulk Si positions up to the fourth layer at least. For the Sb-assisted Ge growth, a Sb(1 × 2)/Si(001) surface was first prepared and Sb 3d XPD patterns were measured to find that Sb forms dimers on the substrate. 1 ML of Ge was deposited onto the Sb(1 × 2)/Si(001) surface and then the surface was annealed at 600°C. Ge LMM AED and Sb 3d XPD patterns measured for this surface showed that surfactant Sb atoms are indeed present on the first layer forming dimers and that Ge atoms are present mainly on the second layer with a substantial amount of Ge diffused into the third and fourth layers.

Hybrid region merging method for segmentation of high-resolution remote sensing images

NASA Astrophysics Data System (ADS)

Zhang, Xueliang; Xiao, Pengfeng; Feng, Xuezhi; Wang, Jiangeng; Wang, Zuo

2014-12-01

Image segmentation remains a challenging problem for object-based image analysis. In this paper, a hybrid region merging (HRM) method is proposed to segment high-resolution remote sensing images. HRM integrates the advantages of global-oriented and local-oriented region merging strategies into a unified framework. The globally most-similar pair of regions is used to determine the starting point of a growing region, which provides an elegant way to avoid the problem of starting point assignment and to enhance the optimization ability for local-oriented region merging. During the region growing procedure, the merging iterations are constrained within the local vicinity, so that the segmentation is accelerated and can reflect the local context, as compared with the global-oriented method. A set of high-resolution remote sensing images is used to test the effectiveness of the HRM method, and three region-based remote sensing image segmentation methods are adopted for comparison, including the hierarchical stepwise optimization (HSWO) method, the local-mutual best region merging (LMM) method, and the multiresolution segmentation (MRS) method embedded in eCognition Developer software. Both the supervised evaluation and visual assessment show that HRM performs better than HSWO and LMM by combining both their advantages. The segmentation results of HRM and MRS are visually comparable, but HRM can describe objects as single regions better than MRS, and the supervised and unsupervised evaluation results further prove the superiority of HRM.

DURIP: Super-Resolution Module for Confocal Microscopy of Reconfigurable Matter

DTIC Science & Technology

2014-09-28

Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 superresolution microscopy, colloidal particles, self-assembly REPORT...previously have been resolved by optical microscopy. Results of Super Resolution Technique Evaluation Commercially available superresolution imaging...Weaknesses of the method are that is fundamentally a measurement that can only be deployed for fixed samples. Because superresolution is obtained by

On-axis programmable microscope using liquid crystal spatial light modulator

NASA Astrophysics Data System (ADS)

García-Martínez, Pascuala; Martínez, José Luís.; Moreno, Ignacio

2017-06-01

Spatial light modulators (SLM) are currently used in many applications in optical microscopy and imaging. One of the most promising methods is the use of liquid crystal displays (LCD) as programmable phase diffractive optical elements (DOE) placed in the Fourier plane giving access to the spatial frequencies which can be phased shifted individually, allowing to emulate a wealth of contrast enhancing methods for both amplitude and phase samples. We use phase and polarization modulation of LCD to implement an on-axis microscope optical system. The LCD used are Hamamatsu liquid crystal on silicon (LCOS) SLM free of flicker, thus showing a full profit of the SLM space bandwidth, as opposed to optical systems in the literature forced to work off-axis due to the strong zero-order component. Taking benefits of the phase modulation of the LCOS we have implemented different microscopic imaging operations, such as high-pass and low-pass filtering in parallel using programmable blazed gratings. Moreover, we are able to control polarization modulation to display two orthogonal linear state of polarization images than can be subtracted or added by changing the period of the blazed grating. In that sense, Differential Interference Contrast (DIC) microscopy can be easily done by generating two images exploiting the polarization splitting properties when a blazed grating is displayed in the SLM. Biological microscopy samples are also used.

Synchronous-digitization for Video Rate Polarization Modulated Beam Scanning Second Harmonic Generation Microscopy.

PubMed

Sullivan, Shane Z; DeWalt, Emma L; Schmitt, Paul D; Muir, Ryan M; Simpson, Garth J

2015-03-09

Fast beam-scanning non-linear optical microscopy, coupled with fast (8 MHz) polarization modulation and analytical modeling have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and linear Stokes ellipsometry imaging at video rate (15 Hz). NOSE enables recovery of the complex-valued Jones tensor that describes the polarization-dependent observables, in contrast to polarimetry, in which the polarization stated of the exciting beam is recorded. Each data acquisition consists of 30 images (10 for each detector, with three detectors operating in parallel), each of which corresponds to polarization-dependent results. Processing of this image set by linear fitting contracts down each set of 10 images to a set of 5 parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the fundamental laser beam. Using these parameters, it is possible to recover the Jones tensor elements of the sample at video rate. Video rate imaging is enabled by performing synchronous digitization (SD), in which a PCIe digital oscilloscope card is synchronized to the laser (the laser is the master clock.) Fast polarization modulation was achieved by modulating an electro-optic modulator synchronously with the laser and digitizer, with a simple sine-wave at 1/10th the period of the laser, producing a repeating pattern of 10 polarization states. This approach was validated using Z-cut quartz, and NOSE microscopy was performed for micro-crystals of naproxen.

Synchronous-digitization for video rate polarization modulated beam scanning second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Sullivan, Shane Z.; DeWalt, Emma L.; Schmitt, Paul D.; Muir, Ryan D.; Simpson, Garth J.

2015-03-01

Fast beam-scanning non-linear optical microscopy, coupled with fast (8 MHz) polarization modulation and analytical modeling have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and linear Stokes ellipsometry imaging at video rate (15 Hz). NOSE enables recovery of the complex-valued Jones tensor that describes the polarization-dependent observables, in contrast to polarimetry, in which the polarization stated of the exciting beam is recorded. Each data acquisition consists of 30 images (10 for each detector, with three detectors operating in parallel), each of which corresponds to polarization-dependent results. Processing of this image set by linear fitting contracts down each set of 10 images to a set of 5 parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the fundamental laser beam. Using these parameters, it is possible to recover the Jones tensor elements of the sample at video rate. Video rate imaging is enabled by performing synchronous digitization (SD), in which a PCIe digital oscilloscope card is synchronized to the laser (the laser is the master clock.) Fast polarization modulation was achieved by modulating an electro-optic modulator synchronously with the laser and digitizer, with a simple sine-wave at 1/10th the period of the laser, producing a repeating pattern of 10 polarization states. This approach was validated using Z-cut quartz, and NOSE microscopy was performed for micro-crystals of naproxen.

Parametric Amplification Protocol for Frequency-Modulated Magnetic Resonance Force Microscopy Signals

NASA Astrophysics Data System (ADS)

Harrell, Lee; Moore, Eric; Lee, Sanggap; Hickman, Steven; Marohn, John

2011-03-01

We present data and theoretical signal and noise calculations for a protocol using parametric amplification to evade the inherent tradeoff between signal and detector frequency noise in force-gradient magnetic resonance force microscopy signals, which are manifested as a modulated frequency shift of a high- Q microcantilever. Substrate-induced frequency noise has a 1 / f frequency dependence, while detector noise exhibits an f2 dependence on modulation frequency f . Modulation of sample spins at a frequency that minimizes these two contributions typically results in a surface frequency noise power an order of magnitude or more above the thermal limit and may prove incompatible with sample spin relaxation times as well. We show that the frequency modulated force-gradient signal can be used to excite the fundamental resonant mode of the cantilever, resulting in an audio frequency amplitude signal that is readily detected with a low-noise fiber optic interferometer. This technique allows us to modulate the force-gradient signal at a sufficiently high frequency so that substrate-induced frequency noise is evaded without subjecting the signal to the normal f2 detector noise of conventional demodulation.

Two-dimensional profiling of carriers in terahertz quantum cascade lasers using calibrated scanning spreading resistance microscopy and scanning capacitance microscopy.

PubMed

Dhar, R S; Ban, D

2013-07-01

The distribution of charge carriers inside the active region of a terahertz (THz) quantum cascade laser (QCL) has been measured with scanning spreading resistance microscopy (SSRM) and scanning capacitance microscopy (SCM). Individual quantum well-barrier modules with a 35.7-nm single module thickness in the active region of the device have been resolved for the first time using high-resolution SSRM and SCM techniques at room temperature. SSRM and SCM measurements on the quantum well-barrier structure were calibrated utilizing known GaAs dopant staircase samples. Doping concentrations derived from SSRM and SCM measurements were found to be in quantitative agreement with the designed average doping values of the n-type active region in the terahertz quantum cascade laser. The secondary ion mass spectroscopy provides a partial picture of internal device parameters, and we have demonstrated with our results the efficacy of uniting calibrated SSRM and SCM to delineate quantitatively the transverse cross-sectional structure of complex two-dimensional terahertz quantum cascade laser devices. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Combined frequency modulated atomic force microscopy and scanning tunneling microscopy detection for multi-tip scanning probe microscopy applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morawski, Ireneusz; Institute of Experimental Physics, University of Wrocław, pl. M. Borna 9, 50-204 Wrocław; Spiegelberg, Richard

A method which allows scanning tunneling microscopy (STM) tip biasing independent of the sample bias during frequency modulated atomic force microscopy (AFM) operation is presented. The AFM sensor is supplied by an electronic circuit combining both a frequency shift signal and a tunneling current signal by means of an inductive coupling. This solution enables a control of the tip potential independent of the sample potential. Individual tip biasing is specifically important in order to implement multi-tip STM/AFM applications. An extensional quartz sensor (needle sensor) with a conductive tip is applied to record simultaneously topography and conductivity of the sample. Themore » high resonance frequency of the needle sensor (1 MHz) allows scanning of a large area of the surface being investigated in a reasonably short time. A recipe for the amplitude calibration which is based only on the frequency shift signal and does not require the tip being in contact is presented. Additionally, we show spectral measurements of the mechanical vibration noise of the scanning system used in the investigations.« less

Direct Imaging of Lipid-Ion Network Formation under Physiological Conditions by Frequency Modulation Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Fukuma, Takeshi; Higgins, Michael J.; Jarvis, Suzanne P.

2007-03-01

Various metal cations in physiological solutions interact with lipid headgroups in biological membranes, having an impact on their structure and stability, yet little is known about the molecular-scale dynamics of the lipid-ion interactions. Here we directly investigate the extensive lipid-ion interaction networks and their transient formation between headgroups in a dipalmitoylphosphatidylcholine bilayer under physiological conditions. The spatial distribution of ion occupancy is imaged in real space by frequency modulation atomic force microscopy with sub-Ångstrom resolution.

Application of Hoffman modulation contrast microscopy coupled with three-wavelength two-beam interferometry to the in situ direct observation of the growth process of a crystal in microgravity

NASA Technical Reports Server (NTRS)

Tsukamoto, Katsuo

1988-01-01

Direct visualization of three dimensional transfer process of both heat and mass around a growing crystal and mono-molecular growth layers on the surface is possible in situ by means of high resolution Hoffman modulation contrast microscopy coupled with three wavelength two beam Mach-Zehnder interferometry. This in situ observation is very suitable for the verification of the growth mechanism of a crystal in a solution or a melt in microgravity.

MoS2 Heterojunctions by Thickness Modulation

PubMed Central

Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; Ko, Changhyun; Seuk Kang, Jeong; Lien, Der-Hsien; Najmzadeh, Mohammad; Tongay, Sefaattin; Wu, Junqiao; Javey, Ali

2015-01-01

In this work, we report lateral heterojunction formation in as-exfoliated MoS2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. The work presents experimental and theoretical understanding of the band alignment and photoresponse of thickness modulated MoS2 junctions with important implications for exploring novel optoelectronic devices. PMID:26121940

MoS 2 Heterojunctions by Thickness Modulation

DOE PAGES

Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; ...

2015-06-30

In this work, we report lateral heterojunction formation in as-exfoliated MoS 2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. Finally, the work presents experimental and theoretical understanding of the band alignmentmore » and photoresponse of thickness modulated MoS 2 junctions with important implications for exploring novel optoelectronic devices.« less

Mapping power-law rheology of living cells using multi-frequency force modulation atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Ryosuke; Okajima, Takaharu, E-mail: okajima@ist.hokudai.ac.jp

We present multi-frequency force modulation atomic force microscopy (AFM) for mapping the complex shear modulus G* of living cells as a function of frequency over the range of 50–500 Hz in the same measurement time as the single-frequency force modulation measurement. The AFM technique enables us to reconstruct image maps of rheological parameters, which exhibit a frequency-dependent power-law behavior with respect to G{sup *}. These quantitative rheological measurements reveal a large spatial variation in G* in this frequency range for single cells. Moreover, we find that the reconstructed images of the power-law rheological parameters are much different from those obtained inmore » force-curve or single-frequency force modulation measurements. This indicates that the former provide information about intracellular mechanical structures of the cells that are usually not resolved with the conventional force measurement methods.« less

Bimodal atomic force microscopy driving the higher eigenmode in frequency-modulation mode: Implementation, advantages, disadvantages and comparison to the open-loop case.

PubMed

Ebeling, Daniel; Solares, Santiago D

2013-01-01

We present an overview of the bimodal amplitude-frequency-modulation (AM-FM) imaging mode of atomic force microscopy (AFM), whereby the fundamental eigenmode is driven by using the amplitude-modulation technique (AM-AFM) while a higher eigenmode is driven by using either the constant-excitation or the constant-amplitude variant of the frequency-modulation (FM-AFM) technique. We also offer a comparison to the original bimodal AFM method, in which the higher eigenmode is driven with constant frequency and constant excitation amplitude. General as well as particular characteristics of the different driving schemes are highlighted from theoretical and experimental points of view, revealing the advantages and disadvantages of each. This study provides information and guidelines that can be useful in selecting the most appropriate operation mode to characterize different samples in the most efficient and reliable way.

Spectrally-broad coherent anti-Stokes Raman scattering hyper-microscopy utilizing a Stokes supercontinuum pumped at 800 nm

PubMed Central

Porquez, Jeremy G.; Cole, Ryan A.; Tabarangao, Joel T.; Slepkov, Aaron D.

2016-01-01

We demonstrate spectral-focusing based coherent anti-Stokes Raman scattering (SF-CARS) hyper-microscopy capable of probing vibrational frequencies from 630 cm−1 to 3250 cm−1 using a single Ti:Sapphire femtosecond laser operating at 800 nm, and a commercially-available supercontinuum-generating fibre module. A broad Stokes supercontinuum with significant spectral power at wavelengths between 800 nm and 940 nm is generated by power tuning the fibre module using atypically long and/or chirped ~200 fs pump pulses, allowing convenient access to lower vibrational frequencies in the fingerprint spectral region. This work significantly reduces the instrumental and technical requirements for multimodal CARS microscopy, while expanding the spectral capabilities of an established approach to SF-CARS. PMID:27867735

Quartz tuning fork-based frequency modulation atomic force spectroscopy and microscopy with all digital phase-locked loop

NASA Astrophysics Data System (ADS)

An, Sangmin; Hong, Mun-heon; Kim, Jongwoo; Kwon, Soyoung; Lee, Kunyoung; Lee, Manhee; Jhe, Wonho

2012-11-01

We present a platform for the quartz tuning fork (QTF)-based, frequency modulation atomic force microscopy (FM-AFM) system for quantitative study of the mechanical or topographical properties of nanoscale materials, such as the nano-sized water bridge formed between the quartz tip (˜100 nm curvature) and the mica substrate. A thermally stable, all digital phase-locked loop is used to detect the small frequency shift of the QTF signal resulting from the nanomaterial-mediated interactions. The proposed and demonstrated novel FM-AFM technique provides high experimental sensitivity in the measurement of the viscoelastic forces associated with the confined nano-water meniscus, short response time, and insensitivity to amplitude noise, which are essential for precision dynamic force spectroscopy and microscopy.

Quartz tuning fork-based frequency modulation atomic force spectroscopy and microscopy with all digital phase-locked loop.

PubMed

An, Sangmin; Hong, Mun-heon; Kim, Jongwoo; Kwon, Soyoung; Lee, Kunyoung; Lee, Manhee; Jhe, Wonho

2012-11-01

We present a platform for the quartz tuning fork (QTF)-based, frequency modulation atomic force microscopy (FM-AFM) system for quantitative study of the mechanical or topographical properties of nanoscale materials, such as the nano-sized water bridge formed between the quartz tip (~100 nm curvature) and the mica substrate. A thermally stable, all digital phase-locked loop is used to detect the small frequency shift of the QTF signal resulting from the nanomaterial-mediated interactions. The proposed and demonstrated novel FM-AFM technique provides high experimental sensitivity in the measurement of the viscoelastic forces associated with the confined nano-water meniscus, short response time, and insensitivity to amplitude noise, which are essential for precision dynamic force spectroscopy and microscopy.

Imaging contrast and tip-sample interaction of non-contact amplitude modulation atomic force microscopy with Q-control

NASA Astrophysics Data System (ADS)

Shi, Shuai; Guo, Dan; Luo, Jianbin

2017-10-01

Active quality factor (Q) exhibits many promising properties in dynamic atomic force microscopy. Energy dissipation and image contrasts are investigated in the non-contact amplitude modulation atomic force microscopy (AM-AFM) with an active Q-control circuit in the ambient air environment. Dissipated power and virial were calculated to compare the highly nonlinear interaction of tip-sample and image contrasts with different Q gain values. Greater free amplitudes and lower effective Q values show better contrasts for the same setpoint ratio. Active quality factor also can be employed to change tip-sample interaction force in non-contact regime. It is meaningful that non-destructive and better contrast images can be realized in non-contact AM-AFM by applying an active Q-control to the dynamic system.

Virtual k -Space Modulation Optical Microscopy

NASA Astrophysics Data System (ADS)

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Zheng, Guoan; Fang, Yue; Xu, Yingke; Liu, Xu; So, Peter T. C.

2016-07-01

We report a novel superresolution microscopy approach for imaging fluorescence samples. The reported approach, termed virtual k -space modulation optical microscopy (VIKMOM), is able to improve the lateral resolution by a factor of 2, reduce the background level, improve the optical sectioning effect and correct for unknown optical aberrations. In the acquisition process of VIKMOM, we used a scanning confocal microscope setup with a 2D detector array to capture sample information at each scanned x -y position. In the recovery process of VIKMOM, we first modulated the captured data by virtual k -space coding and then employed a ptychography-inspired procedure to recover the sample information and correct for unknown optical aberrations. We demonstrated the performance of the reported approach by imaging fluorescent beads, fixed bovine pulmonary artery endothelial (BPAE) cells, and living human astrocytes (HA). As the VIKMOM approach is fully compatible with conventional confocal microscope setups, it may provide a turn-key solution for imaging biological samples with ˜100 nm lateral resolution, in two or three dimensions, with improved optical sectioning capabilities and aberration correcting.

Q-controlled amplitude modulation atomic force microscopy in liquids: An analysis

NASA Astrophysics Data System (ADS)

Hölscher, H.; Schwarz, U. D.

2006-08-01

An analysis of amplitude modulation atomic force microscopy in liquids is presented with respect to the application of the Q-Control technique. The equation of motion is solved by numerical and analytic methods with and without Q-Control in the presence of a simple model interaction force adequate for many liquid environments. In addition, the authors give an explicit analytical formula for the tip-sample indentation showing that higher Q factors reduce the tip-sample force. It is found that Q-Control suppresses unwanted deformations of the sample surface, leading to the enhanced image quality reported in several experimental studies.

Optically coupled methods for microwave impedance microscopy

NASA Astrophysics Data System (ADS)

Johnston, Scott R.; Ma, Eric Yue; Shen, Zhi-Xun

2018-04-01

Scanning Microwave Impedance Microscopy (MIM) measurement of photoconductivity with 50 nm resolution is demonstrated using a modulated optical source. The use of a modulated source allows for the measurement of photoconductivity in a single scan without a reference region on the sample, as well as removing most topographical artifacts and enhancing signal to noise as compared with unmodulated measurement. A broadband light source with a tunable monochrometer is then used to measure energy resolved photoconductivity with the same methodology. Finally, a pulsed optical source is used to measure local photo-carrier lifetimes via MIM, using the same 50 nm resolution tip.

Magnetoelectric force microscopy based on magnetic force microscopy with modulated electric field.

PubMed

Geng, Yanan; Wu, Weida

2014-05-01

We present the realization of a mesoscopic imaging technique, namely, the Magnetoelectric Force Microscopy (MeFM), for visualization of local magnetoelectric effect. The basic principle of MeFM is the lock-in detection of local magnetoelectric response, i.e., the electric field-induced magnetization, using magnetic force microscopy. We demonstrate MeFM capability by visualizing magnetoelectric domains on single crystals of multiferroic hexagonal manganites. Results of several control experiments exclude artifacts or extrinsic origins of the MeFM signal. The parameters are tuned to optimize the signal to noise ratio.

Fast myopic 2D-SIM super resolution microscopy with joint modulation pattern estimation

NASA Astrophysics Data System (ADS)

Orieux, François; Loriette, Vincent; Olivo-Marin, Jean-Christophe; Sepulveda, Eduardo; Fragola, Alexandra

2017-12-01

Super-resolution in structured illumination microscopy (SIM) is obtained through de-aliasing of modulated raw images, in which high frequencies are measured indirectly inside the optical transfer function. Usual approaches that use 9 or 15 images are often too slow for dynamic studies. Moreover, as experimental conditions change with time, modulation parameters must be estimated within the images. This paper tackles the problem of image reconstruction for fast super resolution in SIM, where the number of available raw images is reduced to four instead of nine or fifteen. Within an optimization framework, the solution is inferred via a joint myopic criterion for image and modulation (or acquisition) parameters, leading to what is frequently called a myopic or semi-blind inversion problem. The estimate is chosen as the minimizer of the nonlinear criterion, numerically calculated by means of a block coordinate optimization algorithm. The effectiveness of the proposed method is demonstrated for simulated and experimental examples. The results show precise estimation of the modulation parameters jointly with the reconstruction of the super resolution image. The method also shows its effectiveness for thick biological samples.

Conditional Random Fields for Fast, Large-Scale Genome-Wide Association Studies

PubMed Central

Huang, Jim C.; Meek, Christopher; Kadie, Carl; Heckerman, David

2011-01-01

Understanding the role of genetic variation in human diseases remains an important problem to be solved in genomics. An important component of such variation consist of variations at single sites in DNA, or single nucleotide polymorphisms (SNPs). Typically, the problem of associating particular SNPs to phenotypes has been confounded by hidden factors such as the presence of population structure, family structure or cryptic relatedness in the sample of individuals being analyzed. Such confounding factors lead to a large number of spurious associations and missed associations. Various statistical methods have been proposed to account for such confounding factors such as linear mixed-effect models (LMMs) or methods that adjust data based on a principal components analysis (PCA), but these methods either suffer from low power or cease to be tractable for larger numbers of individuals in the sample. Here we present a statistical model for conducting genome-wide association studies (GWAS) that accounts for such confounding factors. Our method scales in runtime quadratic in the number of individuals being studied with only a modest loss in statistical power as compared to LMM-based and PCA-based methods when testing on synthetic data that was generated from a generalized LMM. Applying our method to both real and synthetic human genotype/phenotype data, we demonstrate the ability of our model to correct for confounding factors while requiring significantly less runtime relative to LMMs. We have implemented methods for fitting these models, which are available at http://www.microsoft.com/science. PMID:21765897

Ultra-Thin, Triple-Bandgap GaInP/GaAs/GaInAs Monolithic Tandem Solar Cells

NASA Technical Reports Server (NTRS)

Wanlass, M. W.; Ahrenkiel, S. P.; Albin, D. S.; Carapella, J. J.; Duda, A.; Emery, K.; Geisz, J. F.; Jones, K.; Kurtz, Sarah; Moriarty, T.;

Effect of condensed tannins from Ficus infectoria and Psidium guajava leaf meal mixture on nutrient metabolism, methane emission and performance of lambs.

PubMed

Pathak, A K; Dutta, Narayan; Pattanaik, A K; Chaturvedi, V B; Sharma, K

2017-12-01

The study examined the effect of condensed tannins (CT) containing Ficus infectoria and Psidium guajava leaf meal mixture (LMM) supplementation on nutrient metabolism, methane emission and performance of lambs. Twenty four lambs of ~6 months age (average body weight 10.1±0.60 kg) were randomly divided into 4 dietary treatments (CT-0, CT-1, CT-1.5, and CT-2 containing 0, 1.0, 1.5, and 2.0 percent CT through LMM, respectively) consisting of 6 lambs each in a completely randomized design. All the lambs were offered a basal diet of wheat straw ad libitum, oat hay (100 g/d) along with required amount of concentrate mixture to meet their nutrient requirements for a period of 6 months. After 3 months of experimental feeding, a metabolism trial of 6 days duration was conducted on all 24 lambs to determine nutrient digestibility and nitrogen balance. Urinary excretion of purine derivatives and microbial protein synthesis were determined using high performance liquid chromatography. Respiration chamber study was started at the mid of 5th month of experimental feeding trial. Whole energy balance trials were conducted on individual lamb one after the other, in an open circuit respiration calorimeter. Intake of dry matter and organic matter (g/d) was significantly (p<0.05) higher in CT-1.5 than control. Digestibility of various nutrients did not differ irrespective of treatments. Nitrogen retention and microbial nitrogen synthesis (g/d) was significantly (p<0.01) higher in CT-1.5 and CT-2 groups relative to CT-0. Total body weight gain (kg) and average daily gain (g) were significantly (linear, p<0.01) higher in CT-1.5 followed by CT-1 and CT-0, respectively. Feed conversion ratio (FCR) by lambs was significantly (linear, p<0.01) better in CT-1.5 followed by CT-2 and CT-0, respectively. Total wool yield (g; g/d) was linearly (p<0.05) higher for CT-1.5 than CT-0. Methane emission was linearly decreased (p<0.05) in CT groups and reduction was highest (p<0.01) in CT-2 followed by CT-1.5 and CT-1. Methane energy (kcal/d) was linearly decreased (p<0.05) in CT groups. The CT supplementation at 1% to 2% of the diet through Ficus infectoria and Psidium guajava LMM significantly improved nitrogen metabolism, growth performance, wool yield, FCR and reduced methane emission by lambs.

Investigating the performance of reconstruction methods used in structured illumination microscopy as a function of the illumination pattern's modulation frequency

NASA Astrophysics Data System (ADS)

Shabani, H.; Sánchez-Ortiga, E.; Preza, C.

2016-03-01

Surpassing the resolution of optical microscopy defined by the Abbe diffraction limit, while simultaneously achieving optical sectioning, is a challenging problem particularly for live cell imaging of thick samples. Among a few developing techniques, structured illumination microscopy (SIM) addresses this challenge by imposing higher frequency information into the observable frequency band confined by the optical transfer function (OTF) of a conventional microscope either doubling the spatial resolution or filling the missing cone based on the spatial frequency of the pattern when the patterned illumination is two-dimensional. Standard reconstruction methods for SIM decompose the low and high frequency components from the recorded low-resolution images and then combine them to reach a high-resolution image. In contrast, model-based approaches rely on iterative optimization approaches to minimize the error between estimated and forward images. In this paper, we study the performance of both groups of methods by simulating fluorescence microscopy images from different type of objects (ranging from simulated two-point sources to extended objects). These simulations are used to investigate the methods' effectiveness on restoring objects with various types of power spectrum when modulation frequency of the patterned illumination is changing from zero to the incoherent cut-off frequency of the imaging system. Our results show that increasing the amount of imposed information by using a higher modulation frequency of the illumination pattern does not always yield a better restoration performance, which was found to be depended on the underlying object. Results from model-based restoration show performance improvement, quantified by an up to 62% drop in the mean square error compared to standard reconstruction, with increasing modulation frequency. However, we found cases for which results obtained with standard reconstruction methods do not always follow the same trend.

The combination of scanning electron and scanning probe microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapozhnikov, I. D.; Gorbenko, O. M., E-mail: gorolga64@gmail.com; Felshtyn, M. L.

2016-06-17

We suggest the SPM module to combine SEM and SPM methods for studying surfaces. The module is based on the original mechanical moving and scanning system. The examples of studies of the steel surface microstructure in both SEM and SPM modes are presented.

Phase modulation atomic force microscope with true atomic resolution

NASA Astrophysics Data System (ADS)

Fukuma, Takeshi; Kilpatrick, Jason I.; Jarvis, Suzanne P.

2006-12-01

We have developed a dynamic force microscope (DFM) working in a novel operation mode which is referred to as phase modulation atomic force microscopy (PM-AFM). PM-AFM utilizes a fixed-frequency excitation signal to drive a cantilever, which ensures stable imaging even with occasional tip crash and adhesion to the surface. The tip-sample interaction force is detected as a change of the phase difference between the cantilever deflection and excitation signals and hence the time response is not influenced by the Q factor of the cantilever. These features make PM-AFM more suitable for high-speed imaging than existing DFM techniques such as amplitude modulation and frequency modulation atomic force microscopies. Here we present the basic principle of PM-AFM and the theoretical limit of its performance. The design of the developed PM-AFM is described and its theoretically limited noise performance is demonstrated. Finally, we demonstrate the true atomic resolution imaging capability of the developed PM-AFM by imaging atomic-scale features of mica in water.

Effects of pipette modulation and imaging distances on ion currents measured with scanning ion conductance microscopy (SICM).

PubMed

Chen, Chiao-Chen; Baker, Lane A

2011-01-07

Local conductance variations can be estimated by measuring ion current magnitudes with scanning ion conductance microscopy (SICM). Factors which influence image quality and quantitation of ion currents measured with SICM have been evaluated. Specifically, effects of probe-sample separation and pipette modulation have been systematically studied for the case of imaging conductance variations at pores in a polymer membrane under transmembrane concentration gradients. The influence of probe-sample separation on ion current images was evaluated using distance-modulated (ac) feedback. Approach curves obtained using non-modulated (dc) feedback were also recorded to determine the relative influence of pipette-generated convection by comparison of ion currents measured with both ac and dc feedback modes. To better interpret results obtained, comparison to a model based on a disk-shaped geometry for nanopores in the membrane, as well as relevant position-dependent parameters of the experiment is described. These results advance our current understanding of conductance measurements with SICM.

Vector electric field measurement via position-modulated Kelvin probe force microscopy

NASA Astrophysics Data System (ADS)

Dwyer, Ryan P.; Smieska, Louisa M.; Tirmzi, Ali Moeed; Marohn, John A.

2017-10-01

High-quality spatially resolved measurements of electric fields are critical to understanding charge injection, charge transport, and charge trapping in semiconducting materials. Here, we report a variation of frequency-modulated Kelvin probe force microscopy that enables spatially resolved measurements of the electric field. We measure electric field components along multiple directions simultaneously by employing position modulation and lock-in detection in addition to numeric differentiation of the surface potential. We demonstrate the technique by recording linescans of the in-plane electric field vector in the vicinity of a patch of trapped charge in a 2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT) organic field-effect transistor. This technique is simple to implement and should be especially useful for studying electric fields in spatially inhomogeneous samples like organic transistors and photovoltaic blends.

A review of demodulation techniques for amplitude-modulation atomic force microscopy

PubMed Central

Harcombe, David M; Ragazzon, Michael R P; Moheimani, S O Reza; Fleming, Andrew J

2017-01-01

In this review paper, traditional and novel demodulation methods applicable to amplitude-modulation atomic force microscopy are implemented on a widely used digital processing system. As a crucial bandwidth-limiting component in the z-axis feedback loop of an atomic force microscope, the purpose of the demodulator is to obtain estimates of amplitude and phase of the cantilever deflection signal in the presence of sensor noise or additional distinct frequency components. Specifically for modern multifrequency techniques, where higher harmonic and/or higher eigenmode contributions are present in the oscillation signal, the fidelity of the estimates obtained from some demodulation techniques is not guaranteed. To enable a rigorous comparison, the performance metrics tracking bandwidth, implementation complexity and sensitivity to other frequency components are experimentally evaluated for each method. Finally, the significance of an adequate demodulator bandwidth is highlighted during high-speed tapping-mode atomic force microscopy experiments in constant-height mode. PMID:28900596

Performance Prediction for Coatings. Proceedings of a Workshop at the Naval Civil Engineering Laboratory, 15 September 1986

DTIC Science & Technology

1987-10-01

Facilities" (A-65) Summary: Samples of the coating systems prepared for NCEL performance prediction studies were tested by alternate immersion in salt...coating sample where the yeast growth is inhibited over a 72-hour period. 5 - .. -, a . - - tL .naa t ~ ~S ~* r* J.r~ ¶Sf ~ ~t~ 9n~ PbP. bPjht fLMM...which is employed as a means of measuring the decibels of attenuation of the echoes caused by the sample on the line. The exponential decay of the

Cellular Actions and Interactions of Anticholinesterases and Their Antidotes in Mammalian Autonomic Neurons.

DTIC Science & Technology

1985-07-29

significant ( p ɘ.Ol) - 13 - ’ A MeCh t A MeCh A MeCh DFP OluM WASH AMeCh A MeCh A MeCh DFP lmM WASH Fig. 6 Facilitation and depression of muscarinic...N.J. and Karczmar, A.G. 1982. Substance P : A putative sensory transmitter in mammalian autonomic ganglia. Science, 217, 739-741. 22. Kiraly, M., Ma...neurons and on ganglionic transmission; and (2) clarification of the site and mechanism of action of a cholinesterase (ChE) reactivator, pyridinealdoxime

Epigenome-wide association studies without the need for cell-type composition.

PubMed

Zou, James; Lippert, Christoph; Heckerman, David; Aryee, Martin; Listgarten, Jennifer

2014-03-01

In epigenome-wide association studies, cell-type composition often differs between cases and controls, yielding associations that simply tag cell type rather than reveal fundamental biology. Current solutions require actual or estimated cell-type composition--information not easily obtainable for many samples of interest. We propose a method, FaST-LMM-EWASher, that automatically corrects for cell-type composition without the need for explicit knowledge of it, and then validate our method by comparison with the state-of-the-art approach. Corresponding software is available from http://www.microsoft.com/science/.

Challenges and complexities of multifrequency atomic force microscopy in liquid environments.

PubMed

Solares, Santiago D

2014-01-01

This paper illustrates through numerical simulation the complexities encountered in high-damping AFM imaging, as in liquid enviroments, within the specific context of multifrequency atomic force microscopy (AFM). The focus is primarily on (i) the amplitude and phase relaxation of driven higher eigenmodes between successive tip-sample impacts, (ii) the momentary excitation of non-driven higher eigenmodes and (iii) base excitation artifacts. The results and discussion are mostly applicable to the cases where higher eigenmodes are driven in open loop and frequency modulation within bimodal schemes, but some concepts are also applicable to other types of multifrequency operations and to single-eigenmode amplitude and frequency modulation methods.

Stimulated emission and spontaneous loss pump-probe microscopy for background removal

NASA Astrophysics Data System (ADS)

Das, Subir; Ho, Bo-Wei; Kao, Fu-Jen

2018-02-01

In this work, we have established a double modulation lock-in detection technique using two semiconductor laser diodes in stimulated emission based pump-probe microscopy. By modulating the pump and probe beams at two different frequencies, f1 and f2, the signal is then recovered with the sum frequency, (f1+ f2), so as to minimize the leak-through noise due to the spontaneous emission caused by the pump beam. In this way, the DC background that is often attributed to the stimulated emission is effectively removed. Our technique has implemented in ATTO647N fluorescent dye which is applicable for many biological applications.

Measurement of Intramolecular Energy Dissipation and Stiffness of a Single Peptide Molecule by Magnetically Modulated Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Kageshima, Masami; Takeda, Seiji; Ptak, Arkadiusz; Nakamura, Chikashi; Jarvis, Suzanne P.; Tokumoto, Hiroshi; Miyake, Jun

2004-12-01

A method for measuring intramolecular energy dissipation as well as stiffness variation in a single biomolecule in situ by atomic force microscopy (AFM) is presented. An AFM cantilever is magnetically modulated at an off-resonance frequency while it elongates a single peptide molecule in buffer solution. The molecular stiffness and the energy dissipation are measured via the amplitude and phase lag in the response signal. Data showing a peculiar feature in both profiles of stiffness and dissipation is presented. This suggests that the present method is more sensitive to the state of the molecule than the conventional force-elongation measurement is.

Conservative and dissipative force imaging of switchable rotaxanes with frequency-modulation atomic force microscopy

NASA Astrophysics Data System (ADS)

Farrell, Alan A.; Fukuma, Takeshi; Uchihashi, Takayuki; Kay, Euan R.; Bottari, Giovanni; Leigh, David A.; Yamada, Hirofumi; Jarvis, Suzanne P.

2005-09-01

We compare constant amplitude frequency modulation atomic force microscopy (FM-AFM) in ambient conditions to ultrahigh vacuum (UHV) experiments by analysis of thin films of rotaxane molecules. Working in ambient conditions is important for the development of real-world molecular devices. We show that the FM-AFM technique allows quantitative measurement of conservative and dissipative forces without instabilities caused by any native water layer. Molecular resolution is achieved despite the low Q-factor in the air. Furthermore, contrast in the energy dissipation is observed even at the molecular level. This should allow investigations into stimuli-induced sub-molecular motion of organic films.

Length-extension resonator as a force sensor for high-resolution frequency-modulation atomic force microscopy in air.

PubMed

Beyer, Hannes; Wagner, Tino; Stemmer, Andreas

2016-01-01

Frequency-modulation atomic force microscopy has turned into a well-established method to obtain atomic resolution on flat surfaces, but is often limited to ultra-high vacuum conditions and cryogenic temperatures. Measurements under ambient conditions are influenced by variations of the dew point and thin water layers present on practically every surface, complicating stable imaging with high resolution. We demonstrate high-resolution imaging in air using a length-extension resonator operating at small amplitudes. An additional slow feedback compensates for changes in the free resonance frequency, allowing stable imaging over a long period of time with changing environmental conditions.

R and D work on the constrained vapor bubble system for a microgravity experiment

NASA Technical Reports Server (NTRS)

Wayner, P. C., Jr.; Plawsky, J. L.

2005-01-01

We are working with Project Scientists R. Balasubramanian and Sang Young Son, and a NASA Projects Team headed by Sue Motil at the Glenn Research Center on the design and development of an experimental system for use on the International Space Station during the year 2006. John Eustace is the coordinator for the flight experiment at Zin-Tech (previously Northrop-Grumman) for the design and development of the Constrained Vapor Bubble Heat Exchanger, CVBHX, cell which will fit into the Light Microscope Module, LMM. Good progress is being made. The CDR for the LMM being developed was held on December 10-1 1,2003. Experimental results obtained under microgravity conditions will be compared with those obtained at Rensselaer. Basic and applied research at Rensselaer continues on the experimental and theoretical details associated with passive phase change heat transfer processes controlled by interfacial forces in the CVBHX. The extensive results of our current research are presented in the 23 external publications listed below. Twenty-two external presentations have been given. Briefly, evaporation/condensation data from both vertical and horizontal CVBHX systems were obtained and analyzed for both polar (wetting) and apolar (partially wetting) fluids. The vertical system is axi-symmetric, but strongly effected by gravity. Whereas, the horizontal system is asymmetric, but weakly effected by gravity. Therefore, there will be significant differences in the operation of the cell in the earth s environment versus the operation under microgravity conditions. Due to its relative large size, the system s performance should be optimum under micro-gravity conditions, where the CVBHX should be a very effective passive heat exchanger. The CVBHX was found to be an ideal experimental setup in which to study the effects of interfacial phenomena on both the evaporation and drop-wise condensation processes. The optical technique (Image Analyzing Interferometry, IAI), which is based on the measurement and analysis of the reflectivity pattern of a thin film, was significantly improved. The accuracy of the IAI system is of critical importance to the success of the mission because it is used to measure the details of the pressure field in the liquid by measuring the film thickness profile. The accuracy was found to be excellent and various publications/presentations documenting these new results were written. Significant new results were also obtained for the effect of the oscillating contact line region on evaporation. Three doctoral students graduated under this grant. All three work in US industry, two for Intel. Another doctoral student is in his third year of study and will finish under an extension of the NASA grant: # NNC05GA27G.

Force determination in lateral magnetic tweezers combined with TIRF microscopy.

PubMed

Madariaga-Marcos, J; Hormeño, S; Pastrana, C L; Fisher, G L M; Dillingham, M S; Moreno-Herrero, F

2018-03-01

Combining single-molecule techniques with fluorescence microscopy has attracted much interest because it allows the correlation of mechanical measurements with directly visualized DNA : protein interactions. In particular, its combination with total internal reflection fluorescence microscopy (TIRF) is advantageous because of the high signal-to-noise ratio this technique achieves. This, however, requires stretching long DNA molecules across the surface of a flow cell to maximize polymer exposure to the excitation light. In this work, we develop a module to laterally stretch DNA molecules at a constant force, which can be easily implemented in regular or combined magnetic tweezers (MT)-TIRF setups. The pulling module is further characterized in standard flow cells of different thicknesses and glass capillaries, using two types of micrometer size superparamagnetic beads, long DNA molecules, and a home-built device to rotate capillaries with mrad precision. The force range achieved by the magnetic pulling module was between 0.1 and 30 pN. A formalism for estimating forces in flow-stretched tethered beads is also proposed, and the results compared with those of lateral MT, demonstrating that lateral MT achieve higher forces with lower dispersion. Finally, we show the compatibility with TIRF microscopy and the parallelization of measurements by characterizing DNA binding by the centromere-binding protein ParB from Bacillus subtilis. Simultaneous MT pulling and fluorescence imaging demonstrate the non-specific binding of BsParB on DNA under conditions restrictive to condensation.

Compact three-dimensional super-resolution system based on fluorescence emission difference microscopy

NASA Astrophysics Data System (ADS)

Zhu, Dazhao; Chen, Youhua; Fang, Yue; Hussain, Anwar; Kuang, Cuifang; Zhou, Xiaoxu; Xu, Yingke; Liu, Xu

2017-12-01

A compact microscope system for three-dimensional (3-D) super-resolution imaging is presented. The super-resolution capability of the system is based on a size-reduced effective 3-D point spread function generated through the fluorescence emission difference (FED) method. The appropriate polarization direction distribution and manipulation allows the panel active area of the spatial light modulator to be fully utilized. This allows simultaneous modulation of the incident light by two kinds of phase masks to be performed with a single spatial light modulator in order to generate a 3-D negative spot. The system is more compact than standard 3-D FED systems while maintaining all the advantages of 3-D FED microscopy. The experimental results demonstrated the improvement in 3-D resolution by nearly 1.7 times and 1.6 times compared to the classic confocal resolution in the lateral and axial directions, respectively.

A low-noise measurement system for scanning thermal microscopy resistive nanoprobes based on a transformer ratio-arm bridge

NASA Astrophysics Data System (ADS)

Świątkowski, Michał; Wojtuś, Arkadiusz; Wielgoszewski, Grzegorz; Rudek, Maciej; Piasecki, Tomasz; Jóźwiak, Grzegorz; Gotszalk, Teodor

2018-04-01

Atomic force microscopy (AFM) is a widely used technology for the investigation and characterization of nanomaterials. Its functionality can be easily expanded by applying dedicated extension modules, which can measure the electrical conductivity or temperature of a sample. In this paper, we introduce a transformer ratio-arm bridge setup dedicated to AFM-based thermal imaging. One of the key features of the thermal module is the use of a low-power driving signal that prevents undesirable tip heating during resistance measurement, while the other is the sensor location in a ratio-arm transformer bridge working in the audio frequency range and ensuring galvanic isolation of the tip, enabling contact-mode scanning of electronic circuits. The proposed expansion module is compact and it can be integrated onto the AFM head close to the cantilever. The calibration process and the resolution of 11 mK of the proposed setup are shown.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes.

PubMed

Dettweiler, Ulrich; Becker, Christoph; Auestad, Bjørn H; Simon, Perikles; Kirsch, Peter

2017-04-30

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children's normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol ( p = 0.857), despite being higher in the intervention group ( p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child's diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon.

Intricate interactions between the bloom-forming cyanobacterium Microcystis aeruginosa and foreign genetic elements, revealed by diversified clustered regularly interspaced short palindromic repeat (CRISPR) signatures.

PubMed

Kuno, Sotaro; Yoshida, Takashi; Kaneko, Takakazu; Sako, Yoshihiko

2012-08-01

Clustered regularly interspaced short palindromic repeats (CRISPR) confer sequence-dependent, adaptive resistance in prokaryotes against viruses and plasmids via incorporation of short sequences, called spacers, derived from foreign genetic elements. CRISPR loci are thus considered to provide records of past infections. To describe the host-parasite (i.e., cyanophages and plasmids) interactions involving the bloom-forming freshwater cyanobacterium Microcystis aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two previously sequenced genomes. The number of spacers in each locus was larger than the average among prokaryotes. All spacers were strain specific, except for a string of 11 spacers shared in two closely related strains, suggesting diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes were identified in a natural cyanobacterial community. Among 995 unique spacers obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of these, six spacers showed only silent or conservative nucleotide mutations compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert CRISPR immunity dependent on nucleotide identity. These results imply that host-phage interactions can be divided into M. aeruginosa-cyanophage combinations rather than pandemics of population-wide infectious cyanophages. Spacer similarity also showed frequent exposure of M. aeruginosa to small cryptic plasmids that were observed only in a few strains. Thus, the diversification of CRISPR implies that M. aeruginosa has been challenged by diverse communities (almost entirely uncharacterized) of cyanophages and plasmids.

Intricate Interactions between the Bloom-Forming Cyanobacterium Microcystis aeruginosa and Foreign Genetic Elements, Revealed by Diversified Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Signatures

PubMed Central

Kuno, Sotaro; Kaneko, Takakazu; Sako, Yoshihiko

2012-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) confer sequence-dependent, adaptive resistance in prokaryotes against viruses and plasmids via incorporation of short sequences, called spacers, derived from foreign genetic elements. CRISPR loci are thus considered to provide records of past infections. To describe the host-parasite (i.e., cyanophages and plasmids) interactions involving the bloom-forming freshwater cyanobacterium Microcystis aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two previously sequenced genomes. The number of spacers in each locus was larger than the average among prokaryotes. All spacers were strain specific, except for a string of 11 spacers shared in two closely related strains, suggesting diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes were identified in a natural cyanobacterial community. Among 995 unique spacers obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of these, six spacers showed only silent or conservative nucleotide mutations compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert CRISPR immunity dependent on nucleotide identity. These results imply that host-phage interactions can be divided into M. aeruginosa-cyanophage combinations rather than pandemics of population-wide infectious cyanophages. Spacer similarity also showed frequent exposure of M. aeruginosa to small cryptic plasmids that were observed only in a few strains. Thus, the diversification of CRISPR implies that M. aeruginosa has been challenged by diverse communities (almost entirely uncharacterized) of cyanophages and plasmids. PMID:22636003

How preview space/time translates into preview cost/benefit for fixation durations during reading.

PubMed

Kliegl, Reinhold; Hohenstein, Sven; Yan, Ming; McDonald, Scott A

2013-01-01

Eye-movement control during reading depends on foveal and parafoveal information. If the parafoveal preview of the next word is suppressed, reading is less efficient. A linear mixed model (LMM) reanalysis of McDonald (2006) confirmed his observation that preview benefit may be limited to parafoveal words that have been selected as the saccade target. Going beyond the original analyses, in the same LMM, we examined how the preview effect (i.e., the difference in single-fixation duration, SFD, between random-letter and identical preview) depends on the gaze duration on the pretarget word and on the amplitude of the saccade moving the eye onto the target word. There were two key results: (a) The shorter the saccade amplitude (i.e., the larger preview space), the shorter a subsequent SFD with an identical preview; this association was not observed with a random-letter preview. (b) However, the longer the gaze duration on the pretarget word, the longer the subsequent SFD on the target, with the difference between random-letter string and identical previews increasing with preview time. A third pattern-increasing cost of a random-letter string in the parafovea associated with shorter saccade amplitudes-was observed for target gaze durations. Thus, LMMs revealed that preview effects, which are typically summarized under "preview benefit", are a complex mixture of preview cost and preview benefit and vary with preview space and preview time. The consequence for reading is that parafoveal preview may not only facilitate, but also interfere with lexical access.

Impact of exercise programs among helicopter pilots with transient LBP.

PubMed

Andersen, Knut; Baardsen, Roald; Dalen, Ingvild; Larsen, Jan Petter

2017-06-20

Flight related low back pain (LBP) among helicopter pilots is frequent and may influence flight performance. Prolonged confined sitting during flights seems to weaken lumbar trunk (LT) muscles with associated secondary transient pain. Aim of the study was to investigate if structured training could improve muscular function and thus improve LBP related to flying. 39 helicopter pilots (35 men and 4 women), who reported flying related LBP on at least 1 of 3 missions last month, were allocated to two training programs over a 3-month period. Program A consisted of 10 exercises recommended for general LBP. Program B consisted of 4 exercises designed specifically to improve LT muscular endurance. The pilots were examined before and after the training using questionnaires for pain, function, quality of health and tests of LT muscular endurance as well as ultrasound measurements of the contractility of the lumbar multifidus muscle (LMM). Approximately half of the participants performed the training per-protocol. Participants in this subset group had comparable baseline characteristics as the total study sample. Pre and post analysis of all pilots included, showed participants had marked improvement in endurance and contractility of the LMM following training. Similarly, participants had improvement in function and quality of health. Participants in program B had significant improvement in pain, function and quality of health. This study indicates that participants who performed a three months exercise program had improved muscle endurance at the end of the program. The helicopter pilots also experienced improved function and quality of health. Identifier: NCT01788111 Registration date; February 5th, 2013, verified April 2016.

[Virtual microscopy in pathology teaching and postgraduate training (continuing education)].

PubMed

Sinn, H P; Andrulis, M; Mogler, C; Schirmacher, P

2008-11-01

As with conventional microscopy, virtual microscopy permits histological tissue sections to be viewed on a computer screen with a free choice of viewing areas and a wide range of magnifications. This, combined with the possibility of linking virtual microscopy to E-Learning courses, make virtual microscopy an ideal tool for teaching and postgraduate training in pathology. Uses of virtual microscopy in pathology teaching include blended learning with the presentation of digital teaching slides in the internet parallel to presentation in the histology lab, extending student access to histology slides beyond the lab. Other uses are student self-learning in the Internet, as well as the presentation of virtual slides in the classroom with or without replacing real microscopes. Successful integration of virtual microscopy depends on its embedding in the virtual classroom and the creation of interactive E-learning content. Applications derived from this include the use of virtual microscopy in video clips, podcasts, SCORM modules and the presentation of virtual microscopy using interactive whiteboards in the classroom.

Cross-phase modulation spectral shifting: nonlinear phase contrast in a pump-probe microscope

PubMed Central

Wilson, Jesse W.; Samineni, Prathyush; Warren, Warren S.; Fischer, Martin C.

2012-01-01

Microscopy with nonlinear phase contrast is achieved by a simple modification to a nonlinear pump-probe microscope. The technique measures cross-phase modulation by detecting a pump-induced spectral shift in the probe pulse. Images with nonlinear phase contrast are acquired both in transparent and absorptive media. In paraffin-embedded biopsy sections, cross-phase modulation complements the chemically-specific pump-probe images with structural context. PMID:22567580

Wideband digital frequency detector with subtraction-based phase comparator for frequency modulation atomic force microscopy.

PubMed

Mitani, Yuji; Kubo, Mamoru; Muramoto, Ken-ichiro; Fukuma, Takeshi

2009-08-01

We have developed a wideband digital frequency detector for high-speed frequency modulation atomic force microscopy (FM-AFM). We used a subtraction-based phase comparator (PC) in a phase-locked loop circuit instead of a commonly used multiplication-based PC, which has enhanced the detection bandwidth to 100 kHz. The quantitative analysis of the noise performance revealed that the internal noise from the developed detector is small enough to provide the theoretically limited noise performance in FM-AFM experiments in liquid. FM-AFM imaging of mica in liquid was performed with the developed detector, showing its stability and applicability to true atomic-resolution imaging in liquid.

Challenges and complexities of multifrequency atomic force microscopy in liquid environments

PubMed Central

2014-01-01

Summary This paper illustrates through numerical simulation the complexities encountered in high-damping AFM imaging, as in liquid enviroments, within the specific context of multifrequency atomic force microscopy (AFM). The focus is primarily on (i) the amplitude and phase relaxation of driven higher eigenmodes between successive tip–sample impacts, (ii) the momentary excitation of non-driven higher eigenmodes and (iii) base excitation artifacts. The results and discussion are mostly applicable to the cases where higher eigenmodes are driven in open loop and frequency modulation within bimodal schemes, but some concepts are also applicable to other types of multifrequency operations and to single-eigenmode amplitude and frequency modulation methods. PMID:24778952

Stability, resolution, and ultra-low wear amplitude modulation atomic force microscopy of DNA: Small amplitude small set-point imaging

NASA Astrophysics Data System (ADS)

Santos, Sergio; Barcons, Victor; Christenson, Hugo K.; Billingsley, Daniel J.; Bonass, William A.; Font, Josep; Thomson, Neil H.

2013-08-01

A way to operate fundamental mode amplitude modulation atomic force microscopy is introduced which optimizes stability and resolution for a given tip size and shows negligible tip wear over extended time periods (˜24 h). In small amplitude small set-point (SASS) imaging, the cantilever oscillates with sub-nanometer amplitudes in the proximity of the sample, without the requirement of using large drive forces, as the dynamics smoothly lead the tip to the surface through the water layer. SASS is demonstrated on single molecules of double-stranded DNA in ambient conditions where sharp silicon tips (R ˜ 2-5 nm) can resolve the right-handed double helix.

Manipulating Si(100) at 5 K using qPlus frequency modulated atomic force microscopy: Role of defects and dynamics in the mechanical switching of atoms

NASA Astrophysics Data System (ADS)

Sweetman, A.; Jarvis, S.; Danza, R.; Bamidele, J.; Kantorovich, L.; Moriarty, P.

2011-08-01

We use small-amplitude qPlus frequency modulated atomic force microscopy (FM-AFM), at 5 K, to investigate the atomic-scale mechanical stability of the Si(100) surface. By operating at zero applied bias the effect of tunneling electrons is eliminated, demonstrating that surface manipulation can be performed by solely mechanical means. Striking differences in surface response are observed between different regions of the surface, most likely due to variations in strain associated with the presence of surface defects. We investigate the variation in local energy surface by ab initio simulation, and comment on the dynamics observed during force spectroscopy.

Quantitative measurements of nanoscale permittivity and conductivity using tuning-fork-based microwave impedance microscopy

NASA Astrophysics Data System (ADS)

Wu, Xiaoyu; Hao, Zhenqi; Wu, Di; Zheng, Lu; Jiang, Zhanzhi; Ganesan, Vishal; Wang, Yayu; Lai, Keji

2018-04-01

We report quantitative measurements of nanoscale permittivity and conductivity using tuning-fork (TF) based microwave impedance microscopy (MIM). The system is operated under the driving amplitude modulation mode, which ensures satisfactory feedback stability on samples with rough surfaces. The demodulated MIM signals on a series of bulk dielectrics are in good agreement with results simulated by finite-element analysis. Using the TF-MIM, we have visualized the evolution of nanoscale conductance on back-gated MoS2 field effect transistors, and the results are consistent with the transport data. Our work suggests that quantitative analysis of mesoscopic electrical properties can be achieved by near-field microwave imaging with small distance modulation.

Reliability of light microscopy and a computer-assisted replica measurement technique for evaluating the fit of dental copings.

PubMed

Rudolph, Heike; Ostertag, Silke; Ostertag, Michael; Walter, Michael H; Luthardt, Ralph Gunnar; Kuhn, Katharina

2018-02-01

The aim of this in vitro study was to assess the reliability of two measurement systems for evaluating the marginal and internal fit of dental copings. Sixteen CAD/CAM titanium copings were produced for a prepared maxillary canine. To modify the CAD surface model using different parameters (data density; enlargement in different directions), varying fit was created. Five light-body silicone replicas representing the gap between the canine and the coping were made for each coping and for each measurement method: (1) light microscopy measurements (LMMs); and (2) computer-assisted measurements (CASMs) using an optical digitizing system. Two investigators independently measured the marginal and internal fit using both methods. The inter-rater reliability [intraclass correlation coefficient (ICC)] and agreement [Bland-Altman (bias) analyses]: mean of the differences (bias) between two measurements [the closer to zero the mean (bias) is, the higher the agreement between the two measurements] were calculated for several measurement points (marginal-distal, marginal-buccal, axial-buccal, incisal). For the LMM technique, one investigator repeated the measurements to determine repeatability (intra-rater reliability and agreement). For inter-rater reliability, the ICC was 0.848-0.998 for LMMs and 0.945-0.999 for CASMs, depending on the measurement point. Bland-Altman bias was -15.7 to 3.5 μm for LMMs and -3.0 to 1.9 μm for CASMs. For LMMs, the marginal-distal and marginal-buccal measurement points showed the lowest ICC (0.848/0.978) and the highest bias (-15.7 μm/-7.6 μm). With the intra-rater reliability and agreement (repeatability) for LMMs, the ICC was 0.970-0.998 and bias was -1.3 to 2.3 μm. LMMs showed lower interrater reliability and agreement at the marginal measurement points than CASMs, which indicates a more subjective influence with LMMs at these measurement points. The values, however, were still clinically acceptable. LMMs showed very high intra-rater reliability and agreement for all measurement points, indicating high repeatability.

Reliability of light microscopy and a computer-assisted replica measurement technique for evaluating the fit of dental copings

PubMed Central

Rudolph, Heike; Ostertag, Silke; Ostertag, Michael; Walter, Michael H.; LUTHARDT, Ralph Gunnar; Kuhn, Katharina

2018-01-01

Abstract The aim of this in vitro study was to assess the reliability of two measurement systems for evaluating the marginal and internal fit of dental copings. Material and Methods Sixteen CAD/CAM titanium copings were produced for a prepared maxillary canine. To modify the CAD surface model using different parameters (data density; enlargement in different directions), varying fit was created. Five light-body silicone replicas representing the gap between the canine and the coping were made for each coping and for each measurement method: (1) light microscopy measurements (LMMs); and (2) computer-assisted measurements (CASMs) using an optical digitizing system. Two investigators independently measured the marginal and internal fit using both methods. The inter-rater reliability [intraclass correlation coefficient (ICC)] and agreement [Bland-Altman (bias) analyses]: mean of the differences (bias) between two measurements [the closer to zero the mean (bias) is, the higher the agreement between the two measurements] were calculated for several measurement points (marginal-distal, marginal-buccal, axial-buccal, incisal). For the LMM technique, one investigator repeated the measurements to determine repeatability (intra-rater reliability and agreement). Results For inter-rater reliability, the ICC was 0.848-0.998 for LMMs and 0.945-0.999 for CASMs, depending on the measurement point. Bland-Altman bias was −15.7 to 3.5 μm for LMMs and −3.0 to 1.9 μm for CASMs. For LMMs, the marginal-distal and marginal-buccal measurement points showed the lowest ICC (0.848/0.978) and the highest bias (-15.7 μm/-7.6 μm). With the intra-rater reliability and agreement (repeatability) for LMMs, the ICC was 0.970-0.998 and bias was −1.3 to 2.3 μm. Conclusion LMMs showed lower interrater reliability and agreement at the marginal measurement points than CASMs, which indicates a more subjective influence with LMMs at these measurement points. The values, however, were still clinically acceptable. LMMs showed very high intra-rater reliability and agreement for all measurement points, indicating high repeatability. PMID:29412364

Dynamical Imaging using Spatial Nonlinearity

DTIC Science & Technology

2014-01-29

643. [5] R. Heintzmann, C. Cremer , Lateral modulated excitation microscopy: Improvement of resolution by using a diffraction grating, Proceedings...by stochastic optical reconstruction microscopy (STORM), Nat Methods, 3 ( 2006 ) 793-795. [14] E. Betzig, G.H. Patterson, R. Sougrat, O.W. Lindwasser...Science, 313 ( 2006 ) 1642-1645. [15] W. Lukosz, M. Marchand, Optischen Abbildung Unter Überschreitung der Beugungsbedingten Auflösungsgrenze, Optica

Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules

PubMed Central

2017-01-01

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’. PMID:28093559

Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules.

PubMed

Liu, Kang K L; Hagan, Michael F; Lisman, John E

2017-03-05

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'. © 2017 The Author(s).

Laser-Excited Electronic and Thermal Elastic Vibrations in a Semiconductor Rectangular Plate

NASA Astrophysics Data System (ADS)

Todorović, D. M.; Cretin, B.; Vairac, P.; Song, Y. Q.; Rabasović, M. D.; Markushev, D. D.

2013-09-01

Photoacoustic and photothermal effects can be important as driven mechanisms for micro-(opto)-electro-mechanical structures (MOEMS). A new approach for a producing a compact, lightweight, highly sensitive detector is provided by MOEMS technology, which is based on the elastic bending of microstructure generated by absorption of modulated optical power. The electronic and thermal elastic vibrations (the electronic deformation and thermoelastic mechanisms of elastic wave generation) in a semiconductor rectangular simply supported plate (3D geometry), photogenerated by a focused and intensity-modulated laser beam, were studied. The theoretical model for the elastic displacements space and frequency distribution by using the Green function method was given. The amplitude of the elastic bending in the rectangular plate was calculated and analyzed, including the thermalization and surface and volume recombination heat sources. The theoretical results were compared with the experimental data. These investigations are important for many practical experimental situations (atomic force microscopy, thermal microscopy, thermoelastic microscopy, etc.) and sensors and actuators.

Daily haemodialysis improves indices of protein glycation.

PubMed

Floridi, Ardesio; Antolini, Francesco; Galli, Francesco; Fagugli, Riccardo Maria; Floridi, Emanuela; Buoncristiani, Umberto

2002-05-01

Advanced glycation end-products (AGEs) accumulate in uraemia, regardless of hyperglycaemic conditions, and may contribute to the onset of some long-term complications, such as atherosclerosis, amyloidosis, and neurodegenerative processes. In this study, we compare a daily with a standard 3 times/week dialysis rhythm (DHD and SHD, respectively) in correcting some protein glycation indices in end-stage renal disease (ESRD) patients. Twenty-one normoglycaemic and 11 diabetic patients on chronic haemodialysis (HD) with low-flux dialysers were studied in a prospective protocol to compare two different dialysis schedules, namely: 4 h, 3 times/week (SHD) and 2 h, 6 times/week (DHD). The patients were studied before and after 6 months of DHD. To further check the effect of DHD on glycation parameters, 4 normoglycaemic HD patients were studied in a third step in which they returned for 3 months to the SHD rhythm. Also, 11 chronic renal failure (CRF) patients not yet on HD and 11 age- and sex-matched healthy controls were studied. A new HPLC method was used to measure the following glycation indexes on plasma: the early product furosine and the advanced products protein-bound and free pentosidine, and two heterogeneous classes of low molecular mass (LMM) AGE peptides. All the parameters studied showed an accumulation that worsened with the progression of renal failure (controls

Dietary Intake of Proteins and Calories Is Inversely Associated With The Oxidation State of Plasma Thiols in End-Stage Renal Disease Patients.

PubMed

Fanti, Paolo; Giustarini, Daniela; Rossi, Ranieri; Cunningham, Sue E D; Folli, Franco; Khazim, Khaled; Cornell, John; Matteucci, Elena; Bansal, Shweta

2015-11-01

Oxidative stress contributes to the pathogenesis of protein-energy wasting in maintenance hemodialysis (MHD) patients, but knowledge of specific effectors and mechanisms remains fragmented. Aim of the study was to define whether and how food intake is involved in the causal relationship between oxidative stress and protein-energy wasting. Seventy-one adult MHD patients and 24 healthy subjects (control) were studied cross-sectionally with analyses of diet record and of oxidative stress, as measured by a battery of plasma thiols including the protein sulfhydryl (-SH) group (PSH) levels (a marker of total protein-SH reducing capacity), the protein thiolation index (PTI, the ratio between disulfide, i.e., oxidized and reduced -SH groups in proteins), low molecular mass (LMM) thiols, LMM disulfides, and mixed LMM-protein disulfides. In addition, interleukin-6 (IL-6), albumin, C-reactive protein, and neutrophil gelatinase-associated lipocalin (NGAL) were measured as markers of inflammation. The patients showed low energy (22.0 ± 8.4 kcal/kg/day) and adequate protein (1.0 ± 0.4 g/kg/day) intakes, high levels of cystine (CySS; patients vs. 113.5 [90.9-132.8] vs. 68.2 [56.2-75.7] μM), cysteinylated proteins (CySSP; 216.0 [182.8-254.0] vs. 163.5 [150.0-195.5] μM), and high PTI (0.76 [0.61-0.88] vs. 0.43 [0.40-0.54]; P < .001 in all comparisons). In patients, variation of CySSP was explained by a standard regression model (R = 0.775; P = .00001) that included significant contributions of protein intake (β = -0.361), NGAL (β = 0.387), age (β = 0.295), and albumin (β = 0.457). In the same model, variation of PTI (R = 0.624; P = .01) was explained by protein intake (β = -0.384) and age (β = 0.326) and NGAL (β = 0.311). However, when PSH was entered as dependent variable (R = 0.730; P = .0001), only serum albumin (β = 0.495) and age (β = -0.280), but not dietary intake or NGAL, contributed to the model. In MHD, markers of thiol oxidation including CySSP and PTI show independent association with dietary intake and NGAL, whereas PSH, a marker of thiol-reducing capacity, did not associate with these same variables. The mechanism(s) responsible for inverse association between oxidative stress and food intake in MHD remain undefined. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Review of advanced imaging techniques

PubMed Central

Chen, Yu; Liang, Chia-Pin; Liu, Yang; Fischer, Andrew H.; Parwani, Anil V.; Pantanowitz, Liron

2012-01-01

Pathology informatics encompasses digital imaging and related applications. Several specialized microscopy techniques have emerged which permit the acquisition of digital images (“optical biopsies”) at high resolution. Coupled with fiber-optic and micro-optic components, some of these imaging techniques (e.g., optical coherence tomography) are now integrated with a wide range of imaging devices such as endoscopes, laparoscopes, catheters, and needles that enable imaging inside the body. These advanced imaging modalities have exciting diagnostic potential and introduce new opportunities in pathology. Therefore, it is important that pathology informaticists understand these advanced imaging techniques and the impact they have on pathology. This paper reviews several recently developed microscopic techniques, including diffraction-limited methods (e.g., confocal microscopy, 2-photon microscopy, 4Pi microscopy, and spatially modulated illumination microscopy) and subdiffraction techniques (e.g., photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy). This article serves as a primer for pathology informaticists, highlighting the fundamentals and applications of advanced optical imaging techniques. PMID:22754737

Modulated structures and associated microstructures in the ferroelectric phase of Ba1-xSrxAl2O4 for 0.7 ≤ x ≤ 1.0

NASA Astrophysics Data System (ADS)

Tsukasaki, Hirofumi; Ishii, Yui; Tanaka, Eri; Kurushima, Kosuke; Mori, Shigeo

2016-01-01

In order to understand the ferroelectric and ferroelastic phases in Ba1-xSrxAl2O4 for 0.7 ≤ x ≤ 1.0, we have investigated the crystal structures and their associated microstructures of the ferroelectric and ferroelastic phases mainly by transmission electron microscopy (TEM) and scanning transmission electron microscopy-high-angle angular dark-field (STEM-HAADF) experiments, combined with powder X-ray diffraction experiments. Electron diffraction experiments showed that the ferroelectric and ferroelastic phases of Ba1-xSrxAl2O4 for 0.7 ≤ x ≤ 1.0 should be characterized as a modulated structure with the modulation vector of \\boldsymbol{{q}} = 0,1/2,0, whose space group should be monoclinic P21. High-resolution TEM experiments revealed that the microstructures in the monoclinic phase can be characterized as twin structures and nanometer-sized planar defects due to the monoclinic structure with the modulated structures, which are responsible for anomalous elastic behaviors and mechanoelectro-optical properties. In addition, subatomic-resolution STEM-HAADF images clearly indicated that the displacement of Al3+ ions involved in the AlO4 tetrahedra should play a crucial role in the formation of the modulated structures and twin structures.

Quantitative measurements of nanoscale permittivity and conductivity using tuning-fork-based microwave impedance microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xiaoyu; Hao, Zhenqi; Wu, Di

Here, we report quantitative measurements of nanoscale permittivity and conductivity using tuning-fork (TF) based microwave impedance microscopy (MIM). The system is operated under the driving amplitude modulation mode, which ensures satisfactory feedback stability on samples with rough surfaces. The demodulated MIM signals on a series of bulk dielectrics are in good agreement with results simulated by finite-element analysis. Using the TF-MIM, we have visualized the evolution of nanoscale conductance on back-gated MoS 2 field effect transistors, and the results are consistent with the transport data. Our work suggests that quantitative analysis of mesoscopic electrical properties can be achieved by near-fieldmore » microwave imaging with small distance modulation.« less

Quantitative measurements of nanoscale permittivity and conductivity using tuning-fork-based microwave impedance microscopy

DOE PAGES

Wu, Xiaoyu; Hao, Zhenqi; Wu, Di; ...

2018-04-01

Here, we report quantitative measurements of nanoscale permittivity and conductivity using tuning-fork (TF) based microwave impedance microscopy (MIM). The system is operated under the driving amplitude modulation mode, which ensures satisfactory feedback stability on samples with rough surfaces. The demodulated MIM signals on a series of bulk dielectrics are in good agreement with results simulated by finite-element analysis. Using the TF-MIM, we have visualized the evolution of nanoscale conductance on back-gated MoS 2 field effect transistors, and the results are consistent with the transport data. Our work suggests that quantitative analysis of mesoscopic electrical properties can be achieved by near-fieldmore » microwave imaging with small distance modulation.« less

Extending Single-Molecule Microscopy Using Optical Fourier Processing

PubMed Central

2015-01-01

This article surveys the recent application of optical Fourier processing to the long-established but still expanding field of single-molecule imaging and microscopy. A variety of single-molecule studies can benefit from the additional image information that can be obtained by modulating the Fourier, or pupil, plane of a widefield microscope. After briefly reviewing several current applications, we present a comprehensive and computationally efficient theoretical model for simulating single-molecule fluorescence as it propagates through an imaging system. Furthermore, we describe how phase/amplitude-modulating optics inserted in the imaging pathway may be modeled, especially at the Fourier plane. Finally, we discuss selected recent applications of Fourier processing methods to measure the orientation, depth, and rotational mobility of single fluorescent molecules. PMID:24745862

Index mismatch aberration correction over long working distances using spatial light modulation.

PubMed

Gjonaj, Bergin; Johnson, Patrick; Bonn, Mischa; Domke, Katrin F

2012-11-20

For many microscopy applications, millimeters-long free working distances (LWD) are required. However, the high resolution and contrast of LWD objectives operated in air are lost when introducing glass and/or liquid with the sample. We propose to use spatial light modulation to correct for such beam aberrations caused by refractive index mismatches. Focusing a monochromatic laser beam with a 10 mm working distance air objective (50×, 0.5 NA) through air, glass, and water, we manage to restore a sharp, intense focus (FWHM<2λ) by adaptive beam phase shaping. Our approach offers a practical and cost-effective route to high resolution and contrast microscopy using LWD air objectives, extending their usage beyond applications in air.

Extending single-molecule microscopy using optical Fourier processing.

PubMed

Backer, Adam S; Moerner, W E

2014-07-17

This article surveys the recent application of optical Fourier processing to the long-established but still expanding field of single-molecule imaging and microscopy. A variety of single-molecule studies can benefit from the additional image information that can be obtained by modulating the Fourier, or pupil, plane of a widefield microscope. After briefly reviewing several current applications, we present a comprehensive and computationally efficient theoretical model for simulating single-molecule fluorescence as it propagates through an imaging system. Furthermore, we describe how phase/amplitude-modulating optics inserted in the imaging pathway may be modeled, especially at the Fourier plane. Finally, we discuss selected recent applications of Fourier processing methods to measure the orientation, depth, and rotational mobility of single fluorescent molecules.

Coherent nonlinear optical imaging: beyond fluorescence microscopy.

PubMed

Min, Wei; Freudiger, Christian W; Lu, Sijia; Xie, X Sunney

2011-01-01

The quest for ultrahigh detection sensitivity with spectroscopic contrasts other than fluorescence has led to various novel approaches to optical microscopy of biological systems. Coherent nonlinear optical imaging, especially the recently developed nonlinear dissipation microscopy (including stimulated Raman scattering and two-photon absorption) and pump-probe microscopy (including excited-state absorption, stimulated emission, and ground-state depletion), provides new image contrasts for nonfluorescent species. Thanks to the high-frequency modulation transfer scheme, these imaging techniques exhibit superb detection sensitivity. By directly interrogating vibrational and/or electronic energy levels of molecules, they offer high molecular specificity. Here we review the underlying principles and excitation and detection schemes, as well as exemplary biomedical applications of this emerging class of molecular imaging techniques.

Modulation of electrical potential and conductivity in an atomic-layer semiconductor heterojunction

PubMed Central

Kobayashi, Yu; Yoshida, Shoji; Sakurada, Ryuji; Takashima, Kengo; Yamamoto, Takahiro; Saito, Tetsuki; Konabe, Satoru; Taniguchi, Takashi; Watanabe, Kenji; Maniwa, Yutaka; Takeuchi, Osamu; Shigekawa, Hidemi; Miyata, Yasumitsu

2016-01-01

Semiconductor heterojunction interfaces have been an important topic, both in modern solid state physics and in electronics and optoelectronics applications. Recently, the heterojunctions of atomically-thin transition metal dichalcogenides (TMDCs) are expected to realize one-dimensional (1D) electronic systems at their heterointerfaces due to their tunable electronic properties. Herein, we report unique conductivity enhancement and electrical potential modulation of heterojunction interfaces based on TMDC bilayers consisted of MoS2 and WS2. Scanning tunneling microscopy/spectroscopy analyses showed the formation of 1D confining potential (potential barrier) in the valence (conduction) band, as well as bandgap narrowing around the heterointerface. The modulation of electronic properties were also probed as the increase of current in conducting atomic force microscopy. Notably, the observed band bending can be explained by the presence of 1D fixed charges around the heterointerface. The present findings indicate that the atomic layer heterojunctions provide a novel approach to realizing tunable 1D electrical potential for embedded quantum wires and ultrashort barriers of electrical transport. PMID:27515115

The TRacking Adolescents' Individual Lives Survey (TRAILS): design, current status, and selected findings.

PubMed

Ormel, Johan; Oldehinkel, Albertine J; Sijtsema, Jelle; van Oort, Floor; Raven, Dennis; Veenstra, Rene; Vollebergh, Wilma A M; Verhulst, Frank C

2012-10-01

The objectives of this study were as follows: to present a concise overview of the sample, outcomes, determinants, non-response and attrition of the ongoing TRacking Adolescents' Individual Lives Survey (TRAILS), which started in 2001; to summarize a selection of recent findings on continuity, discontinuity, risk, and protective factors of mental health problems; and to document the development of psychopathology during adolescence, focusing on whether the increase of problem behavior often seen in adolescence is a general phenomenon or more prevalent in vulnerable teens, thereby giving rise to diverging developmental pathways. The first and second objectives were achieved using descriptive statistics and selective review of previous TRAILS publications; and the third objective by analyzing longitudinal data on internalizing and externalizing problems using Linear Mixed Models (LMM). The LMM analyses supported the notion of diverging pathways for rule-breaking behaviors but not for anxiety, depression, or aggression. Overall, rule-breaking (in both genders) and withdrawn/depressed behavior (in girls) increased, whereas aggression and anxious/depressed behavior decreased during adolescence. TRAILS has produced a wealth of data and has contributed substantially to our understanding of mental health problems and social development during adolescence. Future waves will expand this database into adulthood. The typical development of problem behaviors in adolescence differs considerably across both problem dimensions and gender. Developmental pathways during adolescence suggest accumulation of risk (i.e., diverging pathways) for rule-breaking behavior. However, those of anxiety, depression and aggression slightly converge, suggesting the influence of counter-forces and changes in risk unrelated to initial problem levels and underlying vulnerability. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli.

PubMed

González-Leiza, Silvia M; de Pedro, Miguel A; Ayala, Juan A

2011-12-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional DD-endopeptidase and DD-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (k(cat)/K(m)) of 1,200 M(-1) s(-1) and 670 M(-1) s(-1), respectively, and removed the terminal D-alanine from muropeptides with a C-terminal D-Ala-D-Ala dipeptide. Both DD-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10(-3) nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the DD-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes

PubMed Central

Dettweiler, Ulrich; Becker, Christoph; Auestad, Bjørn H.; Simon, Perikles; Kirsch, Peter

2017-01-01

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children’s normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol (p = 0.857), despite being higher in the intervention group (p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child’s diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon. PMID:28468292

Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis.

PubMed

Lall, Rahul K; Syed, Deeba N; Khan, Mohammad Imran; Adhami, Vaqar M; Gong, Yuansheng; Lucey, John A; Mukhtar, Hasan

2016-09-01

We and others have shown previously that fisetin, a plant flavonoid, has therapeutic potential against many cancer types. Here, we examined the probable mechanism of its action in prostate cancer (PCa) using a global metabolomics approach. HPLC-ESI-MS analysis of tumor xenografts from fisetin-treated animals identified several metabolic targets with hyaluronan (HA) as the most affected. Efficacy of fisetin on HA was then evaluated in vitro and also in vivo in the transgenic TRAMP mouse model of PCa. Size exclusion chromatography-multiangle laser light scattering (SEC-MALS) was performed to analyze the molar mass (Mw) distribution of HA. Fisetin treatment downregulated intracellular and secreted HA levels both in vitro and in vivo Fisetin inhibited HA synthesis and degradation enzymes, which led to cessation of HA synthesis and also repressed the degradation of the available high-molecular-mass (HMM)-HA. SEC-MALS analysis of intact HA fragment size revealed that cells and animals have more abundance of HMM-HA and less of low-molecular-mass (LMM)-HA upon fisetin treatment. Elevated HA levels have been shown to be associated with disease progression in certain cancer types. Biological responses triggered by HA mainly depend on the HA polymer length where HMM-HA represses mitogenic signaling and has anti-inflammatory properties whereas LMM-HA promotes proliferation and inflammation. Similarly, Mw analysis of secreted HA fragment size revealed less HMM-HA is secreted that allowed more HMM-HA to be retained within the cells and tissues. Our findings establish that fisetin is an effective, non-toxic, potent HA synthesis inhibitor, which increases abundance of antiangiogenic HMM-HA and could be used for the management of PCa. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CD133+ cell content correlates with tumour growth in melanomas from skin with chronic sun-induced damage.

PubMed

González-Herrero, I; Romero-Camarero, I; Cañueto, J; Cardeñoso-Álvarez, E; Fernández-López, E; Pérez-Losada, J; Sánchez-García, I; Román-Curto, C

2013-10-01

Melanoma is responsible for almost 80% of the deaths attributed to skin cancer. Stem cells, defined by CD133 expression, have been implicated in melanoma tumour growth, but their specific role is still uncertain. We hypothesized that the phenotypic heterogeneity of human cutaneous melanomas is related to their content of CD133+ cells. We compared the percentages of CD133+ cells in 29 tumours from four classic types of melanoma: lentigo maligna melanoma (LMM), superficial spreading melanoma, nodular melanoma and acral lentiginous melanoma (ALM). Also, we compared the percentages of CD133+ cells in melanomas with different degrees of exposure to ultraviolet radiation: 16 melanomas from skin with chronic sun-induced damage and 13 melanomas from skin without such damage. We found a statistically significant increase of CD133+ cells in three different contexts: in melanomas arising on skin with signs of chronic sun-induced damage vs. nonexposed skin, in melanomas in situ vs. invasive melanomas, and in LMM vs. ALM. The proportions of CD133+ cells did not differ among samples of normal skin with different degrees of sun exposure. A distinct subpopulation of CD133+CXCR4+ cancer stem cells (CSCs) was identified and shown to be related to the invasive phenotype of the tumours. Here, we provide evidence showing, for the first time, that an increase in the CD133+ cell content is associated both with melanomas arising on skin with signs of chronic sun-induced damage and in melanomas in situ with better prognosis. Moreover, our study further confirms the existence of a subpopulation of CD133+CXCR4+ CSCs in cutaneous melanomas with invasive phenotype and poor prognosis. © 2013 British Association of Dermatologists.

Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos

PubMed Central

Conomos, Matthew P.; Laurie, Cecelia A.; Stilp, Adrienne M.; Gogarten, Stephanie M.; McHugh, Caitlin P.; Nelson, Sarah C.; Sofer, Tamar; Fernández-Rhodes, Lindsay; Justice, Anne E.; Graff, Mariaelisa; Young, Kristin L.; Seyerle, Amanda A.; Avery, Christy L.; Taylor, Kent D.; Rotter, Jerome I.; Talavera, Gregory A.; Daviglus, Martha L.; Wassertheil-Smoller, Sylvia; Schneiderman, Neil; Heiss, Gerardo; Kaplan, Robert C.; Franceschini, Nora; Reiner, Alex P.; Shaffer, John R.; Barr, R. Graham; Kerr, Kathleen F.; Browning, Sharon R.; Browning, Brian L.; Weir, Bruce S.; Avilés-Santa, M. Larissa; Papanicolaou, George J.; Lumley, Thomas; Szpiro, Adam A.; North, Kari E.; Rice, Ken; Thornton, Timothy A.; Laurie, Cathy C.

2016-01-01

US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness. PMID:26748518

AmpH, a Bifunctional dd-Endopeptidase and dd-Carboxypeptidase of Escherichia coli▿

PubMed Central

González-Leiza, Silvia M.; de Pedro, Miguel A.; Ayala, Juan A.

2011-01-01

In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display dd-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional dd–endopeptidase and dd-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (kcat/Km) of 1,200 M−1 s−1 and 670 M−1 s−1, respectively, and removed the terminal d-alanine from muropeptides with a C-terminal d-Ala-d-Ala dipeptide. Both dd-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10−3 nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the dd-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling. PMID:22001512

A Bayesian Framework for Generalized Linear Mixed Modeling Identifies New Candidate Loci for Late-Onset Alzheimer’s Disease

PubMed Central

Wang, Xulong; Philip, Vivek M.; Ananda, Guruprasad; White, Charles C.; Malhotra, Ankit; Michalski, Paul J.; Karuturi, Krishna R. Murthy; Chintalapudi, Sumana R.; Acklin, Casey; Sasner, Michael; Bennett, David A.; De Jager, Philip L.; Howell, Gareth R.; Carter, Gregory W.

2018-01-01

Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost, whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages. To address these issues, we have devised a method for genomic association studies that implements a generalized LMM (GLMM) in a Bayesian framework, called Bayes-GLMM. Bayes-GLMM has four major features: (1) support of categorical, binary, and quantitative variables; (2) cohesive integration of previous GWAS results for related traits; (3) correction for sample relatedness by mixed modeling; and (4) model estimation by both Markov chain Monte Carlo sampling and maximal likelihood estimation. We applied Bayes-GLMM to the whole-genome sequencing cohort of the Alzheimer’s Disease Sequencing Project. This study contains 570 individuals from 111 families, each with Alzheimer’s disease diagnosed at one of four confidence levels. Using Bayes-GLMM we identified four variants in three loci significantly associated with Alzheimer’s disease. Two variants, rs140233081 and rs149372995, lie between PRKAR1B and PDGFA. The coded proteins are localized to the glial-vascular unit, and PDGFA transcript levels are associated with Alzheimer’s disease-related neuropathology. In summary, this work provides implementation of a flexible, generalized mixed-model approach in a Bayesian framework for association studies. PMID:29507048

lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals.

PubMed

Ziyatdinov, Andrey; Vázquez-Santiago, Miquel; Brunel, Helena; Martinez-Perez, Angel; Aschard, Hugues; Soria, Jose Manuel

2018-02-27

Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models. Apart from applications in linkage studies of related individuals, such functionalities are of high interest for association studies in situations where multiple covariance matrices need to be modeled, a scenario not covered by many genome-wide association study (GWAS) software. To address the aforementioned limitations, we developed a new R package lme4qtl as an extension of lme4. First, lme4qtl contributes new models for genetic studies within a single tool integrated with lme4 and its companion packages. Second, lme4qtl offers a flexible framework for scenarios with multiple levels of relatedness and becomes efficient when covariance matrices are sparse. We showed the value of our package using real family-based data in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2) project. Our software lme4qtl enables QTL mapping models with a versatile structure of random effects and efficient computation for sparse covariances. lme4qtl is available at https://github.com/variani/lme4qtl .

Creatinine and myoglobin are poor predictors of anaerobic threshold in colorectal cancer and health

PubMed Central

Nyasavajjala, Sitaramachandra M; Phillips, Beth E; Lund, Jon N; Williams, John P

2015-01-01

Aims Myoglobin is a haem protein produced in skeletal muscles. Serum concentrations of myoglobin have been proposed as a surrogate marker of muscle mass and function in both cachectic cancer patients and healthy non-cancer individuals. Creatinine, a metabolite of creatine phosphate, an energy store found in skeletal muscle, is produced at a constant rate from skeletal muscle. Urinary and plasma creatinine have been used in clinical practice as indicators of skeletal muscle mass in health and disease. Our study aimed to test the hypothesis that plasma myoglobin and creatinine concentration could accurately predict skeletal muscle mass and aerobic capacity in colorectal cancer (CRC) patients and matched healthy controls and thereby an indicative of aerobic performance. Methods We recruited 47 patients with CRC and matching number of healthy volunteers for this study. All participants had their body composition measured by dual-energy X-ray absorptiometry scan, aerobic capacity measured to anaerobic threshold (AT) by cardiopulmonary exercise testing and filled in objective questionnaires to assess the qualitative functions. This study was carried out in accordance with the Declaration of Helsinki, after approval by the local National Health Service (NHS) Research Ethics Committee. Results Age-matched groups had similar serum myoglobin and creatinine concentrations in spite of differences in their aerobic capacity. AT was significantly lower in the CRC group compared with matched controls (1.18 ± 0.44 vs. 1.41 ± 0.71 L/min; P < 0.01). AT had significant correlation with lean muscle mass (LMM) among these groups, but myoglobin and creatinine had poor correlation with LMM and AT. Conclusions Serum myoglobin is a poor predictor of muscle mass, and serum myoglobin and creatinine concentrations do not predict aerobic performance in CRC patients or healthy matched controls. PMID:26136188

The Utility of 5 Hypothetical Health States in Heart Failure Using Time Trade-Off (TTO) and EQ-5D-5L in Korea.

PubMed

Hong, Sung-Hyun; Lee, Jae-Yeon; Park, Sun-Kyeong; Nam, Jin Hyun; Song, Hyun Jin; Park, Sun-Young; Lee, Eui-Kyung

2018-05-26

Utility provides a preference for specific health state in economic evaluation, and they obtained from general population could be useful in respect of societal resource allocation. We aimed to investigate the utilities of health states for heart failure (HF), a major and growing public health problem, related to hospitalization and adverse drug effects by interrogating the general Korean population. Five health states for patients with HF were developed based on literature reviews: stable chronic heart failure (SCHF), hospitalization, SCHF + cough, SCHF + hypotension, and SCHF + hyperkalemia. We selected 100 individuals from the general population through quota sampling by age, sex, and region, and conducted face-to-face interviews. We measured utilities for 5 hypothetical health states of HF using both time trade-off (TTO) and EuroQol-5 dimensions-5 levels (EQ-5D-5L). Repeated-measures analysis of variance compared the utilities between all health states for each instrument. To identify the factors affecting the utility, a linear mixed model (LMM) analysis was performed. The mean utility value for SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization was calculated as 0.815, 0.732, 0.646, 0.548, and 0.360, respectively, by using TTO. The respective values using EQ-5D-5L were 0.871, 0.793, 0.710, 0.589, and 0.215. The utilities for HF significantly differed between all health states in each instrument (p < 0.001). In LMM analysis, hospitalization had a significantly negative effect on the utilities of both instruments. The utilities decreased in order of SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization. These results can be useful for decision making in resource allocation for HF interventions.

Sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) versus dynapenia as a risk factor for mortality in the elderly.

PubMed

Alexandre, T da Silva; Duarte, Y A de Oliveira; Santos, J L Ferreira; Wong, R; Lebrão, M L

2014-01-01

Sarcopenia and dynapenia have been associated with poorer physical performance, disability and death. The aim of this study was to compare the association between sarcopenia and dynapenia with mortality. We studied 1,149 Brazilians aged 60 years or older residing in São Paulo. Sarcopenia was defined according to the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP), which includes three components: low muscle mass (LMM) assessed by skeletal muscle mass index ≤ 8.90kg/m2 (men) and ≤ 6.37kg/m2 (women); low muscle strength (LMS) assessed by handgrip strength <30kg (men) and < 20kg (women); and low physical performance (LPP) assessed by walking speed ≤ 0.8m/s. Diagnosis of sarcopenia required presence of LMM plus LMS or LPP. Dynapenia was defined as handgrip strength < 30kg (men) and < 20kg (women). Covariates included socio-demographic and behavioral variables, medical conditions, hospitalization, depressive symptoms, cognition, and disability in activities of daily living or instrumental activities of daily living. The outcome was all-cause mortality over five-year follow-up. During the five-year follow-up, 187 subjects died. The mortality rate for those with or without sarcopenia were 65.9/1,000 person/years and 20.1/1,000 person/years and for dynapenia were 44.3/1,000 person/years and 14.9/1,000 person/years. The adjusted model showed that sarcopenia (HR=1.52, 95%CI: 1.06 - 2.19) and dynapenia (HR=2.04, 95%CI: 1.24 - 3.37) are independent risk factors for death. The EWGSOP definition of sarcopenia and dynapenia can help to determine risk for mortality and can be used as a screening instrument in public health.

Aberration correction considering curved sample surface shape for non-contact two-photon excitation microscopy with spatial light modulator.

PubMed

Matsumoto, Naoya; Konno, Alu; Inoue, Takashi; Okazaki, Shigetoshi

2018-06-18

In this paper, excitation light wavefront modulation is performed considering the curved sample surface shape to demonstrate high-quality deep observation using two-photon excitation microscopy (TPM) with a dry objective lens. A large spherical aberration typically occurs when the refractive index (RI) interface between air and the sample is a plane perpendicular to the optical axis. Moreover, the curved sample surface shape and the RI mismatch cause various aberrations, including spherical ones. Consequently, the fluorescence intensity and resolution of the obtained image are degraded in the deep regions. To improve them, we designed a pre-distortion wavefront for correcting the aberration caused by the curved sample surface shape by using a novel, simple optical path length difference calculation method. The excitation light wavefront is modulated to the pre-distortion wavefront by a spatial light modulator incorporated in the TPM system before passing through the interface, where the RI mismatch occurs. Thus, the excitation light is condensed without aberrations. Blood vessels were thereby observed up to an optical depth of 2,000 μm in a cleared mouse brain by using a dry objective lens.

Functional Scanning Probe Imaging of Nanostructured Solar Energy Materials.

PubMed

Giridharagopal, Rajiv; Cox, Phillip A; Ginger, David S

2016-09-20

From hybrid perovskites to semiconducting polymer/fullerene blends for organic photovoltaics, many new materials being explored for energy harvesting and storage exhibit performance characteristics that depend sensitively on their nanoscale morphology. At the same time, rapid advances in the capability and accessibility of scanning probe microscopy methods over the past decade have made it possible to study processing/structure/function relationships ranging from photocurrent collection to photocarrier lifetimes with resolutions on the scale of tens of nanometers or better. Importantly, such scanning probe methods offer the potential to combine measurements of local structure with local function, and they can be implemented to study materials in situ or devices in operando to better understand how materials evolve in time in response to an external stimulus or environmental perturbation. This Account highlights recent advances in the development and application of scanning probe microscopy methods that can help address such questions while filling key gaps between the capabilities of conventional electron microscopy and newer super-resolution optical methods. Focusing on semiconductor materials for solar energy applications, we highlight a range of electrical and optoelectronic scanning probe microscopy methods that exploit the local dynamics of an atomic force microscope tip to probe key properties of the solar cell material or device structure. We discuss how it is possible to extract relevant device properties using noncontact scanning probe methods as well as how these properties guide materials development. Specifically, we discuss intensity-modulated scanning Kelvin probe microscopy (IM-SKPM), time-resolved electrostatic force microscopy (trEFM), frequency-modulated electrostatic force microscopy (FM-EFM), and cantilever ringdown imaging. We explain these developments in the context of classic atomic force microscopy (AFM) methods that exploit the physics of cantilever motion and photocarrier generation to provide robust, nanoscale measurements of materials physics that are correlated with device operation. We predict that the multidimensional data sets made possible by these types of methods will become increasingly important as advances in data science expand capabilities and opportunities for image correlation and discovery.

Artifacts in time-resolved Kelvin probe force microscopy

DOE PAGES

Sadewasser, Sascha; Nicoara, Nicoleta; Solares, Santiago D.

2018-04-24

Kelvin probe force microscopy (KPFM) has been used for the characterization of metals, insulators, and semiconducting materials on the nanometer scale. Especially in semiconductors, the charge dynamics are of high interest. Recently, several techniques for time-resolved measurements with time resolution down to picoseconds have been developed, many times using a modulated excitation signal, e.g. light modulation or bias modulation that induces changes in the charge carrier distribution. For fast modulation frequencies, the KPFM controller measures an average surface potential, which contains information about the involved charge carrier dynamics. Here, we show that such measurements are prone to artifacts due tomore » frequency mixing, by performing numerical dynamics simulations of the cantilever oscillation in KPFM subjected to a bias-modulated signal. For square bias pulses, the resulting time-dependent electrostatic forces are very complex and result in intricate mixing of frequencies that may, in some cases, have a component at the detection frequency, leading to falsified KPFM measurements. Additionally, we performed fast Fourier transform (FFT) analyses that match the results of the numerical dynamics simulations. Small differences are observed that can be attributed to transients and higher-order Fourier components, as a consequence of the intricate nature of the cantilever driving forces. These results are corroborated by experimental measurements on a model system. In the experimental case, additional artifacts are observed due to constructive or destructive interference of the bias modulation with the cantilever oscillation. Also, in the case of light modulation, we demonstrate artifacts due to unwanted illumination of the photodetector of the beam deflection detection system. Lastly, guidelines for avoiding such artifacts are given.« less

Artifacts in time-resolved Kelvin probe force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadewasser, Sascha; Nicoara, Nicoleta; Solares, Santiago D.

Kelvin probe force microscopy (KPFM) has been used for the characterization of metals, insulators, and semiconducting materials on the nanometer scale. Especially in semiconductors, the charge dynamics are of high interest. Recently, several techniques for time-resolved measurements with time resolution down to picoseconds have been developed, many times using a modulated excitation signal, e.g. light modulation or bias modulation that induces changes in the charge carrier distribution. For fast modulation frequencies, the KPFM controller measures an average surface potential, which contains information about the involved charge carrier dynamics. Here, we show that such measurements are prone to artifacts due tomore » frequency mixing, by performing numerical dynamics simulations of the cantilever oscillation in KPFM subjected to a bias-modulated signal. For square bias pulses, the resulting time-dependent electrostatic forces are very complex and result in intricate mixing of frequencies that may, in some cases, have a component at the detection frequency, leading to falsified KPFM measurements. Additionally, we performed fast Fourier transform (FFT) analyses that match the results of the numerical dynamics simulations. Small differences are observed that can be attributed to transients and higher-order Fourier components, as a consequence of the intricate nature of the cantilever driving forces. These results are corroborated by experimental measurements on a model system. In the experimental case, additional artifacts are observed due to constructive or destructive interference of the bias modulation with the cantilever oscillation. Also, in the case of light modulation, we demonstrate artifacts due to unwanted illumination of the photodetector of the beam deflection detection system. Lastly, guidelines for avoiding such artifacts are given.« less

Modulated CMOS camera for fluorescence lifetime microscopy.

PubMed

Chen, Hongtao; Holst, Gerhard; Gratton, Enrico

2015-12-01

Widefield frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate method to measure the fluorescence lifetime of entire images. However, the complexity and high costs involved in construction of such a system limit the extensive use of this technique. PCO AG recently released the first luminescence lifetime imaging camera based on a high frequency modulated CMOS image sensor, QMFLIM2. Here we tested and provide operational procedures to calibrate the camera and to improve the accuracy using corrections necessary for image analysis. With its flexible input/output options, we are able to use a modulated laser diode or a 20 MHz pulsed white supercontinuum laser as the light source. The output of the camera consists of a stack of modulated images that can be analyzed by the SimFCS software using the phasor approach. The nonuniform system response across the image sensor must be calibrated at the pixel level. This pixel calibration is crucial and needed for every camera settings, e.g. modulation frequency and exposure time. A significant dependency of the modulation signal on the intensity was also observed and hence an additional calibration is needed for each pixel depending on the pixel intensity level. These corrections are important not only for the fundamental frequency, but also for the higher harmonics when using the pulsed supercontinuum laser. With these post data acquisition corrections, the PCO CMOS-FLIM camera can be used for various biomedical applications requiring a large frame and high speed acquisition. © 2015 Wiley Periodicals, Inc.

Invited Review Article: Imaging techniques for harmonic and multiphoton absorption fluorescence microscopy

PubMed Central

Carriles, Ramón; Schafer, Dawn N.; Sheetz, Kraig E.; Field, Jeffrey J.; Cisek, Richard; Barzda, Virginijus; Sylvester, Anne W.; Squier, Jeffrey A.

2009-01-01

We review the current state of multiphoton microscopy. In particular, the requirements and limitations associated with high-speed multiphoton imaging are considered. A description of the different scanning technologies such as line scan, multifoci approaches, multidepth microscopy, and novel detection techniques is given. The main nonlinear optical contrast mechanisms employed in microscopy are reviewed, namely, multiphoton excitation fluorescence, second harmonic generation, and third harmonic generation. Techniques for optimizing these nonlinear mechanisms through a careful measurement of the spatial and temporal characteristics of the focal volume are discussed, and a brief summary of photobleaching effects is provided. Finally, we consider three new applications of multiphoton microscopy: nonlinear imaging in microfluidics as applied to chemical analysis and the use of two-photon absorption and self-phase modulation as contrast mechanisms applied to imaging problems in the medical sciences. PMID:19725639

Adaptive optics in spinning disk microscopy: improved contrast and brightness by a simple and fast method.

PubMed

Fraisier, V; Clouvel, G; Jasaitis, A; Dimitrov, A; Piolot, T; Salamero, J

2015-09-01

Multiconfocal microscopy gives a good compromise between fast imaging and reasonable resolution. However, the low intensity of live fluorescent emitters is a major limitation to this technique. Aberrations induced by the optical setup, especially the mismatch of the refractive index and the biological sample itself, distort the point spread function and further reduce the amount of detected photons. Altogether, this leads to impaired image quality, preventing accurate analysis of molecular processes in biological samples and imaging deep in the sample. The amount of detected fluorescence can be improved with adaptive optics. Here, we used a compact adaptive optics module (adaptive optics box for sectioning optical microscopy), which was specifically designed for spinning disk confocal microscopy. The module overcomes undesired anomalies by correcting for most of the aberrations in confocal imaging. Existing aberration detection methods require prior illumination, which bleaches the sample. To avoid multiple exposures of the sample, we established an experimental model describing the depth dependence of major aberrations. This model allows us to correct for those aberrations when performing a z-stack, gradually increasing the amplitude of the correction with depth. It does not require illumination of the sample for aberration detection, thus minimizing photobleaching and phototoxicity. With this model, we improved both signal-to-background ratio and image contrast. Here, we present comparative studies on a variety of biological samples. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Ultrafast, large-field multiphoton microscopy based on an acousto-optic deflector and a spatial light modulator.

PubMed

Shao, Yonghong; Qin, Wan; Liu, Honghai; Qu, Junle; Peng, Xiang; Niu, Hanben; Gao, Bruce Z

2012-07-01

We present an ultrafast, large-field multiphoton excitation fluorescence microscope with high lateral and axial resolutions based on a two-dimensional (2-D) acousto-optical deflector (AOD) scanner and spatial light modulator (SLM). When a phase-only SLM is used to shape the near-infrared light from a mode-locked titanium:sapphire laser into a multifocus array including the 0-order beam, a 136 μm × 136 μm field of view is achieved with a 60× objective using a 2-D AOD scanner without any mechanical scan element. The two-photon fluorescence image of a neuronal network that was obtained using this system demonstrates that our microscopy permits observation of dynamic biological events in a large field with high-temporal and -spatial resolution.

A multi-modal stereo microscope based on a spatial light modulator.

PubMed

Lee, M P; Gibson, G M; Bowman, R; Bernet, S; Ritsch-Marte, M; Phillips, D B; Padgett, M J

2013-07-15

Spatial Light Modulators (SLMs) can emulate the classic microscopy techniques, including differential interference (DIC) contrast and (spiral) phase contrast. Their programmability entails the benefit of flexibility or the option to multiplex images, for single-shot quantitative imaging or for simultaneous multi-plane imaging (depth-of-field multiplexing). We report the development of a microscope sharing many of the previously demonstrated capabilities, within a holographic implementation of a stereo microscope. Furthermore, we use the SLM to combine stereo microscopy with a refocusing filter and with a darkfield filter. The instrument is built around a custom inverted microscope and equipped with an SLM which gives various imaging modes laterally displaced on the same camera chip. In addition, there is a wide angle camera for visualisation of a larger region of the sample.

Structural properties of GaAsN grown on (001) GaAs by metalorganic molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Ok, Young-Woo; Choi, Chel-Jong; Seong, Tae-Yeon; Uesugi, K.; Suemune, I.

2001-07-01

Detailed transmission electron microscopy (TEM) and transmission electron diffraction (TED) examination has been made of metalorganic molecular beam epitaxial GaAsN layers grown on (001) GaAs substrates. TEM results show that lateral composition modulation occurs in the GaAs1-xNx layer (x 6.75%). It is shown that increasing N composition and Se (dopant) concentration leads to poor crystallinity. It is also shown that the addition of Se increases N composition. Atomic force microscopy (AFM) results show that the surfaces of the samples experience a morphological change from faceting to islanding, as the N composition and Se concentration increase. Based on the TEM and AFM results, a simple model is given to explain the formation of the lateral composition modulation.

Boxcar detection for high-frequency modulation in stimulated Raman scattering microscopy

NASA Astrophysics Data System (ADS)

Fimpel, P.; Riek, C.; Ebner, L.; Leitenstorfer, A.; Brida, D.; Zumbusch, A.

2018-04-01

Stimulated Raman scattering (SRS) microscopy is an important non-linear optical technique for the investigation of unlabeled samples. The SRS signal manifests itself as a small intensity exchange between the laser pulses involved in coherent excitation of Raman modes. Usually, high-frequency modulation is applied in one pulse train, and the signal is then detected on the other pulse train via lock-in amplification. While allowing shot-noise limited detection sensitivity, lock-in detection, which corresponds to filtering the signal in the frequency domain, is not the most efficient way of using the excitation light. In this manuscript, we show that boxcar averaging, which is equivalent to temporal filtering, is better suited for the detection of low-duty-cycle signals as encountered in SRS microscopy. We demonstrate that by employing suitable gating windows, the signal-to-noise ratios achievable with lock-in detection can be realized in shorter time with boxcar averaging. Therefore, high-quality images are recorded at a faster rate and lower irradiance which is an important factor, e.g., for minimizing degradation of biological samples.

Magnetic domain structure imaging near sample surface with alternating magnetic force microscopy by using AC magnetic field modulated superparamagnetic tip.

PubMed

Cao, Yongze; Nakayama, Shota; Kumar, Pawan; Zhao, Yue; Kinoshita, Yukinori; Yoshimura, Satoru; Saito, Hitoshi

2018-05-03

For magnetic domain imaging with a very high spatial resolution by magnetic force microscopy the tip-sample distance should be as small as possible. However, magnetic imaging near sample surface is very difficult with conventional MFM because the interactive forces between tip and sample includes van der Waals and electrostatic forces along with magnetic force. In this study, we proposed an alternating magnetic force microscopy (A-MFM) which extract only magnetic force near sample surface without any topographic and electrical crosstalk. In the present method, the magnetization of a FeCo-GdOx superparamagnetic tip is modulated by an external AC magnetic field in order to measure the magnetic domain structure without any perturbation from the other forces near the sample surface. Moreover, it is demonstrated that the proposed method can also measure the strength and identify the polarities of the second derivative of the perpendicular stray field from a thin-film permanent magnet with DC demagnetized state and remanent state. © 2018 IOP Publishing Ltd.

Kilohertz binary phase modulator for pulsed laser sources using a digital micromirror device.

PubMed

Hoffmann, Maximilian; Papadopoulos, Ioannis N; Judkewitz, Benjamin

2018-01-01

The controlled modulation of an optical wavefront is required for aberration correction, digital phase conjugation, or patterned photostimulation. For most of these applications, it is desirable to control the wavefront modulation at the highest rates possible. The digital micromirror device (DMD) presents a cost-effective solution to achieve high-speed modulation and often exceeds the speed of the more conventional liquid crystal spatial light modulator but is inherently an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction complicates its use with pulsed laser sources, such as those used in nonlinear microscopy. Here we introduce a DMD-based optical design that overcomes these limitations and achieves dispersion-free high-speed binary phase modulation. We show that this phase modulation can be used to switch through binary phase patterns at the rate of 20 kHz in two-photon excitation fluorescence applications.

Kilohertz binary phase modulator for pulsed laser sources using a digital micromirror device

NASA Astrophysics Data System (ADS)

Hoffmann, Maximilian; Papadopoulos, Ioannis N.; Judkewitz, Benjamin

2018-01-01

The controlled modulation of an optical wavefront is required for aberration correction, digital phase conjugation or patterned photostimulation. For most of these applications it is desirable to control the wavefront modulation at the highest rates possible. The digital micromirror device (DMD) presents a cost-effective solution to achieve high-speed modulation and often exceeds the speed of the more conventional liquid crystal spatial light modulator, but is inherently an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction complicates its use with pulsed laser sources, such as those used in nonlinear microscopy. Here we introduce a DMD-based optical design that overcomes these limitations and achieves dispersion-free high-speed binary phase modulation. We show that this phase modulation can be used to switch through binary phase patterns at the rate of 20 kHz in two-photon excitation fluorescence applications.

Tidal and Lunar Data for Point Mugu, San Nicolas Island, and the Barking Sands Area During 1988.

DTIC Science & Technology

1987-12-31

C l vNvN-A -0%Ow’!’N N r--Me’a In v-(v0r-v inav -f -X W WI- 0 -!)0 N~o CD NI- 0V NMQ-N o ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ V KU LMM tt-y d tL) J O’ed.ci I o -a NM...Commander Third Fleet 1 Pearl Harbor, HI 96860-7500 Commander Naval Weapons Center Attn: Earth and Planetary Sciences Division 1 Code 343 (Technical...Center P.O. Box 271 Attn: Fishery-Oceanographic Group La Jolla, CA 92037 University of California Department of Biological Sciences Attn: Dr. A. M

Microstructure characterization of the non-modulated martensite in Ni-Mn-Ga alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, M.; Bennett, J.C.; Gharghouri, M.A.

2008-06-15

The microstructure of the non-modulated martensite in a Ni-Mn-Ga alloy has been characterized in detail by conventional transmission electron microscopy. Bright field images show that the martensite exhibits an internal substructure consisting of a high density of narrow twins. Using electron diffraction, it is found that the martensite has a tetragonal crystal structure. The lattice correspondence between the parent phase and the non-modulated martensite is investigated. Furthermore, the four twinning elements describing the microtwinning have been graphically and quantitatively determined. The results indicate that the microtwinning within the non-modulated martensite belongs to the compound type.

Note: Design of FPGA based system identification module with application to atomic force microscopy

NASA Astrophysics Data System (ADS)

Ghosal, Sayan; Pradhan, Sourav; Salapaka, Murti

2018-05-01

The science of system identification is widely utilized in modeling input-output relationships of diverse systems. In this article, we report field programmable gate array (FPGA) based implementation of a real-time system identification algorithm which employs forgetting factors and bias compensation techniques. The FPGA module is employed to estimate the mechanical properties of surfaces of materials at the nano-scale with an atomic force microscope (AFM). The FPGA module is user friendly which can be interfaced with commercially available AFMs. Extensive simulation and experimental results validate the design.

Nanoscale surface characterization using laser interference microscopy

NASA Astrophysics Data System (ADS)

Ignatyev, Pavel S.; Skrynnik, Andrey A.; Melnik, Yury A.

2018-03-01

Nanoscale surface characterization is one of the most significant parts of modern materials development and application. The modern microscopes are expensive and complicated tools, and its use for industrial tasks is limited due to laborious sample preparation, measurement procedures, and low operation speed. The laser modulation interference microscopy method (MIM) for real-time quantitative and qualitative analysis of glass, metals, ceramics, and various coatings has a spatial resolution of 0.1 nm for vertical and up to 100 nm for lateral. It is proposed as an alternative to traditional scanning electron microscopy (SEM) and atomic force microscopy (AFM) methods. It is demonstrated that in the cases of roughness metrology for super smooth (Ra >1 nm) surfaces the application of a laser interference microscopy techniques is more optimal than conventional SEM and AFM. The comparison of semiconductor test structure for lateral dimensions measurements obtained with SEM and AFM and white light interferometer also demonstrates the advantages of MIM technique.

Super resolution imaging of HER2 gene amplification

NASA Astrophysics Data System (ADS)

Okada, Masaya; Kubo, Takuya; Masumoto, Kanako; Iwanaga, Shigeki

2016-02-01

HER2 positive breast cancer is currently examined by counting HER2 genes using fluorescence in situ hybridization (FISH)-stained breast carcinoma samples. In this research, two-dimensional super resolution fluorescence microscopy based on stochastic optical reconstruction microscopy (STORM), with a spatial resolution of approximately 20 nm in the lateral direction, was used to more precisely distinguish and count HER2 genes in a FISH-stained tissue section. Furthermore, by introducing double-helix point spread function (DH-PSF), an optical phase modulation technique, to super resolution microscopy, three-dimensional images were obtained of HER2 in a breast carcinoma sample approximately 4 μm thick.

Surface potential measurement of n-type organic semiconductor thin films by mist deposition via Kelvin probe microscopy

NASA Astrophysics Data System (ADS)

Odaka, Akihiro; Satoh, Nobuo; Katori, Shigetaka

2017-08-01

We partially deposited fullerene (C60) and phenyl-C61-butyric acid methyl ester thin films that are typical n-type semiconductor materials on indium-tin oxide by mist deposition at various substrate temperatures. The topographic and surface potential images were observed via dynamic force microscopy/Kelvin probe force microscopy with the frequency modulation detection method. We proved that the area where a thin film is deposited depends on the substrate temperature during deposition from the topographic images. It was also found that the surface potential depends on the substrate temperature from the surface potential images.

Trade-offs in sensitivity and sampling depth in bimodal atomic force microscopy and comparison to the trimodal case

PubMed Central

Eslami, Babak; Ebeling, Daniel

2014-01-01

Summary This paper presents experiments on Nafion® proton exchange membranes and numerical simulations illustrating the trade-offs between the optimization of compositional contrast and the modulation of tip indentation depth in bimodal atomic force microscopy (AFM). We focus on the original bimodal AFM method, which uses amplitude modulation to acquire the topography through the first cantilever eigenmode, and drives a higher eigenmode in open-loop to perform compositional mapping. This method is attractive due to its relative simplicity, robustness and commercial availability. We show that this technique offers the capability to modulate tip indentation depth, in addition to providing sample topography and material property contrast, although there are important competing effects between the optimization of sensitivity and the control of indentation depth, both of which strongly influence the contrast quality. Furthermore, we demonstrate that the two eigenmodes can be highly coupled in practice, especially when highly repulsive imaging conditions are used. Finally, we also offer a comparison with a previously reported trimodal AFM method, where the above competing effects are minimized. PMID:25161847

Frequency modulation detection atomic force microscopy in the liquid environment

NASA Astrophysics Data System (ADS)

Jarvis, S. P.; Ishida, T.; Uchihashi, T.; Nakayama, Y.; Tokumoto, H.

True atomic resolution imaging using frequency modulation detection is already well established in ultra-high vacuum. In this paper we demonstrate that it also has great potential in the liquid environment. Using a combination of magnetic activation and high-aspect-ratio carbon nanotube probes, we show that imaging can be readily combined with point spectroscopy, revealing both the tip-sample interaction and the structure of the intermediate liquid.

A Mobile Nanoscience and Electron Microscopy Outreach Program

NASA Astrophysics Data System (ADS)

Coffey, Tonya; Kelley, Kyle

2013-03-01

We have established a mobile nanoscience laboratory outreach program in Western NC that puts scanning electron microscopy (SEM) directly in the hands of K-12 students and the general public. There has been a recent push to develop new active learning materials to educate students at all levels about nanoscience and nanotechnology. Previous projects, such as Bugscope, nanoManipulator, or SPM Live! allowed remote access to advanced microscopies. However, placing SEM directly in schools has not often been possible because the cost and steep learning curve of these technologies were prohibitive, making this project quite novel. We have developed new learning modules for a microscopy outreach experience with a tabletop SEM (Hitachi TM3000). We present here an overview of our outreach and results of the assessment of our program to date.

Quantitative force measurements in liquid using frequency modulation atomic force microscopy

NASA Astrophysics Data System (ADS)

Uchihashi, Takayuki; Higgins, Michael J.; Yasuda, Satoshi; Jarvis, Suzanne P.; Akita, Seiji; Nakayama, Yoshikazu; Sader, John E.

2004-10-01

The measurement of short-range forces with the atomic force microscope (AFM) typically requires implementation of dynamic techniques to maintain sensitivity and stability. While frequency modulation atomic force microscopy (FM-AFM) is used widely for high-resolution imaging and quantitative force measurements in vacuum, quantitative force measurements using FM-AFM in liquids have proven elusive. Here we demonstrate that the formalism derived for operation in vacuum can also be used in liquids, provided certain modifications are implemented. To facilitate comparison with previous measurements taken using surface forces apparatus, we choose a model system (octamethylcyclotetrasiloxane) that is known to exhibit short-ranged structural ordering when confined between two surfaces. Force measurements obtained are found to be in excellent agreement with previously reported results. This study therefore establishes FM-AFM as a powerful tool for the quantitative measurement of forces in liquid.

A line scanned light-sheet microscope with phase shaped self-reconstructing beams.

PubMed

Fahrbach, Florian O; Rohrbach, Alexander

2010-11-08

We recently demonstrated that Microscopy with Self-Reconstructing Beams (MISERB) increases both image quality and penetration depth of illumination beams in strongly scattering media. Based on the concept of line scanned light-sheet microscopy, we present an add-on module to a standard inverted microscope using a scanned beam that is shaped in phase and amplitude by a spatial light modulator. We explain technical details of the setup as well as of the holograms for the creation, positioning and scaling of static light-sheets, Gaussian beams and Bessel beams. The comparison of images from identical sample areas illuminated by different beams allows a precise assessment of the interconnection between beam shape and image quality. The superior propagation ability of Bessel beams through inhomogeneous media is demonstrated by measurements on various scattering media.

Versatile derivatives of carbohydrate-binding modules for imaging of complex carbohydrates approaching the molecular level of resolution.

PubMed

Ding, Shi-You; Xu, Qi; Ali, Mursheda K; Baker, John O; Bayer, Edward A; Barak, Yoav; Lamed, Raphael; Sugiyama, Junji; Rumbles, Garry; Himmel, Michael E

2006-10-01

The innate binding specificity of different carbohydrate-binding modules (CBMs) offers a versatile approach for mapping the chemistry and structure of surfaces that contain complex carbohydrates. We have employed the distinct recognition properties of a double His-tagged recombinant CBM tagged with semiconductor quantum dots for direct imaging of crystalline cellulose at the molecular level of resolution, using transmission and scanning transmission electron microscopy. In addition, three different types of CBMs from families 3, 6, and 20 that exhibit different carbohydrate specificities were each fused with either green fluorescent protein (GFP) or red fluorescent protein (RFP) and employed for double-labeling fluorescence microscopy studies of primary cell walls and various mixtures of complex carbohydrate target molecules. CBM probes can be used for characterizing both native complex carbohydrates and engineered biomaterials.

Acceptance testing and commissioning of Kodak Directview CR-850 digital radiography system.

PubMed

Bezak, E; Nelligan, R A

2006-03-01

This Technical Paper describes Acceptance Testing and Commissioning of the Kodak DirectView CR-850 digital radiography system installed at the Royal Adelaide Hospital. The first of its type installed in Australia, the system is a "dry" image processor, for which no chemicals are required to develop images. Rather, latent radiographic images are stored on photostimulable phosphor screens, which are scanned and displayed by a reader unit. The image can be digitally processed and enhanced before it is forwarded to a storage device, printer or workstation display, thereby alleviating the need to re-expose patients to achieve satisfactory quality images. The phosphor screens are automatically erased, ready for re-use. Results are reported of tests carried out using the optional "Total Quality Tool" quality assurance package installed with the system. This package includes analysis and reporting software which provides for simple testing and reporting of many important characteristics of the system, such as field uniformity, aspect ratio, line and pixel positions, image and system noise, exposure response, scan linearity, modulation transfer function (MTF) and image artefacts. Acceptance Tests were performed for kV and MV exposures. Resolution for MV exposures was at least 0.8 l/mm, and measured phantom dimensions were within 1.05% of expected magnification. Reproducibility between cassettes was within 1.6%. The mean pixel values on the central axis were close to linear for MV exposures from 3 to 10 MU and reached saturation level at around 20 MU for 6 MV and around 30 MV for 23 MV beams. Noise levels were below 0.2 %.

A Study of the Effects of High Power Pulsed 2450 MHz Microwaves, ELF modulated Microwaves, and ELF Fields on Human Lymphocytes and Selected Cell Lines

DTIC Science & Technology

1993-01-27

Considerable effect was expended in investigating shifts in intercellular calcium of one particular cell line, Jurket, using flow cytometry methods. No...culture. The following analysis were used to characterize the immortalized cell lines: flow cytometry , electron microscopy, two-dimensional protein gel...further characterized by flow cytometry , electron microscopy, two dimensional protein electrophoresis and nuclear run-off assay. Flow cytometric analysis of

Investigating PID shunting in polycrystalline silicon modules via multiscale, multitechnique characterization

DOE PAGES

Harvey, Steven P.; Moseley, John; Norman, Andrew; ...

2018-02-27

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

Functional Scanning Probe Imaging of Nanostructured Solar Energy Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giridharagopal, Rajiv; Cox, Phillip A.; Ginger, David S.

From hybrid perovskites to semiconducting polymer/fullerene blends for organic photovoltaics, many new materials being explored for energy harvesting and storage exhibit performance characteristics that depend sensitively on their nanoscale morphology. At the same time, rapid advances in the capability and accessibility of scanning probe microscopy methods over the past decade have made it possible to study processing/structure/function relationships ranging from photocurrent collection to photocarrier lifetimes with resolutions on the scale of tens of nanometers or better. Importantly, such scanning probe methods offer the potential to combine measurements of local structure with local function, and they can be implemented to studymore » materials in situ or devices in operando to better understand how materials evolve in time in response to an external stimulus or environmental perturbation. This Account highlights recent advances in the development and application of scanning probe microscopy methods that can help address such questions while filling key gaps between the capabilities of conventional electron microscopy and newer super-resolution optical methods. Focusing on semiconductor materials for solar energy applications, we highlight a range of electrical and optoelectronic scanning probe microscopy methods that exploit the local dynamics of an atomic force microscope tip to probe key properties of the solar cell material or device structure. We discuss how it is possible to extract relevant device properties using noncontact scanning probe methods as well as how these properties guide materials development. Specifically, we discuss intensity-modulated scanning Kelvin probe microscopy (IM-SKPM), time-resolved electrostatic force microscopy (trEFM), frequency-modulated electrostatic force microscopy (FM-EFM), and cantilever ringdown imaging. We explain these developments in the context of classic atomic force microscopy (AFM) methods that exploit the physics of cantilever motion and photocarrier generation to provide robust, nanoscale measurements of materials physics that are correlated with device operation. We predict that the multidimensional data sets made possible by these types of methods will become increasingly important as advances in data science expand capabilities and opportunities for image correlation and discovery.« less

Functional Scanning Probe Imaging of Nanostructured Solar Energy Materials

DOE PAGES

Giridharagopal, Rajiv; Cox, Phillip A.; Ginger, David S.

2016-08-30

From hybrid perovskites to semiconducting polymer/fullerene blends for organic photovoltaics, many new materials being explored for energy harvesting and storage exhibit performance characteristics that depend sensitively on their nanoscale morphology. At the same time, rapid advances in the capability and accessibility of scanning probe microscopy methods over the past decade have made it possible to study processing/structure/function relationships ranging from photocurrent collection to photocarrier lifetimes with resolutions on the scale of tens of nanometers or better. Importantly, such scanning probe methods offer the potential to combine measurements of local structure with local function, and they can be implemented to studymore » materials in situ or devices in operando to better understand how materials evolve in time in response to an external stimulus or environmental perturbation. This Account highlights recent advances in the development and application of scanning probe microscopy methods that can help address such questions while filling key gaps between the capabilities of conventional electron microscopy and newer super-resolution optical methods. Focusing on semiconductor materials for solar energy applications, we highlight a range of electrical and optoelectronic scanning probe microscopy methods that exploit the local dynamics of an atomic force microscope tip to probe key properties of the solar cell material or device structure. We discuss how it is possible to extract relevant device properties using noncontact scanning probe methods as well as how these properties guide materials development. Specifically, we discuss intensity-modulated scanning Kelvin probe microscopy (IM-SKPM), time-resolved electrostatic force microscopy (trEFM), frequency-modulated electrostatic force microscopy (FM-EFM), and cantilever ringdown imaging. We explain these developments in the context of classic atomic force microscopy (AFM) methods that exploit the physics of cantilever motion and photocarrier generation to provide robust, nanoscale measurements of materials physics that are correlated with device operation. We predict that the multidimensional data sets made possible by these types of methods will become increasingly important as advances in data science expand capabilities and opportunities for image correlation and discovery.« less

Use of astronomy filters in fluorescence microscopy.

PubMed

Piper, Jörg

2012-02-01

Monochrome astronomy filters are well suited for use as excitation or suppression filters in fluorescence microscopy. Because of their particular optical design, such filters can be combined with standard halogen light sources for excitation in many fluorescent probes. In this "low energy excitation," photobleaching (fading) or other irritations of native specimens are avoided. Photomicrographs can be taken from living motile fluorescent specimens also with a flash so that fluorescence images can be created free from indistinctness caused by movement. Special filter cubes or dichroic mirrors are not needed for our method. By use of suitable astronomy filters, fluorescence microscopy can be carried out with standard laboratory microscopes equipped with condensers for bright-field (BF) and dark-field (DF) illumination in transmitted light. In BF excitation, the background brightness can be modulated in tiny steps up to dark or black. Moreover, standard industry microscopes fitted with a vertical illuminator for examinations of opaque probes in DF or BF illumination based on incident light (wafer inspections, for instance) can also be used for excitation in epi-illumination when adequate astronomy filters are inserted as excitatory and suppression filters in the illuminating and imaging light path. In all variants, transmission bands can be modulated by transmission shift.

Simultaneous off-axis multiplexed holography and regular fluorescence microscopy of biological cells.

PubMed

Nygate, Yoav N; Singh, Gyanendra; Barnea, Itay; Shaked, Natan T

2018-06-01

We present a new technique for obtaining simultaneous multimodal quantitative phase and fluorescence microscopy of biological cells, providing both quantitative phase imaging and molecular specificity using a single camera. Our system is based on an interferometric multiplexing module, externally positioned at the exit of an optical microscope. In contrast to previous approaches, the presented technique allows conventional fluorescence imaging, rather than interferometric off-axis fluorescence imaging. We demonstrate the presented technique for imaging fluorescent beads and live biological cells.

Disentangling atomic-layer-specific x-ray absorption spectra by Auger electron diffraction spectroscopy

NASA Astrophysics Data System (ADS)

Matsui, Fumihiko; Matsushita, Tomohiro; Kato, Yukako; Hashimoto, Mie; Daimon, Hiroshi

2009-11-01

In order to investigate the electronic and magnetic structures of each atomic layer at subsurface, we have proposed a new method, Auger electron diffraction spectroscopy, which is the combination of x-ray absorption spectroscopy (XAS) and Auger electron diffraction (AED) techniques. We have measured a series of Ni LMM AED patterns of the Ni film grown on Cu(001) surface for various thicknesses. Then we deduced a set of atomic-layer-specific AED patterns in a numerical way. Furthermore, we developed an algorithm to disentangle XANES spectra from different atomic layers using these atomic-layer-specific AED patterns. Surface and subsurface core level shift were determined for each atomic layer.

Correlative microscopy of a carbide-free bainitic steel.

PubMed

Hofer, Christina; Bliznuk, Vitaliy; Verdiere, An; Petrov, Roumen; Winkelhofer, Florian; Clemens, Helmut; Primig, Sophie

2016-02-01

In this work a carbide-free bainitic steel was examined by a novel correlative microscopy approach using transmission Kikuchi diffraction (TKD) and transmission electron microscopy (TEM). The individual microstructural constituents could be identified by TKD based on their different crystal structure for bainitic ferrite and retained austenite and by image quality for the martensite-austenite (M-A) constituent. Subsequently, the same area was investigated in the TEM and a good match of these two techniques regarding the identification of the area position and crystal orientation could be proven. Additionally, the M-A constituent was examined in the TEM for the first time after preceded unambiguous identification using a correlative microscopy approach. The selected area diffraction pattern showed satellites around the main reflexes which might indicate a structural modulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Scanning Probe Microscopy for Identifying the Component Materials of a Nanostripe Structure

NASA Astrophysics Data System (ADS)

Mizuno, Akira; Ando, Yasuhisa

2010-08-01

The authors prepared a nanostripe structure in which two types of metal are arranged alternately, and successfully identified the component materials using scanning probe microscopy (SPM) to measure the lateral force distribution image. The nanostripe structure was prepared using a new method developed by the authors and joint development members. The lateral force distribution image was measured in both friction force microscopy (FFM) and lateral modulation friction force microscopy (LM-FFM) modes. In FFM mode, the effect of slope angle appeared in the lateral force distribution image; therefore, no difference in the type of material was observed. On the other hand, in LM-FFM mode, the effect of surface curvature was observed in the lateral force distribution image. A higher friction force on chromium than on gold was identified, enabling material identification.

Scanning capacitance microscopy of ErAs nanoparticles embedded in GaAs pn junctions

NASA Astrophysics Data System (ADS)

Park, K. W.; Nair, H. P.; Crook, A. M.; Bank, S. R.; Yu, E. T.

2011-09-01

Scanning capacitance microscopy is used to characterize the electronic properties of ErAs nanoparticles embedded in GaAs pn junctions grown by molecular beam epitaxy. Voltage-dependent capacitance images reveal localized variations in subsurface electronic structure near buried ErAs nanoparticles at lateral length scales of 20-30 nm. Numerical modeling indicates that these variations arise from inhomogeneities in charge modulation due to Fermi level pinning behavior associated with the embedded ErAs nanoparticles. Statistical analysis of image data yields an average particle radius of 6-8 nm—well below the direct resolution limit in scanning capacitance microscopy but discernible via analysis of patterns in nanoscale capacitance images.

Faster and less phototoxic 3D fluorescence microscopy using a versatile compressed sensing scheme

PubMed Central

Woringer, Maxime; Darzacq, Xavier; Zimmer, Christophe

2017-01-01

Three-dimensional fluorescence microscopy based on Nyquist sampling of focal planes faces harsh trade-offs between acquisition time, light exposure, and signal-to-noise. We propose a 3D compressed sensing approach that uses temporal modulation of the excitation intensity during axial stage sweeping and can be adapted to fluorescence microscopes without hardware modification. We describe implementations on a lattice light sheet microscope and an epifluorescence microscope, and show that images of beads and biological samples can be reconstructed with a 5-10 fold reduction of light exposure and acquisition time. Our scheme opens a new door towards faster and less damaging 3D fluorescence microscopy. PMID:28788909

Optical imaging module for astigmatic detection system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei-Min; Cheng, Chung-Hsiang; Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan

2016-05-15

In this paper, an optical imaging module design for an astigmatic detection system (ADS) is presented. The module is based on a commercial optical pickup unit (OPU) and it contains a coaxial illuminant for illuminating a specimen. Furthermore, the imaging module facilitates viewing the specimen and the detection laser spot of the ADS with a lateral resolution of approximately 1 μm without requiring the removal of an element of the OPU. Two polarizers and one infrared filter are used to eliminate stray laser light in the OPU and stray light produced by the illuminant. Imaging modules designed for digital versatilemore » disks (DVDs) and Blu-ray DVDs were demonstrated. Furthermore, the module can be used for imaging a small cantilever with approximate dimensions of 2 μm (width) × 5 μm (length), and therefore, it has the potential to be used in high-speed atomic force microscopy.« less

Photothermoelastic contrast in nanoscale infrared spectroscopy

NASA Astrophysics Data System (ADS)

Morozovska, Anna N.; Eliseev, Eugene A.; Borodinov, Nikolay; Ovchinnikova, Olga S.; Morozovsky, Nicholas V.; Kalinin, Sergei V.

2018-01-01

The contrast formation mechanism in nanoscale Infrared (IR) Spectroscopy is analyzed. The temperature distribution and elastic displacement across the illuminated T-shape boundary between two materials with different IR-radiation absorption coefficients and thermo-physical and elastic properties located on a rigid substrate are calculated self-consistently for different frequencies f ˜ (1 kHz-1 MHz) of IR-radiation modulation (fully coupled problem). Analytical expressions for the temperature and displacement profiles across the "thermo-elastic step" are derived in the decoupling approximation for f = 0 ("static limit"), and conditions for approximation validity at low frequencies of IR-modulation are established. The step height was found to be thickness-independent for thick layers and proportional to the square of the thickness for very thin films. The theoretical results will be of potential interest for applications in the scanning thermo-ionic and thermal infrared microscopies for relatively long sample thermalization times and possibly for photothermal induced resonance microscopy using optomechanical probes.

Minimising the effect of nanoparticle deformation in intermittent contact amplitude modulation atomic force microscopy measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Babic, Bakir, E-mail: bakir.babic@measurement.gov.au; Lawn, Malcolm A.; Coleman, Victoria A.

The results of systematic height measurements of polystyrene (PS) nanoparticles using intermittent contact amplitude modulation atomic force microscopy (IC-AM-AFM) are presented. The experimental findings demonstrate that PS nanoparticles deform during AFM imaging, as indicated by a reduction in the measured particle height. This deformation depends on the IC-AM-AFM imaging parameters, material composition, and dimensional properties of the nanoparticles. A model for nanoparticle deformation occurring during IC-AM-AFM imaging is developed as a function of the peak force which can be calculated for a particular set of experimental conditions. The undeformed nanoparticle height can be estimated from the model by extrapolation tomore » zero peak force. A procedure is proposed to quantify and minimise nanoparticle deformation during IC-AM-AFM imaging, based on appropriate adjustments of the experimental control parameters.« less

Microscope-Based Fluid Physics Experiments in the Fluids and Combustion Facility on ISS

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Motil, Susan M.; Snead, John H.; Malarik, Diane C.

2000-01-01

At the NASA Glenn Research Center, the Microgravity Science Program is planning to conduct a large number of experiments on the International Space Station in both the Fluid Physics and Combustion Science disciplines, and is developing flight experiment hardware for use within the International Space Station's Fluids and Combustion Facility. Four fluids physics experiments that require an optical microscope will be sequentially conducted within a subrack payload to the Fluids Integrated Rack of the Fluids and Combustion Facility called the Light Microscopy Module, which will provide the containment, changeout, and diagnostic capabilities to perform the experiments. The Light Microscopy Module is planned as a fully remotely controllable on-orbit microscope facility, allowing flexible scheduling and control of experiments within International Space Station resources. This paper will focus on the four microscope-based experiments, specifically, their objectives and the sample cell and instrument hardware to accommodate their requirements.

Spatiotemporal polarization modulation microscopy with a microretarder array

NASA Astrophysics Data System (ADS)

Ding, Changqin; Ulcickas, James R. W.; Simpson, Garth J.

2018-02-01

A patterned microretarder array positioned in the rear conjugate plane of a microscope enables rapid polarizationdependent nonlinear optical microscopy. The pattern introduced to the array results in periodic modulation of the polarization-state of the incident light as a function of position within the field of view with no moving parts or active control. Introduction of a single stationary optical element and a fixed polarizer into the beam of a nonlinear optical microscope enabled nonlinear optical tensor recovery, which informs on local structure and orientation. Excellent agreement was observed between the measured and predicted second harmonic generation (SHG) of z-cut quartz, selected as a test system with well-established nonlinear optical properties. Subsequent studies of spatially varying samples further support the general applicability of this relatively simple strategy for detailed polarization analysis in both conventional and nonlinear optical imaging of structurally diverse samples.

Design of a fiber-optic multiphoton microscopy handheld probe

PubMed Central

Zhao, Yuan; Sheng, Mingyu; Huang, Lin; Tang, Shuo

2016-01-01

We have developed a fiber-optic multiphoton microscopy (MPM) system with handheld probe using femtosecond fiber laser. Here we present the detailed optical design and analysis of the handheld probe. The optical systems using Lightpath 352140 and 352150 as objective lens were analyzed. A custom objective module that includes Lightpath 355392 and two customized corrective lenses was designed. Their performances were compared by wavefront error, field curvature, astigmatism, F-θ error, and tolerance in Zemax simulation. Tolerance analysis predicted the focal spot size to be 1.13, 1.19 and 0.83 µm, respectively. Lightpath 352140 and 352150 were implemented in experiment and the measured lateral resolution was 1.22 and 1.3 µm, respectively, which matched with the prediction. MPM imaging by the handheld probe were conducted on leaf, fish scale and rat tail tendon. The MPM resolution can potentially be improved by the custom objective module. PMID:27699109

Design of a fiber-optic multiphoton microscopy handheld probe.

PubMed

Zhao, Yuan; Sheng, Mingyu; Huang, Lin; Tang, Shuo

2016-09-01

We have developed a fiber-optic multiphoton microscopy (MPM) system with handheld probe using femtosecond fiber laser. Here we present the detailed optical design and analysis of the handheld probe. The optical systems using Lightpath 352140 and 352150 as objective lens were analyzed. A custom objective module that includes Lightpath 355392 and two customized corrective lenses was designed. Their performances were compared by wavefront error, field curvature, astigmatism, F-θ error, and tolerance in Zemax simulation. Tolerance analysis predicted the focal spot size to be 1.13, 1.19 and 0.83 µm, respectively. Lightpath 352140 and 352150 were implemented in experiment and the measured lateral resolution was 1.22 and 1.3 µm, respectively, which matched with the prediction. MPM imaging by the handheld probe were conducted on leaf, fish scale and rat tail tendon. The MPM resolution can potentially be improved by the custom objective module.

Microrheology of growing Escherichia coli biofilms investigated by using magnetic force modulation atomic force microscopy.

PubMed

Gan, Tiansheng; Gong, Xiangjun; Schönherr, Holger; Zhang, Guangzhao

2016-12-01

Microrheology of growing biofilms provides insightful information about its structural evolution and properties. In this study, the authors have investigated the microrheology of Escherichia coli (strain HCB1) biofilms at different indentation depth (δ) by using magnetic force modulation atomic force microscopy as a function of disturbing frequency (f). As δ increases, the dynamic stiffness (k s ) for the biofilms in the early stage significantly increases. However, it levels off when the biofilms are matured. The facts indicate that the biofilms change from inhomogeneous to homogeneous in structure. Moreover, k s is scaled to f, which coincides with the rheology of soft glasses. The exponent increases with the incubation time, indicating the fluidization of biofilms. In contrast, the upper layer of the matured biofilms is solidlike in that the storage modulus is always larger than the loss modulus, and its viscoelasticity is slightly influenced by the shear stress.

Accurate formula for dissipative interaction in frequency modulation atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Kazuhiro; Matsushige, Kazumi; Yamada, Hirofumi

2014-12-08

Much interest has recently focused on the viscosity of nano-confined liquids. Frequency modulation atomic force microscopy (FM-AFM) is a powerful technique that can detect variations in the conservative and dissipative forces between a nanometer-scale tip and a sample surface. We now present an accurate formula to convert the dissipation power of the cantilever measured during the experiment to damping of the tip-sample system. We demonstrated the conversion of the dissipation power versus tip-sample separation curve measured using a colloidal probe cantilever on a mica surface in water to the damping curve, which showed a good agreement with the theoretical curve.more » Moreover, we obtained the damping curve from the dissipation power curve measured on the hydration layers on the mica surface using a nanometer-scale tip, demonstrating that the formula allows us to quantitatively measure the viscosity of a nano-confined liquid using FM-AFM.« less

Sodium accumulation at potential-induced degradation shunted areas in polycrystalline silicon modules

DOE PAGES

Harvey, Steven P.; Aguiar, Jeffery A.; Hacke, Peter; ...

2016-09-19

Here, we investigated potential-induced degradation (PID) in silicon mini-modules that were subjected to accelerated stressing to induce PID conditions. Shunted areas on the cells were identified with photoluminescence and dark lock-in thermography (DLIT) imaging. The identical shunted areas were then analyzed via time-of-flight secondary-ion mass spectrometry (TOFSIMS) imaging, 3-D tomography, and high-resolution transmission electron microscopy. The TOF-SIMS imaging indicates a high concentration of sodium in the shunted areas, and 3-D tomography reveals that the sodium extends more than 2 um from the surface below shunted regions. Transmission electron microscopy investigation reveals that a stacking fault is present at an areamore » identified as shunted by DLIT imaging. After the removal of surface sodium, tomography reveals persistent sodium present around the junction depth of 300 nm and a drastic difference in sodium content at the junction when comparing shunted and nonshunted regions.« less

Electron cryo-microscopy structure of the canonical TRPC4 ion channel

PubMed Central

Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

2018-01-01

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

High-magnification super-resolution FINCH microscopy using birefringent crystal lens interferometers

NASA Astrophysics Data System (ADS)

Siegel, Nisan; Lupashin, Vladimir; Storrie, Brian; Brooker, Gary

2016-12-01

Fresnel incoherent correlation holography (FINCH) microscopy is a promising approach for high-resolution biological imaging but has so far been limited to use with low-magnification, low-numerical-aperture configurations. We report the use of in-line incoherent interferometers made from uniaxial birefringent α-barium borate (α-BBO) or calcite crystals that overcome the aberrations and distortions present with previous implementations that employed spatial light modulators or gradient refractive index lenses. FINCH microscopy incorporating these birefringent elements and high-numerical-aperture oil immersion objectives could outperform standard wide-field fluorescence microscopy, with, for example, a 149 nm lateral point spread function at a wavelength of 590 nm. Enhanced resolution was confirmed with sub-resolution fluorescent beads. Taking the Golgi apparatus as a biological example, three different proteins labelled with GFP and two other fluorescent dyes in HeLa cells were resolved with an image quality that is comparable to similar samples captured by structured illumination microscopy.

Laser scanning saturated structured illumination microscopy based on phase modulation

NASA Astrophysics Data System (ADS)

Huang, Yujia; Zhu, Dazhao; Jin, Luhong; Kuang, Cuifang; Xu, Yingke; Liu, Xu

2017-08-01

Wide-field saturated structured illumination microscopy has not been widely used due to the requirement of high laser power. We propose a novel method called laser scanning saturated structured illumination microscopy (LS-SSIM), which introduces high order of harmonics frequency and greatly reduces the required laser power for SSIM imaging. To accomplish that, an excitation PSF with two peaks is generated and scanned along different directions on the sample. Raw images are recorded cumulatively by a CCD detector and then reconstructed to form a high-resolution image with extended optical transfer function (OTF). Our theoretical analysis and simulation results show that LS-SSIM method reaches a resolution of 0.16 λ, equivalent to 2.7-fold resolution than conventional wide-field microscopy. In addition, LS-SSIM greatly improves the optical sectioning capability of conventional wide-field illumination system by diminishing our-of-focus light. Furthermore, this modality has the advantage of implementation in multi-photon microscopy with point scanning excitation to image samples in greater depths.

Correlation between surface carbon concentration and adhesive strength at the Si cell/EVA interface in a PV module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhere, N.G.; Wollam, M.E.; Gadre, K.S.

1997-12-31

Silicon solar cell/EVA composite is being studied with an objective to further improve the manufacturing technology of PV modules. Sample extraction and adhesion strength measurement process has been modified. Silicon and EVA samples were extracted from solar cells of new and field-deployed modules. Optical microscopy, SEM, and AES of samples from new modules revealed EVA islands covering most of the silicon cell surface indicating a cohesive failure. A good correlation was observed between the adhesive strength and surface concentration of carbon. A low carbon concentration which indicated less EVA clinging to cell surface always resulted in low adhesive strengths. Themore » correlation provides a simple technique for inferring properties of EVA.« less

Spatial and spectral imaging of point-spread functions using a spatial light modulator

NASA Astrophysics Data System (ADS)

Munagavalasa, Sravan; Schroeder, Bryce; Hua, Xuanwen; Jia, Shu

2017-12-01

We develop a point-spread function (PSF) engineering approach to imaging the spatial and spectral information of molecular emissions using a spatial light modulator (SLM). We show that a dispersive grating pattern imposed upon the emission reveals spectral information. We also propose a deconvolution model that allows the decoupling of the spectral and 3D spatial information in engineered PSFs. The work is readily applicable to single-molecule measurements and fluorescent microscopy.

Detecting the magnetic response of iron oxide capped organosilane nanostructures using magnetic sample modulation and atomic force microscopy.

PubMed

Li, Jie-Ren; Lewandowski, Brian R; Xu, Song; Garno, Jayne C

2009-06-15

A new imaging strategy using atomic force microscopy (AFM) is demonstrated for mapping magnetic domains at size regimes below 100 nm. The AFM-based imaging mode is referred to as magnetic sample modulation (MSM), since the flux of an AC-generated electromagnetic field is used to induce physical movement of magnetic nanomaterials on surfaces during imaging. The AFM is operated in contact mode using a soft, nonmagnetic tip to detect the physical motion of the sample. By slowly scanning an AFM probe across a vibrating area of the sample, the frequency and amplitude of vibration induced by the magnetic field is tracked by changes in tip deflection. Thus, the AFM tip serves as a force and motion sensor for mapping the vibrational response of magnetic nanomaterials. Essentially, MSM is a hybrid of contact mode AFM combined with selective modulation of magnetic domains. The positional feedback loop for MSM imaging is the same as that used for force modulation and contact mode AFM; however, the vibration of the sample is analyzed using channels of a lock-in amplifier. The investigations are facilitated by nanofabrication methods combining particle lithography with organic vapor deposition and electroless deposition of iron oxide, to prepare designed test platforms of magnetic materials at nanometer length scales. Custom test platforms furnished suitable surfaces for MSM characterizations at the level of individual metal nanostructures.

In vivo confocal microscopy of the cornea: New developments in image acquisition, reconstruction and analysis using the HRT-Rostock Corneal Module

PubMed Central

Petroll, W. Matthew; Robertson, Danielle M.

2015-01-01

The optical sectioning ability of confocal microscopy allows high magnification images to be obtained from different depths within a thick tissue specimen, and is thus ideally suited to the study of intact tissue in living subjects. In vivo confocal microscopy has been used in a variety of corneal research and clinical applications since its development over 25 years ago. In this article we review the latest developments in quantitative corneal imaging with the Heidelberg Retinal Tomograph with Rostock Corneal Module (HRT-RCM). We provide an overview of the unique strengths and weaknesses of the HRT-RCM. We discuss techniques for performing 3-D imaging with the HRT-RCM, including hardware and software modifications that allow full thickness confocal microscopy through focusing (CMTF) of the cornea, which can provide quantitative measurements of corneal sublayer thicknesses, stromal cell and extracellular matrix backscatter, and depth dependent changes in corneal keratocyte density. We also review current approaches for quantitative imaging of the subbasal nerve plexus, which require a combination of advanced image acquisition and analysis procedures, including wide field mapping and 3-D reconstruction of nerve structures. The development of new hardware, software, and acquisition techniques continues to expand the number of applications of the HRT-RCM for quantitative in vivo corneal imaging at the cellular level. Knowledge of these rapidly evolving strategies should benefit corneal clinicians and basic scientists alike. PMID:25998608

High viscosity environments: an unexpected route to obtain true atomic resolution with atomic force microscopy.

PubMed

Weber, Stefan A L; Kilpatrick, Jason I; Brosnan, Timothy M; Jarvis, Suzanne P; Rodriguez, Brian J

2014-05-02

Atomic force microscopy (AFM) is widely used in liquid environments, where true atomic resolution at the solid-liquid interface can now be routinely achieved. It is generally expected that AFM operation in more viscous environments results in an increased noise contribution from the thermal motion of the cantilever, thereby reducing the signal-to-noise ratio (SNR). Thus, viscous fluids such as ionic and organic liquids have been generally avoided for high-resolution AFM studies despite their relevance to, e.g. energy applications. Here, we investigate the thermal noise limitations of dynamic AFM operation in both low and high viscosity environments theoretically, deriving expressions for the amplitude, phase and frequency noise resulting from the thermal motion of the cantilever, thereby defining the performance limits of amplitude modulation, phase modulation and frequency modulation AFM. We show that the assumption of a reduced SNR in viscous environments is not inherent to the technique and demonstrate that SNR values comparable to ultra-high vacuum systems can be obtained in high viscosity environments under certain conditions. Finally, we have obtained true atomic resolution images of highly ordered pyrolytic graphite and mica surfaces, thus revealing the potential of high-resolution imaging in high viscosity environments.

The polarization modulation and fabrication method of two dimensional silica photonic crystals based on UV nanoimprint lithography and hot imprint

PubMed Central

Guo, Shuai; Niu, Chunhui; Liang, Liang; Chai, Ke; Jia, Yaqing; Zhao, Fangyin; Li, Ya; Zou, Bingsuo; Liu, Ruibin

2016-01-01

Based on a silica sol-gel technique, highly-structurally ordered silica photonic structures were fabricated by UV lithography and hot manual nanoimprint efforts, which makes large-scale fabrication of silica photonic crystals easy and results in low-cost. These photonic structures show perfect periodicity, smooth and flat surfaces and consistent aspect ratios, which are checked by scanning electron microscopy (SEM) and atomic force microscopy (AFM). In addition, glass substrates with imprinted photonic nanostructures show good diffraction performance in both transmission and reflection mode. Furthermore, the reflection efficiency can be enhanced by 5 nm Au nanoparticle coating, which does not affect the original imprint structure. Also the refractive index and dielectric constant of the imprinted silica is close to that of the dielectric layer in nanodevices. In addition, the polarization characteristics of the reflected light can be modulated by stripe nanostructures through changing the incident light angle. The experimental findings match with theoretical results, making silica photonic nanostructures functional integration layers in many optical or optoelectronic devices, such as LED and microlasers to enhance the optical performance and modulate polarization properties in an economical and large-scale way. PMID:27698465

High viscosity environments: an unexpected route to obtain true atomic resolution with atomic force microscopy

NASA Astrophysics Data System (ADS)

Weber, Stefan A. L.; Kilpatrick, Jason I.; Brosnan, Timothy M.; Jarvis, Suzanne P.; Rodriguez, Brian J.

2014-05-01

Atomic force microscopy (AFM) is widely used in liquid environments, where true atomic resolution at the solid-liquid interface can now be routinely achieved. It is generally expected that AFM operation in more viscous environments results in an increased noise contribution from the thermal motion of the cantilever, thereby reducing the signal-to-noise ratio (SNR). Thus, viscous fluids such as ionic and organic liquids have been generally avoided for high-resolution AFM studies despite their relevance to, e.g. energy applications. Here, we investigate the thermal noise limitations of dynamic AFM operation in both low and high viscosity environments theoretically, deriving expressions for the amplitude, phase and frequency noise resulting from the thermal motion of the cantilever, thereby defining the performance limits of amplitude modulation, phase modulation and frequency modulation AFM. We show that the assumption of a reduced SNR in viscous environments is not inherent to the technique and demonstrate that SNR values comparable to ultra-high vacuum systems can be obtained in high viscosity environments under certain conditions. Finally, we have obtained true atomic resolution images of highly ordered pyrolytic graphite and mica surfaces, thus revealing the potential of high-resolution imaging in high viscosity environments.

The polarization modulation and fabrication method of two dimensional silica photonic crystals based on UV nanoimprint lithography and hot imprint.

PubMed

Guo, Shuai; Niu, Chunhui; Liang, Liang; Chai, Ke; Jia, Yaqing; Zhao, Fangyin; Li, Ya; Zou, Bingsuo; Liu, Ruibin

2016-10-04

Based on a silica sol-gel technique, highly-structurally ordered silica photonic structures were fabricated by UV lithography and hot manual nanoimprint efforts, which makes large-scale fabrication of silica photonic crystals easy and results in low-cost. These photonic structures show perfect periodicity, smooth and flat surfaces and consistent aspect ratios, which are checked by scanning electron microscopy (SEM) and atomic force microscopy (AFM). In addition, glass substrates with imprinted photonic nanostructures show good diffraction performance in both transmission and reflection mode. Furthermore, the reflection efficiency can be enhanced by 5 nm Au nanoparticle coating, which does not affect the original imprint structure. Also the refractive index and dielectric constant of the imprinted silica is close to that of the dielectric layer in nanodevices. In addition, the polarization characteristics of the reflected light can be modulated by stripe nanostructures through changing the incident light angle. The experimental findings match with theoretical results, making silica photonic nanostructures functional integration layers in many optical or optoelectronic devices, such as LED and microlasers to enhance the optical performance and modulate polarization properties in an economical and large-scale way.

Substrate specificity of low-molecular mass bacterial DD-peptidases.

PubMed

Nemmara, Venkatesh V; Dzhekieva, Liudmila; Sarkar, Kumar Subarno; Adediran, S A; Duez, Colette; Nicholas, Robert A; Pratt, R F

2011-11-22

The bacterial DD-peptidases or penicillin-binding proteins (PBPs) catalyze the formation and regulation of cross-links in peptidoglycan biosynthesis. They are classified into two groups, the high-molecular mass (HMM) and low-molecular mass (LMM) enzymes. The latter group, which is subdivided into classes A-C (LMMA, -B, and -C, respectively), is believed to catalyze DD-carboxypeptidase and endopeptidase reactions in vivo. To date, the specificity of their reactions with particular elements of peptidoglycan structure has not, in general, been defined. This paper describes the steady-state kinetics of hydrolysis of a series of specific peptidoglycan-mimetic peptides, representing various elements of stem peptide structure, catalyzed by a range of LMM PBPs (the LMMA enzymes, Escherichia coli PBP5, Neisseria gonorrhoeae PBP4, and Streptococcus pneumoniae PBP3, and the LMMC enzymes, the Actinomadura R39 dd-peptidase, Bacillus subtilis PBP4a, and N. gonorrhoeae PBP3). The R39 enzyme (LMMC), like the previously studied Streptomyces R61 DD-peptidase (LMMB), specifically and rapidly hydrolyzes stem peptide fragments with a free N-terminus. In accord with this result, the crystal structures of the R61 and R39 enzymes display a binding site specific to the stem peptide N-terminus. These are water-soluble enzymes, however, with no known specific function in vivo. On the other hand, soluble versions of the remaining enzymes of those noted above, all of which are likely to be membrane-bound and/or associated in vivo and have been assigned particular roles in cell wall biosynthesis and maintenance, show little or no specificity for peptides containing elements of peptidoglycan structure. Peptidoglycan-mimetic boronate transition-state analogues do inhibit these enzymes but display notable specificity only for the LMMC enzymes, where, unlike peptide substrates, they may be able to effectively induce a specific active site structure. The manner in which LMMA (and HMM) DD-peptidases achieve substrate specificity, both in vitro and in vivo, remains unknown. © 2011 American Chemical Society

Ecological momentary assessment of fatigue, sleepiness, and exhaustion in ESKD.

PubMed

Abdel-Kader, Khaled; Jhamb, Manisha; Mandich, Lee Anne; Yabes, Jonathan; Keene, Robert M; Beach, Scott; Buysse, Daniel J; Unruh, Mark L

2014-02-06

Many patients on maintenance dialysis experience significant sleepiness and fatigue. However, the influence of the hemodialysis (HD) day and circadian rhythms on patients' symptoms have not been well characterized. We sought to use ecological momentary assessment to evaluate day-to-day and diurnal variability of fatigue, sleepiness, exhaustion and related symptoms in thrice-weekly maintenance HD patients. Subjects used a modified cellular phone to access an interactive voice response system that administered the Daytime Insomnia Symptom Scale (DISS). The DISS assessed subjective vitality, mood, and alertness through 19 questions using 7- point Likert scales. Subjects completed the DISS 4 times daily for 7 consecutive days. Factor analysis was conducted and a mean composite score of fatigue-sleepiness-exhaustion was created. Linear mixed regression models (LMM) were used to examine the association of time of day, dialysis day and fatigue, sleepiness, and exhaustion composite scores. The 55 participants completed 1,252 of 1,540 (81%) possible assessments over the 7 day period. Multiple symptoms related to mood (e.g., feeling sad, feeling tense), cognition (e.g., difficulty concentrating), and fatigue (e.g., exhaustion, feeling sleepy) demonstrated significant daily and diurnal variation, with higher overall symptom scores noted on hemodialysis days and later in the day. In factor analysis, 4 factors explained the majority of the observed variance for DISS symptoms. Fatigue, sleepiness, and exhaustion loaded onto the same factor and were highly intercorrelated. In LMM, mean composite fatigue-sleepiness-exhaustion scores were associated with dialysis day (coefficient and 95% confidence interval [CI] 0.21 [0.02 - 0.39]) and time of day (coefficient and 95% CI 0.33 [0.25 - 0.41]. Observed associations were minimally affected by adjustment for demographics and common confounders. Maintenance HD patients experience fatigue-sleepiness-exhaustion symptoms that demonstrate significant daily and diurnal variation. The variability in symptoms may contribute to poor symptom awareness by providers and greater misclassification bias of fatigue related symptoms in clinical studies.

Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field.

PubMed

Lindahl, Paul A; Moore, Michael J

2016-08-02

Iron, copper, zinc, manganese, cobalt, and molybdenum play important roles in mitochondrial biochemistry, serving to help catalyze reactions in numerous metalloenzymes. These metals are also found in labile "pools" within mitochondria. Although the composition and cellular function of these pools are largely unknown, they are thought to be comprised of nonproteinaceous low-molecular-mass (LMM) metal complexes. Many problems must be solved before these pools can be fully defined, especially problems stemming from the lability of such complexes. This lability arises from inherently weak coordinate bonds between ligands and metals. This is an advantage for catalysis and trafficking, but it makes characterization difficult. The most popular strategy for investigating such pools is to detect them using chelator probes with fluorescent properties that change upon metal coordination. Characterization is limited because of the inevitable destruction of the complexes during their detection. Moreover, probes likely react with more than one type of metal complex, confusing analyses. An alternative approach is to use liquid chromatography (LC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). With help from a previous lab member, the authors recently developed an LC-ICP-MS approach to analyze LMM extracts from yeast and mammalian mitochondria. They detected several metal complexes, including Fe580, Fe1100, Fe1500, Cu5000, Zn1200, Zn1500, Mn1100, Mn2000, Co1200, Co1500, and Mo780 (numbers refer to approximate masses in daltons). Many of these may be used to metalate apo-metalloproteins as they fold inside the organelle. The LC-based approach also has challenges, e.g., in distinguishing artifactual metal complexes from endogenous ones, due to the fact that cells must be disrupted to form extracts before they are passed through chromatography columns prior to analysis. Ultimately, both approaches will be needed to characterize these intriguing complexes and to elucidate their roles in mitochondrial biochemistry.

Applying the Longitudinal Model from Item Response Theory to Assess Health-Related Quality of Life in the PRODIGE 4/ACCORD 11 Randomized Trial.

PubMed

Barbieri, Antoine; Anota, Amélie; Conroy, Thierry; Gourgou-Bourgade, Sophie; Juzyna, Beata; Bonnetain, Franck; Lavergne, Christian; Bascoul-Mollevi, Caroline

2016-07-01

A new longitudinal statistical approach was compared to the classical methods currently used to analyze health-related quality-of-life (HRQoL) data. The comparison was made using data in patients with metastatic pancreatic cancer. Three hundred forty-two patients from the PRODIGE4/ACCORD 11 study were randomly assigned to FOLFIRINOX versus gemcitabine regimens. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The classical analysis uses a linear mixed model (LMM), considering an HRQoL score as a good representation of the true value of the HRQoL, following EORTC recommendations. In contrast, built on the item response theory (IRT), our approach considered HRQoL as a latent variable directly estimated from the raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (longitudinal partial credit model [LPCM]), thereby modeling the latent trait as a function of time and other covariates. Both models gave the same conclusions on 11 of 15 HRQoL dimensions. HRQoL evolution was similar between the 2 treatment arms, except for the symptoms of pain. Indeed, regarding the LPCM, pain perception was significantly less important in the FOLFIRINOX arm than in the gemcitabine arm. For most of the scales, HRQoL changes over time, and no difference was found between treatments in terms of HRQoL. The use of LMM to study the HRQoL score does not seem appropriate. It is an easy-to-use model, but the basic statistical assumptions do not check. Our IRT model may be more complex but shows the same qualities and gives similar results. It has the additional advantage of being more precise and suitable because of its direct use of raw data. © The Author(s) 2015.

Nitrogen deposition outweighs climatic variability in driving annual growth rate of canopy beech trees: Evidence from long-term growth reconstruction across a geographic gradient.

PubMed

Gentilesca, Tiziana; Rita, Angelo; Brunetti, Michele; Giammarchi, Francesco; Leonardi, Stefano; Magnani, Federico; van Noije, Twan; Tonon, Giustino; Borghetti, Marco

2018-07-01

In this study, we investigated the role of climatic variability and atmospheric nitrogen deposition in driving long-term tree growth in canopy beech trees along a geographic gradient in the montane belt of the Italian peninsula, from the Alps to the southern Apennines. We sampled dominant trees at different developmental stages (from young to mature tree cohorts, with tree ages spanning from 35 to 160 years) and used stem analysis to infer historic reconstruction of tree volume and dominant height. Annual growth volume (G V ) and height (G H ) variability were related to annual variability in model simulated atmospheric nitrogen deposition and site-specific climatic variables, (i.e. mean annual temperature, total annual precipitation, mean growing period temperature, total growing period precipitation, and standard precipitation evapotranspiration index) and atmospheric CO 2 concentration, including tree cambial age among growth predictors. Generalized additive models (GAM), linear mixed-effects models (LMM), and Bayesian regression models (BRM) were independently employed to assess explanatory variables. The main results from our study were as follows: (i) tree age was the main explanatory variable for long-term growth variability; (ii) GAM, LMM, and BRM results consistently indicated climatic variables and CO 2 effects on G V and G H were weak, therefore evidence of recent climatic variability influence on beech annual growth rates was limited in the montane belt of the Italian peninsula; (iii) instead, significant positive nitrogen deposition (N dep ) effects were repeatedly observed in G V and G H ; the positive effects of N dep on canopy height growth rates, which tended to level off at N dep values greater than approximately 1.0 g m -2  y -1 , were interpreted as positive impacts on forest stand above-ground net productivity at the selected study sites. © 2018 John Wiley & Sons Ltd.

Creatinine and myoglobin are poor predictors of anaerobic threshold in colorectal cancer and health.

PubMed

Nyasavajjala, Sitaramachandra M; Phillips, Beth E; Lund, Jon N; Williams, John P

2015-06-01

Myoglobin is a haem protein produced in skeletal muscles. Serum concentrations of myoglobin have been proposed as a surrogate marker of muscle mass and function in both cachectic cancer patients and healthy non-cancer individuals. Creatinine, a metabolite of creatine phosphate, an energy store found in skeletal muscle, is produced at a constant rate from skeletal muscle. Urinary and plasma creatinine have been used in clinical practice as indicators of skeletal muscle mass in health and disease. Our study aimed to test the hypothesis that plasma myoglobin and creatinine concentration could accurately predict skeletal muscle mass and aerobic capacity in colorectal cancer (CRC) patients and matched healthy controls and thereby an indicative of aerobic performance. We recruited 47 patients with CRC and matching number of healthy volunteers for this study. All participants had their body composition measured by dual-energy X-ray absorptiometry scan, aerobic capacity measured to anaerobic threshold (AT) by cardiopulmonary exercise testing and filled in objective questionnaires to assess the qualitative functions. This study was carried out in accordance with the Declaration of Helsinki, after approval by the local National Health Service (NHS) Research Ethics Committee. Age-matched groups had similar serum myoglobin and creatinine concentrations in spite of differences in their aerobic capacity. AT was significantly lower in the CRC group compared with matched controls (1.18 ± 0.44 vs. 1.41 ± 0.71 L/min; P < 0.01). AT had significant correlation with lean muscle mass (LMM) among these groups, but myoglobin and creatinine had poor correlation with LMM and AT. Serum myoglobin is a poor predictor of muscle mass, and serum myoglobin and creatinine concentrations do not predict aerobic performance in CRC patients or healthy matched controls. © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

Modulation of the pupil function of microscope objective lens for multifocal multi-photon microscopy using a spatial light modulator

NASA Astrophysics Data System (ADS)

Matsumoto, Naoya; Okazaki, Shigetoshi; Takamoto, Hisayoshi; Inoue, Takashi; Terakawa, Susumu

2014-02-01

We propose a method for high precision modulation of the pupil function of a microscope objective lens to improve the performance of multifocal multi-photon microscopy (MMM). To modulate the pupil function, we adopt a spatial light modulator (SLM) and place it at the conjugate position of the objective lens. The SLM can generate an arbitrary number of spots to excite the multiple fluorescence spots (MFS) at the desired positions and intensities by applying an appropriate computer-generated hologram (CGH). This flexibility allows us to control the MFS according to the photobleaching level of a fluorescent protein and phototoxicity of a specimen. However, when a large number of excitation spots are generated, the intensity distribution of the MFS is significantly different from the one originally designed due to misalignment of the optical setup and characteristics of the SLM. As a result, the image of a specimen obtained using laser scanning for the MFS has block noise segments because the SLM could not generate a uniform MFS. To improve the intensity distribution of the MFS, we adaptively redesigned the CGH based on the observed MFS. We experimentally demonstrate an improvement in the uniformity of a 10 × 10 MFS grid using a dye solution. The simplicity of the proposed method will allow it to be applied for calibration of MMM before observing living tissue. After the MMM calibration, we performed laser scanning with two-photon excitation to observe a real specimen without detecting block noise segments.

The effects of viscoelastic polymer substrates on adult stem cell differentiation

NASA Astrophysics Data System (ADS)

Chang, Chungchueh; Fields, Adam; Ramek, Alex; Jurukovski, Vladimir; Simon, Marcia; Rafailovich, Miriam

2009-03-01

Dental Pulp Stem Cells (DPSCs) are known to differentiate in either bone, dentine, or nerve tissue by different environment signals. In this study, we have determined whether differentiation could only through modification of the substrate mechanics. Atomic Force Microscopy (AFM) on Shear Modulation Force Microscopy (SMFM) mode indicated that the spun-cast polybutadiene (PB) thin films could be used to provide different stiffness substrates by changing the thicknesses of thin films. DPSCs were then plated on these substrates and cultured in standard media. After 28 days incubation, Lasar Scanning Confocal Microscopy (LSCM) with mercury lamp indicated that the crystals were observed only on hard surfaces. The Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX analysis) indicated that the crystals are calcium phosphates. The Glancing Incidence Diffraction (GID) was also used to determine the structure of crystals. These results indicate that DPSCs could be differentiated into osteoblasts by mechanical stimuli from substrate mechanics.

Three-Dimensional Visualization of Interfacial Phenomena Using Confocal Microscopy

NASA Astrophysics Data System (ADS)

Shieh, Ian C.

Surfactants play an integral role in numerous functions ranging from stabilizing the emulsion in a favorite salad dressing to organizing the cellular components that make life possible. We are interested in lung surfactant, which is a mixture of lipids and proteins essential for normal respiration because it modulates the surface tension of the air-liquid interface of the thin fluid lining in the lungs. Through this surface tension modulation, lung surfactant ensures effortless lung expansion and prevents lung collapse during exhalation, thereby effecting proper oxygenation of the bloodstream. The function of lung surfactant, as well as numerous interfacial lipid systems, is not solely dictated by the behavior of materials confined to the two-dimensional interface. Rather, the distributions of materials in the liquid subphase also greatly influence the performance of interfacial films of lung surfactant. Therefore, to better understand the behavior of lung surfactant and other interfacial lipid systems, we require a three-dimensional characterization technique. In this dissertation, we have developed a novel confocal microscopy methodology for investigating the interfacial phenomena of surfactants at the air-liquid interface of a Langmuir trough. Confocal microscopy provides the excellent combination of in situ, fast, three-dimensional visualization of multiple components of the lung surfactant system that other characterization techniques lack. We detail the solutions to the numerous challenges encountered when imaging a dynamic air-liquid interface with a high-resolution technique like confocal microscopy. We then use confocal microscopy to elucidate the distinct mechanisms by which a polyelectrolyte (chitosan) and nonadsorbing polymer (polyethylene glycol) restore the function of lung surfactant under inhibitory conditions mimicking the effects of lung trauma. Beyond this physiological model, we also investigate several one- and two-component interfacial films of the various lipid constituents of lung surfactant. Confocal microscopy allows us to use a water-soluble, cationic fluorophore that partitions into the disordered phases of lipid monolayers. By exploiting the properties of this water-soluble fluorophore, we investigate both the phase behavior and electrostatics of the interfacial lipid systems. Overall, we believe the work presented in this dissertation provides the building blocks for establishing confocal microscopy as a ubiquitous characterization technique in the interfacial and surface sciences.

Direct observation of magnetic domains by Kerr microscopy in a Ni-Mn-Ga magnetic shape-memory alloy

NASA Astrophysics Data System (ADS)

Perevertov, O.; Heczko, O.; Schäfer, R.

2017-04-01

The magnetic domains in a magnetic shape-memory Ni-Mn-Ga alloy were observed by magneto-optical Kerr microscopy using monochromatic blue LED light. The domains were observed for both single- and multivariant ferroelastic states of modulated martensite. The multivariant state with very fine twins was spontaneously formed after transformation from high-temperature austenite. For both cases, bar domains separated by 180∘ domain walls were found and their dynamics was studied. A quasidomain model was applied to explain the domains in the multivariant state.

Langasite as a piezoelectric material for near-field microscopy resonant cantilevers.

PubMed

Douchet, Gabrielle; Sthal, Fabrice; Leblois, Thérèse; Bigler, Emmanuel

2010-11-01

Quartz length-extension resonators have already been used to obtain atomically-resolved images by frequency-modulation atomic force microscopy. Other piezoelectric materials such as gallium orthophosphate (GaPO(4)), langatate (LGT), and langasite (LGS) could be appropriate for this application. In this paper, the advantages of langasite crystal are presented and the fabrication of similar microsensors in langasite temperature-compensated cuts by chemical etching is proved. A monolithic length extension resonator, with a tip at its end, is obtained which constitutes a real advantage in regard to the existing quartz devices.

Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

NASA Astrophysics Data System (ADS)

Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

2016-08-01

Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm-1) and lipid (~2845 cm-1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

Polarization-modulated second harmonic generation ellipsometric microscopy at video rate.

PubMed

DeWalt, Emma L; Sullivan, Shane Z; Schmitt, Paul D; Muir, Ryan D; Simpson, Garth J

2014-08-19

Fast 8 MHz polarization modulation coupled with analytical modeling, fast beam-scanning, and synchronous digitization (SD) have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and polarized laser transmittance imaging with image acquisition rates up to video rate. In contrast to polarimetry, in which the polarization state of the exiting beam is recorded, NOSE enables recovery of the complex-valued Jones tensor of the sample that describes all polarization-dependent observables of the measurement. Every video-rate scan produces a set of 30 images (10 for each detector with three detectors operating in parallel), each of which corresponds to a different polarization-dependent result. Linear fitting of this image set contracts it down to a set of five parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the incident beam. These parameters can in turn be used to recover the Jones tensor elements of the sample. Following validation of the approach using z-cut quartz, NOSE microscopy was performed for microcrystals of both naproxen and glucose isomerase. When weighted by the measurement time, NOSE microscopy was found to provide a substantial (>7 decades) improvement in the signal-to-noise ratio relative to our previous measurements based on the rotation of optical elements and a 3-fold improvement relative to previous single-point NOSE approaches.

Microscopy illumination engineering using a low-cost liquid crystal display.

PubMed

Guo, Kaikai; Bian, Zichao; Dong, Siyuan; Nanda, Pariksheet; Wang, Ying Min; Zheng, Guoan

2015-02-01

Illumination engineering is critical for obtaining high-resolution, high-quality images in microscope settings. In a typical microscope, the condenser lens provides sample illumination that is uniform and free from glare. The associated condenser diaphragm can be manually adjusted to obtain the optimal illumination numerical aperture. In this paper, we report a programmable condenser lens for active illumination control. In our prototype setup, we used a $15 liquid crystal display as a transparent spatial light modulator and placed it at the back focal plane of the condenser lens. By setting different binary patterns on the display, we can actively control the illumination and the spatial coherence of the microscope platform. We demonstrated the use of such a simple scheme for multimodal imaging, including bright-field microscopy, darkfield microscopy, phase-contrast microscopy, polarization microscopy, 3D tomographic imaging, and super-resolution Fourier ptychographic imaging. The reported illumination engineering scheme is cost-effective and compatible with most existing platforms. It enables a turnkey solution with high flexibility for researchers in various communities. From the engineering point-of-view, the reported illumination scheme may also provide new insights for the development of multimodal microscopy and Fourier ptychographic imaging.

Huygens' optical vector wave field synthesis via in-plane electric dipole metasurface.

PubMed

Park, Hyeonsoo; Yun, Hansik; Choi, Chulsoo; Hong, Jongwoo; Kim, Hwi; Lee, Byoungho

2018-04-16

We investigate Huygens' optical vector wave field synthesis scheme for electric dipole metasurfaces with the capability of modulating in-plane polarization and complex amplitude and discuss the practical issues involved in realizing multi-modulation metasurfaces. The proposed Huygens' vector wave field synthesis scheme identifies the vector Airy disk as a synthetic unit element and creates a designed vector optical field by integrating polarization-controlled and complex-modulated Airy disks. The metasurface structure for the proposed vector field synthesis is analyzed in terms of the signal-to-noise ratio of the synthesized field distribution. The design of practical metasurface structures with true vector modulation capability is possible through the analysis of the light field modulation characteristics of various complex modulated geometric phase metasurfaces. It is shown that the regularization of meta-atoms is a key factor that needs to be considered in field synthesis, given that it is essential for a wide range of optical field synthetic applications, including holographic displays, microscopy, and optical lithography.

Image recombination transform algorithm for superresolution structured illumination microscopy

PubMed Central

Zhou, Xing; Lei, Ming; Dan, Dan; Yao, Baoli; Yang, Yanlong; Qian, Jia; Chen, Guangde; Bianco, Piero R.

2016-01-01

Abstract. Structured illumination microscopy (SIM) is an attractive choice for fast superresolution imaging. The generation of structured illumination patterns made by interference of laser beams is broadly employed to obtain high modulation depth of patterns, while the polarizations of the laser beams must be elaborately controlled to guarantee the high contrast of interference intensity, which brings a more complex configuration for the polarization control. The emerging pattern projection strategy is much more compact, but the modulation depth of patterns is deteriorated by the optical transfer function of the optical system, especially in high spatial frequency near the diffraction limit. Therefore, the traditional superresolution reconstruction algorithm for interference-based SIM will suffer from many artifacts in the case of projection-based SIM that possesses a low modulation depth. Here, we propose an alternative reconstruction algorithm based on image recombination transform, which provides an alternative solution to address this problem even in a weak modulation depth. We demonstrated the effectiveness of this algorithm in the multicolor superresolution imaging of bovine pulmonary arterial endothelial cells in our developed projection-based SIM system, which applies a computer controlled digital micromirror device for fast fringe generation and multicolor light-emitting diodes for illumination. The merit of the system incorporated with the proposed algorithm allows for a low excitation intensity fluorescence imaging even less than 1  W/cm2, which is beneficial for the long-term, in vivo superresolved imaging of live cells and tissues. PMID:27653935

Increasing the space-time product of super-resolution structured illumination microscopy by means of two-pattern illumination

NASA Astrophysics Data System (ADS)

Inochkin, F. M.; Pozzi, P.; Bezzubik, V. V.; Belashenkov, N. R.

2017-06-01

Superresolution image reconstruction method based on the structured illumination microscopy (SIM) principle with reduced and simplified pattern set is presented. The method described needs only 2 sinusoidal patterns shifted by half a period for each spatial direction of reconstruction, instead of the minimum of 3 for the previously known methods. The method is based on estimating redundant frequency components in the acquired set of modulated images. Digital processing is based on linear operations. When applied to several spatial orientations, the image set can be further reduced to a single pattern for each spatial orientation, complemented by a single non-modulated image for all the orientations. By utilizing this method for the case of two spatial orientations, the total input image set is reduced up to 3 images, providing up to 2-fold improvement in data acquisition time compared to the conventional 3-pattern SIM method. Using the simplified pattern design, the field of view can be doubled with the same number of spatial light modulator raster elements, resulting in a total 4-fold increase in the space-time product. The method requires precise knowledge of the optical transfer function (OTF). The key limitation is the thickness of object layer that scatters or emits light, which requires to be sufficiently small relatively to the lens depth of field. Numerical simulations and experimental results are presented. Experimental results are obtained on the SIM setup with the spatial light modulator based on the 1920x1080 digital micromirror device.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harvey, Steven P.; Moseley, John; Norman, Andrew

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

Accurate formulas for interaction force and energy in frequency modulation force spectroscopy

NASA Astrophysics Data System (ADS)

Sader, John E.; Jarvis, Suzanne P.

2004-03-01

Frequency modulation atomic force microscopy utilizes the change in resonant frequency of a cantilever to detect variations in the interaction force between cantilever tip and sample. While a simple relation exists enabling the frequency shift to be determined for a given force law, the required complementary inverse relation does not exist for arbitrary oscillation amplitudes of the cantilever. In this letter we address this problem and present simple yet accurate formulas that enable the interaction force and energy to be determined directly from the measured frequency shift. These formulas are valid for any oscillation amplitude and interaction force, and are therefore of widespread applicability in frequency modulation dynamic force spectroscopy.

A Simple Configuration for Quantitative Phase Contrast Microscopy of Transmissible Samples

NASA Astrophysics Data System (ADS)

Sengupta, Chandan; Dasgupta, Koustav; Bhattacharya, K.

Phase microscopy attempts to visualize and quantify the phase distribution of samples which are otherwise invisible under microscope without the use of stains. The two principal approaches to phase microscopy are essentially those of Fourier plane modulation and interferometric techniques. Although the former, first proposed by Zernike, had been the harbinger of phase microscopy, it was the latter that allowed for quantitative evaluation of phase samples. However interferometric techniques are fraught with associated problems such as complicated setup involving mirrors and beam-splitters, the need for a matched objective in the reference arm and also the need for vibration isolation. The present work proposes a single element cube beam-splitter (CBS) interferometer combined with a microscope objective (MO) for interference microscopy. Because of the monolithic nature of the interferometer, the system is almost insensitive to vibrations and relatively simple to align. It will be shown that phase shifting properties may also be introduced by suitable and proper use of polarizing devices. Initial results showing the quantitative three dimensional phase profiles of simulated and actual biological specimens are presented.

Heat shock protein 47 expression in aged normal human fibroblasts: modulation by Salix alba extract.

PubMed

Nizard, Carine; Noblesse, Emmanuelle; Boisdé, Cécille; Moreau, Marielle; Faussat, Anne-Marie; Schnebert, Sylvianne; Mahé, Christian

2004-06-01

Heat shock protein (HSP) 47 is a specific chaperone of procollagen. This heat shock protein is responsible for the correct three-dimensional organization of procollagen and its control-quality prior secretion. The aim of the study is to evaluate the level of HSP 47 in aged, photoaged, and senescent fibroblasts and its modulation by a plant extract (Salix alba). The level of HSP 47 and/or procollagen expression in fibroblasts was measured by real-time RT-PCR (mRNA transcripts) and by flow cytometry (immunochemistry technique for measurement of arbitrary fluorescence intensity). Immunochemistry techniques and confocal microscopy were used to visualize the cellular localization of HSP 47 and procollagen. These parameters were compared with different age donors, nonsenescent, and senescent fibroblasts. Fibroblasts were irradiated by a noncytotoxic dose of UVA (6 J/cm(2)), and HSP 47 level was evaluated. S. alba extract was tested for its capacity to modulate HSP 47 expression. Colocalization of HSP 47 and procollagen was shown by confocal microscopy, indicating that HSP 47 could play a role of procollagen molecular chaperone in the cellular model. It was also shown that the HSP 47 level is decreased in old-donor cells, senescent, and irradiated cells. This decrease can be modulated by a S. alba extract (polyphenols rich) in a dose-dependent manner. The evaluation of HSP 47 expression in the experimental conditions can lead to a new approach of aging and photoaging, pointing out the implication of this chaperone in these pathophysiologic phenomena. Modulation of HSP 47 expression by this family of molecules could be of cosmetic and/or dermatologic interest.

Scanning Tunneling Optical Resonance Microscopy

NASA Technical Reports Server (NTRS)

Bailey, Sheila; Wilt, Dave; Raffaelle, Ryne; Gennett, Tom; Tin, Padetha; Lau, Janice; Castro, Stephanie; Jenkins, Philip; Scheiman, Dave

2003-01-01

Scanning tunneling optical resonance microscopy (STORM) is a method, now undergoing development, for measuring optoelectronic properties of materials and devices on the nanoscale by means of a combination of (1) traditional scanning tunneling microscopy (STM) with (2) tunable laser spectroscopy. In STORM, an STM tip probing a semiconductor is illuminated with modulated light at a wavelength in the visible-to-near-infrared range and the resulting photoenhancement of the tunneling current is measured as a function of the illuminating wavelength. The photoenhancement of tunneling current occurs when the laser photon energy is sufficient to excite charge carriers into the conduction band of the semiconductor. Figure 1 schematically depicts a proposed STORM apparatus. The light for illuminating the semiconductor specimen at the STM would be generated by a ring laser that would be tunable across the wavelength range of interest. The laser beam would be chopped by an achromatic liquid-crystal modulator. A polarization-maintaining optical fiber would couple the light to the tip/sample junction of a commercial STM. An STM can be operated in one of two modes: constant height or constant current. A STORM apparatus would be operated in the constant-current mode, in which the height of the tip relative to the specimen would be varied in order to keep the tunneling current constant. In this mode, a feedback control circuit adjusts the voltage applied to a piezoelectric actuator in the STM that adjusts the height of the STM tip to keep the tunneling current constant. The exponential relationship between the tunneling current and tip-to-sample distance makes it relatively easy to implement this mode of operation. The choice of method by which the photoenhanced portion of the tunneling current would be measured depends on choice of the frequency at which the input illumination would be modulated (chopped). If the frequency of modulation were low enough (typically < 10 Hz) that the feedback circuit could respond, then the voltage applied to the piezoelectric tip-height actuator could be measured by use of a lock-in amplifier locked to the modulation (chopping) signal. However, at a high modulation frequency (typically in the kilohertz range or higher), the feedback circuit would be unable to respond. In this case, the photoenhanced portion of the tunneling current could be measured directly. For this purpose, the tunneling current would be passed through a precise resistor and the voltage drop would be measured by use of the lock-in amplifier.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polat, Ozgur; Ertugrul, Memhet; Thompson, James R

To obtain an engineered surface for deposition of high-Tc superconductors, nanoscale modulations of the surface of the underlying LaMnO3 (LMO) cap layer is a potential source for generating microstructural defects in YBa2Cu3O7- (YBCO) films. These defects may improve the flux-pinning and consequently increase the critical current density, Jc. To provide such nanoscale modulation via a practical and scalable process, tantalum (Ta) and palladium (Pd) nano-islands were deposited using dc-magnetron sputtering on the surface of the cap layer of commercial metal tape templates for second-generation wires. The size and density of these nano-islands can be controlled by changing sputtering conditions suchmore » as the power and deposition time. Compared to the reference sample grown on an untreated LMO cap layer, the YBCO films grown on the LMO cap layers with Ta or Pd nano-islands exhibited improved in-field Jc performance. Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) were used to assess the evolving size and density of the nano-islands.« less

Imaging surface nanobubbles at graphite-water interfaces with different atomic force microscopy modes.

PubMed

Yang, Chih-Wen; Lu, Yi-Hsien; Hwang, Ing-Shouh

2013-05-08

We have imaged nanobubbles on highly ordered pyrolytic graphite (HOPG) surfaces in pure water with different atomic force microscopy (AFM) modes, including the frequency-modulation, the tapping, and the PeakForce techniques. We have compared the performance of these modes in obtaining the surface profiles of nanobubbles. The frequency-modulation mode yields a larger height value than the other two modes and can provide more accurate measurement of the surface profiles of nanobubbles. Imaging with PeakForce mode shows that a nanobubble appears smaller and shorter with increasing peak force and disappears above a certain peak force, but the size returns to the original value when the peak force is reduced. This indicates that imaging with high peak forces does not cause gas removal from the nanobubbles. Based on the presented findings and previous AFM observations, the existing models for nanobubbles are reviewed and discussed. The model of gas aggregate inside nanobubbles provides a better explanation for the puzzles of the high stability and the contact angle of surface nanobubbles.

Complexation of amyloid fibrils with charged conjugated polymers.

PubMed

Ghosh, Dhiman; Dutta, Paulami; Chakraborty, Chanchal; Singh, Pradeep K; Anoop, A; Jha, Narendra Nath; Jacob, Reeba S; Mondal, Mrityunjoy; Mankar, Shruti; Das, Subhadeep; Malik, Sudip; Maji, Samir K

2014-04-08

It has been suggested that conjugated charged polymers are amyloid imaging agents and promising therapeutic candidates for neurological disorders. However, very less is known about their efficacy in modulating the amyloid aggregation pathway. Here, we studied the modulation of Parkinson's disease associated α-synuclein (AS) amyloid assembly kinetics using conjugated polyfluorene polymers (PF, cationic; PFS, anionic). We also explored the complexation of these charged polymers with the various AS aggregated species including amyloid fibrils and oligomers using multidisciplinary biophysical techniques. Our data suggests that both polymers irrespective of their different charges in the side chains increase the fibrilization kinetics of AS and also remarkably change the morphology of the resultant amyloid fibrils. Both polymers were incorporated/aligned onto the AS amyloid fibrils as evident from electron microscopy (EM) and atomic force microscopy (AFM), and the resultant complexes were structurally distinct from their pristine form of both polymers and AS supported by FTIR study. Additionally, we observed that the mechanism of interactions between the polymers with different species of AS aggregates were markedly different.

Frequency modulation atomic force microscopy: a dynamic measurement technique for biological systems

NASA Astrophysics Data System (ADS)

Higgins, Michael J.; Riener, Christian K.; Uchihashi, Takayuki; Sader, John E.; McKendry, Rachel; Jarvis, Suzanne P.

2005-03-01

Frequency modulation atomic force microscopy (FM-AFM) has been modified to operate in a liquid environment within an atomic force microscope specifically designed for investigating biological samples. We demonstrate the applicability of FM-AFM to biological samples using the spectroscopy mode to measure the unbinding forces of a single receptor-ligand (biotin-avidin) interaction. We show that quantitative adhesion force measurements can only be obtained provided certain modifications are made to the existing theory, which is used to convert the detected frequency shifts to an interaction force. Quantitative force measurements revealed that the unbinding forces for the biotin-avidin interaction were greater than those reported in previous studies. This finding was due to the use of high average tip velocities, which were calculated to be two orders of magnitude greater than those typically used in unbinding receptor-ligand experiments. This study therefore highlights the potential use of FM-AFM to study a range of biological systems, including living cells and/or single biomolecule interactions.

Quantitative measurement of solvation shells using frequency modulated atomic force microscopy

NASA Astrophysics Data System (ADS)

Uchihashi, T.; Higgins, M.; Nakayama, Y.; Sader, J. E.; Jarvis, S. P.

2005-03-01

The nanoscale specificity of interaction measurements and additional imaging capability of the atomic force microscope make it an ideal technique for measuring solvation shells in a variety of liquids next to a range of materials. Unfortunately, the widespread use of atomic force microscopy for the measurement of solvation shells has been limited by uncertainties over the dimensions, composition and durability of the tip during the measurements, and problems associated with quantitative force calibration of the most sensitive dynamic measurement techniques. We address both these issues by the combined use of carbon nanotube high aspect ratio probes and quantifying the highly sensitive frequency modulation (FM) detection technique using a recently developed analytical method. Due to the excellent reproducibility of the measurement technique, additional information regarding solvation shell size as a function of proximity to the surface has been obtained for two very different liquids. Further, it has been possible to identify differences between chemical and geometrical effects in the chosen systems.

Precise, motion-free polarization control in Second Harmonic Generation microscopy using a liquid crystal modulator in the infinity space.

PubMed

Lien, Chi-Hsiang; Tilbury, Karissa; Chen, Shean-Jen; Campagnola, Paul J

2013-01-01

Second Harmonic Generation (SHG) microscopy coupled with polarization analysis has great potential for use in tissue characterization, as molecular and supramolecular structural details can be extracted. Such measurements are difficult to perform quickly and accurately. Here we present a new method that uses a liquid crystal modulator (LCM) located in the infinity space of a SHG laser scanning microscope that allows the generation of any desired linear or circular polarization state. As the device contains no moving parts, polarization can be rotated accurately and faster than by manual or motorized control. The performance in terms of polarization purity was validated using Stokes vector polarimetry, and found to have minimal residual polarization ellipticity. SHG polarization imaging characteristics were validated against well-characterized specimens having cylindrical and/or linear symmetries. The LCM has a small footprint and can be implemented easily in any standard microscope and is cost effective relative to other technologies.

Study on superstructure in ion co-doped BiFeO3 by using transmission electron microscopy

NASA Astrophysics Data System (ADS)

Pu, Shi-Zhou; Guo, Chao; Li, Mei-Ya; Chen, Zhen-Lian; Zou, Hua-Min

2015-04-01

La3+ and V5+ co-doped BiFeO3 ceramics are synthesized by rapid liquid sintering technique. The modulated structure in Bi0.85La0.15Fe0.97V0.03O3 is investigated by using transmission electron microscopy (TEM). Two kinds of superstructures are observed in the samples. One is the component modulated superstructure and twin-domain, which is generated by La3+ ordered substitution for Bi3+ and frequently appears. The chemical composition of the superstructure is explored by x-ray energy dispersive spectroscopy (EDS). The model of the ordered structure is proposed. Simulation based on the model is conducted. The second is the fluorite-type δ-Bi2O3 related superstructure. The relation between the ferroelectric property and the microstructure of the sample is also discussed. Project supported by the National Natural Science Foundation of China (Grant Nos. 51372174, 11074193, and 51132001) and the Fundamental Research Funds for the Central Universities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Tomoharu; Yamada, Hirofumi, E-mail: h-yamada@kuee.kyoto-u.ac.jp; Kobayashi, Kei

The device performances of organic thin film transistors are often limited by the metal–organic interface because of the disordered molecular layers at the interface and the energy barriers against the carrier injection. It is important to study the local impedance at the interface without being affected by the interface morphology. We combined frequency modulation atomic force microscopy with scanning impedance microscopy (SIM) to sensitively measure the ac responses of the interface to an ac voltage applied across the interface and the dc potential drop at the interface. By using the frequency-modulation SIM (FM-SIM) technique, we characterized the interface impedance ofmore » a Pt electrode and a single pentacene grain as a parallel circuit of a contact resistance and a capacitance. We found that the reduction of the contact resistance was caused by the reduction of the energy level mismatch at the interface by the FM-SIM measurements, demonstrating the usefulness of the FM-SIM technique for investigation of the local interface impedance without being affected by its morphology.« less

X-ray micro-modulated luminescence tomography (XMLT)

PubMed Central

Cong, Wenxiang; Liu, Fenglin; Wang, Chao; Wang, Ge

2014-01-01

Imaging depth of optical microscopy has been fundamentally limited to millimeter or sub-millimeter due to strong scattering of light in a biological sample. X-ray microscopy can resolve spatial details of few microns deep inside a sample but contrast resolution is inadequate to depict heterogeneous features at cellular or sub-cellular levels. To enhance and enrich biological contrast at large imaging depth, various nanoparticles are introduced and become essential to basic research and molecular medicine. Nanoparticles can be functionalized as imaging probes, similar to fluorescent and bioluminescent proteins. LiGa5O8:Cr3+ nanoparticles were recently synthesized to facilitate luminescence energy storage with x-ray pre-excitation and subsequently stimulated luminescence emission by visible/near-infrared (NIR) light. In this paper, we propose an x-ray micro-modulated luminescence tomography (XMLT, or MLT to be more general) approach to quantify a nanophosphor distribution in a thick biological sample with high resolution. Our numerical simulation studies demonstrate the feasibility of the proposed approach. PMID:24663898

Precise, motion-free polarization control in Second Harmonic Generation microscopy using a liquid crystal modulator in the infinity space

PubMed Central

Lien, Chi-Hsiang; Tilbury, Karissa; Chen, Shean-Jen; Campagnola, Paul J.

2013-01-01

Second Harmonic Generation (SHG) microscopy coupled with polarization analysis has great potential for use in tissue characterization, as molecular and supramolecular structural details can be extracted. Such measurements are difficult to perform quickly and accurately. Here we present a new method that uses a liquid crystal modulator (LCM) located in the infinity space of a SHG laser scanning microscope that allows the generation of any desired linear or circular polarization state. As the device contains no moving parts, polarization can be rotated accurately and faster than by manual or motorized control. The performance in terms of polarization purity was validated using Stokes vector polarimetry, and found to have minimal residual polarization ellipticity. SHG polarization imaging characteristics were validated against well-characterized specimens having cylindrical and/or linear symmetries. The LCM has a small footprint and can be implemented easily in any standard microscope and is cost effective relative to other technologies. PMID:24156059

Imaging of viscoelastic soft matter with small indentation using higher eigenmodes in single-eigenmode amplitude-modulation atomic force microscopy.

PubMed

Nikfarjam, Miead; López-Guerra, Enrique A; Solares, Santiago D; Eslami, Babak

2018-01-01

In this short paper we explore the use of higher eigenmodes in single-eigenmode amplitude-modulation atomic force microscopy (AFM) for the small-indentation imaging of soft viscoelastic materials. In viscoelastic materials, whose response depends on the deformation rate, the tip-sample forces generated as a result of sample deformation increase as the tip velocity increases. Since the eigenfrequencies in a cantilever increase with eigenmode order, and since higher oscillation frequencies lead to higher tip velocities for a given amplitude (in viscoelastic materials), the sample indentation can in some cases be reduced by using higher eigenmodes of the cantilever. This effect competes with the lower sensitivity of higher eigenmodes, due to their larger force constant, which for elastic materials leads to greater indentation for similar amplitudes, compared with lower eigenmodes. We offer a short theoretical discussion of the key underlying concepts, along with numerical simulations and experiments to illustrate a simple recipe for imaging soft viscoelastic matter with reduced indentation.

Three-dimensional atomic force microscopy mapping at the solid-liquid interface with fast and flexible data acquisition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Söngen, Hagen, E-mail: soengen@uni-mainz.de; Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz; Nalbach, Martin

2016-06-15

We present the implementation of a three-dimensional mapping routine for probing solid-liquid interfaces using frequency modulation atomic force microscopy. Our implementation enables fast and flexible data acquisition of up to 20 channels simultaneously. The acquired data can be directly synchronized with commercial atomic force microscope controllers, making our routine easily extendable for related techniques that require additional data channels, e.g., Kelvin probe force microscopy. Moreover, the closest approach of the tip to the sample is limited by a user-defined threshold, providing the possibility to prevent potential damage to the tip. The performance of our setup is demonstrated by visualizing themore » hydration structure above the calcite (10.4) surface in water.« less

Optimizing single-nanoparticle two-photon microscopy by in situ adaptive control of femtosecond pulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Donghai; Deng, Yongkai; Chu, Saisai

2016-07-11

Single-nanoparticle two-photon microscopy shows great application potential in super-resolution cell imaging. Here, we report in situ adaptive optimization of single-nanoparticle two-photon luminescence signals by phase and polarization modulations of broadband laser pulses. For polarization-independent quantum dots, phase-only optimization was carried out to compensate the phase dispersion at the focus of the objective. Enhancement of the two-photon excitation fluorescence intensity under dispersion-compensated femtosecond pulses was achieved. For polarization-dependent single gold nanorod, in situ polarization optimization resulted in further enhancement of two-photon photoluminescence intensity than phase-only optimization. The application of in situ adaptive control of femtosecond pulse provides a way for object-orientedmore » optimization of single-nanoparticle two-photon microscopy for its future applications.« less

A simple tool for stereological assessment of digital images: the STEPanizer.

PubMed

Tschanz, S A; Burri, P H; Weibel, E R

2011-07-01

STEPanizer is an easy-to-use computer-based software tool for the stereological assessment of digitally captured images from all kinds of microscopical (LM, TEM, LSM) and macroscopical (radiology, tomography) imaging modalities. The program design focuses on providing the user a defined workflow adapted to most basic stereological tasks. The software is compact, that is user friendly without being bulky. STEPanizer comprises the creation of test systems, the appropriate display of digital images with superimposed test systems, a scaling facility, a counting module and an export function for the transfer of results to spreadsheet programs. Here we describe the major workflow of the tool illustrating the application on two examples from transmission electron microscopy and light microscopy, respectively. © 2011 The Authors Journal of Microscopy © 2011 Royal Microscopical Society.

Inhibition of melanosome transfer results in skin lightening.

PubMed

Seiberg, M; Paine, C; Sharlow, E; Andrade-Gordon, P; Costanzo, M; Eisinger, M; Shapiro, S S

2000-08-01

The chemical basis of melanogenesis is well documented, but the mechanism of melanosome transfer and the regulation of pigmentation by keratinocyte-melanocyte interactions are not well understood. Therefore we examined the effects of serine protease inhibitors on skin pigmentation and found that the protease-activated receptor 2, expressed on keratinocytes, may regulate pigmentation via keratinocyte-melanocyte interactions. Here we show that modulation of protease-activated receptor 2 activation affects melanosome transfer into keratinocytes, resulting in changes in pigment production and deposition. SLIGRL, the protease-activated receptor 2 activating peptide, enhanced melanosome ingestion by keratinocytes, thus increasing pigment deposition. RWJ-50353, a serine protease inhibitor, led to reduced pigment deposition in melanocytes and depigmentation. Electron microscopy studies illustrated an accumulation of immature melanosomes inside melanocytes and abnormal dendrite dynamics in RWJ-50353-treated epidermal equivalents. RWJ-50353 induced a visible and dose-dependent skin lightening effect in the dark-skinned Yucatan swine. Examinations by electron microscopy indicated that the in vivo transfer of melanosomes from melanocytes to keratinocytes was affected. Our data suggest that modulation of keratinocyte-melanocyte interactions via the protease-activated receptor 2 pathway affects melanosome transfer. The use of RWJ-50353 to modulate protease-activated receptor 2 activation could lead to a new class of depigmenting agents.

A single molecule study of cellulase hydrolysis of crystalline cellulose

NASA Astrophysics Data System (ADS)

Liu, Yu-San; Luo, Yonghua; Baker, John O.; Zeng, Yining; Himmel, Michael E.; Smith, Steve; Ding, Shi-You

2010-02-01

Cellobiohydrolase-I (CBH I), a processive exoglucanase secreted by Trichoderma reesei, is one of the key enzyme components in a commercial cellulase mixture currently used for processing biomass to biofuels. CBH I contains a family 7 glycoside hydrolase catalytic module, a family 1 carbohydrate-binding module (CBM), and a highlyglycosylated linker peptide. It has been proposed that the CBH I cellulase initiates the hydrolysis from the reducing end of one cellulose chain and successively cleaves alternate β-1,4-glycosidic bonds to release cellobiose as its principal end product. The role each module of CBH I plays in the processive hydrolysis of crystalline cellulose has yet to be convincingly elucidated. In this report, we use a single-molecule approach that combines optical (Total Internal Reflection Fluorescence microscopy, or TIRF-M) and non-optical (Atomic Force Microscopy, or AFM) imaging techniques to analyze the molecular motion of CBM tagged with green fluorescence protein (GFP), and to investigate the surface structure of crystalline cellulose and changes made in the structure by CBM and CBH I. The preliminary results have revealed a confined nanometer-scale movement of the TrCBM1-GFP bound to cellulose, and decreases in cellulose crystal size as well as increases in surface roughness during CBH I hydrolysis of crystalline cellulose.

Fast spatial beam shaping by acousto-optic diffraction for 3D non-linear microscopy.

PubMed

Akemann, Walther; Léger, Jean-François; Ventalon, Cathie; Mathieu, Benjamin; Dieudonné, Stéphane; Bourdieu, Laurent

2015-11-02

Acousto-optic deflection (AOD) devices offer unprecedented fast control of the entire spatial structure of light beams, most notably their phase. AOD light modulation of ultra-short laser pulses, however, is not straightforward to implement because of intrinsic chromatic dispersion and non-stationarity of acousto-optic diffraction. While schemes exist to compensate chromatic dispersion, non-stationarity remains an obstacle. In this work we demonstrate an efficient AOD light modulator for stable phase modulation using time-locked generation of frequency-modulated acoustic waves at the full repetition rate of a high power laser pulse amplifier of 80 kHz. We establish the non-local relationship between the optical phase and the generating acoustic frequency function and verify the system for temporal stability, phase accuracy and generation of non-linear two-dimensional phase functions.

Tunable self-organization of nanocomposite multilayers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, C. Q.; Pei, Y. T.; Shaha, K. P.

In this letter we report the controlled growth and microstructural evolution of self-assembled nanocomposite multilayers that are induced by surface ion-impingement. The nanoscale structures together with chemical composition, especially at the growing front, have been investigated with high-resolution transmission electron microscopy. Concurrent ion impingement of growing films produces an amorphous capping layer 3 nm in thickness where spatially modulated phase separation is initiated. It is shown that the modulation of multilayers as controlled by the self-organization of nanocrystallites below the capping layer, can be tuned through the entire film.

Ferroelectric or non-ferroelectric: Why so many materials exhibit “ferroelectricity” on the nanoscale

DOE PAGES

Vasudevan, Rama K.; Balke, Nina; Maksymovych, Peter; ...

2017-05-01

Here, ferroelectric materials have remained one of the major focal points of condensed matter physics and materials science for over 50 years. In the last 20 years, the development of voltage-modulated scanning probe microscopy techniques, exemplified by Piezoresponse force microscopy (PFM) and associated time- and voltage spectroscopies, opened a pathway to explore these materials on a single-digit nanometer level. Consequently, domain structures and walls and polarization dynamics can now be imaged in real space. More generally, PFM has allowed studying electromechanical coupling in a broad variety of materials ranging from ionics to biological systems.

Quantification of Bacterial Twitching Motility in Dense Colonies Using Transmitted Light Microscopy and Computational Image Analysis.

PubMed

Smith, Benjamin; Li, Jianfang; Metruccio, Matteo; Wan, Stephanie; Evans, David; Fleiszig, Suzanne

2018-04-20

A method was developed to allow the quantification and mapping of relative bacterial twitching motility in dense samples, where tracking of individual bacteria was not feasible. In this approach, movies of bacterial films were acquired using differential interference contrast microscopy (DIC), and bacterial motility was then indirectly quantified by the degree to which the bacteria modulated the intensity of light in the field-of-view over time. This allowed the mapping of areas of relatively high and low motility within a single field-of-view, and comparison of the total distribution of motility between samples.

Isotropic differential phase contrast microscopy for quantitative phase bio-imaging.

PubMed

Chen, Hsi-Hsun; Lin, Yu-Zi; Luo, Yuan

2018-05-16

Quantitative phase imaging (QPI) has been investigated to retrieve optical phase information of an object and applied to biological microscopy and related medical studies. In recent examples, differential phase contrast (DPC) microscopy can recover phase image of thin sample under multi-axis intensity measurements in wide-field scheme. Unlike conventional DPC, based on theoretical approach under partially coherent condition, we propose a new method to achieve isotropic differential phase contrast (iDPC) with high accuracy and stability for phase recovery in simple and high-speed fashion. The iDPC is simply implemented with a partially coherent microscopy and a programmable thin-film transistor (TFT) shield to digitally modulate structured illumination patterns for QPI. In this article, simulation results show consistency of our theoretical approach for iDPC under partial coherence. In addition, we further demonstrate experiments of quantitative phase images of a standard micro-lens array, as well as label-free live human cell samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measurement of replication structures at the nanometer scale using super-resolution light microscopy

PubMed Central

Baddeley, D.; Chagin, V. O.; Schermelleh, L.; Martin, S.; Pombo, A.; Carlton, P. M.; Gahl, A.; Domaing, P.; Birk, U.; Leonhardt, H.; Cremer, C.; Cardoso, M. C.

2010-01-01

DNA replication, similar to other cellular processes, occurs within dynamic macromolecular structures. Any comprehensive understanding ultimately requires quantitative data to establish and test models of genome duplication. We used two different super-resolution light microscopy techniques to directly measure and compare the size and numbers of replication foci in mammalian cells. This analysis showed that replication foci vary in size from 210 nm down to 40 nm. Remarkably, spatially modulated illumination (SMI) and 3D-structured illumination microscopy (3D-SIM) both showed an average size of 125 nm that was conserved throughout S-phase and independent of the labeling method, suggesting a basic unit of genome duplication. Interestingly, the improved optical 3D resolution identified 3- to 5-fold more distinct replication foci than previously reported. These results show that optical nanoscopy techniques enable accurate measurements of cellular structures at a level previously achieved only by electron microscopy and highlight the possibility of high-throughput, multispectral 3D analyses. PMID:19864256

High speed wavefront sensorless aberration correction in digital micromirror based confocal microscopy.

PubMed

Pozzi, P; Wilding, D; Soloviev, O; Verstraete, H; Bliek, L; Vdovin, G; Verhaegen, M

2017-01-23

The quality of fluorescence microscopy images is often impaired by the presence of sample induced optical aberrations. Adaptive optical elements such as deformable mirrors or spatial light modulators can be used to correct aberrations. However, previously reported techniques either require special sample preparation, or time consuming optimization procedures for the correction of static aberrations. This paper reports a technique for optical sectioning fluorescence microscopy capable of correcting dynamic aberrations in any fluorescent sample during the acquisition. This is achieved by implementing adaptive optics in a non conventional confocal microscopy setup, with multiple programmable confocal apertures, in which out of focus light can be separately detected, and used to optimize the correction performance with a sampling frequency an order of magnitude faster than the imaging rate of the system. The paper reports results comparing the correction performances to traditional image optimization algorithms, and demonstrates how the system can compensate for dynamic changes in the aberrations, such as those introduced during a focal stack acquisition though a thick sample.

In situ study of Li-ions diffusion and deformation in Li-rich cathode materials by using scanning probe microscopy techniques

NASA Astrophysics Data System (ADS)

Zeng, Kaiyang; Li, Tao; Tian, Tian

2017-08-01

In this paper, the scanning probe microscopy (SPM) based techniques, namely, conductive-AFM, electrochemical strain microscopy (ESM) and AM-FM (amplitude modulation-frequency modulation) techniques, are used to in situ characterize the changes in topography, conductivity and elastic properties of Li-rich layered oxide cathode (Li1.2Mn0.54Ni0.13Co0.13O2) materials, in the form of nanoparticles, when subject to the external electric field. Nanoparticles are the basic building blocks for composite cathode in a Li-ion rechargeable battery. Characterization of the structure and electrochemical properties of the nanoparticles is very important to understand the performance and reliability of the battery materials and devices. In this study, the conductivity, deformation and mechanical properties of the Li-rich oxide nanoparticles under different polarities of biases are studied using the above-mentioned SPM techniques. This information can be correlated with the Li+-ion diffusion and migration in the particles under external electrical field. The results also confirm that the SPM techniques are ideal tools to study the changes in various properties of electrode materials at nano- to micro-scales during or after the ‘simulated’ battery operation conditions. These techniques can also be used to in situ characterize the electrochemical performances of other energy storage materials, especially in the form of the nanoparticles.

Portable fiber-optic taper coupled optical microscopy platform

NASA Astrophysics Data System (ADS)

Wang, Weiming; Yu, Yan; Huang, Hui; Ou, Jinping

2017-04-01

The optical fiber taper coupled with CMOS has advantages of high sensitivity, compact structure and low distortion in the imaging platform. So it is widely used in low light, high speed and X-ray imaging systems. In the meanwhile, the peculiarity of the coupled structure can meet the needs of the demand in microscopy imaging. Toward this end, we developed a microscopic imaging platform based on the coupling of cellphone camera module and fiber optic taper for the measurement of the human blood samples and ascaris lumbricoides. The platform, weighing 70 grams, is based on the existing camera module of the smartphone and a fiber-optic array which providing a magnification factor of 6x.The top facet of the taper, on which samples are placed, serves as an irregular sampling grid for contact imaging. The magnified images of the sample, located on the bottom facet of the fiber, are then projected onto the CMOS sensor. This paper introduces the portable medical imaging system based on the optical fiber coupling with CMOS, and theoretically analyzes the feasibility of the system. The image data and process results either can be stored on the memory or transmitted to the remote medical institutions for the telemedicine. We validate the performance of this cell-phone based microscopy platform using human blood samples and test target, achieving comparable results to a standard bench-top microscope.

A versatile variable field module for Asylum Cypher scanning probe system

NASA Astrophysics Data System (ADS)

Liu, Hongxue; Comes, Ryan; Lu, Jiwei; Wolf, Stuart; Hodgson, Jim; Rutgers, Maarten

2013-03-01

Atomic force microscopy (AFM) has become one of the most widely used techniques for measuring and manipulating various characteristics of materials at the nanoscale. However, there are very limited option for the characterization of field dependence properties. In this work, we demonstrate a versatile variable field module (VFM) with magnetic field up to 1800 Oe for the Asylum Research Cypher system. The magnetic field is changed by adjusting the distance between a rare earth magnet and the AFM probe. A built-in Hall sensor makes it possible to perform in-situ measurements of the field. Rotating the magnet makes it possible to do angular field dependent measurements. The capability of the VFM system is demonstrated by degaussing a floppy disk media with increasing magnetic field. The written bits are erased at about 800 Oe. Angular dependence measurements clearly show the evolution of magnetic domain structures. A completely reversible magnetic force microscopy (MFM) phase contrast is observed when the magnetic field is rotated by 180°. Further demonstration of successful magnetic switching of CoFe2O4 pillars in CoFe2O4-BiFeO3 nanocomposites will be presented and field dependent MFM and piezoresponse force microscopy (PFM) will be discussed. The work at University of Virginia was supported by DARPA under contract no. HR-0011-10-1-0072.

Dissolution Processes at Step Edges of Calcite in Water Investigated by High-Speed Frequency Modulation Atomic Force Microscopy and Simulation.

PubMed

Miyata, Kazuki; Tracey, John; Miyazawa, Keisuke; Haapasilta, Ville; Spijker, Peter; Kawagoe, Yuta; Foster, Adam S; Tsukamoto, Katsuo; Fukuma, Takeshi

2017-07-12

The microscopic understanding of the crystal growth and dissolution processes have been greatly advanced by the direct imaging of nanoscale step flows by atomic force microscopy (AFM), optical interferometry, and X-ray microscopy. However, one of the most fundamental events that govern their kinetics, namely, atomistic events at the step edges, have not been well understood. In this study, we have developed high-speed frequency modulation AFM (FM-AFM) and enabled true atomic-resolution imaging in liquid at ∼1 s/frame, which is ∼50 times faster than the conventional FM-AFM. With the developed AFM, we have directly imaged subnanometer-scale surface structures around the moving step edges of calcite during its dissolution in water. The obtained images reveal that the transition region with typical width of a few nanometers is formed along the step edges. Building upon insight in previous studies, our simulations suggest that the transition region is most likely to be a Ca(OH) 2 monolayer formed as an intermediate state in the dissolution process. On the basis of this finding, we improve our understanding of the atomistic dissolution model of calcite in water. These results open up a wide range of future applications of the high-speed FM-AFM to the studies on various dynamic processes at solid-liquid interfaces with true atomic resolution.

Reversible optical control of cyanine fluorescence in fixed and living cells: optical lock-in detection immunofluorescence imaging microscopy

PubMed Central

Yan, Yuling; Petchprayoon, Chutima; Mao, Shu; Marriott, Gerard

2013-01-01

Optical switch probes undergo rapid and reversible transitions between two distinct states, one of which may fluoresce. This class of probe is used in various super-resolution imaging techniques and in the high-contrast imaging technique of optical lock-in detection (OLID) microscopy. Here, we introduce optimized optical switches for studies in living cells under standard conditions of cell culture. In particular, a highly fluorescent cyanine probe (Cy or Cy3) is directly or indirectly linked to naphthoxazine (NISO), a highly efficient optical switch that undergoes robust, 405/532 nm-driven transitions between a colourless spiro (SP) state and a colourful merocyanine (MC) state. The intensity of Cy fluorescence in these Cy/Cy3-NISO probes is reversibly modulated between a low and high value in SP and MC states, respectively, as a result of Förster resonance energy transfer. Cy/Cy3-NISO probes are targeted to specific proteins in living cells where defined waveforms of Cy3 fluorescence are generated by optical switching of the SP and MC states. Finally, we introduce a new imaging technique (called OLID-immunofluorescence microscopy) that combines optical modulation of Cy3 fluorescence from Cy3/NISO co-labelled antibodies within fixed cells and OLID analysis to significantly improve image contrast in samples having high background or rare antigens. PMID:23267183

Investigating Intermolecular Interactions via Scanning Tunneling Microscopy: An Experiment for the Physical Chemistry Laboratory

ERIC Educational Resources Information Center

Pullman, David; Peterson, Karen I.

2004-01-01

A scanning tunneling microscope (STM) project designed as a module for the undergraduate physical chemistry laboratory is described. The effects of van der Waals interactions on the condensed-phase structure are examined by the analysis of the pattern of the monolayer structures.

Design of the soft x-ray tomography beamline at Taiwan photon source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Yi-Jr, E-mail: su.yj@nsrrc.org.tw; Fu, Huang-Wen; Chung, Shih-Chun

2016-07-27

The optical design of the varied-line-spacing plane-grating monochromator for transmission full-field imaging of frozen-hydrated biological samples at NSRRC is presented. This monochromator consists of a plane mirror and three interchangeable gratings with groove densities 600, 1200 and 2400 l/mm to cover the energy range 260 – 2600 eV. The groove parameters of the varied-line-spacing plane gratings are designed to minimize the effect of coma and spherical aberration to maintain the exit slit in focus for any value of incident angle. All parameters of optical components at the beamline are verified with a ray-tracing method. In the beamline design, the calculatedmore » results from the ray-tracing codes and the expected performances are discussed.« less

Charge Sharing and Charge Loss in a Cadmium-Zinc-Telluride Fine-Pixel Detector Array

NASA Technical Reports Server (NTRS)

Gaskin, J. A.; Sharma, D. P.; Ramsey, B. D.; Six, N. Frank (Technical Monitor)

2002-01-01

Because of its high atomic number, room temperature operation, low noise, and high spatial resolution a Cadmium-Zinc-Telluride (CZT) multi-pixel detector is ideal for hard x-ray astrophysical observation. As part of on-going research at MSFC (Marshall Space Flight Center) to develop multi-pixel CdZnTe detectors for this purpose, we have measured charge sharing and charge loss for a 4x4 (750micron pitch), lmm thick pixel array and modeled these results using a Monte-Carlo simulation. This model was then used to predict the amount of charge sharing for a much finer pixel array (with a 300micron pitch). Future work will enable us to compare the simulated results for the finer array to measured values.

Establishment of replacement batches for heparin low-molecular-mass for calibration CRS, and the International Standard Low Molecular Weight Heparin for Calibration.

PubMed

Mulloy, B; Heath, A; Behr-Gross, M-E

2007-12-01

An international collaborative study involving fourteen laboratories has taken place, organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) with National Institute for Biological Standards & Control (NIBSC) (in its capacity as a World Health Organisation (WHO) Laboratory for Biological Standardisation) to provide supporting data for the establishment of replacement batches of Heparin Low-Molecular-Mass (LMM) for Calibration Chemical Reference Substance (CRS), and of the International Reference Reagent (IRR) Low Molecular Weight Heparin for Molecular Weight Calibration. A batch of low-molecular-mass heparin was donated to the organisers and candidate preparations of freeze-dried heparin were produced at NIBSC and EDQM. The establishment study was organised in two phases: a prequalification (phase 1, performed in 3 laboratories in 2005) followed by an international collaborative study (phase 2). In phase 2, started in March 2006, molecular mass parameters were determined for seven different LMM heparin samples using the current CRS batch and two batches of candidate replacement material with a defined number average relative molecular mass (Mn) of 3,700, determined in phase 1. The values calculated using the candidates as standard were systematically different from values calculated using the current batch with its assigned number-average molecular mass (Mna) of 3,700. Using raw data supplied by participants, molecular mass parameters were recalculated using the candidates as standard with values for Mna of 3,800 and 3,900. Values for these parameters agreed more closely with those calculated using the current batch supporting the fact that the candidates, though similar to batch 1 in view of the production processes used, differ slightly in terms of molecular mass distribution. Therefore establishment of the candidates was recommended with an assigned Mna value of 3,800 that is both consistent with phase 1 results and guarantees continuity with the current CRS batch. In phase 2, participants also determined molecular weight parameters for the seven different LMM heparin samples using both the 1st IRR (90/686) and its Broad Standard Table and the candidate World Health Organization (WHO) 2nd International Standard (05/112) (2nd IS) using a Broad Standard Table established in phase 1. Mean molecular weights calculated using 2nd IS were slightly higher than with 1st IRR, and participants in the study indicated that this systematic difference precluded establishment of 2nd IS with the table supplied. A replacement Broad Standard Table has been devised on the basis of the central recalculations of raw data supplied by participants; this table gives improved agreement between values derived using the 1st IRR and the candidate 2nd IS. On the basis of this study a recommendation was made for the establishment of 2nd IS and its proposed Broad Standard Table as a replacement for the 1st International Reference Reagent Low Molecular Weight Heparin for Molecular Weight Calibration. Unlike the 1st IRR however, the candidate material 2nd IS is not suitable for use with the method of Nielsen. The candidate materials were established as heparin low-molecular-mass for calibration batches 2 and 3 by the Ph. Eur. Commission in March 2007 and as 2nd IS low-molecular-weight heparin for molecular weight calibration (05/112) by the Expert Committee on Biological Standardization in November 2007.

A STED-FLIM microscope applied to imaging the natural killer cell immune synapse

NASA Astrophysics Data System (ADS)

Lenz, M. O.; Brown, A. C. N.; Auksorius, E.; Davis, D. M.; Dunsby, C.; Neil, M. A. A.; French, P. M. W.

2011-03-01

We present a stimulated emission depletion (STED) fluorescence lifetime imaging (FLIM) microscope, excited by a microstructured optical fibre supercontinuum source that is pumped by a femtosecond Ti:Sapphire-laser, which is also used for depletion. Implemented using a piezo-scanning stage on a laser scanning confocal fluorescence microscope system with FLIM realised using time correlated single photon counting (TCSPC), this provides convenient switching between confocal and STED-FLIM with spatial resolution down to below 60 nm. We will present our design considerations to make a robust instrument for biological applications including a comparison between fixed phase plate and spatial light modulator (SLM) approaches to shape the STED beam and the correlation of STED and confocal FLIM microscopy. Following our previous application of FLIM-FRET to study intercellular signalling at the immunological synapse (IS), we are employing STED microscopy to characterize the spatial distribution of cellular molecules with subdiffraction resolution at the IS. In particular, we are imaging cytoskeletal structure at the Natural Killer cell activated immune synapse. We will also present our progress towards multilabel STED microscopy to determine how relative spatial molecular organization, previously undetectable by conventional microscopy techniques, is important for NK cell cytotoxic function. Keywords: STED, Stimulated Emission Depletion Microscopy, Natural Killer (NK) cell, Fluorescence lifetime imaging, FLIM, Super resolution microscopy.

Module for multiphoton high-resolution hyperspectral imaging and spectroscopy

NASA Astrophysics Data System (ADS)

Zeytunyan, Aram; Baldacchini, Tommaso; Zadoyan, Ruben

2018-02-01

We developed a module for dual-output, dual-wavelength lasers that facilitates multiphoton imaging and spectroscopy experiments and enables hyperspectral imaging with spectral resolution up to 5 cm-1. High spectral resolution is achieved by employing spectral focusing. Specifically, two sets of grating pairs are used to control the chirps in each laser beam. In contrast with the approach that uses fixed-length glass rods, grating pairs allow matching the spectral resolution and the linewidths of the Raman lines of interest. To demonstrate the performance of the module, we report the results of spectral focusing CARS and SRS microscopy experiments for various test samples and Raman shifts. The developed module can be used for a variety of multimodal imaging and spectroscopy applications, such as single- and multi-color two-photon fluorescence, second harmonic generation, third harmonic generation, pump-probe, transient absorption, and others.

Comparative study of the energy potential of cyanide waters using two osmotic membrane modules under dead-end flow

NASA Astrophysics Data System (ADS)

García-Díaz, Y.; Quiñones-Bolaños, E.; Bustos-Blanco, C.; Vives-Pérez, L.; Bustillo-Lecompte, C.; Saba, M.

2017-12-01

The energy potential of the osmotic pressure gradient of cyanide waters is evaluated using two membrane modules, horizontal and vertical, operated under dead-end flow. The membrane was characterized using Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS). The membrane is mainly composed of carbon, oxygen, and sulphur. The properties of the membrane were unchanged and had no pore clogging after exposure to the cyanide waters. Potentials of 1.78×10-4 and 6.36×10-5Wm-2 were found for the horizontal and vertical modules, respectively, using the Van’t Hoff equation. Likewise, the permeability coefficient of the membrane was higher in the vertical module. Although the energy potential is low under the studied conditions the vertical configuration has a greater potential due to the action of gravity and the homogenous contact of the fluid with the membrane.

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

The quest for four-dimensional imaging in plant cell biology: it's just a matter of time

PubMed Central

Domozych, David S.

2012-01-01

Background Analysis of plant cell dynamics over time, or four-dimensional imaging (4-DI), represents a major goal of plant science. The ability to resolve structures in the third dimension within the cell or tissue during developmental events or in response to environmental or experimental stresses (i.e. 4-DI) is critical to our understanding of gene expression, post-expression modulations of macromolecules and sub-cellular system interactions. Scope Microscopy-based technologies have been profoundly integral to this type of investigation, and new and refined microscopy technologies now allow for the visualization of cell dynamics with unprecedented resolution, contrast and experimental versatility. However, certain realities of light and electron microscopy, choice of specimen and specimen preparation techniques limit the scope of readily attaining 4-DI. Today, the plant microscopist must use a combinatorial strategy whereby multiple microscopy-based investigations are used. Modern fluorescence, confocal laser scanning, transmission electron and scanning electron microscopy provide effective conduits for synthesizing data detailing live cell dynamics and highly resolved snapshots of specific cell structures that will ultimately lead to 4-DI. This review provides a synopsis of such technologies available. PMID:22628381

Part 1: Participatory Ergonomics Approach to Waste Container Handling Utilizing a Multidisciplinary Team

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zalk, D.M.; Tittiranonda, P.; Burastero, S.

2000-02-07

This multidisciplinary team approach to waste container handling, developed within the Grassroots Ergonomics process, presents participatory ergonomic interpretations of quantitative and qualitative aspects of this process resulting in a peer developed training. The lower back, shoulders, and wrists were identified as frequently injured areas, so these working postures were a primary focus for the creation of the workers' training. Handling procedures were analyzed by the team to identify common cycles involving one 5 gallon (60 pounds), two 5 gallons (60 and 54 pounds), 30 gallon (216 pounds), and 55 gallon (482 pounds) containers: lowering from transporting to/from transport vehicles, loading/unloadingmore » on transport vehicles, and loading onto pallet. Eleven experienced waste container handlers participated in this field analysis. Ergonomic exposure assessment tools measuring these field activities included posture analysis, posture targeting, Lumbar Motion Monitor{trademark} (LMM), and surface electromyography (sEMG) for the erector spinae, infraspinatus, and upper trapezius muscles. Posture analysis indicates that waste container handlers maintained non-neutral lower back postures (flexion, lateral bending, and rotation) for a mean of 51.7% of the time across all activities. The right wrist was in non-neutral postures (radial, ulnar, extension, and flexion) a mean of 30.5% of the time and the left wrist 31.4%. Non-neutral shoulder postures (elevation) were the least common, occurring 17.6% and 14.0% of the time in the right and left shoulders respectively. For training applications, each cycle had its own synchronized posture analysis and posture target diagram. Visual interpretations relating to the peak force modifications of the posture target diagrams proved to be invaluable for the workers' understanding of LMM and sEMG results (refer to Part II). Results were reviewed by the team's field technicians and their interpretations were developed into ergonomic training that address the issues originally raised. This training includes intervention methods, ergonomic tools used, dam acquired, and effects of waste container handling techniques on lower back, shoulder, and wrists and methods to help proactively reduce injuries associated with this profession.« less

Label-free structural characterization of mitomycin C-modulated wound healing after photorefractive keratectomy by the use of multiphoton microscopy

NASA Astrophysics Data System (ADS)

Lo, Wen; Wang, Tsung-Jen; Chen, Wei-Liang; Hsueh, Chiu-Mei; Chen, Shean-Jen; Chen, Yang-Fang; Chou, Hsiu-Chu; Lin, Pi-Jung; Hu, Fung-Rong; Dong, Chen-Yuan

2010-05-01

We applied multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) microscopy to monitor corneal wound healing after photorefractive keratectomy (PRK). Our results show that keratocyte activation can be observed by an increase in its MAF, while SHG imaging of corneal stroma can show the depletion of Bowman's layer after PRK and the reticular collagen deposition in the wound healing stage. Furthermore, quantification of the keratocyte activation and collagen deposition in conjunction with immunohistochemistry and histological images demonstrate the effectiveness of mitomycin C (MMC) in suppressing myofibroblast proliferation and collagen regeneration in the post-PRK wound healing process.

Artifact-free dynamic atomic force microscopy reveals monotonic dissipation for a simple confined liquid

NASA Astrophysics Data System (ADS)

Kaggwa, G. B.; Kilpatrick, J. I.; Sader, J. E.; Jarvis, S. P.

2008-07-01

We present definitive interaction measurements of a simple confined liquid (octamethylcyclotetrasiloxane) using artifact-free frequency modulation atomic force microscopy. We use existing theory to decouple the conservative and dissipative components of the interaction, for a known phase offset from resonance (90° phase shift), that has been deliberately introduced into the experiment. Further we show the qualitative influence on the conservative and dissipative components of the interaction of a phase error deliberately introduced into the measurement, highlighting that artifacts, such as oscillatory dissipation, can be readily observed when the phase error is not compensated for in the force analysis.

Low temperature laser scanning microscopy of a superconducting radio-frequency cavity

DOE PAGES

Ciovati, G.; Anlage, Steven M.; Baldwin, C.; ...

2012-03-16

An apparatus was created to obtain, for the first time, 2D maps of the surface resistance of the inner surface of an operating superconducting radio-frequency niobium cavity by a low-temperature laser scanning microscopy technique. This allows identifying non-uniformities of the surface resistance with a spatial resolution of about one order of magnitude better than with earlier methods. A signal-to-noise ratio of about 10 dB was obtained with 240 mW laser power and 1 Hz modulation frequency. The various components of the apparatus, the experimental procedure and results are discussed in details in this contribution.

The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense.

PubMed

Siuti, Piro; Green, Calvin; Edwards, Amanda Nicole; Doktycz, Mitchel J; Alexandre, Gladys

2011-10-01

The Azospirillum brasilense chemotaxis-like Che1 signal transduction pathway was recently shown to modulate changes in adhesive cell surface properties that, in turn, affect cell-to-cell aggregation and flocculation behaviors rather than flagellar-mediated chemotaxis. Attachment to surfaces and root colonization may be functions related to flocculation. Here, the conditions under which A. brasilense wild-type Sp7 and che1 mutant strains attach to abiotic and biotic surfaces were examined using in vitro attachment and biofilm assays combined with atomic force microscopy and confocal microscopy. The nitrogen source available for growth is found to be a major modulator of surface attachment by A. brasilense and could be promoted in vitro by lectins, suggesting that it depends on interaction with surface-exposed residues within the extracellular matrix of cells. However, Che1-dependent signaling is shown to contribute indirectly to surface attachment, indicating that distinct mechanisms are likely underlying flocculation and attachment to surfaces in A. brasilense. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

New Insights on Subsurface Imaging of Carbon Nanotubes in Polymer Composites via Scanning Electron Microscopy

NASA Technical Reports Server (NTRS)

Zhao, Minhua; Ming, Bin; Kim, Jae-Woo; Gibbons, Luke J.; Gu, Xiaohong; Nguyen, Tinh; Park, Cheol; Lillehei, Peter T.; Villarrubia, J. S.; Vladar, Andras E.;

Low cost label-free live cell imaging for biological samples

NASA Astrophysics Data System (ADS)

Seniya, C.; Towers, C. E.; Towers, D. P.

2017-02-01

This paper reports the progress to develop a practical phase measuring microscope offering new capabilities in terms of phase measurement accuracy and quantification of cell:cell interactions over the longer term. A novel, low cost phase interference microscope for imaging live cells (label-free) is described. The method combines the Zernike phase contrast approach with a dual mirror design to enable phase modulation between the scattered and un-scattered optical fields. Two designs are proposed and demonstrated, one of which retains the common path nature of Zernike's original microscopy concept. In both setups the phase shift is simple to control via a piezoelectric driven mirror in the back focal plane of the imaging system. The approach is significantly cheaper to implement than those based on spatial light modulators (SLM) at approximately 20% of the cost. A quantitative assessment of the performance of a set of phase shifting algorithms is also presented, specifically with regard to broad bandwidth illumination in phase contrast microscopy. The simulation results show that the phase measurement accuracy is strongly dependent on the algorithm selected and the optical path difference in the sample.

Isotropic image in structured illumination microscopy patterned with a spatial light modulator.

PubMed

Chang, Bo-Jui; Chou, Li-Jun; Chang, Yun-Ching; Chiang, Su-Yu

2009-08-17

We developed a structured illumination microscopy (SIM) system that uses a spatial light modulator (SLM) to generate interference illumination patterns at four orientations - 0 degrees, 45 degrees, 90 degrees, and 135 degrees, to reconstruct a high-resolution image. The use of a SLM for pattern alterations is rapid and precise, without mechanical calibration; moreover, our design of SLM patterns allows generating the four illumination patterns of high contrast and nearly equivalent periods to achieve a near isotropic enhancement in lateral resolution. We compare the conventional image of 100-nm beads with those reconstructed from two (0 degrees +90 degrees or 45 degrees +135 degrees) and four (0 degrees +45 degrees +90 degrees +135 degrees) pattern orientations to show the differences in resolution and image, with the support of simulations. The reconstructed images of 200-nm beads at various depths and fine structures of actin filaments near the edge of a HeLa cell are presented to demonstrate the intensity distributions in the axial direction and the prospective application to biological systems. (c) 2009 Optical Society of America

Three-dimensional hydration layer mapping on the (10.4) surface of calcite using amplitude modulation atomic force microscopy.

PubMed

Marutschke, Christoph; Walters, Deron; Walters, Deron; Hermes, Ilka; Bechstein, Ralf; Kühnle, Angelika

2014-08-22

Calcite, the most stable modification of calcium carbonate, is a major mineral in nature. It is, therefore, highly relevant in a broad range of fields such as biomineralization, sea water desalination and oil production. Knowledge of the surface structure and reactivity of the most stable cleavage plane, calcite (10.4), is pivotal for understanding the role of calcite in these diverse areas. Given the fact that most biological processes and technical applications take place in an aqueous environment, perhaps the most basic - yet decisive - question addresses the interaction of water molecules with the calcite (10.4) surface. In this work, amplitude modulation atomic force microscopy is used for three-dimensional (3D) mapping of the surface structure and the hydration layers above the surface. An easy-to-use scanning protocol is implemented for collecting reliable 3D data. We carefully discuss a comprehensible criterion for identifying the solid-liquid interface within our data. In our data three hydration layers form a characteristic pattern that is commensurate with the underlying calcite surface.

Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

NASA Astrophysics Data System (ADS)

Fukuma, Takeshi; Mostaert, Anika S.; Serpell, Louise C.; Jarvis, Suzanne P.

2008-09-01

We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and α-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Ångström-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual β-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-β structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of α-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30° from the axis, suggesting the possibility of β-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils.

Digital micromirror device-based laser-illumination Fourier ptychographic microscopy

PubMed Central

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Lee, Justin; Barbastathis, George; Dasari, Ramachandra R.; Yaqoob, Zahid; So, Peter T. C.

2015-01-01

We report a novel approach to Fourier ptychographic microscopy (FPM) by using a digital micromirror device (DMD) and a coherent laser source (532 nm) for generating spatially modulated sample illumination. Previously demonstrated FPM systems are all based on partially-coherent illumination, which offers limited throughput due to insufficient brightness. Our FPM employs a high power coherent laser source to enable shot-noise limited high-speed imaging. For the first time, a digital micromirror device (DMD), imaged onto the back focal plane of the illumination objective, is used to generate spatially modulated sample illumination field for ptychography. By coding the on/off states of the micromirrors, the illumination plane wave angle can be varied at speeds more than 4 kHz. A set of intensity images, resulting from different oblique illuminations, are used to numerically reconstruct one high-resolution image without obvious laser speckle. Experiments were conducted using a USAF resolution target and a fiber sample, demonstrating high-resolution imaging capability of our system. We envision that our approach, if combined with a coded-aperture compressive-sensing algorithm, will further improve the imaging speed in DMD-based FPM systems. PMID:26480361

Digital micromirror device-based laser-illumination Fourier ptychographic microscopy.

PubMed

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Lee, Justin; Barbastathis, George; Dasari, Ramachandra R; Yaqoob, Zahid; So, Peter T C

2015-10-19

We report a novel approach to Fourier ptychographic microscopy (FPM) by using a digital micromirror device (DMD) and a coherent laser source (532 nm) for generating spatially modulated sample illumination. Previously demonstrated FPM systems are all based on partially-coherent illumination, which offers limited throughput due to insufficient brightness. Our FPM employs a high power coherent laser source to enable shot-noise limited high-speed imaging. For the first time, a digital micromirror device (DMD), imaged onto the back focal plane of the illumination objective, is used to generate spatially modulated sample illumination field for ptychography. By coding the on/off states of the micromirrors, the illumination plane wave angle can be varied at speeds more than 4 kHz. A set of intensity images, resulting from different oblique illuminations, are used to numerically reconstruct one high-resolution image without obvious laser speckle. Experiments were conducted using a USAF resolution target and a fiber sample, demonstrating high-resolution imaging capability of our system. We envision that our approach, if combined with a coded-aperture compressive-sensing algorithm, will further improve the imaging speed in DMD-based FPM systems.

An investigation on the photoelectrochemical properties of dye-sensitized solar cells based on graphene-TiO2 composite photoanodes

NASA Astrophysics Data System (ADS)

Zhu, Menghua; Li, Xin; Liu, Weiwei; Cui, Ying

2014-09-01

The graphene-TiO2 nanocomposite has been prepared by mixing graphene oxide (GO) and tetra-n-butyl titanate (TBT) followed by the facile hydrothermal process when the reduction of GO to reduced graphene oxide (RGO) and the hydrolysis of TBT to TiO2 happen. Characterization of the graphene-TiO2 nanostructures is investigated in detail by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. A dye-sensitized solar cell (DSSC) based on graphene-TiO2 composite photoelectrode exhibits a high energy conversion efficiency of 4.28%, compared with a DSSC based on pure TiO2 photoelectrode (3.11%), accompanied by an increment in both short-circuit photocurrent density and open-circuit voltage. The significant enhancement in performance of DSSC is investigated through intensity-modulated photovoltage spectroscopy, intensity-modulated photocurrent spectroscopy, and electrochemical impedance spectroscopy. It is found that the incorporation of two-dimensional graphene nanosheets in the TiO2 electrodes is the key factor leading to the improved photogenerated electron transfer ability and reduced charge recombination.

Correlative nanoscale imaging of actin filaments and their complexes

NASA Astrophysics Data System (ADS)

Sharma, Shivani; Zhu, Huanqi; Grintsevich, Elena E.; Reisler, Emil; Gimzewski, James K.

2013-06-01

Actin remodeling is an area of interest in biology in which correlative microscopy can bring a new way to analyze protein complexes at the nanoscale. Advances in EM, X-ray diffraction, fluorescence, and single molecule techniques have provided a wealth of information about the modulation of the F-actin structure and its regulation by actin binding proteins (ABPs). Yet, there are technological limitations of these approaches to achieving quantitative molecular level information on the structural and biophysical changes resulting from ABPs interaction with F-actin. Fundamental questions about the actin structure and dynamics and how these determine the function of ABPs remain unanswered. Specifically, how local and long-range structural and conformational changes result in ABPs induced remodeling of F-actin needs to be addressed at the single filament level. Advanced, sensitive and accurate experimental tools for detailed understanding of ABP-actin interactions are much needed. This article discusses the current understanding of nanoscale structural and mechanical modulation of F-actin by ABPs at the single filament level using several correlative microscopic techniques, focusing mainly on results obtained by Atomic Force Microscopy (AFM) analysis of ABP-actin complexes.

Spatially Resolved Imaging on Photocarrier Generations and Band Alignments at Perovskite/PbI2 Heterointerfaces of Perovskite Solar Cells by Light-Modulated Scanning Tunneling Microscopy.

PubMed

Shih, Min-Chuan; Li, Shao-Sian; Hsieh, Cheng-Hua; Wang, Ying-Chiao; Yang, Hung-Duen; Chiu, Ya-Ping; Chang, Chia-Seng; Chen, Chun-Wei

2017-02-08

The presence of the PbI 2 passivation layers at perovskite crystal grains has been found to considerably affect the charge carrier transport behaviors and device performance of perovskite solar cells. This work demonstrates the application of a novel light-modulated scanning tunneling microscopy (LM-STM) technique to reveal the interfacial electronic structures at the heterointerfaces between CH 3 NH 3 PbI 3 perovskite crystals and PbI 2 passivation layers of individual perovskite grains under light illumination. Most importantly, this technique enabled the first observation of spatially resolved mapping images of photoinduced interfacial band bending of valence bands and conduction bands and the photogenerated electron and hole carriers at the heterointerfaces of perovskite crystal grains. By systematically exploring the interfacial electronic structures of individual perovskite grains, enhanced charge separation and reduced back recombination were observed when an optimal design of interfacial PbI 2 passivation layers consisting of a thickness less than 20 nm at perovskite crystal grains was applied.

Chemical bond imaging using higher eigenmodes of tuning fork sensors in atomic force microscopy

NASA Astrophysics Data System (ADS)

Ebeling, Daniel; Zhong, Qigang; Ahles, Sebastian; Chi, Lifeng; Wegner, Hermann A.; Schirmeisen, André

2017-05-01

We demonstrate the ability of resolving the chemical structure of single organic molecules using non-contact atomic force microscopy with higher normal eigenmodes of quartz tuning fork sensors. In order to achieve submolecular resolution, CO-functionalized tips at low temperatures are used. The tuning fork sensors are operated in ultrahigh vacuum in the frequency modulation mode by exciting either their first or second eigenmode. Despite the high effective spring constant of the second eigenmode (on the order of several tens of kN/m), the force sensitivity is sufficiently high to achieve atomic resolution above the organic molecules. This is observed for two different tuning fork sensors with different tip geometries (small tip vs. large tip). These results represent an important step towards resolving the chemical structure of single molecules with multifrequency atomic force microscopy techniques where two or more eigenmodes are driven simultaneously.

Diffraction and microscopy with attosecond electron pulse trains

NASA Astrophysics Data System (ADS)

Morimoto, Yuya; Baum, Peter

2018-03-01

Attosecond spectroscopy1-7 can resolve electronic processes directly in time, but a movie-like space-time recording is impeded by the too long wavelength ( 100 times larger than atomic distances) or the source-sample entanglement in re-collision techniques8-11. Here we advance attosecond metrology to picometre wavelength and sub-atomic resolution by using free-space electrons instead of higher-harmonic photons1-7 or re-colliding wavepackets8-11. A beam of 70-keV electrons at 4.5-pm de Broglie wavelength is modulated by the electric field of laser cycles into a sequence of electron pulses with sub-optical-cycle duration. Time-resolved diffraction from crystalline silicon reveals a < 10-as delay of Bragg emission and demonstrates the possibility of analytic attosecond-ångström diffraction. Real-space electron microscopy visualizes with sub-light-cycle resolution how an optical wave propagates in space and time. This unification of attosecond science with electron microscopy and diffraction enables space-time imaging of light-driven processes in the entire range of sample morphologies that electron microscopy can access.

Low-cost mobile phone microscopy with a reversed mobile phone camera lens.

PubMed

Switz, Neil A; D'Ambrosio, Michael V; Fletcher, Daniel A

2014-01-01

The increasing capabilities and ubiquity of mobile phones and their associated digital cameras offer the possibility of extending low-cost, portable diagnostic microscopy to underserved and low-resource areas. However, mobile phone microscopes created by adding magnifying optics to the phone's camera module have been unable to make use of the full image sensor due to the specialized design of the embedded camera lens, exacerbating the tradeoff between resolution and field of view inherent to optical systems. This tradeoff is acutely felt for diagnostic applications, where the speed and cost of image-based diagnosis is related to the area of the sample that can be viewed at sufficient resolution. Here we present a simple and low-cost approach to mobile phone microscopy that uses a reversed mobile phone camera lens added to an intact mobile phone to enable high quality imaging over a significantly larger field of view than standard microscopy. We demonstrate use of the reversed lens mobile phone microscope to identify red and white blood cells in blood smears and soil-transmitted helminth eggs in stool samples.

Comparative analysis of imaging configurations and objectives for Fourier microscopy.

PubMed

Kurvits, Jonathan A; Jiang, Mingming; Zia, Rashid

2015-11-01

Fourier microscopy is becoming an increasingly important tool for the analysis of optical nanostructures and quantum emitters. However, achieving quantitative Fourier space measurements requires a thorough understanding of the impact of aberrations introduced by optical microscopes that have been optimized for conventional real-space imaging. Here we present a detailed framework for analyzing the performance of microscope objectives for several common Fourier imaging configurations. To this end, we model objectives from Nikon, Olympus, and Zeiss using parameters that were inferred from patent literature and confirmed, where possible, by physical disassembly. We then examine the aberrations most relevant to Fourier microscopy, including the alignment tolerances of apodization factors for different objective classes, the effect of magnification on the modulation transfer function, and vignetting-induced reductions of the effective numerical aperture for wide-field measurements. Based on this analysis, we identify an optimal objective class and imaging configuration for Fourier microscopy. In addition, the Zemax files for the objectives and setups used in this analysis have been made publicly available as a resource for future studies.

Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens

PubMed Central

Fletcher, Daniel A.

2014-01-01

The increasing capabilities and ubiquity of mobile phones and their associated digital cameras offer the possibility of extending low-cost, portable diagnostic microscopy to underserved and low-resource areas. However, mobile phone microscopes created by adding magnifying optics to the phone's camera module have been unable to make use of the full image sensor due to the specialized design of the embedded camera lens, exacerbating the tradeoff between resolution and field of view inherent to optical systems. This tradeoff is acutely felt for diagnostic applications, where the speed and cost of image-based diagnosis is related to the area of the sample that can be viewed at sufficient resolution. Here we present a simple and low-cost approach to mobile phone microscopy that uses a reversed mobile phone camera lens added to an intact mobile phone to enable high quality imaging over a significantly larger field of view than standard microscopy. We demonstrate use of the reversed lens mobile phone microscope to identify red and white blood cells in blood smears and soil-transmitted helminth eggs in stool samples. PMID:24854188

Total variation based image deconvolution for extended depth-of-field microscopy images

NASA Astrophysics Data System (ADS)

Hausser, F.; Beckers, I.; Gierlak, M.; Kahraman, O.

2015-03-01

One approach for a detailed understanding of dynamical cellular processes during drug delivery is the use of functionalized biocompatible nanoparticles and fluorescent markers. An appropriate imaging system has to detect these moving particles so as whole cell volumes in real time with high lateral resolution in a range of a few 100 nm. In a previous study Extended depth-of-field microscopy (EDF-microscopy) has been applied to fluorescent beads and tradiscantia stamen hair cells and the concept of real-time imaging has been proved in different microscopic modes. In principle a phase retardation system like a programmable space light modulator or a static waveplate is incorporated in the light path and modulates the wavefront of light. Hence the focal ellipsoid is smeared out and images seem to be blurred in a first step. An image restoration by deconvolution using the known point-spread-function (PSF) of the optical system is necessary to achieve sharp microscopic images of an extended depth-of-field. This work is focused on the investigation and optimization of deconvolution algorithms to solve this restoration problem satisfactorily. This inverse problem is challenging due to presence of Poisson distributed noise and Gaussian noise, and since the PSF used for deconvolution exactly fits in just one plane within the object. We use non-linear Total Variation based image restoration techniques, where different types of noise can be treated properly. Various algorithms are evaluated for artificially generated 3D images as well as for fluorescence measurements of BPAE cells.

Direct Electrical Probing of Periodic Modulation of Zinc-Dopant Distributions in Planar Gallium Arsenide Nanowires.

PubMed

Choi, Wonsik; Seabron, Eric; Mohseni, Parsian K; Kim, Jeong Dong; Gokus, Tobias; Cernescu, Adrian; Pochet, Pascal; Johnson, Harley T; Wilson, William L; Li, Xiuling

2017-02-28

Selective lateral epitaxial (SLE) semiconductor nanowires (NWs), with their perfect in-plane epitaxial alignment, ability to form lateral complex p-n junctions in situ, and compatibility with planar processing, are a distinctive platform for next-generation device development. However, the incorporation and distribution of impurity dopants in these planar NWs via the vapor-liquid-solid growth mechanism remain relatively unexplored. Here, we present a detailed study of SLE planar GaAs NWs containing multiple alternating axial segments doped with Si and Zn impurities by metalorganic chemical vapor deposition. The dopant profile of the lateral multi-p-n junction GaAs NWs was imaged simultaneously with nanowire topography using scanning microwave impedance microscopy and correlated with infrared scattering-type near-field optical microscopy. Our results provide unambiguous evidence that Zn dopants in the periodically twinned and topologically corrugated p-type segments are preferentially segregated at twin plane boundaries, while Si impurity atoms are uniformly distributed within the n-type segments of the NWs. These results are further supported by microwave impedance modulation microscopy. The density functional theory based modeling shows that the presence of Zn dopant atoms reduces the formation energy of these twin planes, and the effect becomes significantly stronger with a slight increase of Zn concentration. This implies that the twin formation is expected to appear when a threshold planar concentration of Zn is achieved, making the onset and twin periodicity dependent on both Zn concentration and nanowire diameter, in perfect agreement with our experimental observations.

Enhanced speed in fluorescence imaging using beat frequency multiplexing

NASA Astrophysics Data System (ADS)

Mikami, Hideharu; Kobayashi, Hirofumi; Wang, Yisen; Hamad, Syed; Ozeki, Yasuyuki; Goda, Keisuke

2016-03-01

Fluorescence imaging using radiofrequency-tagged emission (FIRE) is an emerging technique that enables higher imaging speed (namely, temporal resolution) in fluorescence microscopy compared to conventional fluorescence imaging techniques such as confocal microscopy and wide-field microscopy. It works based on the principle that it uses multiple intensity-modulated fields in an interferometric setup as excitation fields and applies frequency-division multiplexing to fluorescence signals. Unfortunately, despite its high potential, FIRE has limited imaging speed due to two practical limitations: signal bandwidth and signal detection efficiency. The signal bandwidth is limited by that of an acousto-optic deflector (AOD) employed in the setup, which is typically 100-200 MHz for the spectral range of fluorescence excitation (400-600 nm). The signal detection efficiency is limited by poor spatial mode-matching between two interfering fields to produce a modulated excitation field. Here we present a method to overcome these limitations and thus to achieve higher imaging speed than the prior version of FIRE. Our method achieves an increase in signal bandwidth by a factor of two and nearly optimal mode matching, which enables the imaging speed limited by the lifetime of the target fluorophore rather than the imaging system itself. The higher bandwidth and better signal detection efficiency work synergistically because higher bandwidth requires higher signal levels to avoid the contribution of shot noise and amplifier noise to the fluorescence signal. Due to its unprecedentedly high-speed performance, our method has a wide variety of applications in cancer detection, drug discovery, and regenerative medicine.

From molecular to macroscopic engineering: shaping hydrogen-bonded organic nanomaterials.

PubMed

Yoosaf, K; Llanes-Pallas, Anna; Marangoni, Tomas; Belbakra, Abdelhalim; Marega, Riccardo; Botek, Edith; Champagne, Benoît; Bonifazi, Davide; Armaroli, Nicola

2011-03-07

The self-assembly and self-organization behavior of chromophoric acetylenic scaffolds bearing 2,6-bis(acetylamino)pyridine (1, 2) or uracyl-type (3-9) terminal groups has been investigated by photophysical and microscopic methods. Systematic absorption and luminescence studies show that 1 and 2, thanks to a combination of solvophilic/solvophobic forces and π-π stacking interactions, undergo self-organization in apolar solvents (i.e., cyclohexane) and form spherical nanoparticles, as evidenced by wide-field optical microscopy, TEM, and AFM analysis. For the longer molecular module, 2, a more uniform size distribution is found (80-200 nm) compared to 1 (20-1000 nm). Temperature scans in the range 283-353 K show that the self-organized nanoparticles are reversibly formed and destroyed, being stable at lower temperatures. Molecular modules 1 and 2 were then thoroughly mixed with the complementary triply hydrogen-bonding units 3-9. Depending on the specific geometrical structure of 3-9, different nanostructures are evidenced by microscopic investigations. Combination of modules 1 or 2 with 3, which bears only one terminal uracyl unit, leads to the formation of vesicular structures; instead, when 1 is combined with bis-uracyl derivative 4 or 5, a structural evolution from nanoparticles to nanowires is observed. The length of the wires obtained by mixing 1 and 4 or 1 and 5 can be controlled by addition of 3, which prompts transformation of the wires into shorter rods. The replacement of linear system 5 with the related angular modules 6 and 7 enables formation of helical nanostructures, unambiguously evidenced by AFM. Finally, thermally induced self-assembly was studied in parallel with modules 8 and 9, in which the uracyl recognition sites are protected with tert-butyloxycarbonyl (BOC) groups. This strategy allows further control of the self-assembly/self-organization process by temperature, since the BOC group is completely removed on heating. Microscopy studies show that the BOC-protected ditopic modules 8 self-assemble and self-organize with 1 into ordered linear nanostructures, whereas BOC-protected tritopic system 9 gives rise to extended domains of circular nano-objects in combination with 1. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SISGR: Room Temperature Single-Molecule Detection and Imaging by Stimulated Emission Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Xiaoliang Sunney

Single-molecule spectroscopy has made considerable impact on many disciplines including chemistry, physics, and biology. To date, most single-molecule spectroscopy work is accomplished by detecting fluorescence. On the other hand, many naturally occurring chromophores, such as retinal, hemoglobin and cytochromes, do not have detectable fluorescence. There is an emerging need for single-molecule spectroscopy techniques that do not require fluorescence. In the last proposal period, we have successfully demonstrated stimulated emission microscopy, single molecule absorption, and stimulated Raman microscopy based on a high-frequency modulation transfer technique. These first-of-a- kind new spectroscopy/microscopy methods tremendously improved our ability to observe molecules that fluorescence weakly,more » even to the limit of single molecule detection for absorption measurement. All of these methods employ two laser beams: one (pump beam) excites a single molecule to a real or virtual excited state, and the other (probe beam) monitors the absorption/emission property of the single. We extract the intensity change of the probe beam with high sensitivity by implementing a high-frequency phase-sensitive detection scheme, which offers orders of magnitude improvement in detection sensitivity over direct absorption/emission measurement. However, single molecule detection based on fluorescence or absorption is fundamentally limited due to their broad spectral response. It is important to explore other avenues in single molecule detection and imaging which provides higher molecular specificity for studying a wide variety of heterogeneous chemical and biological systems. This proposal aimed to achieve single-molecule detection sensitivity with near resonance stimulated Raman scattering (SRS) microscopy. SRS microscopy was developed in our lab as a powerful technique for imaging heterogeneous samples based on their intrinsic vibrational contrasts, which provides much higher molecular specificity than absorption and fluorescence. Current sensitivity limit of SRS microscopy has not yet reached single molecule detection. We proposed to capitalize on our state-of-the-art SRS microscopy and develop near-resonance enhanced SRS for single molecule detection of carotenoids and heme proteins. The specific aims we pursued are: (1) building the next SRS generation microscope that utilizes near resonance enhancement to allow detection and imaging of single molecules with undetectable fluorescence, such as -carotene. (2) using near-resonance SRS as a contrast mechanism to study dye-sensitize semiconductor interface, elucidating the heterogeneous electron ejection kinetics with high spatial and temporal resolution. (3) studying the binding and unbinding of oxygen in single hemoglobin molecules in order to gain molecular level understanding of the long-standing issue of cooperativity. The new methods developed in the fund period of this grant have advanced the detection sensitivity in many aspects. Near-resonance SRS improved the signal by using shorter wavelengths for SRS microscopy. Frequency modulation and multi-color SRS target the reduction of background to improve the chemical specificity of SRS while maintaining the high imaging speed. Time-domain coherent Raman scattering microscopy targets to reduce the noise floor of coherent Raman microscopy. These methods have already demonstrated first-of-a-kind new applications in biology and medical research. However, we are still one order of magnitude away from single molecule limit. It is important to continue to improve the laser specification and develop new imaging methods to finally achieve label-free single molecule microscopy.« less

Nitroxide amide-BODIPY probe behavior in fibroblasts analyzed by advanced fluorescence microscopy.

PubMed

Liras, M; Simoncelli, S; Rivas-Aravena, A; García, O; Scaiano, J C; Alarcon, E I; Aspée, A

2016-04-26

A novel synthesized nitroxide amide-BODIPY prefluorescent probe was used to study cellular redox balance that modulates nitroxide/hydroxylamine ratio in cultured human fibroblasts. FLIM quantitatively differentiated between nitroxide states of the cytoplasm-localized probe imaged by TIRF, monitoring nitroxide depletion by hydrogen peroxide; eluding incorrect interpretation if only fluorescence intensity is considered.

Harmonic demodulation and minimum enhancement factors in field-enhanced near-field optical microscopy.

PubMed

Scarpettini, A F; Bragas, A V

2015-01-01

Field-enhanced scanning optical microscopy relies on the design and fabrication of plasmonic probes which had to provide optical and chemical contrast at the nanoscale. In order to do so, the scattering containing the near-field information recorded in a field-enhanced scanning optical microscopy experiment, has to surpass the background light, always present due to multiple interferences between the macroscopic probe and sample. In this work, we show that when the probe-sample distance is modulated with very low amplitude, the higher the harmonic demodulation is, the better the ratio between the near-field signal and the interferometric background results. The choice of working at a given n harmonic is dictated by the experiment when the signal at the n + 1 harmonic goes below the experimental noise. We demonstrate that the optical contrast comes from the nth derivative of the near-field scattering, amplified by the interferometric background. By modelling the far and near field we calculate the probe-sample approach curves, which fit very well the experimental ones. After taking a great amount of experimental data for different probes and samples, we conclude with a table of the minimum enhancement factors needed to have optical contrast with field-enhanced scanning optical microscopy. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

Total internal reflection holographic microscopy (TIRHM) for quantitative phase characterization of cell-substrate adhesion

NASA Astrophysics Data System (ADS)

Ash, William Mason, III

Total Internal Reflection Holographic Microscopy (TIRHM) combines near-field microscopy with digital holography to produce a new form of near-field phase microscopy. Using a prism in TIR as a near-field imager, the presence of microscopic organisms, cell-substrate interfaces, and adhesions, causes relative refractive index (RRI) and frustrated TIR (f-TIR) to modulate the object beam's evanescent wave phase front. Quantitative phase images of test specimens such as Amoeba proteus, Dictyostelium Discoideum and cells such as SKOV-3 ovarian cancer and 3T3 fibroblasts are produced without the need to introduce stains or fluorophores. The angular spectrum method of digital holography to compensate for tilt anamorphism due to the inclined TIR plane is also discussed. The results of this work conclusively demonstrate, for the first time, the integration of near-field microscopy with digital holography. The cellular images presented show a correlation between the physical extent of the Amoeba proteus plasma membrane and the adhesions that are quantitatively profiled by phase cross-sectioning of the holographic images obtained by digital holography. With its ability to quantitatively characterise cellular adhesion and motility, it is anticipated that TIRHM can be a tool for characterizing and combating cancer metastasis, as well as improving our understanding of morphogenesis and embryogenesis itself.

TEM study of the (SbS){sub 1+δ}(NbS{sub 2}){sub n}, (n=1, 2, 3; δ~1.14, 1.20) misfit layer phases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gómez-Herrero, A., E-mail: adriangh@pdi.ucm.es; Landa-Cánovas, A.R.; Otero-Díaz, L.C.

In the Sb–Nb–S system four new misfit layer phases have been found and carefully investigated via Transmission Electron Microscopy (TEM). Their structures are of composite modulated structure type with stoichiometries that can be formulated as (SbS){sub 1+δ}(NbS{sub 2}){sub n}; for n=1, δ~1.14 and 1.19; for n=2, δ~1.18 and for n=3, δ~1.19. Selected Area Electron Diffraction (SAED) patterns show an almost commensurate fit between the pseudo-tetragonal (SbS) and the pseudo-orthohexagonal (NbS{sub 2}){sub n} subcells along the misfit direction a, with 3(SbS)≈5(NbS{sub 2}), being b the same for both sub-lattices and c the stacking direction. For n=1, a commensurate phase with 4a{submore » SbS}=7a{sub NbS2} has also been observed. In addition to the characteristic misfit and associated modulation of the two sub-structures, a second modulation is also present which appears to be primarily associated with the (SbS) sub-structure of both the n=1 and n=2 phases. High Resolution Transmission Electron Microscopy (HRTEM) images show ordered stacking sequences between the (SbS) and (NbS{sub 2}){sub n} lamellae for each of the four phases, however, disordered intergrowths were also occasionally found. Most of the crystals showed different kinds of twinning defects on quite a fine scale. Many crystals showed curled up edges. In some cases the lamellar crystals were entirely folded giving rise to similar diffraction patterns as found for cylindrical crystals. - Graphical abstract: Idealized structure models of the first three members of the homologous series (SbS){sub 1+δ}(NbS{sub 2}){sub n}. - Highlights: • Transmission Electron Microscopy study of misfit layer sulfides (SbS){sub 1+δ}(NbS{sub 2}){sub n}. • The structures consist of a (SbS) layer interleaved between n (NbS{sub 2}) layers. • Two different members n=1, one n=2 and one n=3 have been studied. • Twinning, intergrowths and different modulations in the (SbS) substructure.« less

Imaging three-dimensional light propagation through periodic nanohole arrays using scanning aperture microscopy

PubMed Central

Chowdhury, Mustafa H.; Catchmark, Jeffrey M.; Lakowicz, Joseph R.

2009-01-01

The authors introduce a technique for three-dimensional (3D) imaging of the light transmitted through periodic nanoapertures using a scanning probe to perform optical sectioning microscopy. For a 4×4 nanohole array, the transmitted light displays intensity modulations along the propagation axis, with the maximum intensity occurring at 450 μm above the surface. The propagating fields show low divergence, suggesting a beaming effect induced by the array. At distances within 25 μm from the surface, they observe subwavelength confinement of light propagating from the individual nanoholes. Hence, this technique can potentially be used to map the 3D distribution of propagating light, with high spatial resolution. PMID:19696912

A simple and low-cost structured illumination microscopy using a pico-projector

NASA Astrophysics Data System (ADS)

Özgürün, Baturay

2018-02-01

Here, development of a low-cost structured illumination microscopy (SIM) based on a pico-projector is presented. The pico-projector consists of independent red, green and blue LEDs that remove need for an external illumination source. Moreover, display element of the pico-projector serves as a pattern generating spatial light modulator. A simple lens group is employed to couple light from the projector to an epi-illumination port of a commercial microscope system. 2D sub SIM images are acquired and synthesized to surpass the diffraction limit using 40x (0.75 NA) objective. Resolution of the reconstructed SIM images is verified with a dye-and-object object and a fixed cell sample.

Inserting ex vivo fluorescence confocal microscopy perioperatively in Mohs micrographic surgery expedites bedside assessment of excision margins in recurrent basal cell carcinoma.

PubMed

Longo, Caterina; Ragazzi, Moira; Castagnetti, Fabio; Gardini, Stefano; Palmieri, Tamara; Lallas, Aimilios; Moscarella, Elvira; Piana, Simonetta; Pellacani, Giovanni; Zalaudek, Iris; Argenziano, Giuseppe

2013-01-01

Mohs micrographic surgery can be employed in recurrent basal cell carcinoma, although it is a time-consuming technique. Recently, ex vivo fluorescence confocal microscopy (FCM) has been employed to obtain a fast assessment of tumor margins at the bedside. In our case we successfully employed ex vivo FCM to assess the tumor margins and we treated the persistent tumor with intensity-modulated radiation therapy. Our case demonstrates that a multidisciplinary approach is very efficient in managing complex and recurrent tumors and highlights the benefits of FCM as a new technique that can be used in the surgical theater to speed up the entire procedure.

Ultra-fast 3D scanning and holographic illumination in non-linear microscopy using acousto-optic deflectors

NASA Astrophysics Data System (ADS)

Akemann, Walther; Ventalon, Cathie; Léger, Jean-François; Mathieu, Benjamin; Dieudonné, Stéphane; Blochet, Baptiste; Gigan, Sylvain; Bourdieu, Laurent

2017-04-01

Decoding of information in the brain requires the imaging of large neuronal networks using e.g. two-photon microscopy (TPM). Fast control of the focus in 3D can be achieved with phase shaping of the light beam using acoustooptic deflectors (AODs). However, beam shaping using AODs is not straightforward because of non-stationary of acousto-optic diffraction. Here, we demonstrated a new stable AOD-based phase modulator, which operates at a rate of up to about hundred kHz. It provides opportunity for 3D scanning in TPM with the possibility to correct aberrations independently for every focus position or to achieve refocusing of scattered photons in rapidly decorrelating tissues.

Watching Nanoscale Self-Assembly Kinetics of Gold Prisms in Liquids

NASA Astrophysics Data System (ADS)

Kim, Juyeong; Ou, Zihao; Jones, Matthew R.; Chen, Qian

We use liquid-phase transmission electron microscopy to watch self-assembly of gold triangular prisms into polymer-like structures. The in situ dynamics monitoring enabled by liquid-phase transmission electron microscopy, single nanoparticle tracking, and the marked conceptual similarity between molecular reactions and nanoparticle self-assembly combined elucidate the following mechanistic understanding: a step-growth polymerization based assembly statistics, kinetic pathways sampling particle curvature dependent energy minima and their interconversions, and directed assembly into polymorphs (linear or cyclic chains) through in situ modulation of the prism bonding geometry. Our study bridges the constituent kinetics on the molecular and nanoparticle length scales, which enriches the design rules in directed self-assembly of anisotropic nanoparticles.

One-shot synthetic aperture digital holographic microscopy with non-coplanar angular-multiplexing and coherence gating.

PubMed

Lin, Yu-Chih; Tu, Han-Yen; Wu, Xin-Ru; Lai, Xin-Ji; Cheng, Chau-Jern

2018-05-14

This paper proposes one-shot synthetic aperture digital holographic microscopy using a combination of angular-multiplexing and coherence gating. The proposed angular-multiplexing technique uses multiple noncoplanar incident beams into the synthetic aperture to create tight packed passbands so as to extend spatial frequency spectrum. Coherence gating is performed to prevent the self-interference among the multiple beams. Based on the design guideline proposed herein, a phase-only spatial light modulator is employed as an adjustable blazed grating to split multiple noncoplanar beams and perform angular-multiplexing, and then using coherence gating based on low-coherence-light, superresolution imaging is achieved after one-shot acquisition.

Spatially Resolved Nano-Scale Characterization of Electronic States in SrTiO3(001) Surfaces by STM/STS

NASA Astrophysics Data System (ADS)

Iwaya, Katsuya; Ohsawa, Takeo; Shimizu, Ryota; Hashizume, Tomihiro; Hitosugi, Taro

2012-02-01

We have performed low temperature scanning tunneling microscopy/spectroscopy (STM/STS) measurements on TiO2-terminated SrTiO3(001) thin film surfaces. The conductance map exhibited electronic modulations that were completely different from the surface structure. We also found that the electronic modulations were strongly dependent on temperature and the density of atomic defects associated with oxygen vacancies. These results suggest the existence of strongly correlated two-dimensional electronic states near the SrTiO3 surface, implying the importance of electron correlation at the interfaces of SrTiO3-related heterostructures.

Orthorhombic Zr2Co11 phase revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X. -Z.; Zhang, W. Y.; Sellmyer, D. J.

2014-10-01

The structure of the orthorhombic Zr2Co11 phase was revisited in the present work. Selected-area electron diffraction (SAED) and high-resolution electron microscopy (HREM) techniques were used to investigate the structure. They show the orthorhombic Zr2Co11 phase has a 1-D incommensurate modulated structure. The structure can be approximately described as a B-centered orthorhombic lattice. The lattice parameters of the orthorhombic Zr2Co11 phase have been determined by a tilt series of SAED patterns. A hexagonal network with a modulation wave has been observed in the HREM image and the hexagonal motif is considered as the basic structural unit.

Niobium oxide nanocolumns formed via anodic alumina with modulated pore diameters

NASA Astrophysics Data System (ADS)

Pligovka, A.; Zakhlebayeva, A.; Lazavenka, A.

2018-03-01

Niobium oxide nanocolumns with modulated diameters were formed for the first time. An Al/Nb bilayer specimen was prepared by successive sputter-deposition of 300 nm niobium layer and 1200 nm aluminum layer onto silicon wafer. Regular anodic alumina matrix with modulated pore diameters was formed by sequential anodization of initial specimen in tartaric acid at 180 V, and in oxalic acid at 37 V. Further potentiodynamic reanodization of the specimen up to 400 V causes the simultaneous growth of 440 nm continuous niobium oxide layer beneath the alumina film and two types of an array of oxide nanocolumns (thick – with 100 nm width and 630 nm high and thin – with 25 nm width and 170 nm high), which are the filling of the alumina pores. The morphology of the formed anodic niobium oxide nanocolumns with modulated diameters was determined by field emission scanning electron microscopy. The formed nanostructures can be used for perspective devices of nano- and optoelectronics such as photonic crystals.

CARS module for multimodal microscopy

NASA Astrophysics Data System (ADS)

Zadoyan, Ruben; Baldacchini, Tommaso; Carter, John; Kuo, Chun-Hung; Ocepek, David

2011-03-01

We describe a stand alone CARS module allowing upgrade of a two-photon microscope with CARS modality. The Stokes beam is generated in a commercially available photonic crystal fiber (PCF) using fraction of the power of femtosecond excitation laser. The output of the fiber is optimized for broadband CARS at Stokes shifts in 2900cm-1 region. The spectral resolution in CARS signal is 50 cm-1. It is achieved by introducing a bandpass filter in the pump beam. The timing between the pump and Stokes pulses is preset inside the module and can be varied. We demonstrate utility of the device on examples of second harmonic, two-photon fluorescence and CARS images of several biological and non-biological samples. We also present results of studies where we used CARS modality to monitor in real time the process of fabrication of microstructures by two-photon polymerization.

Imaging, microscopic analysis, and modeling of a CdTe module degraded by heat and light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Steve; Albin, David; Hacke, Peter

Photoluminescence (PL), electroluminescence (EL), and dark lock-in thermography are collected during stressing of a CdTe module under one-Sun light at an elevated temperature of 100 degrees C. The PL imaging system is simple and economical. The PL images show differing degrees of degradation across the module and are less sensitive to effects of shunting and resistance that appear on the EL images. Regions of varying degradation are chosen based on avoiding pre-existing shunt defects. These regions are evaluated using time-of-flight secondary ion-mass spectrometry and Kelvin probe force microscopy. Reduced PL intensity correlates to increased Cu concentration at the front interface.more » Numerical modeling and measurements agree that the increased Cu concentration at the junction also correlates to a reduced space charge region.« less

Imaging, microscopic analysis, and modeling of a CdTe module degraded by heat and light

DOE PAGES

Johnston, Steve; Albin, David; Hacke, Peter; ...

2018-01-12

Photoluminescence (PL), electroluminescence (EL), and dark lock-in thermography are collected during stressing of a CdTe module under one-Sun light at an elevated temperature of 100 degrees C. The PL imaging system is simple and economical. The PL images show differing degrees of degradation across the module and are less sensitive to effects of shunting and resistance that appear on the EL images. Regions of varying degradation are chosen based on avoiding pre-existing shunt defects. These regions are evaluated using time-of-flight secondary ion-mass spectrometry and Kelvin probe force microscopy. Reduced PL intensity correlates to increased Cu concentration at the front interface.more » Numerical modeling and measurements agree that the increased Cu concentration at the junction also correlates to a reduced space charge region.« less

Analytical Model of the Nonlinear Dynamics of Cantilever Tip-Sample Surface Interactions for Various Acoustic-Atomic Force Microscopies

NASA Technical Reports Server (NTRS)

Cantrell, John H., Jr.; Cantrell, Sean A.

2008-01-01

A comprehensive analytical model of the interaction of the cantilever tip of the atomic force microscope (AFM) with the sample surface is developed that accounts for the nonlinearity of the tip-surface interaction force. The interaction is modeled as a nonlinear spring coupled at opposite ends to linear springs representing cantilever and sample surface oscillators. The model leads to a pair of coupled nonlinear differential equations that are solved analytically using a standard iteration procedure. Solutions are obtained for the phase and amplitude signals generated by various acoustic-atomic force microscope (A-AFM) techniques including force modulation microscopy, atomic force acoustic microscopy, ultrasonic force microscopy, heterodyne force microscopy, resonant difference-frequency atomic force ultrasonic microscopy (RDF-AFUM), and the commonly used intermittent contact mode (TappingMode) generally available on AFMs. The solutions are used to obtain a quantitative measure of image contrast resulting from variations in the Young modulus of the sample for the amplitude and phase images generated by the A-AFM techniques. Application of the model to RDF-AFUM and intermittent soft contact phase images of LaRC-cp2 polyimide polymer is discussed. The model predicts variations in the Young modulus of the material of 24 percent from the RDF-AFUM image and 18 percent from the intermittent soft contact image. Both predictions are in good agreement with the literature value of 21 percent obtained from independent, macroscopic measurements of sheet polymer material.

Thermal: Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), and Polarized Microscopy Instrumentation for the Analysis of Field-Controlled Anisotropic Nanomaterials

DTIC Science & Technology

2014-11-14

figure 1.2.1, right). The discovery TGA furnace design employs a silicon carbide ( SiC ) inner chamber. Four halogen lamps surrounded by a water...amplification,(13, 17) self-phase modulation (18, 19), and new nonlinear phenomena such as the nonlinear optical mirror ,(20) and the mirrorless optical

Imaging charge carriers in potential-induced degradation defects of c-Si solar cells by scanning capacitance microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, C. -S.; Xiao, C.; Moutinho, H. R.

We report on nm-resolution imaging of charge-carrier distribution around local potential-induced degradation (PID) shunting defects using scanning capacitance microscopy. We imaged on cross sections of heavily field-degraded module areas, cored out and selected by mm-scale photoluminescence imaging. We found localized areas with abnormal carrier behavior induced by the PID defects: the apparent n-type carrier extends vertically into the absorber to ~1-2 um from the cell surface, and laterally in similar lengths; in defect-free areas, the n-type carrier extends ~0.5 um, which is consistent with the junction depth. For comparison, we also investigated areas of the same module exhibiting the leastmore » PID stress, and we found no such heavily damaged junction area. Instead, we found slightly abnormal carrier behavior, where the carrier-type inversion in the absorber did not occur, but the p-type carrier concentration changed slightly in a much smaller lateral length of ~300 nm. These nano-electrical findings may indicate a possible mechanism that the existing extended defects, which may not be significantly harmful to cell performance, can be changed by PID to heavily damaged junction areas.« less

Two-photon microscopy and spectroscopy based on a compact confocal scanning head

NASA Astrophysics Data System (ADS)

Diaspro, Alberto; Chirico, Giberto; Federici, Federico; Cannone, Fabio; Beretta, Sabrina; Robello, Mauro; Olivini, Francesca; Ramoino, Paola

2001-07-01

We have combined a confocal laser scanning head modified for TPE (two-photon excitation) microscopy with some spectroscopic modules to study single molecules and molecular aggregates. The behavior of the TPE microscope unit has been characterized by means of point spread function measurements and of the demonstration of its micropatterning abilities. One-photon and two-photon mode can be simply accomplished by switching from a mono-mode optical fiber (one-photon) coupled to conventional laser sources to an optical module that allows IR laser beam (two- photon/TPE) delivery to the confocal laser scanning head. We have then described the characterization of the two-photon microscope for spectroscopic applications: fluorescence correlation, lifetime and fluorescence polarization anisotropy measurements. We describe the measurement of the response of the two-photon microscope to the light polarization and discuss fluorescence polarization anisotropy measurements on Rhodamine 6G as a function of the viscosity and on a globular protein, the Beta-lactoglobulin B labeled with Alexa 532 at very high dilutions. The average rotational and translational diffusion coefficients measured with fluorescence polarization anisotropy and fluorescence correlation methods are in good agreement with the protein size, therefore validating the use of the microscope for two-photon spectroscopy on biomolecules.

Imaging charge carriers in potential-induced degradation defects of c-Si solar cells by scanning capacitance microscopy

DOE PAGES

Jiang, C. -S.; Xiao, C.; Moutinho, H. R.; ...

2018-02-13

We report on nm-resolution imaging of charge-carrier distribution around local potential-induced degradation (PID) shunting defects using scanning capacitance microscopy. We imaged on cross sections of heavily field-degraded module areas, cored out and selected by mm-scale photoluminescence imaging. We found localized areas with abnormal carrier behavior induced by the PID defects: the apparent n-type carrier extends vertically into the absorber to ~1-2 um from the cell surface, and laterally in similar lengths; in defect-free areas, the n-type carrier extends ~0.5 um, which is consistent with the junction depth. For comparison, we also investigated areas of the same module exhibiting the leastmore » PID stress, and we found no such heavily damaged junction area. Instead, we found slightly abnormal carrier behavior, where the carrier-type inversion in the absorber did not occur, but the p-type carrier concentration changed slightly in a much smaller lateral length of ~300 nm. These nano-electrical findings may indicate a possible mechanism that the existing extended defects, which may not be significantly harmful to cell performance, can be changed by PID to heavily damaged junction areas.« less

Dynamic measurements of flowing cells labeled by gold nanoparticles using full-field photothermal interferometric imaging

NASA Astrophysics Data System (ADS)

Turko, Nir A.; Roitshtain, Darina; Blum, Omry; Kemper, Björn; Shaked, Natan T.

2017-06-01

We present highly dynamic photothermal interferometric phase microscopy for quantitative, selective contrast imaging of live cells during flow. Gold nanoparticles can be biofunctionalized to bind to specific cells, and stimulated for local temperature increase due to plasmon resonance, causing a rapid change of the optical phase. These phase changes can be recorded by interferometric phase microscopy and analyzed to form an image of the binding sites of the nanoparticles in the cells, gaining molecular specificity. Since the nanoparticle excitation frequency might overlap with the sample dynamics frequencies, photothermal phase imaging was performed on stationary or slowly dynamic samples. Furthermore, the computational analysis of the photothermal signals is time consuming. This makes photothermal imaging unsuitable for applications requiring dynamic imaging or real-time analysis, such as analyzing and sorting cells during fast flow. To overcome these drawbacks, we utilized an external interferometric module and developed new algorithms, based on discrete Fourier transform variants, enabling fast analysis of photothermal signals in highly dynamic live cells. Due to the self-interference module, the cells are imaged with and without excitation in video-rate, effectively increasing signal-to-noise ratio. Our approach holds potential for using photothermal cell imaging and depletion in flow cytometry.

Imaging Cellular Dynamics with Spectral Relaxation Imaging Microscopy: Distinct Spectral Dynamics in Golgi Membranes of Living Cells.

PubMed

Lajevardipour, Alireza; Chon, James W M; Chattopadhyay, Amitabha; Clayton, Andrew H A

2016-11-22

Spectral relaxation from fluorescent probes is a useful technique for determining the dynamics of condensed phases. To this end, we have developed a method based on wide-field spectral fluorescence lifetime imaging microscopy to extract spectral relaxation correlation times of fluorescent probes in living cells. We show that measurement of the phase and modulation of fluorescence from two wavelengths permit the identification and determination of excited state lifetimes and spectral relaxation correlation times at a single modulation frequency. For NBD fluorescence in glycerol/water mixtures, the spectral relaxation correlation time determined by our approach exhibited good agreement with published dielectric relaxation measurements. We applied this method to determine the spectral relaxation dynamics in membranes of living cells. Measurements of the Golgi-specific C 6 -NBD-ceramide probe in living HeLa cells revealed sub-nanosecond spectral dynamics in the intracellular Golgi membrane and slower nanosecond spectral dynamics in the extracellular plasma membrane. We interpret the distinct spectral dynamics as a result of structural plasticity of the Golgi membrane relative to more rigid plasma membranes. To the best of our knowledge, these results constitute one of the first measurements of Golgi rotational dynamics.

Examination of humidity effects on measured thickness and interfacial phenomena of exfoliated graphene on silicon dioxide via amplitude modulation atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jinkins, K.; Farina, L.; Wu, Y., E-mail: wuy@uwplatt.edu

2015-12-14

The properties of Few-Layer Graphene (FLG) change with the number of layers and Amplitude Modulation (AM) Atomic Force Microscopy (AFM) is commonly used to determine the thickness of FLG. However, AFM measurements have been shown to be sensitive to environmental conditions such as relative humidity (RH). In the present study, AM-AFM is used to measure the thickness and loss tangent of exfoliated graphene on silicon dioxide (SiO{sub 2}) as RH is increased from 10% to 80%. We show that the measured thickness of graphene is dependent on RH. The loss tangent values of the graphene and oxide regions are bothmore » affected by humidity, with generally higher loss tangent for graphene than SiO{sub 2}. As RH increases, we observe the loss tangent of both materials approaches the same value. We hypothesize that there is a layer of water trapped between the graphene and SiO{sub 2} substrate to explain this observation. Using this interpretation, the loss tangent images also indicate movement and change in this trapped water layer as RH increases, which impacts the measured thickness of graphene using AM-AFM.« less

HRTEMFringeAnalyzer a free python module for an automated analysis of fringe pattern in transmission electron micrographs.

PubMed

Alxneit, Ivo

2018-03-30

A python module (HRTEMFringeAnalyzer) is reported to evaluate the local crystallinity of samples from high-resolution transmission electron microscopy images in a mostly automated fashion. The user only selects the size of a square analyser window and a step size which translates the window in the micrograph. Together they define the resolution of the results obtained. Regions where fringe patterns are visible are identified and their lattice spacing d and direction ϕ as well as the corresponding mean errors σ determined. 1/σd is proportional to the coherence length of the structure, whereas σφ is a measure of how well the direction of the fringes is defined. Maps of these four indicators are computed. The performance of the program is demonstrated on two very different samples: ill-crystalline carbon deposits on a coked Ni/LFNO (reduced LaFe 0.8 Ni 0.2 O3±δ) catalyst and well-crystallized nanoparticles of zinc doped ceria. In the latter case, the automatic segmentation of large aggregates into individual crystalline domains is achieved by ϕ maps. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Photo-Carrier Multi-Dynamical Imaging at the Nanometer Scale in Organic and Inorganic Solar Cells.

PubMed

Fernández Garrillo, Pablo A; Borowik, Łukasz; Caffy, Florent; Demadrille, Renaud; Grévin, Benjamin

2016-11-16

Investigating the photocarrier dynamics in nanostructured and heterogeneous energy materials is of crucial importance from both fundamental and technological points of view. Here, we demonstrate how noncontact atomic force microscopy combined with Kelvin probe force microscopy under frequency-modulated illumination can be used to simultaneously image the surface photopotential dynamics at different time scales with a sub-10 nm lateral resolution. The basic principle of the method consists in the acquisition of spectroscopic curves of the surface potential as a function of the illumination frequency modulation on a two-dimensional grid. We show how this frequency-spectroscopy can be used to probe simultaneously the charging rate and several decay processes involving short-lived and long-lived carriers. With this approach, dynamical images of the trap-filling, trap-delayed recombination and nongeminate recombination processes have been acquired in nanophase segregated organic donor-acceptor bulk heterojunction thin films. Furthermore, the spatial variation of the minority carrier lifetime has been imaged in polycrystalline silicon thin films. These results establish two-dimensional multidynamical photovoltage imaging as a universal tool for local investigations of the photocarrier dynamics in photoactive materials and devices.

Effect of UV/ozone treatment on polystyrene dielectric and its application on organic field-effect transistors

PubMed Central

2014-01-01

The influence of UV/ozone treatment on the property of polystyrene (PS) dielectric surface was investigated, and pentacene organic field-effect transistors (OFETs) based on the treated dielectric was fabricated. The dielectric and pentacene active layers were characterized by atomic force microscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. The results showed that, at short UVO exposure time (<10 s), the chemical composition of PS dielectric surface remained the same. While at long UVO exposure time (>60 s), new chemical groups, including alcohol/ether, carbonyl, and carboxyl/ester groups, were formed. By adjusting the UVO exposure time to 5 s, the hole mobility of the OFETs increased to 0.52 cm2/Vs, and the threshold voltage was positively shifted to -12 V. While the time of UVO treatment exceeded 30 s, the mobility started to shrink, and the off-current was enlarged. These results indicate that, as a simple surface treatment method, UVO treatment could quantitatively modulate the property of PS dielectric surface by controlling the exposure time, and thus, pioneered a new way to modulate the characteristics of organic electronic devices. PMID:25258603

Photo-Activated Localization Microscopy of Single Carbohydrate Binding Modules on Cellulose Nanofibers

NASA Astrophysics Data System (ADS)

Hor, Amy; Dagel, Daryl; Luu, Quocanh; Savaikar, Madhusudan; Ding, Shi-You; Smith, Steve

2015-03-01

Photo Activated Localization Microscopy (PALM) is used to conduct an in vivo study of the binding affinity of polysaccharide-specific Carbohydrate Binding Modules (CBMs) to insoluble cellulose substrates. Two families of CBMs, namely TrCBM1 and CtCBM3, were modified to incorporate photo-activatable mCherry fluorescent protein (PAmCherry), and exposed to highly crystalline Valonia cellulose nano-fibrils. The resulting PALM images show CBMs binding along the nano-fibril long axis in a punctuated linear array, localized with, on average, 10 nm precision. Statistical analysis of the binding events results in nearest neighbor distributions between CBMs. A comparison between TrCBM1 and CtCBM3 reveals a similarity in the nearest neighbor distribution peaks but differences in the overall binding density. The former is attributed to steric hindrance among the CBMs on the nano-fibril whereas the latter is attributed to differences in the CBMs' binding strength. These results are compared to similar distributions derived from TEM measurements of dried samples of CtCBM3-CdSs quantum dot bioconjugates and AFM images of CtCBM3-GFP bound to similar Valonia nano-fibrils. Funding provided by NSF MPS/DMR/BMAT Award # 1206908.

Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment

NASA Astrophysics Data System (ADS)

Rinehart, Matthew T.; LaCroix, Jeffrey; Henderson, Marcus; Katz, David; Wax, Adam

2011-03-01

The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.

Subsurface imaging of carbon nanotube networks in polymers with DC-biased multifrequency dynamic atomic force microscopy.

PubMed

Thompson, Hank T; Barroso-Bujans, Fabienne; Herrero, Julio Gomez; Reifenberger, Ron; Raman, Arvind

2013-04-05

The characterization of dispersion and connectivity of carbon nanotube (CNT) networks inside polymers is of great interest in polymer nanocomposites in new material systems, organic photovoltaics, and in electrodes for batteries and supercapacitors. We focus on a technique using amplitude modulation atomic force microscopy (AM-AFM) in the attractive regime of operation, using both single and dual mode excitation, which upon the application of a DC tip bias voltage allows, via the phase channel, the in situ, nanoscale, subsurface imaging of CNT networks dispersed in a polymer matrix at depths of 10-100 nm. We present an in-depth study of the origins of phase contrast in this technique and demonstrate that an electrical energy dissipation mechanism in the Coulomb attractive regime is key to the formation of the phase contrast which maps the spatial variations in the local capacitance and resistance due to the CNT network. We also note that dual frequency excitation can, under some conditions, improve the contrast for such samples. These methods open up the possibility for DC-biased amplitude modulation AFM to be used for mapping the variations in local capacitance and resistance in nanocomposites with conducting networks.

Amplitude quantification in contact-resonance-based voltage-modulated force spectroscopy

NASA Astrophysics Data System (ADS)

Bradler, Stephan; Schirmeisen, André; Roling, Bernhard

2017-08-01

Voltage-modulated force spectroscopy techniques, such as electrochemical strain microscopy and piezoresponse force microscopy, are powerful tools for characterizing electromechanical properties on the nanoscale. In order to correctly interpret the results, it is important to quantify the sample motion and to distinguish it from the electrostatic excitation of the cantilever resonance. Here, we use a detailed model to describe the cantilever dynamics in contact resonance measurements, and we compare the results with experimental values. We show how to estimate model parameters from experimental values and explain how they influence the sensitivity of the cantilever with respect to the excitation. We explain the origin of different crosstalk effects and how to identify them. We further show that different contributions to the measured signal can be distinguished by analyzing the correlation between the resonance frequency and the measured amplitude. We demonstrate this technique on two representative test samples: (i) ferroelectric periodically poled lithium niobate, and (ii) the Na+-ion conducting soda-lime float glass. We extend our analysis to higher cantilever bending modes and show that non-local electrostatic excitation is strongly reduced in higher bending modes due to the nodes in the lever shape. Based on our analyses, we present practical guidelines for quantitative imaging.

Melanin-targeted nonlinear microscopy for label-free molecular diagnosis and staining (Conference Presentation)

NASA Astrophysics Data System (ADS)

Warren, Warren S.

2017-02-01

Visible absorption in tissue is dominated by a very small number of chromophores (hemoglobins and melanins) with broad optical spectra; for melanins in particular, the optical absorption spectrum is typically featureless. In addition, scattering limits penetration depth. As a result, the most common microscopy application by far is with excised tissue, which can be stained. However, nonlinear optical methods have the additional advantages of greater penetration depth and reduced sensitivity to scattering. Traditional nonlinear microscopy relies on mechanisms which produce light of a different color than the irradiating lasers, such as second harmonic generation or two photon induced fluorescence, and this contrast is sparse in biological issue without expressing or injecting different chromophores. Recently, stable laser sources and pulse shaping/pulse train modulation methods have made it possible to detect a much wider range of nonlinear molecular signatures, even at modest laser powers (much less than a laser pointer). Here we show the utility of a variety of such signatures (pump-probe, pulse-shaped stimulated Raman, cross-phase modulation) to quantitatively image the biochemical composition of transparent or pigmented tissue in a variety of applications, ranging from thin, unstained tissue sections to live knockout mice. The rich biochemical information provided by this method can be used as an indicator of melanocyte activity, which in turn (for example) reflects the status of melanocytic lesions. Comparisons with model systems (synthetic melanin nanoparticles, sepia melanin) and analysis of melanin degradation pathways in vivo have led to a quantitative understanding of the molecular basis of these changes.

Thermal and Optical Modulation of the Carrier Mobility in OTFTs Based on an Azo-anthracene Liquid Crystal Organic Semiconductor.

PubMed

Chen, Yantong; Li, Chao; Xu, Xiuru; Liu, Ming; He, Yaowu; Murtaza, Imran; Zhang, Dongwei; Yao, Chao; Wang, Yongfeng; Meng, Hong

2017-03-01

One of the most striking features of organic semiconductors compared with their corresponding inorganic counterparts is their molecular diversity. The major challenge in organic semiconductor material technology is creating molecular structural motifs to develop multifunctional materials in order to achieve the desired functionalities yet to optimize the specific device performance. Azo-compounds, because of their special photoresponsive property, have attracted extensive interest in photonic and optoelectronic applications; if incorporated wisely in the organic semiconductor groups, they can be innovatively utilized in advanced smart electronic applications, where thermal and photo modulation is applied to tune the electronic properties. On the basis of this aspiration, a novel azo-functionalized liquid crystal semiconductor material, (E)-1-(4-(anthracen-2-yl)phenyl)-2-(4-(decyloxy)phenyl)diazene (APDPD), is designed and synthesized for application in organic thin-film transistors (OTFTs). The UV-vis spectra of APDPD exhibit reversible photoisomerizaton upon photoexcitation, and the thin films of APDPD show a long-range orientational order based on its liquid crystal phase. The performance of OTFTs based on this material as well as the effects of thermal treatment and UV-irradiation on mobility are investigated. The molecular structure, stability of the material, and morphology of the thin films are characterized by thermal gravimetric analysis (TGA), polarizing optical microscopy (POM), (differential scanning calorimetry (DSC), UV-vis spectroscopy, atomic force microscopy (AFM), and scanning tunneling microscopy (STM). This study reveals that our new material has the potential to be applied in optical sensors, memories, logic circuits, and functional switches.

Self-phase modulation and two-photon absorption imaging of cells and active neurons

NASA Astrophysics Data System (ADS)

Fischer, Martin C.; Liu, Henry; Piletic, Ivan R.; Ye, Tong; Yasuda, Ryohei; Warren, Warren S.

2007-02-01

Even though multi-photon fluorescence microscopy offers higher resolution and better penetration depth than traditional fluorescence microscopy, its use is restricted to the detection of molecules that fluoresce. Two-photon absorption (TPA) imaging can provide contrast in non-fluorescent molecules while retaining the high resolution and sectioning capabilities of nonlinear imaging modalities. In the long-wavelength water window, tissue TPA is dominated by the endogenous molecules melanin and hemoglobin with an almost complete absence of endogenous two-photon fluorescence. A complementary nonlinear contrast mechanism is self-phase modulation (SPM), which can provide intrinsic signatures that can depend on local tissue anisotropy, chemical environment, or other structural properties. We have developed a spectral hole refilling measurement technique for TPA and SPM measurements using shaped ultrafast laser pulses. Here we report on a microscopy setup to simultaneously acquire 3D, high-resolution TPA and SPM images. We have acquired data in mounted B16 melanoma cells with very modest laser power levels. We will also discuss the possible application of this measurement technique to neuronal imaging. Since SPM is sensitive to material structure we can expect SPM properties of neurons to change during neuronal firing. Using our hole-refilling technique we have now demonstrated strong novel intrinsic nonlinear signatures of neuronal activation in a hippocampal brain slice. The observed changes in nonlinear signal upon collective activation were up to factors of two, unlike other intrinsic optical signal changes on the percent level. These results show that TPA and SPM imaging can provide important novel functional contrast in tissue using very modest power levels suitable for in vivo applications.

Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy.

PubMed

Sewald, Xaver

2018-06-20

Viral pathogens have adapted to the host organism to exploit the cellular machinery for virus replication and to modulate the host cells for efficient systemic dissemination and immune evasion. Much of our knowledge of the effects that virus infections have on cells originates from in vitro imaging studies using experimental culture systems consisting of cell lines and primary cells. Recently, intravital microscopy using multi-photon excitation of fluorophores has been applied to observe virus dissemination and pathogenesis in real-time under physiological conditions in living organisms. Critical steps during viral infection and pathogenesis could be studied by direct visualization of fluorescent virus particles, virus-infected cells, and the immune response to viral infection. In this review, I summarize the latest research on in vivo studies of viral infections using multi-photon intravital microscopy (MP-IVM). Initially, the underlying principle of multi-photon microscopy is introduced and experimental challenges during microsurgical animal preparation and fluorescent labeling strategies for intravital imaging are discussed. I will further highlight recent studies that combine MP-IVM with optogenetic tools and transcriptional analysis as a powerful approach to extend the significance of in vivo imaging studies of viral pathogens.

Graphene engineering by neon ion beams

DOE PAGES

Iberi, Vighter; Ievlev, Anton V.; Vlassiouk, Ivan; ...

2016-02-18

Achieving the ultimate limits of materials and device performance necessitates the engineering of matter with atomic, molecular, and mesoscale fidelity. While common for organic and macromolecular chemistry, these capabilities are virtually absent for 2D materials. In contrast to the undesired effect of ion implantation from focused ion beam (FIB) lithography with gallium ions, and proximity effects in standard e-beam lithography techniques, the shorter mean free path and interaction volumes of helium and neon ions offer a new route for clean, resist free nanofabrication. Furthermore, with the advent of scanning helium ion microscopy, maskless He + and Ne + beam lithographymore » of graphene based nanoelectronics is coming to the forefront. Here, we will discuss the use of energetic Ne ions in engineering graphene devices and explore the mechanical, electromechanical and chemical properties of the ion-milled devices using scanning probe microscopy (SPM). By using SPM-based techniques such as band excitation (BE) force modulation microscopy, Kelvin probe force microscopy (KPFM) and Raman spectroscopy, we demonstrate that the mechanical, electrical and optical properties of the exact same devices can be quantitatively extracted. Additionally, the effect of defects inherent in ion beam direct-write lithography, on the overall performance of the fabricated devices is elucidated.« less

Sub-diffraction-limit localization imaging of a plasmonic nanoparticle pair with wavelength-resolved dark-field microscopy.

PubMed

Wei, Lin; Ma, Yanhong; Zhu, Xupeng; Xu, Jianghong; Wang, Yaxin; Duan, Huigao; Xiao, Lehui

2017-06-29

In this work, with wavelength-resolved dark-field microscopy, the center-of-mass localization information from nanoparticle pairs (i.e., spherical (45 nm in diameter) and rod (45 × 70 nm) shaped gold nanoparticle pairs with different gap distances and orientations) was explored and compared with the results determined by scanning electron microscopy (SEM) measurements. When the gap distance was less than 20 nm, the scattering spectrum of the nanoparticle pair was seriously modulated by the plasmonic coupling effect. The measured coordinate information determined by the optical method (Gaussian fitting) was not consistent with the true results determined by SEM measurement. A good correlation between the optical and SEM measurements was achieved when the gap distance was further increased (e.g., 20, 40 and 60 nm). Under these conditions, well-defined scattering peaks assigned to the corresponding individual nanoparticles could be distinguished from the obtained scattering spectrum. These results would afford valuable information for the studies on single plasmonic nanoparticle imaging applications with the optical microscopy method such as super-localization imaging, high precision single particle tracking in a crowding environment and so on.

A Comparison between the Rhesus Monkey and the Human on the Effect of Atropine on the Electroencephalogram. Volume 2. Preliminary Statistical Analysis of Spectral EEG Waveforms in Rhesus Monkeys Exposed to Atropine.

DTIC Science & Technology

1994-11-01

20 i 1 19. ABSTRACT (Continue on reverze if necenay and ident•f by block numbierj See other side. • DTIC • ~S EL ECTE . JAN 0 4 1994 ") ~F 20...82171LfOVfO U~) iv0 m 0O El .hC N- HN.- Hr4r- C.N w 000000 000000 000000 000000 000000 1W I.ŕ 00 -r -r .O D ,a o r oL)ria 4-) 0) .I. . . . . . .9 I W) 0...mmmmHmDm HH L’mommLmm mNm mNNmm LOmm)N.mmmm HOWHMMWWH0)N000 ODr4O 0 NOr wr- w w w w. rNMNOVNO V~ El . H H - H v H H -H AA Hr0WHHHNV M ONN~OOH OM UNN

Auger electron diffraction in thin CoO films on Au(1 1 1)

NASA Astrophysics Data System (ADS)

Chassé, A.; Niebergall, L.; Heiler, M.; Neddermeyer, H.; Schindler, K.-M.

The local structure of thin CoO films grown on a single crystal Au(1 1 1) surface has been studied by Auger electron diffraction (AED). Therefore, the angular dependence of the Auger electron intensity of Co-LMM and O-KLL Auger electrons was recorded in the total half-space above the film. Such 2 π-scans immediately reflect the symmetry of the surface and the local structure of the film. The experimental data are compared to multiple-scattering cluster calculations, where both the influence of multiple-scattering effects and effects of Auger transition matrix elements have been investigated. We have found that the AED patterns of a CoO film in forward-scattering conditions do not always provide straightforward information on the local structure of the film, whereas the multiple-scattering approximation applied gives very good agreement between experimental and theoretical results.

Infrastructure for Personalized Medicine at Partners HealthCare

PubMed Central

Weiss, Scott T.; Shin, Meini Sumbada

2016-01-01

Partners HealthCare Personalized Medicine (PPM) is a center within the Partners HealthCare system (founded by Massachusetts General Hospital and Brigham and Women’s Hospital) whose mission is to utilize genetics and genomics to improve the care of patients in a cost effective manner. PPM consists of five interconnected components: (1) Laboratory for Molecular Medicine (LMM), a CLIA laboratory performing genetic testing for patients world-wide; (2) Translational Genomics Core (TGC), a core laboratory providing genomic platforms for Partners investigators; (3) Partners Biobank, a biobank of samples (DNA, plasma and serum) for 50,000 Consented Partners patients; (4) Biobank Portal, an IT infrastructure and viewer to bring together genotypes, samples, phenotypes (validated diagnoses, radiology, and clinical chemistry) from the electronic medical record to Partners investigators. These components are united by (5) a common IT system that brings researchers, clinicians, and patients together for optimal research and patient care. PMID:26927187

Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue

PubMed Central

Chaigneau, Emmanuelle; Wright, Amanda J.; Poland, Simon P.; Girkin, John M.; Silver, R. Angus

2011-01-01

Two-photon (2P) microscopy is widely used in neuroscience, but the optical properties of brain tissue are poorly understood. We have investigated the effect of brain tissue on the 2P point spread function (PSF2P) by imaging fluorescent beads through living cortical slices. By combining this with measurements of the mean free path of the excitation light, adaptive optics and vector-based modeling that includes phase modulation and scattering, we show that tissue-induced wavefront distortions are the main determinant of enlargement and distortion of the PSF2P at intermediate imaging depths. Furthermore, they generate surrounding lobes that contain more than half of the 2P excitation. These effects reduce the resolution of fine structures and contrast and they, together with scattering, limit 2P excitation. Our results disentangle the contributions of scattering and wavefront distortion in shaping the cortical PSF2P, thereby providing a basis for improved 2P microscopy. PMID:22109156

Development of in-situ high-voltage and high-temperature stressing capability on atomic force microscopy platform

DOE PAGES

Xiao, Chuanxiao; Jiang, Chun-Sheng; Johnston, Steve; ...

2017-10-18

Reliability has become an increasingly important issue as photovoltaic technologies mature. However, researching reliability at the nanometer scale is in its infancy; in particular, in-situ studies have not been reported to date. Here, to investigate potential-induced degradation (PID) of solar cell modules, we have developed an in-situ stressing capability with applied high voltage (HV) and high temperature (HT) on an atomic force microscopy (AFM) platform. We designed a sample holder to simultaneously accommodate 1000-V HV and 200 degrees C HT stressing. Three technical challenges have been overcome along with the development: thermal drift at HT, HV interference with measurement, andmore » arc discharge caused by HV. We demonstrated no observable measurement artifact under the stress conditions. Based on our in-situ stressing AFM, Kelvin probe force microscopy potential imaging revealed the evolution of electrical potential across the junction along with the PID stressing time, which provides vital information to further study the PID mechanism.« less

Charge density wave order in 1D mirror twin boundaries of single-layer MoSe 2

DOE PAGES

Barja, Sara; Wickenburg, Sebastian; Liu, Zhen-Fei; ...

2016-04-18

Here, We provide direct evidence for the existence of isolated, one-dimensional charge density waves at mirror twin boundaries (MTBs) of single-layer semiconducting MoSe 2. Such MTBs have been previously observed by transmission electron microscopy and have been predicted to be metallic in MoSe 2 and MoS 2. Our low-temperature scanning tunnelling microscopy/spectroscopy measurements revealed a substantial bandgap of 100 meV opening at the Fermi energy in the otherwise metallic one-dimensional structures. We found a periodic modulation in the density of states along the MTB, with a wavelength of approximately three lattice constants. In addition to mapping the energy-dependent densitymore » of states, we determined the atomic structure and bonding of the MTB through simultaneous high-resolution non-contact atomic force microscopy. Density functional theory calculations based on the observed structure reproduced both the gap opening and the spatially resolved density of states.« less

Optically-sectioned two-shot structured illumination microscopy with Hilbert-Huang processing.

PubMed

Patorski, Krzysztof; Trusiak, Maciej; Tkaczyk, Tomasz

2014-04-21

We introduce a fast, simple, adaptive and experimentally robust method for reconstructing background-rejected optically-sectioned images using two-shot structured illumination microscopy. Our innovative data demodulation method needs two grid-illumination images mutually phase shifted by π (half a grid period) but precise phase displacement between two frames is not required. Upon frames subtraction the input pattern with increased grid modulation is obtained. The first demodulation stage comprises two-dimensional data processing based on the empirical mode decomposition for the object spatial frequency selection (noise reduction and bias term removal). The second stage consists in calculating high contrast image using the two-dimensional spiral Hilbert transform. Our algorithm effectiveness is compared with the results calculated for the same input data using structured-illumination (SIM) and HiLo microscopy methods. The input data were collected for studying highly scattering tissue samples in reflectance mode. Results of our approach compare very favorably with SIM and HiLo techniques.

Immunoactive two-dimensional self-assembly of monoclonal antibodies in aqueous solution revealed by atomic force microscopy

NASA Astrophysics Data System (ADS)

Ido, Shinichiro; Kimiya, Hirokazu; Kobayashi, Kei; Kominami, Hiroaki; Matsushige, Kazumi; Yamada, Hirofumi

2014-03-01

The conformational flexibility of antibodies in solution directly affects their immune function. Namely, the flexible hinge regions of immunoglobulin G (IgG) antibodies are essential in epitope-specific antigen recognition and biological effector function. The antibody structure, which is strongly related to its functions, has been partially revealed by electron microscopy and X-ray crystallography, but only under non-physiological conditions. Here we observed monoclonal IgG antibodies in aqueous solution by high-resolution frequency modulation atomic force microscopy (FM-AFM). We found that monoclonal antibodies self-assemble into hexamers, which form two-dimensional crystals in aqueous solution. Furthermore, by directly observing antibody-antigen interactions using FM-AFM, we revealed that IgG molecules in the crystal retain immunoactivity. As the self-assembled monolayer crystal of antibodies retains immunoactivity at a neutral pH and is functionally stable at a wide range of pH and temperature, the antibody crystal is applicable to new biotechnological platforms for biosensors or bioassays.

Force modulation and electrochemical gating of conductance in a cytochrome

NASA Astrophysics Data System (ADS)

Davis, Jason J.; Peters, Ben; Xi, Wang

2008-09-01

Scanning probe methods have been used to measure the effect of electrochemical potential and applied force on the tunnelling conductance of the redox metalloprotein yeast iso-1-cytochrome c (YCC) at a molecular level. The interaction of a proximal probe with any sample under test will, at this scale, be inherently perturbative. This is demonstrated with conductive probe atomic force microscopy (CP-AFM) current-voltage spectroscopy in which YCC, chemically adsorbed onto pristine Au(111) via its surface cysteine residue, is observed to become increasingly compressed as applied load is increased, with concomitant decrease in junction resistance. Electrical contact at minimal perturbation, where probe-molecule coupling is comparable to that in scanning tunnelling microscopy, brings with it the observation of negative differential resistance, assigned to redox-assisted probe-substrate tunnelling. The role of the redox centre in conductance is also resolved in electrochemical scanning tunnelling microscopy assays where molecular conductance is electrochemically gateable through more than an order of magnitude.

Oufti: An integrated software package for high-accuracy, high-throughput quantitative microscopy analysis

PubMed Central

Paintdakhi, Ahmad; Parry, Bradley; Campos, Manuel; Irnov, Irnov; Elf, Johan; Surovtsev, Ivan; Jacobs-Wagner, Christine

2016-01-01

Summary With the realization that bacteria display phenotypic variability among cells and exhibit complex subcellular organization critical for cellular function and behavior, microscopy has re-emerged as a primary tool in bacterial research during the last decade. However, the bottleneck in today’s single-cell studies is quantitative image analysis of cells and fluorescent signals. Here, we address current limitations through the development of Oufti, a stand-alone, open-source software package for automated measurements of microbial cells and fluorescence signals from microscopy images. Oufti provides computational solutions for tracking touching cells in confluent samples, handles various cell morphologies, offers algorithms for quantitative analysis of both diffraction and non-diffraction-limited fluorescence signals, and is scalable for high-throughput analysis of massive datasets, all with subpixel precision. All functionalities are integrated in a single package. The graphical user interface, which includes interactive modules for segmentation, image analysis, and post-processing analysis, makes the software broadly accessible to users irrespective of their computational skills. PMID:26538279

High-pressure microscopy for tracking dynamic properties of molecular machines.

PubMed

Nishiyama, Masayoshi

2017-12-01

High-pressure microscopy is one of the powerful techniques to visualize the effects of hydrostatic pressures on research targets. It could be used for monitoring the pressure-induced changes in the structure and function of molecular machines in vitro and in vivo. This review focuses on the dynamic properties of the assemblies and machines, analyzed by means of high-pressure microscopy measurement. We developed a high-pressure microscope that is optimized both for the best image formation and for the stability to hydrostatic pressure up to 150 MPa. Application of pressure could change polymerization and depolymerization processes of the microtubule cytoskeleton, suggesting a modulation of the intermolecular interaction between tubulin molecules. A novel motility assay demonstrated that high hydrostatic pressure induces counterclockwise (CCW) to clockwise (CW) reversals of the Escherichia coli flagellar motor. The present techniques could be extended to study how molecular machines in complicated systems respond to mechanical stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.

PubMed

Fischer, Audrey; Garcia-Rodriguez, Consuelo; Geren, Isin; Lou, Jianlong; Marks, James D; Nakagawa, Terunaga; Montal, Mauricio

2008-02-15

Clostridial botulinum neurotoxin (BoNT) causes a neuroparalytic condition recognized as botulism by arresting synaptic vesicle exocytosis. Although the crystal structures of full-length BoNT/A and BoNT/B holotoxins are known, the molecular architecture of the five other serotypes remains elusive. Here, we present the structures of BoNT/A and BoNT/E using single particle electron microscopy. Labeling of the particles with three different monoclonal antibodies raised against BoNT/E revealed the positions of their epitopes in the electron microscopy structure, thereby identifying the three hallmark domains of BoNT (protease, translocation, and receptor binding). Correspondingly, these antibodies selectively inhibit BoNT translocation activity as detected using a single molecule assay. The global structure of BoNT/E is strikingly different from that of BoNT/A despite strong sequence similarity. We postulate that the unique architecture of functionally conserved modules underlies the distinguishing attributes of BoNT/E and contributes to differences with BoNT/A.

Development of in-situ high-voltage and high-temperature stressing capability on atomic force microscopy platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Chuanxiao; Jiang, Chun-Sheng; Johnston, Steve

Reliability has become an increasingly important issue as photovoltaic technologies mature. However, researching reliability at the nanometer scale is in its infancy; in particular, in-situ studies have not been reported to date. Here, to investigate potential-induced degradation (PID) of solar cell modules, we have developed an in-situ stressing capability with applied high voltage (HV) and high temperature (HT) on an atomic force microscopy (AFM) platform. We designed a sample holder to simultaneously accommodate 1000-V HV and 200 degrees C HT stressing. Three technical challenges have been overcome along with the development: thermal drift at HT, HV interference with measurement, andmore » arc discharge caused by HV. We demonstrated no observable measurement artifact under the stress conditions. Based on our in-situ stressing AFM, Kelvin probe force microscopy potential imaging revealed the evolution of electrical potential across the junction along with the PID stressing time, which provides vital information to further study the PID mechanism.« less