Sample records for based clinical microscopy

  1. Mobile phone based clinical microscopy for global health applications.

    Directory of Open Access Journals (Sweden)

    David N Breslauer

    Full Text Available Light microscopy provides a simple, cost-effective, and vital method for the diagnosis and screening of hematologic and infectious diseases. In many regions of the world, however, the required equipment is either unavailable or insufficiently portable, and operators may not possess adequate training to make full use of the images obtained. Counterintuitively, these same regions are often well served by mobile phone networks, suggesting the possibility of leveraging portable, camera-enabled mobile phones for diagnostic imaging and telemedicine. Toward this end we have built a mobile phone-mounted light microscope and demonstrated its potential for clinical use by imaging P. falciparum-infected and sickle red blood cells in brightfield and M. tuberculosis-infected sputum samples in fluorescence with LED excitation. In all cases resolution exceeded that necessary to detect blood cell and microorganism morphology, and with the tuberculosis samples we took further advantage of the digitized images to demonstrate automated bacillus counting via image analysis software. We expect such a telemedicine system for global healthcare via mobile phone -- offering inexpensive brightfield and fluorescence microscopy integrated with automated image analysis -- to provide an important tool for disease diagnosis and screening, particularly in the developing world and rural areas where laboratory facilities are scarce but mobile phone infrastructure is extensive.

  2. Innovative Strategies for Clinical Microscopy Instruction: Virtual Versus Light Microscopy. (United States)

    McDaniel, M Jane; Russell, Gregory B; Crandall, Sonia J


    The purpose of the study was to compare virtual microscopy with light microscopy to determine differences in learning outcomes and learner attitudes in teaching clinical microscopy to physician assistant (PA) students. A prospective, randomized, crossover design study was conducted with a convenience sample of 67 first-year PA students randomized to 2 groups. One group used light microscopes to find microscopic structures, whereas the other group used instructor-directed video streaming of microscopic elements. At the midpoint of the study, the groups switched instructional strategies. Learning outcomes were assessed via posttest after each section of the study, with comparison of final practical examination results to previous cohorts. Attitudes about the 2 educational strategies were assessed through a postcourse questionnaire with a Likert scale. Analysis of the first posttest demonstrated that students in the video-streamed group had significantly better learning outcomes than those in the light microscopy group (P = .004; Cohen's d = 0.74). Analysis of the posttest after crossover showed no differences between the 2 groups (P = .48). Between the 2 posttests, students first assigned to the light microscopy group scored a 6.6 mean point increase (±10.4 SD; p = .0011), whereas students first assigned to the virtual microscopy group scored a 1.3 mean point increase (±7.1 SD; p = .29). The light microscopy group improved more than the virtual microscopy group (P = .019). Analysis of practical examination data revealed higher scores for the study group compared with 5 previous cohorts of first-year students (P virtual microscopy to traditional light microscopy. Virtual microscopy is an effective educational strategy, and students prefer this method when learning to interpret images of clinical specimens.

  3. How Hedstrom files fail during clinical use? A retrieval study based on SEM, optical microscopy and micro-XCT analysis. (United States)

    Zinelis, Spiros; Al Jabbari, Youssef S


    This study was conducted to evaluate the failure mechanism of clinically failed Hedstrom (H)-files. Discarded H-files (n=160) from #8 to #40 ISO sizes were collected from different dental clinics. Retrieved files were classified according to their macroscopic appearance and they were investigated under scanning electron microscopy (SEM) and X-ray micro-computed tomography (mXCT). Then the files were embedded in resin along their longitudinal axis and after metallographic grinding and polishing, studied under an incident light microscope. The macroscopic evaluation showed that small ISO sizes (#08-#15) failed by extensive plastic deformation, while larger sizes (≥#20) tended to fracture. Light microscopy and mXCT results coincided showing that unused and plastically deformed files were free of internal defects, while fractured files demonstrate the presence of intense cracking in the flute region. SEM analysis revealed the presence of striations attributed to the fatigue mechanism. Secondary cracks were also identified by optical microscopy and their distribution was correlated to fatigue under bending loading. Experimental results demonstrated that while overloading of cutting instruments is the predominating failure mechanism of small file sizes (#08-#15), fatigue should be considered the fracture mechanism for larger sizes (≥#20).

  4. Handheld Fluorescence Microscopy based Flow Analyzer. (United States)

    Saxena, Manish; Jayakumar, Nitin; Gorthi, Sai Siva


    Fluorescence microscopy has the intrinsic advantages of favourable contrast characteristics and high degree of specificity. Consequently, it has been a mainstay in modern biological inquiry and clinical diagnostics. Despite its reliable nature, fluorescence based clinical microscopy and diagnostics is a manual, labour intensive and time consuming procedure. The article outlines a cost-effective, high throughput alternative to conventional fluorescence imaging techniques. With system level integration of custom-designed microfluidics and optics, we demonstrate fluorescence microscopy based imaging flow analyzer. Using this system we have imaged more than 2900 FITC labeled fluorescent beads per minute. This demonstrates high-throughput characteristics of our flow analyzer in comparison to conventional fluorescence microscopy. The issue of motion blur at high flow rates limits the achievable throughput in image based flow analyzers. Here we address the issue by computationally deblurring the images and show that this restores the morphological features otherwise affected by motion blur. By further optimizing concentration of the sample solution and flow speeds, along with imaging multiple channels simultaneously, the system is capable of providing throughput of about 480 beads per second.

  5. Clinical applications of corneal confocal microscopy

    Directory of Open Access Journals (Sweden)

    Mitra Tavakoli


    Full Text Available Mitra Tavakoli1, Parwez Hossain2, Rayaz A Malik11Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; 2University of Southampton, Southampton Eye Unit, Southampton General Hospital, Southampton, UKAbstract: Corneal confocal microscopy is a novel clinical technique for the study of corneal cellular structure. It provides images which are comparable to in-vitro histochemical techniques delineating corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium. Because, corneal confocal microscopy is a non invasive technique for in vivo imaging of the living cornea it has huge clinical potential to investigate numerous corneal diseases. Thus far it has been used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post surgical evaluation (PRK, LASIK and LASEK, flap evaluations and Radial Keratotomy, and penetrating keratoplasty. Most recently it has been used as a surrogate for peripheral nerve damage in a variety of peripheral neuropathies and may have potential in acting as a surrogate marker for endothelial abnormalities.Keywords: corneal confocal microscopy, cornea, infective keratitis, corneal dystrophy, neuropathy

  6. Accuracy of two digital implant impression systems based on confocal microscopy with variations in customized software and clinical parameters. (United States)

    Giménez, Beatriz; Pradíes, Guillermo; Martínez-Rus, Francisco; Özcan, Mutlu


    To evaluate the accuracy of two digital impression systems based on the same technology but different postprocessing correction modes of customized software, with consideration of several clinical parameters. A maxillary master model with six implants located in the second molar, second premolar, and lateral incisor positions was fitted with six cylindrical scan bodies. Scan bodies were placed at different angulations or depths apical to the gingiva. Two experienced and two inexperienced operators performed scans with either 3D Progress (MHT) or ZFX Intrascan (Zimmer Dental). Five different distances between implants (scan bodies) were measured, yielding five data points per impression and 100 per impression system. Measurements made with a high-accuracy three-dimensional coordinate measuring machine (CMM) of the master model acted as the true values. The values obtained from the digital impressions were subtracted from the CMM values to identify the deviations. The differences between experienced and inexperienced operators and implant angulation and depth were compared statistically. Experience of the operator, implant angulation, and implant depth were not associated with significant differences in deviation from the true values with both 3D Progress and ZFX Intrascan. Accuracy in the first scanned quadrant was significantly better with 3D Progress, but ZFX Intrascan presented better accuracy in the full arch. Neither of the two systems tested would be suitable for digital impression of multiple-implant prostheses. Because of the errors, further development of both systems is required.

  7. Evaluation of a teaching strategy based on integration of clinical subjects, virtual autopsy, pathology museum, and digital microscopy for medical students. (United States)

    Diaz-Perez, Julio A; Raju, Sharat; Echeverri, Jorge H


    Learning pathology is fundamental for a successful medical practice. In recent years, medical education has undergone a profound transformation toward the development of an integrated curriculum incorporating both basic science and clinical material. Simultaneously, there has been a shift from a magisterial teaching approach to one centered around problem-based learning. Now-a-days, informatics tools are expected to help better implement these strategies. We applied and evaluated a new teaching method based on an active combination of clinical problems, gross pathology, histopathology, and autopsy pathology, all given through informatics tools, to teach a group of medical students at the Universidad de Santander, Colombia. Ninety-four medical students were followed in two consecutive semesters. Students were randomized to receive teaching either through traditional methodology or through the new integrated approach. There was no significant difference between the intervention group and the control group at baseline. At the end of the study, the scores in the intervention group were significantly higher compared to the control group (3.91/5.0 vs. 3.33/5.0, P = 0.0008). Students and tutors endorsed the benefits of the integrated approach. Participants were very satisfied with this training approach and rated the program an 8.7 out of 10, on average. This study confirms that an integrated curriculum utilizing informatics systems provides an excellent opportunity to associate pathology with clinical medicine early in training of medical students. This can be possible with the use of virtual microscopy and digital imaging.

  8. Comparative performance of PCR-based assay versus microscopy and culture for the direct detection of Mycobacterium tuberculosis in clinical respiratory specimens in Lebanon. (United States)

    Araj, G F; Talhouk, R S; Itani, L Y; Jaber, W; Jamaleddine, G W


    American University of Beirut Medical Center, Lebanon. To assess the performance of a polymerase chain reaction (PCR) using primers that flank 542 bp within IS6110 in Mycobacterium tuberculosis (TB) vs. microscopy and BACTEC culture, in the diagnosis of tuberculosis. A total of 82 clinical respiratory pulmonary specimens and 73 samples from BACTEC vials were tested by the three methods. Of 24 smear-positive culture-positive (SP-CP) and 11 smear-negative culture-positive (SN-CP) TB specimens, PCR detected 83% and 64%, respectively. Among 17 specimens yielding mycobacteria other than tuberculosis (MOTT), the PCR was positive in 33% SP-CP and 14% SN-CP specimens. Among the 73 BACTEC vials, PCR was positive in 36 of 38 (95%) yielding culture-positive TB, and in one of 20 (5%) yielding culture positive MOTT. None of the 30 smear-negative culture-negative (SN-CN) clinical specimens and 15 of the CN vials were positive by PCR. The overall sensitivity of PCR was 77% and 95% for TB detection in respiratory specimens and BACTEC vials, respectively, and the specificity was 94% in both. Because a substantial number of TB cases are missed, especially in SN-CP specimens, a PCR-based assay utilizing these primers cannot be used reliably, alone, in clinical laboratory diagnosis of mycobacterial respiratory infections.

  9. Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data. (United States)

    Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J


    The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  10. Atomic Force Microscopy Based Cell Shape Index (United States)

    Adia-Nimuwa, Usienemfon; Mujdat Tiryaki, Volkan; Hartz, Steven; Xie, Kan; Ayres, Virginia


    Stellation is a measure of cell physiology and pathology for several cell groups including neural, liver and pancreatic cells. In the present work, we compare the results of a conventional two-dimensional shape index study of both atomic force microscopy (AFM) and fluorescent microscopy images with the results obtained using a new three-dimensional AFM-based shape index similar to sphericity index. The stellation of astrocytes is investigated on nanofibrillar scaffolds composed of electrospun polyamide nanofibers that has demonstrated promise for central nervous system (CNS) repair. Recent work by our group has given us the ability to clearly segment the cells from nanofibrillar scaffolds in AFM images. The clear-featured AFM images indicated that the astrocyte processes were longer than previously identified at 24h. It was furthermore shown that cell spreading could vary significantly as a function of environmental parameters, and that AFM images could record these variations. The new three-dimensional AFM-based shape index incorporates the new information: longer stellate processes and cell spreading. The support of NSF PHY-095776 is acknowledged.

  11. Microscopy (United States)

    Patricia A. Moss; Les Groom


    Microscopy is the study and interpretation of images produced by a microscope. "Interpretation" is the keyword, because the microscope enables one to see structures that are too small or too close together to be resolved by the unaided eye. (The human eye cannot separate two points or lines that are closer together than 0.1 mm.) it is important to...

  12. Corneal endothelium in xeroderma pigmentosum: clinical specular microscopy study. (United States)

    Mohamed, Ashik; Peguda, Rajini; Ramappa, Muralidhar; Ali, Mohammad Javed; Chaurasia, Sunita


    Xeroderma pigmentosum is a condition caused due to a defective DNA repair mechanism when exposed to ultraviolet radiation. Many of the patients with this disorder develop severely oedematous cornea with varying degrees of anterior corneal haze, which necessitates a full-thickness keratoplasty or selective endothelial keratoplasty. Presence of corneal oedema suggests that these patients have a dysfunctional endothelium. The purpose of this study is to evaluate the corneal endothelium in the patients with xeroderma pigmentosum when clinical specular microscopy was feasible. Thirteen patients with classic skin changes of xeroderma pigmentosum were included in the study conducted during January 2010-December 2012. An age-matched group of 13 volunteers were included as controls who were emmetropes without any history of ocular or systemic illness. Corneal endothelium was assessed using specular microscopy from the central clear area of cornea. The mean age of the patients with xeroderma pigmentosum was 16.6±7.2 years and that of the controls was 17.4±6.9 years (p=0.78). The number of analysed cells and endothelial cell density were significantly higher in controls (pxeroderma pigmentosum (p≤0.007). The specular microscopic findings in patients with xeroderma pigmentosum are suggestive of an accelerated endothelial cell loss. It is pertinent that the treating physicians must be involved in emphasising proper ocular protection from ultraviolet radiation to prevent avoidable blindness from xeroderma pigmentosum. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  13. Portable microscopy platform for the clinical and environmental monitoring (United States)

    Wang, Weiming; Yu, Yan; Huang, Hui; Ou, Jinping


    Light microscopy can not only address various diagnosis needs such as aquatic parasites and bacteria such as E. coli in water, but also provide a method for the screening of red tide. Traditional microscope based on the smartphone created by adding lens couldn't keep the tradeoff between field-of-view(FOV) and the resolution. In this paper, we demonstrate a non-contact, light and cost-effective microscope platform, that can image highly dense samples with a spatial resolution of ~0.8um over a field-of-view(FOV) of >1mm2. After captured the direct images, we performed the pixel super-resolution algorithm to improve the image resolution and overcome the hardware interference. The system would be a good point-of-care diagnostic solution in resource limited settings. We validated the performance of the system by imaging resolution test targets, the squamous cell cancer(SqCC) and green algae that necessary to detect the squamous carcinoma and red tide

  14. Digital differential confocal microscopy based on spatial shift transformation. (United States)

    Liu, J; Wang, Y; Liu, C; Wilson, T; Wang, H; Tan, J


    Differential confocal microscopy is a particularly powerful surface profilometry technique in industrial metrology due to its high axial sensitivity and insensitivity to noise. However, the practical implementation of the technique requires the accurate positioning of point detectors in three-dimensions. We describe a simple alternative based on spatial transformation of a through-focus series of images obtained from a homemade beam scanning confocal microscope. This digital differential confocal microscopy approach is described and compared with the traditional Differential confocal microscopy approach. The ease of use of the digital differential confocal microscopy system is illustrated by performing measurements on a 3D standard specimen. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

  15. Nuclear microscopy in biomedical analysis with special emphasis on clinical metal biology (United States)

    Lindh, Ulf; Frisk, Peter; Nyström, Joakim; Danersund, Antero; Hudecek, Romuald; Lindvall, Anders; Thunell, Stig


    Nuclear microscopy based upon developments in high energy ion beam techniques is by now an accepted technique in many fields of research. The advancements into the biomedical field have, however, been slower than expected. A major factor explaining this tendency is the availability of nuclear microscopy. This paper reviews briefly the biomedical work using nuclear microscopy that has been carried out since the 4 th International Conference on Nuclear Microprobe Technology and Applications held in Shanghai. Nuclear microscopy of isolated individual blood cells from patients adversely affected by metal exposure from dental amalgam has been performed both before and after removal of the metallic fillings. The elemental profile of blood cells was more or less normalised after treatment. Some of these results will be presented to illustrate a medical application. Results from bulk analysis by ICP-MS of erythrocytes and plasma before and after treatment will also be presented to illustrate the difference in information content between these two approaches as well as the need for complementary information in solving biomedical problems. As part of a larger study of acute porphyria, nuclear microscopy of blood cells was included among the 78 laboratory tests. The approach in this study was unbiased in the sense that no hypothesis was formulated as to which laboratory parameters would be the most explanatory for health or disease. Multivariate discriminant analysis was applied to the large amounts of data acquired. This approach led to the hypothesis that oxidative stress increased the synthesis of manganese-dependent superoxide dismutase in the mitochondria of polymorphonuclear leukocytes, explaining the increase of manganese in these cells. Antioxidant therapy was therefore applied to a couple of patients with porphyria, however, without clinical success.

  16. Simple and robust image-based autofocusing for digital microscopy. (United States)

    Yazdanfar, Siavash; Kenny, Kevin B; Tasimi, Krenar; Corwin, Alex D; Dixon, Elizabeth L; Filkins, Robert J


    A simple image-based autofocusing scheme for digital microscopy is demonstrated that uses as few as two intermediate images to bring the sample into focus. The algorithm is adapted to a commercial inverted microscope and used to automate brightfield and fluorescence imaging of histopathology tissue sections.

  17. Reducing microscopy-based malaria misdiagnosis in a low ...

    African Journals Online (AJOL)

    In this paper we report on the outcomes of a simple intervention that utilized a social entrepreneurship approach (SEA) to reduce misdiagnosis associated with hospital-based microscopy of malaria in a low-transmission area of rural Tanzania. A pre-post assessment was conducted on patients presenting to the hospital ...

  18. Boundary fitting based segmentation of fluorescence microscopy images (United States)

    Lee, Soonam; Salama, Paul; Dunn, Kenneth W.; Delp, Edward J.


    Segmentation is a fundamental step in quantifying characteristics, such as volume, shape, and orientation of cells and/or tissue. However, quantification of these characteristics still poses a challenge due to the unique properties of microscopy volumes. This paper proposes a 2D segmentation method that utilizes a combination of adaptive and global thresholding, potentials, z direction refinement, branch pruning, end point matching, and boundary fitting methods to delineate tubular objects in microscopy volumes. Experimental results demonstrate that the proposed method achieves better performance than an active contours based scheme.

  19. Temporal overlap estimation based on interference spectrum in CARS microscopy (United States)

    Zhang, Yongning; Jiang, Junfeng; Liu, Kun; Huang, Can; Wang, Shuang; Zhang, Xuezhi; Liu, Tiegen


    Coherent Anti-Stokes Raman Scattering (CARS) microscopy has attracted lots of attention because of the advantages, such as noninvasive, label-free, chemical specificity, intrinsic three-dimension spatial resolution and so on. However, the temporal overlap of pump and Stokes has not been solved owing to the ultrafast optical pulse used in CARS microscopy. We combine interference spectrum of residual pump in Stokes path and nonlinear Schrodinger equation (NLSE) to realize the temporal overlap of pump pulse and Stokes pulse. At first, based on the interference spectrum of pump pulse and residual pump in Stokes path, the optical delay is defined when optical path difference between pump path and Stokes path is zero. Then the relative optical delay between Stokes pulse and residual pump in PCF can be calculated by NLSE. According to the spectrum interference and NLSE, temporal overlap of pump pulse and Stokes pulse will be realized easily and the imaging speed will be improved in CARS microscopy.

  20. Confocal microscopy patterns in nonmelanoma skin cancer and clinical applications. (United States)

    González, S; Sánchez, V; González-Rodríguez, A; Parrado, C; Ullrich, M


    Reflectance confocal microscopy is currently the most promising noninvasive diagnostic tool for studying cutaneous structures between the stratum corneum and the superficial reticular dermis. This tool gives real-time images parallel to the skin surface; the microscopic resolution is similar to that of conventional histology. Numerous studies have identified the main confocal features of various inflammatory skin diseases and tumors, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. Confocal patterns and diagnostic algorithms have been shown to have high sensitivity and specificity in melanoma and nonmelanoma skin cancer. Possible present and future applications of this noninvasive technology are wide ranging and reach beyond its use in noninvasive diagnosis. This tool can also be used, for example, to evaluate dynamic skin processes that occur after UV exposure or to assess tumor response to noninvasive treatments such as photodynamic therapy. We explain the characteristic confocal features found in the main nonmelanoma skin tumors and discuss possible applications for this novel diagnostic technique in routine dermatology practice. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  1. Automated seeding-based nuclei segmentation in nonlinear optical microscopy. (United States)

    Medyukhina, Anna; Meyer, Tobias; Heuke, Sandro; Vogler, Nadine; Dietzek, Benjamin; Popp, Jürgen


    Nonlinear optical (NLO) microscopy based, e.g., on coherent anti-Stokes Raman scattering (CARS) or two-photon-excited fluorescence (TPEF) is a fast label-free imaging technique, with a great potential for biomedical applications. However, NLO microscopy as a diagnostic tool is still in its infancy; there is a lack of robust and durable nuclei segmentation methods capable of accurate image processing in cases of variable image contrast, nuclear density, and type of investigated tissue. Nonetheless, such algorithms specifically adapted to NLO microscopy present one prerequisite for the technology to be routinely used, e.g., in pathology or intraoperatively for surgical guidance. In this paper, we compare the applicability of different seeding and boundary detection methods to NLO microscopic images in order to develop an optimal seeding-based approach capable of accurate segmentation of both TPEF and CARS images. Among different methods, the Laplacian of Gaussian filter showed the best accuracy for the seeding of the image, while a modified seeded watershed segmentation was the most accurate in the task of boundary detection. The resulting combination of these methods followed by the verification of the detected nuclei performs high average sensitivity and specificity when applied to various types of NLO microscopy images.

  2. CCD-based thermoreflectance microscopy: principles and applications

    International Nuclear Information System (INIS)

    Farzaneh, M; Maize, K; Shakouri, A; Lueerssen, D; Summers, J A; Hudgings, Janice A; Mayer, P M; Ram, R J; Raad, P E; Pipe, K P


    CCD-based thermoreflectance microscopy has emerged as a high resolution, non-contact imaging technique for thermal profiling and performance and reliability analysis of numerous electronic and optoelectronic devices at the micro-scale. This thermography technique, which is based on measuring the relative change in reflectivity of the device surface as a function of change in temperature, provides high-resolution thermal images that are useful for hot spot detection and failure analysis, mapping of temperature distribution, measurement of thermal transient, optical characterization of photonic devices and measurement of thermal conductivity in thin films. In this paper we review the basic physical principle behind thermoreflectance as a thermography tool, discuss the experimental setup, resolutions achieved, signal processing procedures and calibration techniques, and review the current applications of CCD-based thermoreflectance microscopy in various devices. (topical review)

  3. Solid-State Quantum Computer Based on Scanning Tunneling Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Berman, G. P.; Brown, G. W.; Hawley, M. E.; Tsifrinovich, V. I.


    We propose a solid-state nuclear-spin quantum computer based on application of scanning tunneling microscopy (STM) and well-developed silicon technology. It requires the measurement of tunneling-current modulation caused by the Larmor precession of a single electron spin. Our envisioned STM quantum computer would operate at the high magnetic field ({approx}10 T) and at low temperature {approx}1 K .

  4. Solid-State Quantum Computer Based on Scanning Tunneling Microscopy

    International Nuclear Information System (INIS)

    Berman, G. P.; Brown, G. W.; Hawley, M. E.; Tsifrinovich, V. I.


    We propose a solid-state nuclear-spin quantum computer based on application of scanning tunneling microscopy (STM) and well-developed silicon technology. It requires the measurement of tunneling-current modulation caused by the Larmor precession of a single electron spin. Our envisioned STM quantum computer would operate at the high magnetic field (∼10 T) and at low temperature ∼1 K

  5. Clinical applications of in vivo fluorescence confocal laser scanning microscopy (United States)

    Oh, Chilhwan; Park, Sangyong; Kim, Junhyung; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Chun, Byungseon; Gweon, Daegab


    Living skin for basic and clinical research can be evaluated by Confocal Laser Scanning Microscope (CLSM) non-invasively. CLSM imaging system can achieve skin image its native state either "in vivo" or "fresh biopsy (ex vivo)" without fixation, sectioning and staining that is necessary for routine histology. This study examines the potential fluorescent CLSM with a various exogenous fluorescent contrast agent, to provide with more resolution images in skin. In addition, in vivo fluorescent CLSM researchers will be extended a range of potential clinical application. The prototype of our CLSM system has been developed by Prof. Gweon's group. The operating parameters are composed of some units, such as illuminated wavelength 488 nm, argon illumination power up to 20mW on the skin, objective lens, 0.9NA oil immersion, axial resolution 1.0μm, field of view 200μm x 100μm (lateral resolution , 0.3μm). In human volunteer, fluorescein sodium was administrated topically and intradermally. Animal studies were done in GFP transgenic mouse, IRC mouse and pig skin. For imaging of animal skin, fluorescein sodium, acridine orange, and curcumine were used for fluorescein contrast agent. We also used the GFP transgenic mouse for fluorescein CLSM imaging. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. Curcumin is a yellow food dye that has similar fluorescent properties to fluorescein sodium. Acridin Orange can be highlight nuclei in viable keratinocyte. In vivo CLSM of transgenic GFP mouse enable on in vivo, high resolution view of GFP expressing skin tissue. GFP signals are brightest in corneocyte, kertinocyte, hair and eccrine gland. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. In

  6. Multidirectional Image Sensing for Microscopy Based on a Rotatable Robot

    Directory of Open Access Journals (Sweden)

    Yajing Shen


    Full Text Available Image sensing at a small scale is essentially important in many fields, including microsample observation, defect inspection, material characterization and so on. However, nowadays, multi-directional micro object imaging is still very challenging due to the limited field of view (FOV of microscopes. This paper reports a novel approach for multi-directional image sensing in microscopes by developing a rotatable robot. First, a robot with endless rotation ability is designed and integrated with the microscope. Then, the micro object is aligned to the rotation axis of the robot automatically based on the proposed forward-backward alignment strategy. After that, multi-directional images of the sample can be obtained by rotating the robot within one revolution under the microscope. To demonstrate the versatility of this approach, we view various types of micro samples from multiple directions in both optical microscopy and scanning electron microscopy, and panoramic images of the samples are processed as well. The proposed method paves a new way for the microscopy image sensing, and we believe it could have significant impact in many fields, especially for sample detection, manipulation and characterization at a small scale.

  7. Optimal model-based sensorless adaptive optics for epifluorescence microscopy. (United States)

    Pozzi, Paolo; Soloviev, Oleg; Wilding, Dean; Vdovin, Gleb; Verhaegen, Michel


    We report on a universal sample-independent sensorless adaptive optics method, based on modal optimization of the second moment of the fluorescence emission from a point-like excitation. Our method employs a sample-independent precalibration, performed only once for the particular system, to establish the direct relation between the image quality and the aberration. The method is potentially applicable to any form of microscopy with epifluorescence detection, including the practically important case of incoherent fluorescence emission from a three dimensional object, through minor hardware modifications. We have applied the technique successfully to a widefield epifluorescence microscope and to a multiaperture confocal microscope.

  8. Example-Based Super-Resolution Fluorescence Microscopy. (United States)

    Jia, Shu; Han, Boran; Kutz, J Nathan


    Capturing biological dynamics with high spatiotemporal resolution demands the advancement in imaging technologies. Super-resolution fluorescence microscopy offers spatial resolution surpassing the diffraction limit to resolve near-molecular-level details. While various strategies have been reported to improve the temporal resolution of super-resolution imaging, all super-resolution techniques are still fundamentally limited by the trade-off associated with the longer image acquisition time that is needed to achieve higher spatial information. Here, we demonstrated an example-based, computational method that aims to obtain super-resolution images using conventional imaging without increasing the imaging time. With a low-resolution image input, the method provides an estimate of its super-resolution image based on an example database that contains super- and low-resolution image pairs of biological structures of interest. The computational imaging of cellular microtubules agrees approximately with the experimental super-resolution STORM results. This new approach may offer potential improvements in temporal resolution for experimental super-resolution fluorescence microscopy and provide a new path for large-data aided biomedical imaging.

  9. Ultramicrosensors based on transition metal hexacyanoferrates for scanning electrochemical microscopy

    Directory of Open Access Journals (Sweden)

    Maria A. Komkova


    Full Text Available We report here a way for improving the stability of ultramicroelectrodes (UME based on hexacyanoferrate-modified metals for the detection of hydrogen peroxide. The most stable sensors were obtained by electrochemical deposition of six layers of hexacyanoferrates (HCF, more specifically, an alternating pattern of three layers of Prussian Blue and three layers of Ni–HCF. The microelectrodes modified with mixed layers were continuously monitored in 1 mM hydrogen peroxide and proved to be stable for more than 5 h under these conditions. The mixed layer microelectrodes exhibited a stability which is five times as high as the stability of conventional Prussian Blue-modified UMEs. The sensitivity of the mixed layer sensor was 0.32 A·M−1·cm−2, and the detection limit was 10 µM. The mixed layer-based UMEs were used as sensors in scanning electrochemical microscopy (SECM experiments for imaging of hydrogen peroxide evolution.

  10. In vivo confocal microscopy in dermatology: from research to clinical application (United States)

    Ulrich, Martina; Lange-Asschenfeldt, Susanne


    Confocal laser scanning microscopy (CLSM) represents an emerging technique for the noninvasive histomorphological analysis of skin in vivo and has shown its applicability for dermatological research as well as its value as an adjunct tool in the clinical management of skin cancer patients. Herein, we aim to give an overview on the current clinical indications for CLSM in dermatology and also highlight the diverse applications of CLSM in dermatological research.

  11. Magnetoelectric force microscopy based on magnetic force microscopy with modulated electric field. (United States)

    Geng, Yanan; Wu, Weida


    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.

  12. Development of Tuning Fork Based Probes for Atomic Force Microscopy (United States)

    Jalilian, Romaneh; Yazdanpanah, Mehdi M.; Torrez, Neil; Alizadeh, Amirali; Askari, Davood


    This article reports on the development of tuning fork-based AFM/STM probes in NaugaNeedles LLC for use in atomic force microscopy. These probes can be mounted on different carriers per customers' request. (e.g., RHK carrier, Omicron carrier, and tuning fork on a Sapphire disk). We are able to design and engineer tuning forks on any type of carrier used in the market. We can attach three types of tips on the edge of a tuning fork prong (i.e., growing Ag2Ga nanoneedles at any arbitrary angle, cantilever of AFM tip, and tungsten wire) with lengths from 100-500 μm. The nanoneedle is located vertical to the fork. Using a suitable insulation and metallic coating, we can make QPlus sensors that can detect tunneling current during the AFM scan. To make Qplus sensors, the entire quartz fork will be coated with an insulating material, before attaching the nanoneedle. Then, the top edge of one prong is coated with a thin layer of conductive metal and the nanoneedle is attached to the fork end of the metal coated prong. The metal coating provides electrical connection to the tip for tunneling current readout and to the electrodes and used to read the QPlus current. Since the amount of mass added to the fork is minimal, the resonance frequency spectrum does not change and still remains around 32.6 KHz and the Q factor is around 1,200 in ambient condition. These probes can enhance the performance of tuning fork based atomic microscopy.

  13. Spectroscopic scanning tunneling microscopy insights into Fe-based superconductors

    International Nuclear Information System (INIS)

    Hoffman, Jennifer E


    In the first three years since the discovery of Fe-based high T c superconductors, scanning tunneling microscopy (STM) and spectroscopy have shed light on three important questions. First, STM has demonstrated the complexity of the pairing symmetry in Fe-based materials. Phase-sensitive quasiparticle interference (QPI) imaging and low temperature spectroscopy have shown that the pairing order parameter varies from nodal to nodeless s± within a single family, FeTe 1-x Se x . Second, STM has imaged C4 → C2 symmetry breaking in the electronic states of both parent and superconducting materials. As a local probe, STM is in a strong position to understand the interactions between these broken symmetry states and superconductivity. Finally, STM has been used to image the vortex state, giving insights into the technical problem of vortex pinning, and the fundamental problem of the competing states introduced when superconductivity is locally quenched by a magnetic field. Here we give a pedagogical introduction to STM and QPI imaging, discuss the specific challenges associated with extracting bulk properties from the study of surfaces, and report on progress made in understanding Fe-based superconductors using STM techniques.

  14. Optimisation-based wavefront sensorless adaptive optics for microscopy

    NARCIS (Netherlands)

    Antonello, J.


    Microscopy is an essential tool for life sciences. Thanks to the development of confocal and multiphoton microscopy, scientists are able to obtain high-resolution 3D views of biological specimens. Nevertheless, spatial variations in the index of refraction within specimens cause aberrations that

  15. Saturated virtual fluorescence emission difference microscopy based on detector array (United States)

    Liu, Shaocong; Sun, Shiyi; Kuang, Cuifang; Ge, Baoliang; Wang, Wensheng; Liu, Xu


    Virtual fluorescence emission difference microscopy (vFED) has been proposed recently to enhance the lateral resolution of confocal microscopy with a detector array, implemented by scanning a doughnut-shaped pattern. Theoretically, the resolution can be enhanced by around 1.3-fold compared with that in confocal microscopy. For further improvement of the resolving ability of vFED, a novel method is presented utilizing fluorescence saturation for super-resolution imaging, which we called saturated virtual fluorescence emission difference microscopy (svFED). With a point detector array, matched solid and hollow point spread functions (PSF) can be obtained by photon reassignment, and the difference results between them can be used to boost the transverse resolution. Results show that the diffraction barrier can be surpassed by at least 34% compared with that in vFED and the resolution is around 2-fold higher than that in confocal microscopy.

  16. Diagnosis of human fascioliasis in Arusha region, northern Tanzania by microscopy and clinical manifestations in patients. (United States)

    Lukambagire, Abdul-Hamid Settenda; Mchaile, Deborah N; Nyindo, Mramba


    Human fascioliasis (HF) is a zoonotic disease that has been identified in many countries worldwide. This report concerns the identification and clinical management of cases of human fascioliasis in the suburbs of Arusha city, northern Tanzania in 2013. Fascioliasis is included among the WHO's Neglected Tropical Diseases as a plant transmitted trematode infection. Human fascioliasis has not been described before in the East Africa region, including Tanzania. Patients presenting at a primary healthcare centre in Arusha Region, northern Tanzania provided fresh stool samples for routine ova and parasite screening (saline and iodine preparations). Subsequent stool samples were preserved in 5 % formalin in saline and subjected to ether sedimentation for examination. Out of 1460 patients, 305 (21 %) were diagnosed positive for fascioliasis based on the demonstration of brownish, oval eggs with inconspicuous opercula in stool. Two distinct egg sizes were identified; large 170-212.5 by 115-150 μm (mean 194.5 by 130.5 μm) and smaller eggs 120-150 by 87.5 - 112.5 μm (mean 138.8 by 101 μm). Clinically, patients presented with fever (39 - 40 °C) and abdominal pain. Some patients had pruritis around the mouth and their lips were swollen. 3 patients were treated and cured with single dose Triclabendazole. The remaining 302 patients were treated with Nitazoxanide and 122 (40 %) were cleared of infection with a single course. Snails of the genus Lymnaea were found in the surroundings. This report serves to remind medical professionals in East Africa that HF is a probable differential diagnosis in patients presenting with similar symptoms. It is possible to diagnose fascioliasis by light microscopy although specific antigen tests are required for confirmation. Human fascioliasis however, has not been described or reported in Tanzania before and begs further investigation.

  17. Inquiry-Based Instruction of Compound Microscopy Using Simulated Paleobiogeography (United States)

    Hodgson, Jay Y. S.; Mateer, Scott C.


    The compound microscope is an important tool in biology, and mastering it requires repetition. Unfortunately, introductory activities for students can be formulaic, and consequently, students are often unengaged and fail to develop the required experience to become proficient in microscopy. To engage students, increase repetition, and develop…

  18. DNA origami-based standards for quantitative fluorescence microscopy. (United States)

    Schmied, Jürgen J; Raab, Mario; Forthmann, Carsten; Pibiri, Enrico; Wünsch, Bettina; Dammeyer, Thorben; Tinnefeld, Philip


    Validating and testing a fluorescence microscope or a microscopy method requires defined samples that can be used as standards. DNA origami is a new tool that provides a framework to place defined numbers of small molecules such as fluorescent dyes or proteins in a programmed geometry with nanometer precision. The flexibility and versatility in the design of DNA origami microscopy standards makes them ideally suited for the broad variety of emerging super-resolution microscopy methods. As DNA origami structures are durable and portable, they can become a universally available specimen to check the everyday functionality of a microscope. The standards are immobilized on a glass slide, and they can be imaged without further preparation and can be stored for up to 6 months. We describe a detailed protocol for the design, production and use of DNA origami microscopy standards, and we introduce a DNA origami rectangle, bundles and a nanopillar as fluorescent nanoscopic rulers. The protocol provides procedures for the design and realization of fluorescent marks on DNA origami structures, their production and purification, quality control, handling, immobilization, measurement and data analysis. The procedure can be completed in 1-2 d.

  19. Evidence-based clinical practice

    DEFF Research Database (Denmark)

    Gluud, Christian


    , and single clinics. Accordingly, there is an urgent need to improve this situation. Guidelines for Good Clinical (Research) Practice, conduct of more trials as multicentre trials, The Consort Statement, and The Cochrane Collaboration may all help in the application of the best research evidence in clinical......Evidence-based medicine combines the patient's preferences with clinical experience and the best research evidence. Randomized clinical trials are considered the most valid research design for evaluating health-care interventions. However, empirical research shows that intervention effects may...... practice. By investments in education, applied research, and The Cochrane Collaboration, evidence-based medicine may form a stronger basis for clinical practice....

  20. Cytology 3D structure formation based on optical microscopy images (United States)

    Pronichev, A. N.; Polyakov, E. V.; Shabalova, I. P.; Djangirova, T. V.; Zaitsev, S. M.


    The article the article is devoted to optimization of the parameters of imaging of biological preparations in optical microscopy using a multispectral camera in visible range of electromagnetic radiation. A model for the image forming of virtual preparations was proposed. The optimum number of layers was determined for the object scan in depth and holistic perception of its switching according to the results of the experiment.

  1. Cytology 3D structure formation based on optical microscopy images

    International Nuclear Information System (INIS)

    Pronichev, A N; Polyakov, E V; Zaitsev, S M; Shabalova, I P; Djangirova, T V


    The article the article is devoted to optimization of the parameters of imaging of biological preparations in optical microscopy using a multispectral camera in visible range of electromagnetic radiation. A model for the image forming of virtual preparations was proposed. The optimum number of layers was determined for the object scan in depth and holistic perception of its switching according to the results of the experiment. (paper)

  2. X-ray diffraction microscopy based on refractive optics

    DEFF Research Database (Denmark)

    Poulsen, Henning Friis; Jakobsen, A. C.; Simons, Hugh


    A formalism is presented for dark‐field X‐ray microscopy using refractive optics. The new technique can produce three‐dimensional maps of lattice orientation and axial strain within millimetre‐sized sampling volumes and is particularly suited to in situ studies of materials at hard X‐ray energies....... An objective lens in the diffracted beam magnifies the image and acts as a very efficient filter in reciprocal space, enabling the imaging of individual domains of interest with a resolution of 100 nm. Analytical expressions for optical parameters such as numerical aperture, vignetting, and the resolution...

  3. Evidence-based clinical practice

    DEFF Research Database (Denmark)

    Garattini, Silvio; Jakobsen, Janus C; Wetterslev, Jørn


    was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading...

  4. Auditing the use and assessing the clinical utility of microscopy as a point-of-care test for Neisseria gonorrhoeae in a Sexual Health clinic. (United States)

    Mensforth, Sarah; Thorley, Nicola; Radcliffe, Keith


    We assessed whether urethral microscopy was performed as per clinic protocol for male clinic attendees reporting contact with Neisseria gonorrhoeae (GC), urethral symptoms or given a diagnosis of epididymo-orchitis (EO) over a 12-month period (9732 patients). Prevalence of gonorrhoea in the contacts, urethral symptoms and EO groups was 50, 12.7 and 1.6%, respectively. Microscopy was performed reliably for contacts (96%), those with discharge/dysuria with evidence of urethritis on examination (98%), but not those with EO (43%). We explored the clinical utility of microscopy as a point-of-care test for identifying urethral GC in each subgroup, using the APTIMA Combo 2 CT/GC nucleic acid amplification test as the comparator (1710 patients). Sensitivity of microscopy for each subgroup was good; there was no statistical difference between subgroup sensitivity using Fisher's exact test. Microscopy is valuable to ensure prompt diagnosis and contact tracing. All GC contacts were treated 'epidemiologically'; however, half of GC contacts did not have GC. Microscopy identified the majority of GC cases, including amongst contacts (71% of heterosexual contacts, 66% of contacts reporting sex with men). We propose that epidemiological treatment for GC contacts should be reconsidered on the grounds of antibiotic stewardship, favouring use of microscopy to guide treatment decisions.


    Background: All slide-based fluorescence cytometry detections systems basically include an excitation light source, intermediate optics, and a detection device (CCD or PMT). Occasionally, this equipment becomes unstable, generating unreliable and inferior data. Methods: A num...

  6. Four-hour processing of clinical/diagnostic specimens for electron microscopy using microwave technique. (United States)

    Giberson, R T; Demaree, R S; Nordhausen, R W


    A protocol for routine 4-hour microwave tissue processing of clinical or other samples for electron microscopy was developed. Specimens are processed by using a temperature-restrictive probe that can be set to automatically cycle the magnetron to maintain any designated temperature restriction (temperature maximum). In addition, specimen processing during fixation is performed in 1.7-ml microcentrifuge tubes followed by subsequent processing in flow-through baskets. Quality control is made possible during each step through the addition of an RS232 port to the microwave, allowing direct connection of the microwave oven to any personal computer. The software provided with the temperature probe enables the user to monitor time and temperature on a real-time basis. Tissue specimens, goat placenta, mouse liver, mouse kidney, and deer esophagus were processed by conventional and microwave techniques in this study. In all instances, the results for the microwave-processed samples were equal to or better than those achieved by routine processing techniques.

  7. Silicon Nano fabrication by Atomic Force Microscopy-Based Mechanical Processing

    International Nuclear Information System (INIS)

    Miyake, Sh.; Wang, M.; Kim, J.


    This paper reviews silicon nano fabrication processes using atomic force microscopy (AFM). In particular, it summarizes recent results obtained in our research group regarding AFM-based silicon nano fabrication through mechanochemical local oxidation by diamond tip sliding, as well as mechanical, electrical, and electromechanical processing using an electrically conductive diamond tip. Microscopic three-dimensional manufacturing mainly relies on etching, deposition, and lithography. Therefore, a special emphasis was placed on nano mechanical processes, mechanochemical reaction by potassium hydroxide solution etching, and mechanical and electrical approaches. Several important surface characterization techniques consisting of scanning tunneling microscopy and related techniques, such as scanning probe microscopy and AFM, were also discussed.

  8. Pupil-segmentation-based adaptive optics for microscopy (United States)

    Ji, Na; Milkie, Daniel E.; Betzig, Eric


    Inhomogeneous optical properties of biological samples make it difficult to obtain diffraction-limited resolution in depth. Correcting the sample-induced optical aberrations needs adaptive optics (AO). However, the direct wavefront-sensing approach commonly used in astronomy is not suitable for most biological samples due to their strong scattering of light. We developed an image-based AO approach that is insensitive to sample scattering. By comparing images of the sample taken with different segments of the pupil illuminated, local tilt in the wavefront is measured from image shift. The aberrated wavefront is then obtained either by measuring the local phase directly using interference or with phase reconstruction algorithms similar to those used in astronomical AO. We implemented this pupil-segmentation-based approach in a two-photon fluorescence microscope and demonstrated that diffraction-limited resolution can be recovered from nonbiological and biological samples.

  9. All-optical optoacoustic microscopy based on probe beam deflection technique


    Maswadi, Saher M.; Ibey, Bennett L.; Roth, Caleb C.; Tsyboulski, Dmitri A.; Beier, Hope T.; Glickman, Randolph D.; Oraevsky, Alexander A.


    Optoacoustic (OA) microscopy using an all-optical system based on the probe beam deflection technique (PBDT) for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i) efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii) undistorted coupling of acoustic waves to the detector without the need for separa...

  10. Opto-fluidics based microscopy and flow cytometry on a cell phone for blood analysis. (United States)

    Zhu, Hongying; Ozcan, Aydogan


    Blood analysis is one of the most important clinical tests for medical diagnosis. Flow cytometry and optical microscopy are widely used techniques to perform blood analysis and therefore cost-effective translation of these technologies to resource limited settings is critical for various global health as well as telemedicine applications. In this chapter, we review our recent progress on the integration of imaging flow cytometry and fluorescent microscopy on a cell phone using compact, light-weight and cost-effective opto-fluidic attachments integrated onto the camera module of a smartphone. In our cell-phone based opto-fluidic imaging cytometry design, fluorescently labeled cells are delivered into the imaging area using a disposable micro-fluidic chip that is positioned above the existing camera unit of the cell phone. Battery powered light-emitting diodes (LEDs) are butt-coupled to the sides of this micro-fluidic chip without any lenses, which effectively acts as a multimode slab waveguide, where the excitation light is guided to excite the fluorescent targets within the micro-fluidic chip. Since the excitation light propagates perpendicular to the detection path, an inexpensive plastic absorption filter is able to reject most of the scattered light and create a decent dark-field background for fluorescent imaging. With this excitation geometry, the cell-phone camera can record fluorescent movies of the particles/cells as they are flowing through the microchannel. The digital frames of these fluorescent movies are then rapidly processed to quantify the count and the density of the labeled particles/cells within the solution under test. With a similar opto-fluidic design, we have recently demonstrated imaging and automated counting of stationary blood cells (e.g., labeled white blood cells or unlabeled red blood cells) loaded within a disposable cell counting chamber. We tested the performance of this cell-phone based imaging cytometry and blood analysis platform

  11. Research and application on imaging technology of line structure light based on confocal microscopy (United States)

    Han, Wenfeng; Xiao, Zexin; Wang, Xiaofen


    In 2005, the theory of line structure light confocal microscopy was put forward firstly in China by Xingyu Gao and Zexin Xiao in the Institute of Opt-mechatronics of Guilin University of Electronic Technology. Though the lateral resolution of line confocal microscopy can only reach or approach the level of the traditional dot confocal microscopy. But compared with traditional dot confocal microscopy, it has two advantages: first, by substituting line scanning for dot scanning, plane imaging only performs one-dimensional scanning, with imaging velocity greatly improved and scanning mechanism simplified, second, transfer quantity of light is greatly improved by substituting detection hairline for detection pinhole, and low illumination CCD is used directly to collect images instead of photoelectric intensifier. In order to apply the line confocal microscopy to practical system, based on the further research on the theory of the line confocal microscopy, imaging technology of line structure light is put forward on condition of implementation of confocal microscopy. Its validity and reliability are also verified by experiments.

  12. Near-field scanning optical microscopy based nanostructuring of glass

    International Nuclear Information System (INIS)

    Chimmalgi, A; Hwang, D J; Grigoropoulos, C P


    Nanofabrication, at lateral resolutions beyond the capability of conventional optical lithography techniques, is demonstrated here. Femtosecond laser was used in conjunction with Near-field Scanning Optical Microscopes (NSOMs) to nanostructure thin metal films. Also, the possibility of using these nanostructured metal films as masks to effectively transfer the pattern to the underlying substrate by wet etching process is shown. Two different optical nearfiled processing schemes were studied for near-field nanostructuring. In the first scheme, local field enhancement in the near-field of a scanning probe microscope (SPM) probe tip irradiated with femtosecond laser pulses was utilized (apertureless NSOM mode) and as a second approach, femtosecond laser beam was spatially confined by cantilevered NSOM fiber tip (apertured NOSM mode). The minimized heat- and shock-affected areas introduced during ultrafast laser based machining process, allows processing of even high conductivity thin metal films with minimized formation of any interfacial compounds between the metal films and the underlying substrate. Potential applications of this method may be in the fields of nanolithography, nanofluidics, nanoscale chemical and gas sensors, high-density data storage, nano-opto-electronics, as well as biotechnology related applications

  13. Atomic force microscopy and scanning electron microscopy evaluation of efficacy of scaling and root planing using magnification: A randomized controlled clinical study

    Directory of Open Access Journals (Sweden)

    Ranjana Mohan


    Full Text Available Aim: A randomized controlled clinical study was undertaken to evaluate the effectiveness of scaling and root planing (SRP by using Magnifying Loupes (ML and dental operating microscope (DOM. Materials and Methods: A total of 90 human teeth scheduled for extraction from 18 patients aged between 25 and 65 years suffering from generalized chronic severe periodontitis were randomly assigned to three treatment groups. Group 1 consisted SRP performed without using magnification (unaided, Group 2-SRP with ML and Group 3-SRP with DOM. Following extractions, samples were prepared for (i evaluation of surface topography by atomic force microscopy, (ii presence of smear layer, debris by scanning electron microscopy (iii elemental analysis by energy dispersive X-ray analysis. Data was subjected to statistical analysis using analysis of variance, post-hoc (Tukey-HSD and Chi-square test. Results: Statistically significant (P < 0.001 difference was found among the different treatment groups. Group 3 was the best while Group 1 was the least effective technique for SRP. Order of efficacy in terms of the surface was found to be - Palatal < Lingual < Distal ≅ Mesial < Buccal. Efficiency in mandibular to maxillary teeth was found to be significant (P < 0.05, also anterior to posterior teeth (P < 0.05. Conclusion: Magnification tools significantly enhance the efficacy of supragingival and subgingival SRP.

  14. Field-based dynamic light scattering microscopy: theory and numerical analysis. (United States)

    Joo, Chulmin; de Boer, Johannes F


    We present a theoretical framework for field-based dynamic light scattering microscopy based on a spectral-domain optical coherence phase microscopy (SD-OCPM) platform. SD-OCPM is an interferometric microscope capable of quantitative measurement of amplitude and phase of scattered light with high phase stability. Field-based dynamic light scattering (F-DLS) analysis allows for direct evaluation of complex-valued field autocorrelation function and measurement of localized diffusive and directional dynamic properties of biological and material samples with high spatial resolution. In order to gain insight into the information provided by F-DLS microscopy, theoretical and numerical analyses are performed to evaluate the effect of numerical aperture of the imaging optics. We demonstrate that sharp focusing of fields affects the measured diffusive and transport velocity, which leads to smaller values for the dynamic properties in the sample. An approach for accurately determining the dynamic properties of the samples is discussed.

  15. Scanning electron microscopy and transmission electron microscopy study of hot-deformed gamma-TiAl-based alloy microstructure. (United States)

    Chrapoński, J; Rodak, K


    The aim of this work was to assess the changes in the microstructure of hot-deformed specimens made of alloys containing 46-50 at.% Al, 2 at.% Cr and 2 at.% Nb (and alloying additions such as carbon and boron) with the aid of scanning electron microscopy and transmission electron microscopy techniques. After homogenization and heat treatment performed in order to make diverse lamellae thickness, the specimens were compressed at 1000 degrees C. Transmission electron microscopy examinations of specimens after the compression test revealed the presence of heavily deformed areas with a high density of dislocation. Deformation twins were also observed. Dynamically recrystallized grains were revealed. For alloys no. 2 and no. 3, the recovery and recrystallization processes were more extensive than for alloy no. 1.

  16. Atomic force microscopy imaging to measure precipitate volume fraction in nickel-based superalloys

    International Nuclear Information System (INIS)

    Bourhettar, A.; Troyon, M.; Hazotte, A.


    In nickel-based superalloys, quantitative analysis of scanning electron microscopy images fails in providing accurate microstructural data, whereas more efficient techniques are very time-consuming. As an alternative approach, the authors propose to perform quantitative analysis of atomic force microscopy images of polished/etched surfaces (quantitative microprofilometry). This permits the measurement of microstructural parameters and the depth of etching, which is the main source of measurement bias. Thus, nonbiased estimations can be obtained by extrapolation of the measurements up to zero etching depth. In this article, the authors used this approach to estimate the volume fraction of γ' precipitates in a nickel-based superalloy single crystal. Atomic force microscopy images of samples etched for different times show definition, homogeneity, and contrast high enough to perform image analysis. The result after extrapolation is in very good agreement with volume fraction values available from published reports

  17. Identifying Two Common Types of Breast Benign Diseases Based on Multiphoton Microscopy

    Directory of Open Access Journals (Sweden)

    Yan Wu


    Full Text Available Multiphoton microscopy has attracted increasing attention and investigations in the field of breast cancer, based on two-photon excited fluorescence (TPEF and second-harmonic generation (SHG. However, the incidence of breast benign diseases is about 5 to 10 times higher than breast cancer; up to 30% of women suffer from breast benign diseases and require treatment at some time in their lives. Thus, in this study, MPM was applied to image fibroadenoma and fibrocystic lesion, which are two of the most common breast benign diseases. The results show that MPM has the capability to identify the microstructure of lobule and stroma in normal breast tissue, the interaction of compressed ducts with surrounding collagen fiber in fibroadenoma, and the architecture of cysts filled with cystic fluid in fibrocystic disease. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time diagnosis of breast benign diseases in vivo, as well as breast cancer.

  18. Teaching pathology via online digital microscopy: positive learning outcomes for rurally based medical students. (United States)

    Sivamalai, Sundram; Murthy, Shashidhar Venkatesh; Gupta, Tarun Sen; Woolley, Torres


    Technology has revolutionised teaching. Teaching pathology via digital microscopy (DM) is needed to overcome increasing student numbers, a shortage of pathology academics in regional medical schools, and difficulties with teaching students on rural clinical placement. To identify whether an online DM approach, combining digital pathology software, Web-based slides and classroom management software, delivers effective, practical pathology teaching sessions to medical students located both on campus and on rural placement. An online survey collected feedback from fourth and fifth year undergraduate James Cook University medical students on the importance of 16 listed benefits and challenges of using online DM to teach pathology, via a structured five-point Likert survey. Fifty-three students returned the survey (response rate = 33%). Benefits of online DM to teach pathology rated as 'very important' or 'extremely important' by over 50% of students included: higher quality images; faster learning; more convenient; better technology; everyone sees the same image; greater accessibility; helpful annotations on slides; cost savings; and more opportunity for self-paced learning out-of-hours and for collaborative learning in class. Challenges of online DM rated as 'very important' or 'extremely important' by over 50% of students included: Internet availability in more remote locations and potential problems using online technology during class. Nearly all medical students welcomed learning pathology via online digital technology. DM should improve the quantity, quality, cost and accessibility of pathology teaching by regional medical schools, and has significant implications for the growing emphasis in Australia for decentralised medical education and rural clinical placements. © 2011 The Authors. Australian Journal of Rural Health © National Rural Health Alliance Inc.

  19. The Electron Microscopy Outreach Program: A Web-based resource for research and education. (United States)

    Sosinsky, G E; Baker, T S; Hand, G; Ellisman, M H


    We have developed a centralized World Wide Web (WWW)-based environment that serves as a resource of software tools and expertise for biological electron microscopy. A major focus is molecular electron microscopy, but the site also includes information and links on structural biology at all levels of resolution. This site serves to help integrate or link structural biology techniques in accordance with user needs. The WWW site, called the Electron Microscopy (EM) Outreach Program (URL:, provides scientists with computational and educational tools for their research and edification. In particular, we have set up a centralized resource containing course notes, references, and links to image analysis and three-dimensional reconstruction software for investigators wanting to learn about EM techniques either within or outside of their fields of expertise. Copyright 1999 Academic Press.

  20. Numerical tilting compensation in microscopy based on wavefront sensing using transport of intensity equation method (United States)

    Hu, Junbao; Meng, Xin; Wei, Qi; Kong, Yan; Jiang, Zhilong; Xue, Liang; Liu, Fei; Liu, Cheng; Wang, Shouyu


    Wide-field microscopy is commonly used for sample observations in biological research and medical diagnosis. However, the tilting error induced by the oblique location of the image recorder or the sample, as well as the inclination of the optical path often deteriorates the imaging quality. In order to eliminate the tilting in microscopy, a numerical tilting compensation technique based on wavefront sensing using transport of intensity equation method is proposed in this paper. Both the provided numerical simulations and practical experiments prove that the proposed technique not only accurately determines the tilting angle with simple setup and procedures, but also compensates the tilting error for imaging quality improvement even in the large tilting cases. Considering its simple systems and operations, as well as image quality improvement capability, it is believed the proposed method can be applied for tilting compensation in the optical microscopy.

  1. Emulation and design of terahertz reflection-mode confocal scanning microscopy based on virtual pinhole (United States)

    Yang, Yong-fa; Li, Qi


    In the practical application of terahertz reflection-mode confocal scanning microscopy, the size of detector pinhole is an important factor that determines the performance of spatial resolution characteristic of the microscopic system. However, the use of physical pinhole brings some inconvenience to the experiment and the adjustment error has a great influence on the experiment result. Through reasonably selecting the parameter of matrix detector virtual pinhole (VPH), it can efficiently approximate the physical pinhole. By using this approach, the difficulty of experimental calibration is reduced significantly. In this article, an imaging scheme of terahertz reflection-mode confocal scanning microscopy that is based on the matrix detector VPH is put forward. The influence of detector pinhole size on the axial resolution of confocal scanning microscopy is emulated and analyzed. Then, the parameter of VPH is emulated when the best axial imaging performance is reached.

  2. Line-scanning confocal microscopy for high-resolution imaging of upconverting rare-earth-based contrast agents (United States)

    Higgins, Laura M.; Zevon, Margot; Ganapathy, Vidya; Sheng, Yang; Tan, Mei Chee; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.


    Abstract. Rare-earth (RE) doped nanocomposites emit visible luminescence when illuminated with continuous wave near-infrared light, making them appealing candidates for use as contrast agents in biomedical imaging. However, the emission lifetime of these materials is much longer than the pixel dwell times used in scanning intravital microscopy. To overcome this limitation, we have developed a line-scanning confocal microscope for high-resolution, optically sectioned imaging of samples labeled with RE-based nanomaterials. Instrument performance is quantified using calibrated test objects. NaYF4:Er,Yb nanocomposites are imaged in vitro, and in ex vivo tissue specimens, with direct comparison to point-scanning confocal microscopy. We demonstrate that the extended pixel dwell time of line-scanning confocal microscopy enables subcellular-level imaging of these nanomaterials while maintaining optical sectioning. The line-scanning approach thus enables microscopic imaging of this emerging class of contrast agents for preclinical studies, with the potential to be adapted for real-time in vivo imaging in the clinic. PMID:26603495

  3. Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy. (United States)

    Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir


    Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them.

  4. Clinical applications of scanning electron microscopy and energy dispersive X-ray analysis in dermatology--an up-date

    International Nuclear Information System (INIS)

    Forslind, B.


    Dermatological papers comprising scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis data published 1983 through 1986 in international journals are reviewed, as an update to our 1984 paper on Clinical applications of scanning electron microscopy and X-ray microanalysis in dermatology. The present paper not only deals with a review of recent publications in this area but also presents the application of microincineration to hair and cryosectioned freeze-dried skin specimens. Examples of the increased contrast obtained in hair cross sections are presented and a discussion on the feasibility of microincineration at analysis of hair and skin cross sections is given. Particle probe analysis (EDX: energy dispersive X-ray analysis and PMP: proton microprobe analysis) as applied to hair and skin samples are presented with stress put on the proton probe analysis. The complementarity of EDX and PMP is demonstrated and future applications are suggested. 75 references

  5. Reducing microscopy-based malaria misdiagnosis in a low-resource area of Tanzania. (United States)

    Allen, Lisa K; Hatfield, Jennifer M; Manyama, Mange


    Misdiagnosis of malaria is a major problem in Africa leading not only to incorrect individual level treatment, but potentially the acceleration of the spread of drug resistance in low-transmission areas. In this paper we report on the outcomes of a simple intervention that utilized a social entrepreneurship approach (SEA) to reduce misdiagnosis associated with hospital-based microscopy of malaria in a low-transmission area of rural Tanzania. A pre-post assessment was conducted on patients presenting to the hospital outpatient department with malaria and non-malaria like symptoms in January 2009 (pre-intervention) and June 2009 (post-intervention). All participants were asked a health seeking behavior questionnaire and blood samples were taken for local and quality control microscopy. Multivariate logistic regression was conducted to determine magnitude of misdiagnosis with local microscopy pre- versus- post intervention. Local microscopy pre-intervention specificity was 29.5% (95% CI = 21.6% - 38.4%) whereas the post intervention specificity was 68.6% (95% CI = 60.2% - 76.2%). Both pre and post intervention sensitivity were difficult to determine due to an unexpected low number of true positive cases. The proportion of participants misdiagnosed pre-intervention was 70.2% (95%CI = 61.3%-78.0%) as compared to 30.6% (95%CI = 23.2%-38.8%) post-intervention. This resulted in a 39.6% reduction in misdiagnosis of malaria at the local hospital. The magnitude of misdiagnosis for the pre-intervention participants was 5.3 (95%CI = 3.1-9.3) that of the post-intervention participants. In conclusion, this study provides evidence that a simple intervention can meaningfully reduce the magnitude of microscopy-based misdiagnosis of malaria for those individuals seeking treatment for uncomplicated malaria. We anticipate that this intervention will facilitate a valuable and sustainable change in malaria diagnosis at the local hospital.

  6. DMD-based LED-illumination super-resolution and optical sectioning microscopy. (United States)

    Dan, Dan; Lei, Ming; Yao, Baoli; Wang, Wen; Winterhalder, Martin; Zumbusch, Andreas; Qi, Yujiao; Xia, Liang; Yan, Shaohui; Yang, Yanlong; Gao, Peng; Ye, Tong; Zhao, Wei


    Super-resolution three-dimensional (3D) optical microscopy has incomparable advantages over other high-resolution microscopic technologies, such as electron microscopy and atomic force microscopy, in the study of biological molecules, pathways and events in live cells and tissues. We present a novel approach of structured illumination microscopy (SIM) by using a digital micromirror device (DMD) for fringe projection and a low-coherence LED light for illumination. The lateral resolution of 90 nm and the optical sectioning depth of 120 μm were achieved. The maximum acquisition speed for 3D imaging in the optical sectioning mode was 1.6×10(7) pixels/second, which was mainly limited by the sensitivity and speed of the CCD camera. In contrast to other SIM techniques, the DMD-based LED-illumination SIM is cost-effective, ease of multi-wavelength switchable and speckle-noise-free. The 2D super-resolution and 3D optical sectioning modalities can be easily switched and applied to either fluorescent or non-fluorescent specimens.

  7. Nanoparticle discrimination based on wavelength and lifetime-multiplexed cathodoluminescence microscopy. (United States)

    Garming, Mathijs W H; Weppelman, I Gerward C; de Boer, Pascal; Martínez, Felipe Perona; Schirhagl, Romana; Hoogenboom, Jacob P; Moerland, Robert J


    Nanomaterials can be identified in high-resolution electron microscopy images using spectrally-selective cathodoluminescence. Capabilities for multiplex detection can however be limited, e.g., due to spectral overlap or availability of filters. Also, the available photon flux may be limited due to degradation under electron irradiation. Here, we demonstrate single-pass cathodoluminescence-lifetime based discrimination of different nanoparticles, using a pulsed electron beam. We also show that cathodoluminescence lifetime is a robust parameter even when the nanoparticle cathodoluminescence intensity decays over an order of magnitude. We create lifetime maps, where the lifetime of the cathodoluminescence emission is correlated with the emission intensity and secondary-electron images. The consistency of lifetime-based discrimination is verified by also correlating the emission wavelength and the lifetime of nanoparticles. Our results show how cathodoluminescence lifetime provides an additional channel of information in electron microscopy.

  8. Solid-state nuclear-spin quantum computer based on magnetic resonance force microscopy

    International Nuclear Information System (INIS)

    Berman, G. P.; Doolen, G. D.; Hammel, P. C.; Tsifrinovich, V. I.


    We propose a nuclear-spin quantum computer based on magnetic resonance force microscopy (MRFM). It is shown that an MRFM single-electron spin measurement provides three essential requirements for quantum computation in solids: (a) preparation of the ground state, (b) one- and two-qubit quantum logic gates, and (c) a measurement of the final state. The proposed quantum computer can operate at temperatures up to 1 K. (c) 2000 The American Physical Society

  9. Segmentation-based retrospective shading correction in fluorescence microscopy E. coli images for quantitative analysis (United States)

    Mai, Fei; Chang, Chunqi; Liu, Wenqing; Xu, Weichao; Hung, Yeung S.


    Due to the inherent imperfections in the imaging process, fluorescence microscopy images often suffer from spurious intensity variations, which is usually referred to as intensity inhomogeneity, intensity non uniformity, shading or bias field. In this paper, a retrospective shading correction method for fluorescence microscopy Escherichia coli (E. Coli) images is proposed based on segmentation result. Segmentation and shading correction are coupled together, so we iteratively correct the shading effects based on segmentation result and refine the segmentation by segmenting the image after shading correction. A fluorescence microscopy E. Coli image can be segmented (based on its intensity value) into two classes: the background and the cells, where the intensity variation within each class is close to zero if there is no shading. Therefore, we make use of this characteristics to correct the shading in each iteration. Shading is mathematically modeled as a multiplicative component and an additive noise component. The additive component is removed by a denoising process, and the multiplicative component is estimated using a fast algorithm to minimize the intra-class intensity variation. We tested our method on synthetic images and real fluorescence E.coli images. It works well not only for visual inspection, but also for numerical evaluation. Our proposed method should be useful for further quantitative analysis especially for protein expression value comparison.

  10. Liquid crystalthermography as compared to X-ray diagnostics, clinical findings and capillary microscopy in sclerodermia progressiva

    International Nuclear Information System (INIS)

    Loreck, D.; Buehler, G.; Brenke, A.; Schmidt, P.; Heerdegen, I.; Huege, H.


    The hands of 55 patients suffering from progressive sclerodermia were examined by liquid crystal thermography. The findings were compared with those of X-ray diagnosis and with clinical results. In 20 patients also capillary microscopy was applied. All patients revealed hypothermias in the fingers, independent from X-ray results, duration of the disease and Raynaud's phenomenon. Hypothermia could involve all fingers and was localized proximally or distally. In most of the patients also hyperthermias, not to be cooled, were found. They were diarthrodial and vasal, respectively

  11. Clinical applications of scanning electron microscopy and X-ray microanalysis in dermatology

    Energy Technology Data Exchange (ETDEWEB)

    Forslind, B.


    Scanning electron microscopy is frequently applied to dermatological problems, as is evident from a review of the recent literature. In this paper, preparation methods and new techniques allowing experimental studies on the integumentary system are emphasized. Quantitative analysis in the electron microscope by use of energy-dispersive X-ray microanalysis (EDX) has become an important accessory technique. EDX can, for instance, be used to study problems involving physiological changes induced in skin by agents causing contact reactions. Recently, it has been shown that treatment with DNCB, chromate and nickel causes changes in elemental distribution in guinea-pig skin. In addition, elemental uptake in the integumentary system and in pathological inclusions in skin can be analyzed.

  12. Clinical applications of scanning electron microscopy and X-ray microanalysis in dermatology

    International Nuclear Information System (INIS)

    Forslind, B.


    Scanning electron microscopy is frequently applied to dermatological problems, as is evident from a review of the recent literature. In this paper, preparation methods and new techniques allowing experimental studies on the integumentary system are emphasized. Quantitative analysis in the electron microscope by use of energy-dispersive X-ray microanalysis (EDX) has become an important accessory technique. EDX can, for instance, be used to study problems involving physiological changes induced in skin by agents causing contact reactions. Recently, it has been shown that treatment with DNCB, chromate and nickel causes changes in elemental distribution in guinea-pig skin. In addition, elemental uptake in the integumentary system and in pathological inclusions in skin can be analyzed

  13. High-spatial-resolution sub-surface imaging using a laser-based acoustic microscopy technique. (United States)

    Balogun, Oluwaseyi; Cole, Garrett D; Huber, Robert; Chinn, Diane; Murray, Todd W; Spicer, James B


    Scanning acoustic microscopy techniques operating at frequencies in the gigahertz range are suitable for the elastic characterization and interior imaging of solid media with micrometer-scale spatial resolution. Acoustic wave propagation at these frequencies is strongly limited by energy losses, particularly from attenuation in the coupling media used to transmit ultrasound to a specimen, leading to a decrease in the depth in a specimen that can be interrogated. In this work, a laser-based acoustic microscopy technique is presented that uses a pulsed laser source for the generation of broadband acoustic waves and an optical interferometer for detection. The use of a 900-ps microchip pulsed laser facilitates the generation of acoustic waves with frequencies extending up to 1 GHz which allows for the resolution of micrometer-scale features in a specimen. Furthermore, the combination of optical generation and detection approaches eliminates the use of an ultrasonic coupling medium, and allows for elastic characterization and interior imaging at penetration depths on the order of several hundred micrometers. Experimental results illustrating the use of the laser-based acoustic microscopy technique for imaging micrometer-scale subsurface geometrical features in a 70-μm-thick single-crystal silicon wafer with a (100) orientation are presented.

  14. Modelling high-resolution electron microscopy based on core-loss spectroscopy

    International Nuclear Information System (INIS)

    Allen, L.J.; Findlay, S.D.; Oxley, M.P.; Witte, C.; Zaluzec, N.J.


    There are a number of factors affecting the formation of images based on core-loss spectroscopy in high-resolution electron microscopy. We demonstrate unambiguously the need to use a full nonlocal description of the effective core-loss interaction for experimental results obtained from high angular resolution electron channelling electron spectroscopy. The implications of this model are investigated for atomic resolution scanning transmission electron microscopy. Simulations are used to demonstrate that core-loss spectroscopy images formed using fine probes proposed for future microscopes can result in images that do not correspond visually with the structure that has led to their formation. In this context, we also examine the effect of varying detector geometries. The importance of the contribution to core-loss spectroscopy images by dechannelled or diffusely scattered electrons is reiterated here

  15. VEDA: a web-based virtual environment for dynamic atomic force microscopy. (United States)

    Melcher, John; Hu, Shuiqing; Raman, Arvind


    We describe here the theory and applications of virtual environment dynamic atomic force microscopy (VEDA), a suite of state-of-the-art simulation tools deployed on nanoHUB ( for the accurate simulation of tip motion in dynamic atomic force microscopy (dAFM) over organic and inorganic samples. VEDA takes advantage of nanoHUB's cyberinfrastructure to run high-fidelity dAFM tip dynamics computations on local clusters and the teragrid. Consequently, these tools are freely accessible and the dAFM simulations are run using standard web-based browsers without requiring additional software. A wide range of issues in dAFM ranging from optimal probe choice, probe stability, and tip-sample interaction forces, power dissipation, to material property extraction and scanning dynamics over hetereogeneous samples can be addressed.

  16. Invited Article: VEDA: A web-based virtual environment for dynamic atomic force microscopy (United States)

    Melcher, John; Hu, Shuiqing; Raman, Arvind


    We describe here the theory and applications of virtual environment dynamic atomic force microscopy (VEDA), a suite of state-of-the-art simulation tools deployed on nanoHUB ( for the accurate simulation of tip motion in dynamic atomic force microscopy (dAFM) over organic and inorganic samples. VEDA takes advantage of nanoHUB's cyberinfrastructure to run high-fidelity dAFM tip dynamics computations on local clusters and the teragrid. Consequently, these tools are freely accessible and the dAFM simulations are run using standard web-based browsers without requiring additional software. A wide range of issues in dAFM ranging from optimal probe choice, probe stability, and tip-sample interaction forces, power dissipation, to material property extraction and scanning dynamics over hetereogeneous samples can be addressed.

  17. Atomic Force Microscopy Based Nanorobotics Modelling, Simulation, Setup Building and Experiments

    CERN Document Server

    Xie, Hui; Régnier, Stéphane; Sitti, Metin


    The atomic force microscope (AFM) has been successfully used to perform nanorobotic manipulation operations on nanoscale entities such as particles, nanotubes, nanowires, nanocrystals, and DNA since 1990s. There have been many progress on modeling, imaging, teleoperated or automated control, human-machine interfacing, instrumentation, and applications of AFM based nanorobotic manipulation systems in literature. This book aims to include all of such state-of-the-art progress in an organized, structured, and detailed manner as a reference book and also potentially a textbook in nanorobotics and any other nanoscale dynamics, systems and controls related research and education. Clearly written and well-organized, this text introduces designs and prototypes of the nanorobotic systems in detail with innovative principles of three-dimensional manipulation force microscopy and parallel imaging/manipulation force microscopy.

  18. Parallel detecting super-resolution microscopy using correlation based image restoration (United States)

    Yu, Zhongzhi; Liu, Shaocong; Zhu, Dazhao; Kuang, Cuifang; Liu, Xu


    A novel approach to achieve the image restoration is proposed in which each detector's relative position in the detector array is no longer a necessity. We can identify each detector's relative location by extracting a certain area from one of the detector's image and scanning it on other detectors' images. According to this location, we can generate the point spread functions (PSF) for each detector and perform deconvolution for image restoration. Equipped with this method, the microscope with discretionally designed detector array can be easily constructed without the concern of exact relative locations of detectors. The simulated results and experimental results show the total improvement in resolution with a factor of 1.7 compared to conventional confocal fluorescence microscopy. With the significant enhancement in resolution and easiness for application of this method, this novel method should have potential for a wide range of application in fluorescence microscopy based on parallel detecting.

  19. New directions in point-contact spectroscopy based on scanning tunneling microscopy techniques (Review Article)

    International Nuclear Information System (INIS)

    Tartaglini, E.; Verhagen, T.G.A.; Galli, F.; Trouwborst, M.L.; Aarts, J.; Van-Ruitebbeek, J.M.; Muller, R.; Shiota, T.


    Igor Yanson showed 38 years ago for the first time a point-contact measurement where he probed the energy resolved spectroscopy of the electronic scattering inside the metal. Since this first measurement, the pointcontact spectroscopy (PCS) technique improved enormously. The application of the scanning probe microscopy (SPM) techniques in the late 1980s allowed achieving contacts with a diameter of a single atom. With the introduction of the mechanically controlled break junction technique, even spectroscopy on freely suspended chains of atoms could be performed. In this paper, we briefly review the current developments of PCS and show recent experiments in advanced scanning PCS based on SPM techniques. We describe some results obtained with both needle-anvil type of point contacts and scanning tunneling microscopy (STM). We also show our first attempt to lift up with a STM a chain of single gold atoms from a Au(110) surface.

  20. Atomic force microscopy-based repeated machining theory for nanochannels on silicon oxide surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.Q., E-mail: [State Key Laboratory of Robotics, Shenyang Institute of Automation, CAS, Shenyang 110016 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Jiao, N.D. [State Key Laboratory of Robotics, Shenyang Institute of Automation, CAS, Shenyang 110016 (China); Tung, S. [Department of Mechanical Engineering, University of Arkansas, Fayetteville, AR 72701 (United States); Dong, Z.L. [State Key Laboratory of Robotics, Shenyang Institute of Automation, CAS, Shenyang 110016 (China)


    The atomic force microscopy (AFM)-based repeated nanomachining of nanochannels on silicon oxide surfaces is investigated both theoretically and experimentally. The relationships of the initial nanochannel depth vs. final nanochannel depth at a normal force are systematically studied. Using the derived theory and simulation results, the final nanochannel depth can be predicted easily. Meanwhile, if a nanochannel with an expected depth needs to be machined, a right normal force can be selected simply and easily in order to decrease the wear of the AFM tip. The theoretical analysis and simulation results can be effectively used for AFM-based fabrication of nanochannels.

  1. Asymmetric actuating structure generates negligible influence on the supporting base for high performance scanning probe microscopies (United States)

    Yi Yan, Gang; Bin Liu, Yong; Hua Feng, Zhi


    An asymmetric actuating structure generating negligible influence on the supporting base for high performance scanning probe microscopies is proposed in this paper. The actuator structure consists of two piezostacks, one is used for actuating while the other is for counterbalancing. In contrast with balanced structure, the two piezostacks are installed at the same side of the supporting base. The effectiveness of the structure is proved by some experiments with the actuators fixed to the free end of a cantilever. Experimental results show that almost all of the vibration modes of the cantilever are suppressed effectively at a wide frequency range of 90 Hz-10 kHz.

  2. Time-stretch microscopy based on time-wavelength sequence reconstruction from wideband incoherent source

    International Nuclear Information System (INIS)

    Zhang, Chi; Xu, Yiqing; Wei, Xiaoming; Tsia, Kevin K.; Wong, Kenneth K. Y.


    Time-stretch microscopy has emerged as an ultrafast optical imaging concept offering the unprecedented combination of the imaging speed and sensitivity. However, dedicated wideband and coherence optical pulse source with high shot-to-shot stability has been mandated for time-wavelength mapping—the enabling process for ultrahigh speed wavelength-encoded image retrieval. From the practical point of view, exploiting methods to relax the stringent requirements (e.g., temporal stability and coherence) for the source of time-stretch microscopy is thus of great value. In this paper, we demonstrated time-stretch microscopy by reconstructing the time-wavelength mapping sequence from a wideband incoherent source. Utilizing the time-lens focusing mechanism mediated by a narrow-band pulse source, this approach allows generation of a wideband incoherent source, with the spectral efficiency enhanced by a factor of 18. As a proof-of-principle demonstration, time-stretch imaging with the scan rate as high as MHz and diffraction-limited resolution is achieved based on the wideband incoherent source. We note that the concept of time-wavelength sequence reconstruction from wideband incoherent source can also be generalized to any high-speed optical real-time measurements, where wavelength is acted as the information carrier

  3. Improving your four-dimensional image: traveling through a decade of light-sheet-based fluorescence microscopy research. (United States)

    Strobl, Frederic; Schmitz, Alexander; Stelzer, Ernst H K


    Light-sheet-based fluorescence microscopy features optical sectioning in the excitation process. This reduces phototoxicity and photobleaching by up to four orders of magnitude compared with that caused by confocal fluorescence microscopy, simplifies segmentation and quantification for three-dimensional cell biology, and supports the transition from on-demand to systematic data acquisition in developmental biology applications.

  4. A novel multiphoton microscopy images segmentation method based on superpixel and watershed. (United States)

    Wu, Weilin; Lin, Jinyong; Wang, Shu; Li, Yan; Liu, Mingyu; Liu, Gaoqiang; Cai, Jianyong; Chen, Guannan; Chen, Rong


    Multiphoton microscopy (MPM) imaging technique based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) shows fantastic performance for biological imaging. The automatic segmentation of cellular architectural properties for biomedical diagnosis based on MPM images is still a challenging issue. A novel multiphoton microscopy images segmentation method based on superpixels and watershed (MSW) is presented here to provide good segmentation results for MPM images. The proposed method uses SLIC superpixels instead of pixels to analyze MPM images for the first time. The superpixels segmentation based on a new distance metric combined with spatial, CIE Lab color space and phase congruency features, divides the images into patches which keep the details of the cell boundaries. Then the superpixels are used to reconstruct new images by defining an average value of superpixels as image pixels intensity level. Finally, the marker-controlled watershed is utilized to segment the cell boundaries from the reconstructed images. Experimental results show that cellular boundaries can be extracted from MPM images by MSW with higher accuracy and robustness. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Nanograting-based plasmon enhancement for total internal reflection fluorescence microscopy of live cells

    International Nuclear Information System (INIS)

    Kim, Kyujung; Cho, Eun-Jin; Suh, Jin-Suck; Huh, Yong-Min; Kim, Donghyun; Kim, Dong Jun


    We investigated evanescent field enhancement based on subwavelength nanogratings for improved sensitivity in total internal reflection microscopy of live cells. The field enhancement is associated with subwavelength-grating-coupled plasmon excitation. An optimum sample employed a silver grating on a silver film and an SF10 glass substrate. Field intensity was enhanced by approximately 90% when measured by fluorescent excitation of microbeads relative to that on a bare prism as a control, which is in good agreement with numerical results. The subwavelength-grating-mediated field enhancement was also applied to live cell imaging of quantum dots, which confirmed the sensitivity enhancement qualitatively.

  6. Single particle analysis based on Zernike phase contrast transmission electron microscopy. (United States)

    Danev, Radostin; Nagayama, Kuniaki


    We present the first application of Zernike phase-contrast transmission electron microscopy to single-particle 3D reconstruction of a protein, using GroEL chaperonin as the test specimen. We evaluated the performance of the technique by comparing 3D models derived from Zernike phase contrast imaging, with models from conventional underfocus phase contrast imaging. The same resolution, about 12A, was achieved by both imaging methods. The reconstruction based on Zernike phase contrast data required about 30% fewer particles. The advantages and prospects of each technique are discussed.

  7. Silver nanowires for highly reproducible cantilever based AFM-TERS microscopy: towards a universal TERS probe. (United States)

    Walke, Peter; Fujita, Yasuhiko; Peeters, Wannes; Toyouchi, Shuichi; Frederickx, Wout; De Feyter, Steven; Uji-I, Hiroshi


    Tip-enhanced Raman scattering (TERS) microscopy is a unique analytical tool to provide complementary chemical and topographic information of surfaces with nanometric resolution. However, difficulties in reliably producing the necessary metallized scanning probe tips has limited its widespread utilisation, particularly in the case of cantilever-based atomic force microscopy. Attempts to alleviate tip related issues using colloidal or bottom-up engineered tips have so far not reported consistent probes for both Raman and topographic imaging. Here we demonstrate the reproducible fabrication of cantilever-based high-performance TERS probes for both topographic and Raman measurements, based on an approach that utilises noble metal nanowires as the active TERS probe. The tips show 10 times higher TERS contrasts than the most typically used electrochemically-etched tips, and show a reproducibility for TERS greater than 90%, far greater than found with standard methods. We show that TERS can be performed in tapping as well as contact AFM mode, with optical resolutions around or below 15 nm, and with a maximum resolution achieved in tapping-mode of 6 nm. Our work illustrates that superior TERS probes can be produced in a fast and cost-effective manner using simple wet-chemistry methods, leading to reliable and reproducible high-resolution and high-sensitivity TERS, and thus renders the technique applicable for a broad community.

  8. LED-FISH: Fluorescence microscopy based on light emitting diodes for the molecular analysis of Her-2/neu oncogene amplification

    Directory of Open Access Journals (Sweden)

    Vollmer Ekkehard


    Full Text Available Abstract Light emitting diodes (LED, which are available as small monochromatic light sources with characteristic features such as maximum illumination power combined with minimum energy consumption and extremely long lifespan have already proved as a highly potential low-cost alternative for specific diagnostic applications in clinical medicine such as tuberculosis fluorescence microscopy. Likewise, the most reliable evaluation of Her-2/neu (c-erbB2 gene amplification, which has been established in the last few years for routine diagnosis in clinical pathology as determinant towards Herceptin-based treatment of patients with breast cancer, is based on fluorescence in situ hybridization (FISH and corresponding high priced fluorescence equipment. In order to test the possibility to utilize the advantages of low-cost LED technology on FISH analysis of c-erbB2 gene expression for routine diagnostic purposes, the applicability of a standard bright field Carl Zeiss Axiostar Plus microscope equipped with a Fraen AFTER* LED Fluorescence Microscope Kit for the detection of Her-2/neu gene signals was compared to an advanced Nikon Eclipse 80i fluorescence microscope in combination with a conventional 100W mercury vapor lamp. Both microscopes were fitted with the same Quicam FAST CCD digital camera to unequivocally compare the quality of the captured images. C-erbB2 gene expression was analyzed in 30 different human tissue samples of primary invasive breast cancer, following formalin fixation and subsequent paraffin-embedding. The Her2/neu gene signals (green were identifiable in the tumor cells in all cases and images of equal quality were captured under almost identical conditions by 480 nm (blue LED module equipped standard Axiostar microscope as compared to conventional fluorescence microscopy. In this first attempt, these monochromatic LED elements proved in principle to be suitable for the detection of Her-2/neu gene expression by FISH. Thus, our own

  9. Study of crystalline thin films and nanofibers by means of the laser–plasma EUV-source based microscopy

    International Nuclear Information System (INIS)

    Wachulak, P.W.; Bartnik, A.; Baranowska-Korczyc, A.; Pánek, D.; Brůža, P.; Kostecki, J.; Węgrzyński, Ł.; Jarocki, R.; Szczurek, M.; Fronc, K.; Elbaum, D.; Fiedorowicz, H.


    New developments in nanoscience and nanotechnology require nanometer scale resolution imaging tools and techniques such as an extreme ultraviolet (EUV) and soft X-ray (SXR) microscopy, based on Fresnel zone plates. In this paper, we report on applications of a desk-top microscopy using a laser-plasma EUV source based on a gas-puff target for studies of morphology of thin silicon membranes coated with NaCl crystals and samples composed of ZnO nanofibers

  10. Analysis of Point Based Image Registration Errors With Applications in Single Molecule Microscopy. (United States)

    Cohen, E A K; Ober, R J


    We present an asymptotic treatment of errors involved in point-based image registration where control point (CP) localization is subject to heteroscedastic noise; a suitable model for image registration in fluorescence microscopy. Assuming an affine transform, CPs are used to solve a multivariate regression problem. With measurement errors existing for both sets of CPs this is an errors-in-variable problem and linear least squares is inappropriate; the correct method being generalized least squares. To allow for point dependent errors the equivalence of a generalized maximum likelihood and heteroscedastic generalized least squares model is achieved allowing previously published asymptotic results to be extended to image registration. For a particularly useful model of heteroscedastic noise where covariance matrices are scalar multiples of a known matrix (including the case where covariance matrices are multiples of the identity) we provide closed form solutions to estimators and derive their distribution. We consider the target registration error (TRE) and define a new measure called the localization registration error (LRE) believed to be useful, especially in microscopy registration experiments. Assuming Gaussianity of the CP localization errors, it is shown that the asymptotic distribution for the TRE and LRE are themselves Gaussian and the parameterized distributions are derived. Results are successfully applied to registration in single molecule microscopy to derive the key dependence of the TRE and LRE variance on the number of CPs and their associated photon counts. Simulations show asymptotic results are robust for low CP numbers and non-Gaussianity. The method presented here is shown to outperform GLS on real imaging data.

  11. Photon-counting-based diffraction phase microscopy combined with single-pixel imaging (United States)

    Shibuya, Kyuki; Araki, Hiroyuki; Iwata, Tetsuo


    We propose a photon-counting (PC)-based quantitative-phase imaging (QPI) method for use in diffraction phase microscopy (DPM) that is combined with a single-pixel imaging (SPI) scheme (PC-SPI-DPM). This combination of DPM with the SPI scheme overcomes a low optical throughput problem that has occasionally prevented us from obtaining quantitative-phase images in DPM through use of a high-sensitivity single-channel photodetector such as a photomultiplier tube (PMT). The introduction of a PMT allowed us to perform PC with ease and thus solved a dynamic range problem that was inherent to SPI. As a proof-of-principle experiment, we performed a comparison study of analogue-based SPI-DPM and PC-SPI-DPM for a 125-nm-thick indium tin oxide (ITO) layer coated on a silica glass substrate. We discuss the basic performance of the method and potential future modifications of the proposed system.

  12. Electrical tomography using atomic force microscopy and its application towards carbon nanotube-based interconnects

    International Nuclear Information System (INIS)

    Schulze, A; Hantschel, T; Dathe, A; Eyben, P; Vandervorst, W; Ke, X


    The fabrication and integration of low-resistance carbon nanotubes (CNTs) for interconnects in future integrated circuits requires characterization techniques providing structural and electrical information at the nanometer scale. In this paper we present a slice-and-view approach based on electrical atomic force microscopy. Material removal achieved by successive scanning using doped ultra-sharp full-diamond probes, manufactured in-house, enables us to acquire two-dimensional (2D) resistance maps originating from different depths (equivalently different CNT lengths) on CNT-based interconnects. Stacking and interpolating these 2D resistance maps results in a three-dimensional (3D) representation (tomogram). This allows insight from a structural (e.g. size, density, distribution, straightness) and electrical point of view simultaneously. By extracting the resistance evolution over the length of an individual CNT we derive quantitative information about the resistivity and the contact resistance between the CNT and bottom electrode. (paper)

  13. Characterization of LiF-based soft X-ray imaging detectors by confocal fluorescence microscopy

    International Nuclear Information System (INIS)

    Bonfigli, F; Gaudio, P; Lupelli, I; Nichelatti, E; Richetta, M; Vincenti, M A; Montereali, R M


    X-ray microscopy represents a powerful tool to obtain images of samples with very high spatial resolution. The main limitation of this technique is represented by the poor spatial resolution of standard imaging detectors. We proposed an innovative high-performance X-ray imaging detector based on the visible photoluminescence of colour centres in lithium fluoride. In this work, a confocal microscope in fluorescence mode was used to characterize LiF-based imaging detectors measuring CC integrated visible fluorescence signals of LiF crystals and films (grown on several kinds of substrates) irradiated by soft X-rays produced by a laser plasma source in different exposure conditions. The results are compared with the CC photoluminescence spectra measured on the same samples and discussed.

  14. Atomic-resolution single-spin magnetic resonance detection concept based on tunneling force microscopy (United States)

    Payne, A.; Ambal, K.; Boehme, C.; Williams, C. C.


    A study of a force detected single-spin magnetic resonance measurement concept with atomic spatial resolution is presented. The method is based upon electrostatic force detection of spin-selection rule controlled single-electron tunneling between two electrically isolated paramagnetic states. Single-spin magnetic resonance detection is possible by measuring the force detected tunneling charge noise on and off spin resonance. Simulation results of this charge noise, based upon physical models of the tunneling and spin physics, are directly compared to measured atomic force microscopy system noise. The results show that the approach could provide single-spin measurement of electrically isolated qubit states with atomic spatial resolution at room temperature.

  15. Predicting Neisseria gonorrhoeae and Chlamydia trachomatis infection using risk scores, physical examination, microscopy, and leukocyte esterase urine dipsticks among asymptomatic women attending a family planning clinic in Kenya. (United States)

    Tyndall, M W; Kidula, N; Sande, J; Ombette, J; Temmerman, M


    Sexually transmitted infections (STIs) continue to exert a tremendous health burden on women in developing countries. Poor socioeconomic status, inadequate knowledge, lack of diagnostic facilities, and shortages of effective treatment all contribute to the high incidence of STIs. The use of clinical algorithms for the detection and management of STIs has gained widespread acceptance in settings where there are limited resources. Evaluation of these algorithms have been few, especially in women who are not recognized as members of high-risk groups. To develop a simple scoring system based on historical and demographic data, physical findings, microscopy, and leukocyte esterase (LE) urine dipsticks to predict cervical gonococcal and chlamydial infection among asymptomatic women. One thousand and forty-eight women attending an urban family planning clinic in Nairobi were randomly selected to participate. After the identification of factors that were associated with infection, we assigned one point each for: age 25 or younger, single status, two or more sex partners in the past year, cervical discharge, cervical swab leukocytes, and a positive LE urine dipstick. Identification of any one of these six factors gave a sensitivity of 85% and a specificity of 30% for the detection of cervical infections. A positive LE urine dipstick had a sensitivity of 63 % and a specificity of 47% when used alone and did not contribute to the identification of infection if a physical examination was performed. The application of existing clinical algorithms to this population performed poorly. The use of risk scores, physical examination, microscopy, and the urine LE dipstick, used alone or in combination, as predictors of gonococcal or chlamydial cervical infection was of limited utility in low-risk, asymptomatic women. Accurate diagnostic testing is necessary to optimize treatment.

  16. Isometric multimodal photoacoustic microscopy based on optically transparent micro-ring ultrasonic detection. (United States)

    Dong, Biqin; Li, Hao; Zhang, Zhen; Zhang, Kevin; Chen, Siyu; Sun, Cheng; Zhang, Hao F


    Photoacoustic microscopy (PAM) is an attractive imaging tool complementary to established optical microscopic modalities by providing additional molecular specificities through imaging optical absorption contrast. While the development of optical resolution photoacoustic microscopy (ORPAM) offers high lateral resolution, the acoustically-determined axial resolution is limited due to the constraint in ultrasonic detection bandwidth. ORPAM with isometric spatial resolution along both axial and lateral direction is yet to be developed. Although recently developed sophisticated optical illumination and reconstruction methods offer improved axial resolution in ORPAM, the image acquisition procedures are rather complicated, limiting their capabilities for high-speed imaging and being easily integrated with established optical microscopic modalities. Here we report an isometric ORPAM based on an optically transparent micro-ring resonator ultrasonic detector and a commercial inverted microscope platform. Owing to the superior spatial resolution and the ease of integrating our ORPAM with established microscopic modalities, single cell imaging with extrinsic fluorescence staining, intrinsic autofluorescence, and optical absorption can be achieved simultaneously. This technique holds promise to greatly improve the accessibility of PAM to the broader biomedical researchers.

  17. A fast global fitting algorithm for fluorescence lifetime imaging microscopy based on image segmentation. (United States)

    Pelet, S; Previte, M J R; Laiho, L H; So, P T C


    Global fitting algorithms have been shown to improve effectively the accuracy and precision of the analysis of fluorescence lifetime imaging microscopy data. Global analysis performs better than unconstrained data fitting when prior information exists, such as the spatial invariance of the lifetimes of individual fluorescent species. The highly coupled nature of global analysis often results in a significantly slower convergence of the data fitting algorithm as compared with unconstrained analysis. Convergence speed can be greatly accelerated by providing appropriate initial guesses. Realizing that the image morphology often correlates with fluorophore distribution, a global fitting algorithm has been developed to assign initial guesses throughout an image based on a segmentation analysis. This algorithm was tested on both simulated data sets and time-domain lifetime measurements. We have successfully measured fluorophore distribution in fibroblasts stained with Hoechst and calcein. This method further allows second harmonic generation from collagen and elastin autofluorescence to be differentiated in fluorescence lifetime imaging microscopy images of ex vivo human skin. On our experimental measurement, this algorithm increased convergence speed by over two orders of magnitude and achieved significantly better fits. Copyright 2004 Biophysical Society

  18. MISTICA: Minimum Spanning Tree-Based Coarse Image Alignment for Microscopy Image Sequences. (United States)

    Ray, Nilanjan; McArdle, Sara; Ley, Klaus; Acton, Scott T


    Registration of an in vivo microscopy image sequence is necessary in many significant studies, including studies of atherosclerosis in large arteries and the heart. Significant cardiac and respiratory motion of the living subject, occasional spells of focal plane changes, drift in the field of view, and long image sequences are the principal roadblocks. The first step in such a registration process is the removal of translational and rotational motion. Next, a deformable registration can be performed. The focus of our study here is to remove the translation and/or rigid body motion that we refer to here as coarse alignment. The existing techniques for coarse alignment are unable to accommodate long sequences often consisting of periods of poor quality images (as quantified by a suitable perceptual measure). Many existing methods require the user to select an anchor image to which other images are registered. We propose a novel method for coarse image sequence alignment based on minimum weighted spanning trees (MISTICA) that overcomes these difficulties. The principal idea behind MISTICA is to reorder the images in shorter sequences, to demote nonconforming or poor quality images in the registration process, and to mitigate the error propagation. The anchor image is selected automatically making MISTICA completely automated. MISTICA is computationally efficient. It has a single tuning parameter that determines graph width, which can also be eliminated by the way of additional computation. MISTICA outperforms existing alignment methods when applied to microscopy image sequences of mouse arteries.

  19. An atomic force microscopy-based method for line edge roughness measurement

    Energy Technology Data Exchange (ETDEWEB)

    Fouchier, M.; Pargon, E.; Bardet, B. [CNRS/UJF-Grenoble1/CEA LTM, 17 avenue des Martyrs, 38054 Grenoble cedex 9 (France)


    With the constant decrease of semiconductor device dimensions, line edge roughness (LER) becomes one of the most important sources of device variability and needs to be controlled below 2 nm for the future technological nodes of the semiconductor roadmap. LER control at the nanometer scale requires accurate measurements. We introduce a technique for LER measurement based upon the atomic force microscope (AFM). In this technique, the sample is tilted at about 45 Degree-Sign and feature sidewalls are scanned along their length with the AFM tip to obtain three-dimensional images. The small radius of curvature of the tip together with the low noise level of a laboratory AFM result in high resolution images. Half profiles and LER values on all the height of the sidewalls are extracted from the 3D images using a procedure that we developed. The influence of sample angle variations on the measurements is shown to be small. The technique is applied to the study of a full pattern transfer into a simplified gate stack. The images obtained are qualitatively consistent with cross-section scanning electron microscopy images and the average LER values agree with that obtained by critical dimension scanning electron microscopy. In addition to its high resolution, this technique presents several advantages such as the ability to image the foot of photoresist lines, complex multi-layer stacks regardless of the materials, and deep re-entrant profiles.

  20. PScan 1.0: flexible software framework for polygon based multiphoton microscopy (United States)

    Li, Yongxiao; Lee, Woei Ming


    Multiphoton laser scanning microscopes exhibit highly localized nonlinear optical excitation and are powerful instruments for in-vivo deep tissue imaging. Customized multiphoton microscopy has a significantly superior performance for in-vivo imaging because of precise control over the scanning and detection system. To date, there have been several flexible software platforms catered to custom built microscopy systems i.e. ScanImage, HelioScan, MicroManager, that perform at imaging speeds of 30-100fps. In this paper, we describe a flexible software framework for high speed imaging systems capable of operating from 5 fps to 1600 fps. The software is based on the MATLAB image processing toolbox. It has the capability to communicate directly with a high performing imaging card (Matrox Solios eA/XA), thus retaining high speed acquisition. The program is also designed to communicate with LabVIEW and Fiji for instrument control and image processing. Pscan 1.0 can handle high imaging rates and contains sufficient flexibility for users to adapt to their high speed imaging systems.

  1. Deciphering complex, functional structures with synchrotron-based absorption and phase contrast tomographic microscopy (United States)

    Stampanoni, M.; Reichold, J.; Weber, B.; Haberthür, D.; Schittny, J.; Eller, J.; Büchi, F. N.; Marone, F.


    Nowadays, thanks to the high brilliance available at modern, third generation synchrotron facilities and recent developments in detector technology, it is possible to record volumetric information at the micrometer scale within few minutes. High signal-to-noise ratio, quantitative information on very complex structures like the brain micro vessel architecture, lung airways or fuel cells can be obtained thanks to the combination of dedicated sample preparation protocols, in-situ acquisition schemes and cutting-edge imaging analysis instruments. In this work we report on recent experiments carried out at the TOMCAT beamline of the Swiss Light Source [1] where synchrotron-based tomographic microscopy has been successfully used to obtain fundamental information on preliminary models for cerebral fluid flow [2], to provide an accurate mesh for 3D finite-element simulation of the alveolar structure of the pulmonary acinus [3] and to investigate the complex functional mechanism of fuel cells [4]. Further, we introduce preliminary results on the combination of absorption and phase contrast microscopy for the visualization of high-Z nanoparticles in soft tissues, a fundamental information when designing modern drug delivery systems [5]. As an outlook we briefly discuss the new possibilities offered by high sensitivity, high resolution grating interferomtery as well as Zernike Phase contrast nanotomography [6].

  2. All-optical optoacoustic microscopy based on probe beam deflection technique

    Directory of Open Access Journals (Sweden)

    Saher M. Maswadi


    Full Text Available Optoacoustic (OA microscopy using an all-optical system based on the probe beam deflection technique (PBDT for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii undistorted coupling of acoustic waves to the detector without the need for separation of the optical and acoustic paths, (iii high sensitivity and (iv ultrawide bandwidth. Because of the unimpeded optical path in PBDT, diffraction-limited lateral resolution can be readily achieved. The sensitivity of the current PBDT sensor of 22 μV/Pa and its noise equivalent pressure (NEP of 11.4 Pa are comparable with these parameters of the optical micro-ring resonator and commercial piezoelectric ultrasonic transducers. Benefits of the present prototype OA microscope were demonstrated by successfully resolving micron-size details in histological sections of cardiac muscle.

  3. All-optical optoacoustic microscopy based on probe beam deflection technique. (United States)

    Maswadi, Saher M; Ibey, Bennett L; Roth, Caleb C; Tsyboulski, Dmitri A; Beier, Hope T; Glickman, Randolph D; Oraevsky, Alexander A


    Optoacoustic (OA) microscopy using an all-optical system based on the probe beam deflection technique (PBDT) for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i) efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii) undistorted coupling of acoustic waves to the detector without the need for separation of the optical and acoustic paths, (iii) high sensitivity and (iv) ultrawide bandwidth. Because of the unimpeded optical path in PBDT, diffraction-limited lateral resolution can be readily achieved. The sensitivity of the current PBDT sensor of 22 μV/Pa and its noise equivalent pressure (NEP) of 11.4 Pa are comparable with these parameters of the optical micro-ring resonator and commercial piezoelectric ultrasonic transducers. Benefits of the present prototype OA microscope were demonstrated by successfully resolving micron-size details in histological sections of cardiac muscle.

  4. [Comparison of cell elasticity analysis methods based on atomic force microscopy indentation]. (United States)

    Wang, Zhe; Hao, Fengtao; Chen, Xiaohu; Yang, Zhouqi; Ding, Chong; Shang, Peng


    In order to investigate in greater detail the two methods based on Hertz model for analyzing force-distance curve obtained by atomic force microscopy, we acquired the force-distance curves of Hela and MCF-7 cells by atomic force microscopy (AFM) indentation in this study. After the determination of contact point, Young's modulus in different indentation depth were calculated with two analysis methods of "two point" and "slope fitting". The results showed that the Young's modulus of Hela cell was higher than that of MCF-7 cell,which is in accordance with the F-actin distribution of the two types of cell. We found that the Young's modulus of the cells was decreased with increasing indentation depth and the curve trends by "slope fitting". This indicated that the "slope fitting" method could reduce the error caused by the miscalculation of contact point. The purpose of this study was to provide a guidance for researcher to choose an appropriate method for analyzing AFM indentation force-distance curve.

  5. Transmission electron microscopy of InP-based compound semiconductor materials and devices

    International Nuclear Information System (INIS)

    Chu, S.N.G.


    InP/InGaAsP-based heteroepitaxial structures constitute the major optoelectronic devices for state-of-the-art long wavelength optical fiber communication system.s Future advanced device structures will require thin heteroepitaxial quantum wells and superlattices a few tens of angstrom or less in thickness, and lateral dimensions ranging from a few tens angstrom for quantum dots and wires to a few μm in width for buried heterostructure lasers. Due to the increasing complexity of the device structure required by band-gap engineering, the performance of these devices becomes susceptible to any lattice imperfections present in the structure. Transmission electron microscopy (TEM), therefore, becomes the most important technique in characterizing the structural integrity of these materials. Cross-section transmission electron microscopy (XTEM) not only provides the necessary geometric information on the device structure; a careful study of the materials science behind the observed lattice imperfections provides directions for optimization of both the epitaxial growth parameters and device processing conditions. Furthermore, for device reliability studies, TEM is the only technique that unambiguously identifies the cause of device degradation. In this paper, the authors discuss areas of application of various TEM techniques, describe the TEM sample preparation technique, and review case studies to demonstrate the power of the TEM technique

  6. Context based mixture model for cell phase identification in automated fluorescence microscopy

    Directory of Open Access Journals (Sweden)

    Zhou Xiaobo


    Full Text Available Abstract Background Automated identification of cell cycle phases of individual live cells in a large population captured via automated fluorescence microscopy technique is important for cancer drug discovery and cell cycle studies. Time-lapse fluorescence microscopy images provide an important method to study the cell cycle process under different conditions of perturbation. Existing methods are limited in dealing with such time-lapse data sets while manual analysis is not feasible. This paper presents statistical data analysis and statistical pattern recognition to perform this task. Results The data is generated from Hela H2B GFP cells imaged during a 2-day period with images acquired 15 minutes apart using an automated time-lapse fluorescence microscopy. The patterns are described with four kinds of features, including twelve general features, Haralick texture features, Zernike moment features, and wavelet features. To generate a new set of features with more discriminate power, the commonly used feature reduction techniques are used, which include Principle Component Analysis (PCA, Linear Discriminant Analysis (LDA, Maximum Margin Criterion (MMC, Stepwise Discriminate Analysis based Feature Selection (SDAFS, and Genetic Algorithm based Feature Selection (GAFS. Then, we propose a Context Based Mixture Model (CBMM for dealing with the time-series cell sequence information and compare it to other traditional classifiers: Support Vector Machine (SVM, Neural Network (NN, and K-Nearest Neighbor (KNN. Being a standard practice in machine learning, we systematically compare the performance of a number of common feature reduction techniques and classifiers to select an optimal combination of a feature reduction technique and a classifier. A cellular database containing 100 manually labelled subsequence is built for evaluating the performance of the classifiers. The generalization error is estimated using the cross validation technique. The

  7. Characterizing the surface forces between two individual nanowires using optical microscopy based nanomanipulation (United States)

    Xie, Hongtao; Mead, James L.; Wang, Shiliang; Fatikow, Sergej; Huang, Han


    The adhesion and friction between two Al2O3 nanowires (NWs) was characterized by the use of optical microscopy based nanomanipulation, with which peeling, shearing and sliding was performed. The elastically deformed shape of the NWs during peeling and shearing was used to calculate the adhesion and frictional forces; force sensing was not required. The obtained adhesion stress between two Al2O3 NWs varied from 0.14 to 0.25 MPa, lower than that observed for carbon nanotube junctions, and was attributed to van der Waals attraction. Stick-slip was observed during the shearing and sliding of two NWs, and was the consequence of discrete contact between surface asperities. The obtained static and kinetic frictional stresses varied from 0.7 to 1.3 MPa and 0.4 to 0.8 MPa, respectively; significantly greater than the obtained adhesion stress.

  8. Simulation-based Extraction of Key Material Parameters from Atomic Force Microscopy (United States)

    Alsafi, Huseen; Peninngton, Gray

    Models for the atomic force microscopy (AFM) tip and sample interaction contain numerous material parameters that are often poorly known. This is especially true when dealing with novel material systems or when imaging samples that are exposed to complicated interactions with the local environment. In this work we use Monte Carlo methods to extract sample material parameters from the experimental AFM analysis of a test sample. The parameterized theoretical model that we use is based on the Virtual Environment for Dynamic AFM (VEDA) [1]. The extracted material parameters are then compared with the accepted values for our test sample. Using this procedure, we suggest a method that can be used to successfully determine unknown material properties in novel and complicated material systems. We acknowledge Fisher Endowment Grant support from the Jess and Mildred Fisher College of Science and Mathematics,Towson University.

  9. Structural and dynamical aspects of skin studied by multiphoton excitation fluorescence microscopy-based methods

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Brewer, Jonathan R.; Bagatolli, Luis


    ' parameters. Specifically, by applying these methods, spatially resolved maps of water dipolar relaxation (generalized polarization function using the 6-lauroyl-2-(N,N-dimethylamino)naphthale probe), activity of protons (fluorescence lifetime imaging using a proton sensitive fluorescence probe--2,7-bis-(2......-carboxyethyl)-5-(and-6)-carboxyfluorescein) and diffusion coefficients of distinct fluorescence probes (raster imaging correlation spectroscopy) can be obtained from different regions of the tissue. Comparative studies of different tissue strata, but also between equivalent regions of normal and abnormal......This mini-review reports on applications of particular multiphoton excitation microscopy-based methodologies employed in our laboratory to study skin. These approaches allow in-depth optical sectioning of the tissue, providing spatially resolved information on specific fluorescence probes...

  10. Imaging a Large Sample with Selective Plane Illumination Microscopy Based on Multiple Fluorescent Microsphere Tracking (United States)

    Ryu, Inkeon; Kim, Daekeun


    A typical selective plane illumination microscopy (SPIM) image size is basically limited by the field of view, which is a characteristic of the objective lens. If an image larger than the imaging area of the sample is to be obtained, image stitching, which combines step-scanned images into a single panoramic image, is required. However, accurately registering the step-scanned images is very difficult because the SPIM system uses a customized sample mount where uncertainties for the translational and the rotational motions exist. In this paper, an image registration technique based on multiple fluorescent microsphere tracking is proposed in the view of quantifying the constellations and measuring the distances between at least two fluorescent microspheres embedded in the sample. Image stitching results are demonstrated for optically cleared large tissue with various staining methods. Compensation for the effect of the sample rotation that occurs during the translational motion in the sample mount is also discussed.

  11. [In Vivo Study of Chitin in Fungal Hyphae Based on Confocal Raman Microscopy]. (United States)

    Li, Xiao-li; Luo, Liu-bin; Zhou, Bin-xiong; Hu, Xiao-qian; Sun, Chan-jun; He, Yong


    Chitin is an important structural polysaccharide of fungal cell wall. In this paper, aerial hyphae of Colletotrichum camelliae Massee was first studied by confocal Raman microscopy in vivo. Firstly, the optimal experimental parameters of hyphae for collecting the Raman spectra were determined, and the typical Raman spectra of hyphae, chitin standard and background were acquired. By comparing analysis, characteristic peaks of chitin were found in hyphae. Then, a region of interesting on hyphae was selected for Raman scanning. Through principal component analysis, the Raman signal of hyphae and background in the scanning area can be separated clearly. Combined with loading weight plot, two main characteristic peaks of hyphae were obtained, 1 622 cm(-1) was belong to chitin and 1 368 cm(-1) was assigned to pectic polysaccharide. Finally, two and three dimension chemical images of fungal hyphae were realized based on Raman fingerprint spectra of chitin in a nondestructive way.

  12. Passive microrheology of soft materials with atomic force microscopy: A wavelet-based spectral analysis

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Torres, C.; Streppa, L. [CNRS, UMR5672, Laboratoire de Physique, Ecole Normale Supérieure de Lyon, 46 Allée d' Italie, Université de Lyon, 69007 Lyon (France); Arneodo, A.; Argoul, F. [CNRS, UMR5672, Laboratoire de Physique, Ecole Normale Supérieure de Lyon, 46 Allée d' Italie, Université de Lyon, 69007 Lyon (France); CNRS, UMR5798, Laboratoire Ondes et Matière d' Aquitaine, Université de Bordeaux, 351 Cours de la Libération, 33405 Talence (France); Argoul, P. [Université Paris-Est, Ecole des Ponts ParisTech, SDOA, MAST, IFSTTAR, 14-20 Bd Newton, Cité Descartes, 77420 Champs sur Marne (France)


    Compared to active microrheology where a known force or modulation is periodically imposed to a soft material, passive microrheology relies on the spectral analysis of the spontaneous motion of tracers inherent or external to the material. Passive microrheology studies of soft or living materials with atomic force microscopy (AFM) cantilever tips are rather rare because, in the spectral densities, the rheological response of the materials is hardly distinguishable from other sources of random or periodic perturbations. To circumvent this difficulty, we propose here a wavelet-based decomposition of AFM cantilever tip fluctuations and we show that when applying this multi-scale method to soft polymer layers and to living myoblasts, the structural damping exponents of these soft materials can be retrieved.

  13. CINCH (confocal incoherent correlation holography) super resolution fluorescence microscopy based upon FINCH (Fresnel incoherent correlation holography). (United States)

    Siegel, Nisan; Storrie, Brian; Bruce, Marc; Brooker, Gary


    FINCH holographic fluorescence microscopy creates high resolution super-resolved images with enhanced depth of focus. The simple addition of a real-time Nipkow disk confocal image scanner in a conjugate plane of this incoherent holographic system is shown to reduce the depth of focus, and the combination of both techniques provides a simple way to enhance the axial resolution of FINCH in a combined method called "CINCH". An important feature of the combined system allows for the simultaneous real-time image capture of widefield and holographic images or confocal and confocal holographic images for ready comparison of each method on the exact same field of view. Additional GPU based complex deconvolution processing of the images further enhances resolution.

  14. Compact three-dimensional super-resolution system based on fluorescence emission difference microscopy (United States)

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


    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.

  15. Image-based overlay measurement using subsurface ultrasonic resonance force microscopy (United States)

    Tamer, M. S.; van der Lans, M. J.; Sadeghian, H.


    Image Based Overlay (IBO) measurement is one of the most common techniques used in Integrated Circuit (IC) manufacturing to extract the overlay error values. The overlay error is measured using dedicated overlay targets which are optimized to increase the accuracy and the resolution, but these features are much larger than the IC feature size. IBO measurements are realized on the dedicated targets instead of product features, because the current overlay metrology solutions, mainly based on optics, cannot provide sufficient resolution on product features. However, considering the fact that the overlay error tolerance is approaching 2 nm, the overlay error measurement on product features becomes a need for the industry. For sub-nanometer resolution metrology, Scanning Probe Microscopy (SPM) is widely used, though at the cost of very low throughput. The semiconductor industry is interested in non-destructive imaging of buried structures under one or more layers for the application of overlay and wafer alignment, specifically through optically opaque media. Recently an SPM technique has been developed for imaging subsurface features which can be potentially considered as a solution for overlay metrology. In this paper we present the use of Subsurface Ultrasonic Resonance Force Microscopy (SSURFM) used for IBO measurement. We used SSURFM for imaging the most commonly used overlay targets on a silicon substrate and photoresist. As a proof of concept we have imaged surface and subsurface structures simultaneously. The surface and subsurface features of the overlay targets are fabricated with programmed overlay errors of +/-40 nm, +/-20 nm, and 0 nm. The top layer thickness changes between 30 nm and 80 nm. Using SSURFM the surface and subsurface features were successfully imaged and the overlay errors were extracted, via a rudimentary image processing algorithm. The measurement results are in agreement with the nominal values of the programmed overlay errors.

  16. Korean Clinic Based Outcome Measure Studies


    Jongbae Park


    Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented...

  17. High-throughput full-automatic synchrotron-based tomographic microscopy

    International Nuclear Information System (INIS)

    Mader, Kevin; Marone, Federica; Hintermueller, Christoph; Mikuljan, Gordan; Isenegger, Andreas; Stampanoni, Marco


    At the TOMCAT (TOmographic Microscopy and Coherent rAdiology experimenTs) beamline of the Swiss Light Source with an energy range of 8-45 keV and voxel size from 0.37 (micro)m to 7.4 (micro)m, full tomographic datasets are typically acquired in 5 to 10 min. To exploit the speed of the system and enable high-throughput studies to be performed in a fully automatic manner, a package of automation tools has been developed. The samples are automatically exchanged, aligned, moved to the correct region of interest, and scanned. This task is accomplished through the coordination of Python scripts, a robot-based sample-exchange system, sample positioning motors and a CCD camera. The tools are suited for any samples that can be mounted on a standard SEM stub, and require no specific environmental conditions. Up to 60 samples can be analyzed at a time without user intervention. The throughput of the system is dependent on resolution, energy and sample size, but rates of four samples per hour have been achieved with 0.74 (micro)m voxel size at 17.5 keV. The maximum intervention-free scanning time is theoretically unlimited, and in practice experiments have been running unattended as long as 53 h (the average beam time allocation at TOMCAT is 48 h per user). The system is the first fully automated high-throughput tomography station: mounting samples, finding regions of interest, scanning and reconstructing can be performed without user intervention. The system also includes many features which accelerate and simplify the process of tomographic microscopy.

  18. The influence of physical and physiological cues on atomic force microscopy-based cell stiffness assessment.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chiou

    Full Text Available Atomic force microscopy provides a novel technique for differentiating the mechanical properties of various cell types. Cell elasticity is abundantly used to represent the structural strength of cells in different conditions. In this study, we are interested in whether physical or physiological cues affect cell elasticity in Atomic force microscopy (AFM-based assessments. The physical cues include the geometry of the AFM tips, the indenting force and the operating temperature of the AFM. All of these cues show a significant influence on the cell elasticity assessment. Sharp AFM tips create a two-fold increase in the value of the effective Young's modulus (E(eff relative to that of the blunt tips. Higher indenting force at the same loading rate generates higher estimated cell elasticity. Increasing the operation temperature of the AFM leads to decreases in the cell stiffness because the structure of actin filaments becomes disorganized. The physiological cues include the presence of fetal bovine serum or extracellular matrix-coated surfaces, the culture passage number, and the culture density. Both fetal bovine serum and the extracellular matrix are critical for cells to maintain the integrity of actin filaments and consequently exhibit higher elasticity. Unlike primary cells, mouse kidney progenitor cells can be passaged and maintain their morphology and elasticity for a very long period without a senescence phenotype. Finally, cell elasticity increases with increasing culture density only in MDCK epithelial cells. In summary, for researchers who use AFM to assess cell elasticity, our results provide basic and significant information about the suitable selection of physical and physiological cues.

  19. The influence of physical and physiological cues on atomic force microscopy-based cell stiffness assessment. (United States)

    Chiou, Yu-Wei; Lin, Hsiu-Kuan; Tang, Ming-Jer; Lin, Hsi-Hui; Yeh, Ming-Long


    Atomic force microscopy provides a novel technique for differentiating the mechanical properties of various cell types. Cell elasticity is abundantly used to represent the structural strength of cells in different conditions. In this study, we are interested in whether physical or physiological cues affect cell elasticity in Atomic force microscopy (AFM)-based assessments. The physical cues include the geometry of the AFM tips, the indenting force and the operating temperature of the AFM. All of these cues show a significant influence on the cell elasticity assessment. Sharp AFM tips create a two-fold increase in the value of the effective Young's modulus (E(eff)) relative to that of the blunt tips. Higher indenting force at the same loading rate generates higher estimated cell elasticity. Increasing the operation temperature of the AFM leads to decreases in the cell stiffness because the structure of actin filaments becomes disorganized. The physiological cues include the presence of fetal bovine serum or extracellular matrix-coated surfaces, the culture passage number, and the culture density. Both fetal bovine serum and the extracellular matrix are critical for cells to maintain the integrity of actin filaments and consequently exhibit higher elasticity. Unlike primary cells, mouse kidney progenitor cells can be passaged and maintain their morphology and elasticity for a very long period without a senescence phenotype. Finally, cell elasticity increases with increasing culture density only in MDCK epithelial cells. In summary, for researchers who use AFM to assess cell elasticity, our results provide basic and significant information about the suitable selection of physical and physiological cues.

  20. Spline-based image-to-volume registration for three-dimensional electron microscopy

    International Nuclear Information System (INIS)

    Jonic, S.; Sorzano, C.O.S.; Thevenaz, P.; El-Bez, C.; De Carlo, S.; Unser, M.


    This paper presents an algorithm based on a continuous framework for a posteriori angular and translational assignment in three-dimensional electron microscopy (3DEM) of single particles. Our algorithm can be used advantageously to refine the assignment of standard quantized-parameter methods by registering the images to a reference 3D particle model. We achieve the registration by employing a gradient-based iterative minimization of a least-squares measure of dissimilarity between an image and a projection of the volume in the Fourier transform (FT) domain. We compute the FT of the projection using the central-slice theorem (CST). To compute the gradient accurately, we take advantage of a cubic B-spline model of the data in the frequency domain. To improve the robustness of the algorithm, we weight the cost function in the FT domain and apply a 'mixed' strategy for the assignment based on the minimum value of the cost function at registration for several different initializations. We validate our algorithm in a fully controlled simulation environment. We show that the mixed strategy improves the assignment accuracy; on our data, the quality of the angular and translational assignment was better than 2 voxel (i.e., 6.54 A). We also test the performance of our algorithm on real EM data. We conclude that our algorithm outperforms a standard projection-matching refinement in terms of both consistency of 3D reconstructions and speed

  1. Real-time Image Processing for Microscopy-based Label-free Imaging Flow Cytometry in a Microfluidic Chip. (United States)

    Heo, Young Jin; Lee, Donghyeon; Kang, Junsu; Lee, Keondo; Chung, Wan Kyun


    Imaging flow cytometry (IFC) is an emerging technology that acquires single-cell images at high-throughput for analysis of a cell population. Rich information that comes from high sensitivity and spatial resolution of a single-cell microscopic image is beneficial for single-cell analysis in various biological applications. In this paper, we present a fast image-processing pipeline (R-MOD: Real-time Moving Object Detector) based on deep learning for high-throughput microscopy-based label-free IFC in a microfluidic chip. The R-MOD pipeline acquires all single-cell images of cells in flow, and identifies the acquired images as a real-time process with minimum hardware that consists of a microscope and a high-speed camera. Experiments show that R-MOD has the fast and reliable accuracy (500 fps and 93.3% mAP), and is expected to be used as a powerful tool for biomedical and clinical applications.

  2. Statistical region based active contour using a fractional entropy descriptor: Application to nuclei cell segmentation in confocal \\ud microscopy images


    Histace, A; Meziou, B J; Matuszewski, Bogdan; Precioso, F; Murphy, M F; Carreiras, F


    We propose an unsupervised statistical region based active contour approach integrating an original fractional entropy measure for image segmentation with a particular application to single channel actin tagged fluorescence confocal microscopy image segmentation. Following description of statistical based active contour segmentation and the mathematical definition of the proposed fractional entropy descriptor, we demonstrate comparative segmentation results between the proposed approach and s...

  3. Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps. (United States)

    Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan; Stone, John E; Zhao, Jianhua; Schulten, Klaus


    Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2 Å and 3.4 Å resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services.

  4. A wavelet-based Bayesian framework for 3D object segmentation in microscopy (United States)

    Pan, Kangyu; Corrigan, David; Hillebrand, Jens; Ramaswami, Mani; Kokaram, Anil


    In confocal microscopy, target objects are labeled with fluorescent markers in the living specimen, and usually appear with irregular brightness in the observed images. Also, due to the existence of out-of-focus objects in the image, the segmentation of 3-D objects in the stack of image slices captured at different depth levels of the specimen is still heavily relied on manual analysis. In this paper, a novel Bayesian model is proposed for segmenting 3-D synaptic objects from given image stack. In order to solve the irregular brightness and out-offocus problems, the segmentation model employs a likelihood using the luminance-invariant 'wavelet features' of image objects in the dual-tree complex wavelet domain as well as a likelihood based on the vertical intensity profile of the image stack in 3-D. Furthermore, a smoothness 'frame' prior based on the a priori knowledge of the connections of the synapses is introduced to the model for enhancing the connectivity of the synapses. As a result, our model can successfully segment the in-focus target synaptic object from a 3D image stack with irregular brightness.

  5. Sparsity-based multi-height phase recovery in holographic microscopy (United States)

    Rivenson, Yair; Wu, Yichen; Wang, Hongda; Zhang, Yibo; Feizi, Alborz; Ozcan, Aydogan


    High-resolution imaging of densely connected samples such as pathology slides using digital in-line holographic microscopy requires the acquisition of several holograms, e.g., at >6-8 different sample-to-sensor distances, to achieve robust phase recovery and coherent imaging of specimen. Reducing the number of these holographic measurements would normally result in reconstruction artifacts and loss of image quality, which would be detrimental especially for biomedical and diagnostics-related applications. Inspired by the fact that most natural images are sparse in some domain, here we introduce a sparsity-based phase reconstruction technique implemented in wavelet domain to achieve at least 2-fold reduction in the number of holographic measurements for coherent imaging of densely connected samples with minimal impact on the reconstructed image quality, quantified using a structural similarity index. We demonstrated the success of this approach by imaging Papanicolaou smears and breast cancer tissue slides over a large field-of-view of ~20 mm2 using 2 in-line holograms that are acquired at different sample-to-sensor distances and processed using sparsity-based multi-height phase recovery. This new phase recovery approach that makes use of sparsity can also be extended to other coherent imaging schemes, involving e.g., multiple illumination angles or wavelengths to increase the throughput and speed of coherent imaging.

  6. Sparsity-based multi-height phase recovery in holographic microscopy

    KAUST Repository

    Rivenson, Yair


    High-resolution imaging of densely connected samples such as pathology slides using digital in-line holographic microscopy requires the acquisition of several holograms, e.g., at >6–8 different sample-to-sensor distances, to achieve robust phase recovery and coherent imaging of specimen. Reducing the number of these holographic measurements would normally result in reconstruction artifacts and loss of image quality, which would be detrimental especially for biomedical and diagnostics-related applications. Inspired by the fact that most natural images are sparse in some domain, here we introduce a sparsity-based phase reconstruction technique implemented in wavelet domain to achieve at least 2-fold reduction in the number of holographic measurements for coherent imaging of densely connected samples with minimal impact on the reconstructed image quality, quantified using a structural similarity index. We demonstrated the success of this approach by imaging Papanicolaou smears and breast cancer tissue slides over a large field-of-view of ~20 mm2 using 2 in-line holograms that are acquired at different sample-to-sensor distances and processed using sparsity-based multi-height phase recovery. This new phase recovery approach that makes use of sparsity can also be extended to other coherent imaging schemes, involving e.g., multiple illumination angles or wavelengths to increase the throughput and speed of coherent imaging.

  7. A Dual Microscopy-Based Assay To Assess Listeria monocytogenes Cellular Entry and Vacuolar Escape. (United States)

    Quereda, Juan J; Pizarro-Cerdá, Javier; Balestrino, Damien; Bobard, Alexandre; Danckaert, Anne; Aulner, Nathalie; Shorte, Spencer; Enninga, Jost; Cossart, Pascale


    Listeria monocytogenes is a Gram-positive bacterium and a facultative intracellular pathogen that invades mammalian cells, disrupts its internalization vacuole, and proliferates in the host cell cytoplasm. Here, we describe a novel image-based microscopy assay that allows discrimination between cellular entry and vacuolar escape, enabling high-content screening to identify factors specifically involved in these two steps. We first generated L. monocytogenes and Listeria innocua strains expressing a β-lactamase covalently attached to the bacterial cell wall. These strains were then incubated with HeLa cells containing the Förster resonance energy transfer (FRET) probe CCF4 in their cytoplasm. The CCF4 probe was cleaved by the bacterial surface β-lactamase only in cells inoculated with L. monocytogenes but not those inoculated with L. innocua, thereby demonstrating bacterial access to the host cytoplasm. Subsequently, we performed differential immunofluorescence staining to distinguish extracellular versus total bacterial populations in samples that were also analyzed by the FRET-based assay. With this two-step analysis, bacterial entry can be distinguished from vacuolar rupture in a single experiment. Our novel approach represents a powerful tool for identifying factors that determine the intracellular niche of L. monocytogenes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Performance of LED-based fluorescence microscopy to diagnose tuberculosis in a peripheral health centre in Nairobi.

    Directory of Open Access Journals (Sweden)

    Maryline Bonnet

    Full Text Available BACKGROUND: Sputum microscopy is the only tuberculosis (TB diagnostic available at peripheral levels of care in resource limited countries. Its sensitivity is low, particularly in high HIV prevalence settings. Fluorescence microscopy (FM can improve performance of microscopy and with the new light emitting diode (LED technologies could be appropriate for peripheral settings. The study aimed to compare the performance of LED-FM versus Ziehl-Neelsen (ZN microscopy and to assess feasibility of LED-FM at a low level of care in a high HIV prevalence country. METHODS: A prospective study was conducted in an urban health clinic in Nairobi, Kenya. Three sputum specimens were collected over 2 days from suspected TB patients. Each sample was processed with Auramine O and ZN methods and a 4(th specimen was collected for TB culture reference standard. Auramine smears were read using the same microscope, equipped with the FluoLED™ fluorescence illuminator. Inter-reader agreement, reading time and technicians' acceptability assessed feasibility. RESULTS: 497 patients were included and 1394 specimens were collected. The detection yields of LED-FM and ZN microscopy were 20.3% and 20.6% (p = 0.64, respectively. Sensitivity was 73.2% for LED-FM and 72% for ZN microscopy, p = 0.32. It was 96.7% and 95.9% for specificity, p = 0.53. Inter-reader agreement was high (kappa = 0.9. Mean reading time was three times faster than ZN microscopy with very good acceptance by technicians. CONCLUSIONS: Although it did not increase sensitivity, the faster reading time combined with very good acceptance and ease of use supports the introduction of LED-FM at the peripheral laboratory level of high TB and HIV burden countries.

  9. Going Vertical To Improve the Accuracy of Atomic Force Microscopy Based Single-Molecule Force Spectroscopy. (United States)

    Walder, Robert; Van Patten, William J; Adhikari, Ayush; Perkins, Thomas T


    Single-molecule force spectroscopy (SMFS) is a powerful technique to characterize the energy landscape of individual proteins, the mechanical properties of nucleic acids, and the strength of receptor-ligand interactions. Atomic force microscopy (AFM)-based SMFS benefits from ongoing progress in improving the precision and stability of cantilevers and the AFM itself. Underappreciated is that the accuracy of such AFM studies remains hindered by inadvertently stretching molecules at an angle while measuring only the vertical component of the force and extension, degrading both measurements. This inaccuracy is particularly problematic in AFM studies using double-stranded DNA and RNA due to their large persistence length (p ≈ 50 nm), often limiting such studies to other SMFS platforms (e.g., custom-built optical and magnetic tweezers). Here, we developed an automated algorithm that aligns the AFM tip above the DNA's attachment point to a coverslip. Importantly, this algorithm was performed at low force (10-20 pN) and relatively fast (15-25 s), preserving the connection between the tip and the target molecule. Our data revealed large uncorrected lateral offsets for 100 and 650 nm DNA molecules [24 ± 18 nm (mean ± standard deviation) and 180 ± 110 nm, respectively]. Correcting this offset yielded a 3-fold improvement in accuracy and precision when characterizing DNA's overstretching transition. We also demonstrated high throughput by acquiring 88 geometrically corrected force-extension curves of a single individual 100 nm DNA molecule in ∼40 min and versatility by aligning polyprotein- and PEG-based protein-ligand assays. Importantly, our software-based algorithm was implemented on a commercial AFM, so it can be broadly adopted. More generally, this work illustrates how to enhance AFM-based SMFS by developing more sophisticated data-acquisition protocols.

  10. Real time quantitative phase microscopy based on single-shot transport of intensity equation (ssTIE) method (United States)

    Yu, Wei; Tian, Xiaolin; He, Xiaoliang; Song, Xiaojun; Xue, Liang; Liu, Cheng; Wang, Shouyu


    Microscopy based on transport of intensity equation provides quantitative phase distributions which opens another perspective for cellular observations. However, it requires multi-focal image capturing while mechanical and electrical scanning limits its real time capacity in sample detections. Here, in order to break through this restriction, real time quantitative phase microscopy based on single-shot transport of the intensity equation method is proposed. A programmed phase mask is designed to realize simultaneous multi-focal image recording without any scanning; thus, phase distributions can be quantitatively retrieved in real time. It is believed the proposed method can be potentially applied in various biological and medical applications, especially for live cell imaging.

  11. High-resolution MR imaging of the elbow using a microscopy surface coil and a clinical 1.5 T MR machine: preliminary results

    International Nuclear Information System (INIS)

    Yoshioka, Hiroshi; Ueno, Teruko; Takahashi, Nobuyuki; Saida, Yukihisa; Tanaka, Toshikazu; Kujiraoka, Yuka; Shindo, Masashi; Nishiura, Yasumasa; Ochiai, Naoyuki


    To obtain high-resolution MR images of the elbow using a microscopy surface coil with a 1.5 T clinical machine and to evaluate the feasibility of its use for elbow injuries. Five asymptomatic normal volunteers and 13 patients with elbow pain were prospectively studied with MR imaging using a microscopy surface coil 47 mm in diameter. High-resolution MR images using a microscopy coil were obtained with fast spin echo (FSE) proton density-weighted sequence, gradient recalled echo (GRE) T2*-weighted sequence, and short tau inversion recovery (STIR) sequence, with a 1-2 mm slice thickness, a 50-70 mm field of view, an imaging matrix of 140-224 x 512 using zero fill interpolation, and 2-6 excitations. High-resolution MR images of normal volunteers using a microscopy coil clearly showed each structure of the medial and lateral collateral ligaments on GRE T2*-weighted images and FSE proton-density weighted images. Partial medial collateral ligament injury, a small avulsion of the medial epicondyle, and osteochondritis dissecans were well demonstrated on high-resolution MR images. High-resolution MR imaging of the elbow using a microscopy surface coil with a 1.5 T clinical machine is a promising method for accurately characterizing the normal anatomy of the elbow and depicting its lesions in detail. (orig.)

  12. Quantitative nanohistological investigation of scleroderma: an atomic force microscopy-based approach to disease characterization

    Directory of Open Access Journals (Sweden)

    Strange AP


    Full Text Available Adam P Strange,1 Sebastian Aguayo,1 Tarek Ahmed,1 Nicola Mordan,1 Richard Stratton,2 Stephen R Porter,3 Susan Parekh,4 Laurent Bozec1 1Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 2Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, UCL Medical School, 3UCL Eastman Dental Institute, 4Department of Pediatrics, UCL Eastman Dental Institute, London, UK Abstract: Scleroderma (or systemic sclerosis, SSc is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen. Keywords: rheumatology, adjunct diagnosis, picrosirius red, collagen, nanohistology

  13. Development of a laser-based heating system for in situ synchrotron-based X-ray tomographic microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Fife, Julie L., E-mail: [Laboratory for Synchrotron Radiation, Swiss Light Source, Paul Scherrer Institut, Villigen (Switzerland); Computational Materials Laboratory, Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Rappaz, Michel [Computational Materials Laboratory, Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Pistone, Mattia [Institute for Geochemistry and Petrology, Swiss Federal Institute of Technology of Zurich, Zurich (Switzerland); Celcer, Tine [Laboratory for Synchrotron Radiation, Swiss Light Source, Paul Scherrer Institut, Villigen (Switzerland); The Centre of Excellence for Biosensors, Instrumentation and Process Control, Solkan (Slovenia); Mikuljan, Gordan [Laboratory for Synchrotron Radiation, Swiss Light Source, Paul Scherrer Institut, Villigen (Switzerland); Stampanoni, Marco [Laboratory for Synchrotron Radiation, Swiss Light Source, Paul Scherrer Institut, Villigen (Switzerland); Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)


    A laser-based heating system has been developed at the TOMCAT beamline of the Swiss Light Source for in situ observations of moderate-to-high-temperature applications of materials. Understanding the formation of materials at elevated temperatures is critical for determining their final properties. Synchrotron-based X-ray tomographic microscopy is an ideal technique for studying such processes because high spatial and temporal resolutions are easily achieved and the technique is non-destructive, meaning additional analyses can take place after data collection. To exploit the state-of-the-art capabilities at the tomographic microscopy and coherent radiology experiments (TOMCAT) beamline of the Swiss Light Source, a general-use moderate-to-high-temperature furnace has been developed. Powered by two diode lasers, it provides controlled localized heating, from 673 to 1973 K, to examine many materials systems and their dynamics in real time. The system can also be operated in various thermal modalities. For example, near-isothermal conditions at a given sample location can be achieved with a prescribed time-dependent temperature. This mode is typically used to study isothermal phase transformations; for example, the formation of equiaxed grains in metallic systems or to nucleate and grow bubble foams in silicate melts under conditions that simulate volcanic processes. In another mode, the power of the laser can be fixed and the specimen moved at a constant speed in a user-defined thermal gradient. This is similar to Bridgman solidification, where the thermal gradient and cooling rate control the microstructure formation. This paper details the experimental set-up and provides multiple proofs-of-concept that illustrate the versatility of using this laser-based heating system to explore, in situ, many elevated-temperature phenomena in a variety of materials.

  14. The bacterial rhizobiome of hyperaccumulators: future perspectives based on omics analysis and advanced microscopy

    Directory of Open Access Journals (Sweden)

    Giovanna eVisioli


    Full Text Available Hyperaccumulators are plants that can extract heavy metal ions from the soil and translocate those ions to the shoots, where they are sequestered and detoxified. Hyperaccumulation depends not only on the availability of mobilized metal ions in the soil, but also on the enhanced activity of metal transporters and metal chelators which may be provided by the plant or its associated microbes. The rhizobiome is captured by plant root exudates from the complex microbial community in the soil, and may colonize the root surface or infiltrate the root cortex. This community can increase the root surface area by inducing hairy root proliferation. It may also increase the solubility of metals in the rhizosphere and promote the uptake of soluble metals by the plant. The bacterial rhizobiome, a subset of specialized microorganisms that colonize the plant rhizosphere and endosphere, makes an important contribution to the hyperaccumulator phenotype. In this review, we discuss classic and more recent tools that are used to study the interactions between hyperaccumulators and the bacterial rhizobiome, and consider future perspectives based on the use of omics analysis and microscopy to study plant metabolism in the context of metal accumulation. Recent data suggest that metal-resistant bacteria isolated from the hyperaccumulator rhizosphere and endosphere could be useful in applications such as phytoextraction and phytoremediation, although more research is required to determine whether such properties can be transferred successfully to non-accumulator species.

  15. Automatic phase aberration compensation for digital holographic microscopy based on deep learning background detection. (United States)

    Nguyen, Thanh; Bui, Vy; Lam, Van; Raub, Christopher B; Chang, Lin-Ching; Nehmetallah, George


    We propose a fully automatic technique to obtain aberration free quantitative phase imaging in digital holographic microscopy (DHM) based on deep learning. The traditional DHM solves the phase aberration compensation problem by manually detecting the background for quantitative measurement. This would be a drawback in real time implementation and for dynamic processes such as cell migration phenomena. A recent automatic aberration compensation approach using principle component analysis (PCA) in DHM avoids human intervention regardless of the cells' motion. However, it corrects spherical/elliptical aberration only and disregards the higher order aberrations. Traditional image segmentation techniques can be employed to spatially detect cell locations. Ideally, automatic image segmentation techniques make real time measurement possible. However, existing automatic unsupervised segmentation techniques have poor performance when applied to DHM phase images because of aberrations and speckle noise. In this paper, we propose a novel method that combines a supervised deep learning technique with convolutional neural network (CNN) and Zernike polynomial fitting (ZPF). The deep learning CNN is implemented to perform automatic background region detection that allows for ZPF to compute the self-conjugated phase to compensate for most aberrations.

  16. Scanning Auger microscopy study of lanthanum partitioning in sphene-based glass-ceramics

    International Nuclear Information System (INIS)

    Hocking, W.H.; Hayward, P.J.; Watson, D.G.; Allen, G.C.


    Glass-ceramics are being investigated as possible hosts for the radioactive wastes that would result from recycling irradiated nuclear fuels. The partitioning of lanthanum in sphene-based glass-ceramics has been studied by scanning Auger electron microscopy for lanthanum concentrations from 0.2 to 2.0 mol.%. Sphene crystals (CaTiSiO 5 ) were located in the silica-rich glass matrix by recording digital Auger images of the calcium and titanium distributions. The sphene crystals were typically 0.5 to 5 μm in size and occupied approximately 40% of the total specimen volume. Auger spot analyses revealed that lanthanum was strongly partitioned into the sphene phase of phosphorus-free glass-ceramics; however, when a small amount of phosphorus was included in the glass-ceramic composition as a crystal nucleating agent, the lanthanum was concentrated in a third minor phase which also contained calcium, phosphorus and oxygen. Chemical shift effects in the Auger spectra of silicon, titanium and phosphorus showed evidence for electron-stimulated desorption of oxygen. (author)

  17. Development of an automated asbestos counting software based on fluorescence microscopy. (United States)

    Alexandrov, Maxym; Ichida, Etsuko; Nishimura, Tomoki; Aoki, Kousuke; Ishida, Takenori; Hirota, Ryuichi; Ikeda, Takeshi; Kawasaki, Tetsuo; Kuroda, Akio


    An emerging alternative to the commonly used analytical methods for asbestos analysis is fluorescence microscopy (FM), which relies on highly specific asbestos-binding probes to distinguish asbestos from interfering non-asbestos fibers. However, all types of microscopic asbestos analysis require laborious examination of large number of fields of view and are prone to subjective errors and large variability between asbestos counts by different analysts and laboratories. A possible solution to these problems is automated counting of asbestos fibers by image analysis software, which would lower the cost and increase the reliability of asbestos testing. This study seeks to develop a fiber recognition and counting software for FM-based asbestos analysis. We discuss the main features of the developed software and the results of its testing. Software testing showed good correlation between automated and manual counts for the samples with medium and high fiber concentrations. At low fiber concentrations, the automated counts were less accurate, leading us to implement correction mode for automated counts. While the full automation of asbestos analysis would require further improvements in accuracy of fiber identification, the developed software could already assist professional asbestos analysts and record detailed fiber dimensions for the use in epidemiological research.

  18. Pattern of glomerular diseases in oman: A study based on light microscopy and immunofluorescence

    Directory of Open Access Journals (Sweden)

    Nasar Yousuf Alwahaibi


    Full Text Available Light microscopy and immunofluorescence play an important part in the final diagnosis of renal biopsy. The aim of this study was to analyze the pattern of various glomerular diseases in Oman. A total of 424 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital between 1999 and 2010. Focal and segmental glomerulosclerosis (FSGS, minimal change disease (MCD, membranous glomerulopathy (MGN and IgA nephropathy were the most common primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and 8.3%, respectively, of all cases. Lupus nephritis was the most common secondary glomerular disease and was the most prevalent among all biopsies, accounting for 30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of fluorescein isothiocyanatefibrin in all renal cases was low when compared with IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this study, lupus nephritis was the most common of all glomerular diseases and FSGS was the most common primary glomerular disease. The importance of fluorescein isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further investigated.

  19. A confocal microscopy-based atlas of tissue architecture in the tapeworm Hymenolepis diminuta. (United States)

    Rozario, Tania; Newmark, Phillip A


    Tapeworms are pervasive and globally distributed parasites that infect millions of humans and livestock every year, and are the causative agents of two of the 17 neglected tropical diseases prioritized by the World Health Organization. Studies of tapeworm biology and pathology are often encumbered by the complex life cycles of disease-relevant tapeworm species that infect hosts such as foxes, dogs, cattle, pigs, and humans. Thus, studies of laboratory models can help overcome the practical, ethical, and cost-related difficulties faced by tapeworm parasitologists. The rat intestinal tapeworm Hymenolepis diminuta is easily reared in the laboratory and has the potential to enable modern molecular-based experiments that will greatly contribute to our understanding of multiple aspects of tapeworm biology, such as growth and reproduction. As part of our efforts to develop molecular tools for experiments on H. diminuta, we have characterized a battery of lectins, antibodies, and common stains that label different tapeworm tissues and organ structures. Using confocal microscopy, we have assembled an "atlas" of H. diminuta organ architecture that will be a useful resource for helminthologists. The methodologies we describe will facilitate characterization of loss-of-function perturbations using H. diminuta. This toolkit will enable a greater understanding of fundamental tapeworm biology that may elucidate new therapeutic targets toward the eradication of these parasites. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Analyzer-based x-ray phase-contrast microscopy combining channel-cut and asymmetrically cut crystals

    International Nuclear Information System (INIS)

    Hoennicke, M. G.; Cusatis, C.


    An analyzer-based x-ray phase-contrast microscopy (ABM) setup combining a standard analyzer-based x-ray phase-contrast imaging (ABI) setup [nondispersive 4-crystal setup (Bonse-Hart setup)] and diffraction by asymmetrically cut crystals is presented here. An attenuation-contrast microscopy setup with conventional x-ray source and asymmetrically cut crystals is first analyzed. Edge-enhanced effects attributed to phase jumps or refraction/total external reflection on the fiber borders were detected. However, the long exposure times and the possibility to achieve high contrast microscopies by using extremely low attenuation-contrast samples motivated us to assemble the ABM setup using a synchrotron source. This setup was found to be useful for low contrast attenuation samples due to the low exposure time, high contrast, and spatial resolution found. Moreover, thanks to the combination with the nondispersive ABI setup, the diffraction-enhanced x-ray imaging algorithm could be applied

  1. Fluorescence confocal microscopy for pathologists. (United States)

    Ragazzi, Moira; Piana, Simonetta; Longo, Caterina; Castagnetti, Fabio; Foroni, Monica; Ferrari, Guglielmo; Gardini, Giorgio; Pellacani, Giovanni


    Confocal microscopy is a non-invasive method of optical imaging that may provide microscopic images of untreated tissue that correspond almost perfectly to hematoxylin- and eosin-stained slides. Nowadays, following two confocal imaging systems are available: (1) reflectance confocal microscopy, based on the natural differences in refractive indices of subcellular structures within the tissues; (2) fluorescence confocal microscopy, based on the use of fluorochromes, such as acridine orange, to increase the contrast epithelium-stroma. In clinical practice to date, confocal microscopy has been used with the goal of obviating the need for excision biopsies, thereby reducing the need for pathological examination. The aim of our study was to test fluorescence confocal microscopy on different types of surgical specimens, specifically breast, lymph node, thyroid, and colon. The confocal images were correlated to the corresponding histological sections in order to provide a morphologic parallel and to highlight current limitations and possible applications of this technology for surgical pathology practice. As a result, neoplastic tissues were easily distinguishable from normal structures and reactive processes such as fibrosis; the use of fluorescence enhanced contrast and image quality in confocal microscopy without compromising final histologic evaluation. Finally, the fluorescence confocal microscopy images of the adipose tissue were as accurate as those of conventional histology and were devoid of the frozen-section-related artefacts that can compromise intraoperative evaluation. Despite some limitations mainly related to black/white images, which require training in imaging interpretation, this study confirms that fluorescence confocal microscopy may represent an alternative to frozen sections in the assessment of margin status in selected settings or when the conservation of the specimen is crucial. This is the first study to employ fluorescent confocal microscopy on

  2. Transmission electron microscopy of GaN based, doped semiconductor heterostructures

    Energy Technology Data Exchange (ETDEWEB)

    Pretorius, A.


    This thesis addresses the analysis of GaN based heterostructures with transmission electron microscopy (TEM). Basic properties of the material of interest are introduced in chapter 2. These include the structural and optical properties as well as an introduction to the growth methods used for the samples analysed in this work. In chapter 3 a brief theoretical treatment of TEM is given. As one main topic of this work is the determination of the In concentration in InGaN islands using strain state analysis, a detailed description of the method is given. Chapter 4 describes the results obtained for pyramidal defects present in metalorganic vapour phase epitaxy grown GaN:Mg with high dopant concentration. Based on the experimental results and the well established knowledge that GaN of inverted polarity is present inside the pyramidal defects, a variety of basal plane inversion domain boundary models was set up. From these models, HRTEM images were simulated using the multislice approach, followed by a quantitative comparison to experimentally obtained HRTEM images. Another focus of this work is the analysis of In{sub x}Ga{sub 1-x}N islands grown on GaN presented in chapter 5. Following a literature survey which describes different methods used to obtain In{sub x}Ga{sub 1-x}N islands, the first topic is the distinction of In{sub x}Ga{sub 1-x}N islands and metal droplets, which can form during growth. This is followed by the experimental results of molecular beam epitaxy and metalorganic vapour phase epitaxy grown In{sub x}Ga{sub 1-x}N island and quantum dot samples. (orig.)

  3. Cholesteric lyomesophases based on sodium N-lauroyl asparte: characterization of new system by nuclear magnetic resonance and polarizing microscopy

    International Nuclear Information System (INIS)

    Melo, M.V.M.C. de.


    Lyomesophases based on di-sodium N-lauroyl aspartate (SNLA), bi-carboxilated amphiphile obtained from the reaction of n-lauroyl chloride with aspartic acid in racemic or levo form are studies. The different mesophases were characterized by 2 H and 23 Na NMR and by polarizing microscopy. (M.J.C.) [pt

  4. Development and validation of an automated, microscopy-based method for enumeration of groups of intestinal bacteria

    NARCIS (Netherlands)

    Jansen, GJ; Wildeboer-Veloo, ACM; Tonk, RHJ; Franks, AH; Welling, G

    An automated microscopy-based method using fluorescently labelled 16S rRNA-targeted oligonucleotide probes directed against the predominant groups of intestinal bacteria was developed and validated. The method makes use of the Leica 600HR. image analysis system, a Kodak MegaPlus camera model 1.4 and

  5. Vibrational imaging and microspectroscopies based on coherent anti-Stokes Raman scattering microscopy

    International Nuclear Information System (INIS)

    Volkmer, Andreas


    For noninvasive characterization of chemical species or biological components within a complex heterogeneous system, their intrinsic molecular vibrational properties can be used in contrast mechanisms in optical microscopy. A series of recent advances have made coherent anti-Stokes Raman scattering (CARS) microscopy a powerful technique that allows vibrational imaging with high sensitivity, high spectral resolution and three-dimensional sectioning capability. In this review, we discuss theoretical and experimental aspects of CARS microscopy in a collinear excitation beam geometry. Particular attention is given to the underlying physical principles behind the new features of CARS signal generation under tight focusing conditions. We provide a brief overview of the instrumentation of CARS microscopy and its experimental characterization by means of imaging of model systems and live unstained cells. CARS microscopy offers the possibility of spatially resolved vibrational spectroscopy, providing chemical and physical structure information of molecular specimens on the sub-micrometre length scale. We review multiplex CARS microspectroscopy allowing fast acquisition of frequency-resolved CARS spectra, time-resolved CARS microspectroscopy recording ultrafast Raman free induction decays and CARS correlation spectroscopy probing dynamical processes with chemical selectivity. (topical review)

  6. Fluorescence microscopy. (United States)

    Sanderson, Michael J; Smith, Ian; Parker, Ian; Bootman, Martin D


    Fluorescence microscopy is a major tool with which to monitor cell physiology. Although the concepts of fluorescence and its optical separation using filters remain similar, microscope design varies with the aim of increasing image contrast and spatial resolution. The basics of wide-field microscopy are outlined to emphasize the selection, advantages, and correct use of laser scanning confocal microscopy, two-photon microscopy, scanning disk confocal microscopy, total internal reflection, and super-resolution microscopy. In addition, the principles of how these microscopes form images are reviewed to appreciate their capabilities, limitations, and constraints for operation. © 2014 Cold Spring Harbor Laboratory Press.

  7. Modeling of Fibrin Gels Based on Confocal Microscopy and Light-Scattering Data (United States)

    Magatti, Davide; Molteni, Matteo; Cardinali, Barbara; Rocco, Mattia; Ferri, Fabio


    Fibrin gels are biological networks that play a fundamental role in blood coagulation and other patho/physiological processes, such as thrombosis and cancer. Electron and confocal microscopies show a collection of fibers that are relatively monodisperse in diameter, not uniformly distributed, and connected at nodal points with a branching order of ∼3–4. Although in the confocal images the hydrated fibers appear to be quite straight (mass fractal dimension Dm = 1), for the overall system 1Based on the confocal images, we developed a method to generate three-dimensional (3D) in silico gels made of cylindrical sticks of diameter d, density ρ, and average length 〈L〉, joined at randomly distributed nodal points. The resulting 3D network strikingly resembles real fibrin gels and can be sketched as an assembly of densely packed fractal blobs, i.e., regions of size ξ, where the fiber concentration is higher than average. The blobs are placed at a distance ξ0 between their centers of mass so that they are overlapped by a factor η = ξ/ξ0 and have Dm ∼1.2–1.6. The in silico gels’ structure is quantitatively analyzed by its 3D spatial correlation function g3D(r) and corresponding power spectrum I(q) = FFT3D[g3D(r)], from which ρ, d, Dm, η, and ξ0 can be extracted. In particular, ξ0 provides an excellent estimate of the gel mesh size. The in silico gels’ I(q) compares quite well with real gels’ elastic light-scattering measurements. We then derived an analytical form factor for accurately fitting the scattering data, which allowed us to directly recover the gels’ structural parameters. PMID:23473498

  8. Structural properties of silver nanoparticle agglomerates based on transmission electron microscopy: relationship to particle mobility analysis

    International Nuclear Information System (INIS)

    Shin, Weon Gyu; Wang Jing; Mertler, Michael; Sachweh, Bernd; Fissan, Heinz; Pui, David Y. H.


    In this work, the structural properties of silver nanoparticle agglomerates generated using condensation and evaporation method in an electric tube furnace followed by a coagulation process are analyzed using Transmission Electron Microscopy (TEM). Agglomerates with mobility diameters of 80, 120, and 150 nm are sampled using the electrostatic method and then imaged by TEM. The primary particle diameter of silver agglomerates was 13.8 nm with a standard deviation of 2.5 nm. We obtained the relationship between the projected area equivalent diameter (d pa ) and the mobility diameter (d m ), i.e., d pa = 0.92 ± 0.03 d m for particles from 80 to 150 nm. We obtained fractal dimensions of silver agglomerates using three different methods: (1) D f = 1.84 ± 0.03, 1.75 ± 0.06, and 1.74 ± 0.03 for d m = 80, 120, and 150 nm, respectively from projected TEM images using a box counting algorithm; (2) fractal dimension (D fL ) = 1.47 based on maximum projected length from projected TEM images using an empirical equation proposed by Koylu et al. (1995) Combust Flame 100:621-633; and (3) mass fractal-like dimension (D fm ) = 1.71 theoretically derived from the mobility analysis proposed by Lall and Friedlander (2006) J Aerosol Sci 37:260-271. We also compared the number of primary particles in agglomerate and found that the number of primary particles obtained from the projected surface area using an empirical equation proposed by Koylu et al. (1995) Combust Flame 100:621-633 is larger than that from using the relationship, d pa = 0.92 ± 0.03 d m or from using the mobility analysis.

  9. A scanning tunneling microscopy based potentiometry technique and its application to the local sensing of the spin Hall effect

    Directory of Open Access Journals (Sweden)

    Ting Xie


    Full Text Available A scanning tunneling microscopy based potentiometry technique for the measurements of the local surface electric potential is presented. A voltage compensation circuit based on this potentiometry technique is developed and employed to maintain a desired tunneling voltage independent of the bias current flow through the film. The application of this potentiometry technique to the local sensing of the spin Hall effect is outlined and some experimental results are reported.

  10. Visualization of magnetic dipolar interaction based on scanning transmission X-ray microscopy

    International Nuclear Information System (INIS)

    Ohtori, Hiroyuki; Iwano, Kaoru; Takeichi, Yasuo; Ono, Kanta; Mitsumata, Chiharu; Yano, Masao; Kato, Akira; Miyamoto, Noritaka; Shoji, Tetsuya; Manabe, Akira


    Using scanning transmission X-ray microscopy (STXM), in this report we visualized the magnetic dipolar interactions in nanocrystalline Nd-Fe-B magnets and imaged their magnetization distributions at various applied fields. We calculated the magnetic dipolar interaction by analyzing the interaction between the magnetization at each point and those at the other points on the STXM image.

  11. Structured Illumination-Based Super-Resolution Optical Microscopy for Hemato- and Cyto-Pathology Applications

    Directory of Open Access Journals (Sweden)

    Tieqiao Zhang


    Full Text Available Structured illumination fluorescence microscopy utilizes interfering light and the moiré effect to enhance spatial resolution to about a half of that of conventional light microscopy, i.e. approximately 90 nm. In addition to the enhancement in the x and y directions, it also allows enhancement of resolution in the z- direction by the same factor of two (to approximately 220 nm, making it a powerful tool for 3-D morphology studies of fluorescently labeled cells or thin tissue sections. In this report, we applied this technique to several types of blood cells that are commonly seen in hematopathology. Compared with standard brightfield and ordinary fluorescence microscopy images, the 3-D morphology results clearly reveal the morphological features of different types of normal blood cells. We have also used this technique to evaluate morphologies of abnormal erythrocytes and compare them with those recorded on normal cells. The results give a very intuitive presentation of morphological structures of erythrocytes with great details. This research illustrates the potential of this technique to be used in hematology and cyto-pathology studies aimed at identifying nanometer-sized features that cannot be distinguished otherwise with conventional optical microscopy.

  12. Nanoparticle discrimination based on wavelength and lifetime-multiplexed cathodoluminescence microscopy

    NARCIS (Netherlands)

    Garming, Mathijs W H; Weppelman, I Gerward C; de Boer, Pascal; Martínez, Felipe Perona; Schirhagl, Romana; Hoogenboom, Jacob P; Moerland, Robert J


    Nanomaterials can be identified in high-resolution electron microscopy images using spectrally-selective cathodoluminescence. Capabilities for multiplex detection can however be limited, e.g., due to spectral overlap or availability of filters. Also, the available photon flux may be limited due to

  13. Context based support for Clinical Reasoning

    DEFF Research Database (Denmark)

    Vilstrup Pedersen, Klaus


    In many areas of the medical domain, the decision process i.e. reasoning, involving health care professionals is distributed, cooperative and complex. Computer based decision support systems has usually been focusing on the outcome of the decision making and treated it as a single task....... In this paper a framework for a Clinical Reasoning Knowledge Warehouse (CRKW) is presented, intended to support the reasoning process, by providing the decision participants with an analysis platform that captures and enhances information and knowledge. The CRKW mixes theories and models from Artificial...... Intelligence, Knowledge Management Systems and Business Intelligence to make context sensitive, patient case specific analysis and knowledge management. The knowledge base consists of patient health records, reasoning process information and clinical guidelines. Patient specific information and knowledge...

  14. The impact of postoperative expansion initiation timing on breast expander capsular characteristics: a prospective combined clinical and scanning electron microscopy study. (United States)

    Paek, Laurence S; Giot, Jean-Philippe; Tétreault-Paquin, Jean-Olivier; St-Jacques, Samuel; Nelea, Monica; Danino, M Alain


    In the first stage of expander-to-implant breast reconstruction, postoperative expansion is classically initiated at 10 to 14 days (conventional approach). The authors hypothesized that it may be beneficial to wait 6 weeks postoperatively before initiating serial expansion (delayed approach). Clinical and ultrastructural periprosthetic capsule analysis is first required before determining whether a delayed approach ultimately improves capsular tissue adherence and expansion process predictability. Patients undergoing two-stage implant-based breast reconstruction were enrolled prospectively in this study. During expander-to-implant exchange, the clinical presence of "Velcro" effect, biofilm, and double capsule was noted. Periprosthetic capsule samples were also sent for scanning electron microscopic observation of three parameters: surface relief, cellularity, and biofilm. Samples were divided into four groups for data analysis (group 1, conventional/Biocell; group 2, delayed/Biocell; group 3, conventional/Siltex; and group 4, delayed/Siltex). Fifty-six breast reconstructions were included. Each group comprised between 13 and 15 breasts. In group 1, no cases exhibited the Velcro effect and there was a 53.8 percent incidence of both biofilm and double capsule. In group 2, all cases demonstrated the Velcro effect and there were no incidences of biofilm or double capsule. Group 3 and group 4 cases did not exhibit a Velcro effect or double-capsule formation; however, biofilm was present in up to 20.0 percent. All group 2 samples revealed more pronounced three-dimensional relief on scanning electron microscopy. Variations in expansion protocols can lead to observable modifications in periprosthetic capsular architecture. There may be real benefits to delaying expander inflation until 6 weeks postoperatively with Biocell expanders.

  15. High resolution transmission electron microscopy studies of {sigma} phase in Ni-based single crystal superalloys

    Energy Technology Data Exchange (ETDEWEB)

    Sun Fei [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, Jinan 250061 (China); Zhang Jianxin, E-mail: [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, Jinan 250061 (China); Liu Pan [Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing 100124 (China); Feng Qiang [National Center for Materials Service Safety, University of Science and Technology Beijing, Beijing 100083 (China); State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Han Xiaodong; Mao Shengcheng [Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing 100124 (China)


    Graphical abstract: (a) TEM micrograph of {sigma} phase; (b) HRTEM image of {sigma}/{gamma} interface corresponding to the area of the white frame in (a); (c) an enlarged image of area from the white frame in (b). The combination of {sigma}/{gamma} interface appears very well, and a two-atomic-layer step is shown on the {sigma}/{gamma} interface. In addition, {sigma} phase has the orientation relationship of [0 0 1]{sub {gamma}}//[1 1 2{sup Macron }]{sub {sigma}}, (2{sup Macron} 2 0){sub {gamma}}//(1{sup Macron} 1 0){sub {sigma}}, (2{sup Macron }2{sup Macron} 0){sub {gamma}}//(1 1 1){sub {sigma}}; [0 1 1]{sub {gamma}}//[1 1 0]{sub {sigma}}, (1 1{sup Macron} 1){sub {gamma}}//(0 0 1{sup Macron }){sub {sigma}} with the {gamma} phase. Highlights: Black-Right-Pointing-Pointer Elemental characteristic of {sigma} phase is studied by HAADF techniques and EDS analysis. Black-Right-Pointing-Pointer Interfacial characteristics of {sigma}/{gamma} interface are revealed by HRTEM. Black-Right-Pointing-Pointer An atomic structural {sigma}/{gamma} interface with a two-atomic-layer step has been proposed. - Abstract: By means of high resolution transmission electron microscopy (HRTEM) and high-angle annular dark-field image technique (HAADF), morphological of plate-shaped {sigma} phase and interfacial characteristics between plate-shaped {sigma} phase and {gamma} phase in Ni-based single crystal superalloys have been studied. On the basis of HRTEM observations, an atomic structural interface between {sigma} phase and {gamma} phase with a step has been proposed. {sigma} Phase has the relationship of [0 0 1]{sub {gamma}}//[1 1 2{sup Macron }]{sub {sigma}}, (2{sup Macron} 2 0){sub {gamma}}//(1{sup Macron} 1 0){sub {sigma},} (2{sup Macron }2{sup Macron} 0){sub {gamma}}//(1 1 1){sub {sigma}}; [0 1 1]{sub {gamma}}//[1 1 0]{sub {sigma}}, (1 1{sup Macron} 1){sub {gamma}}//(0 0 1{sup Macron }){sub {sigma}} with the {gamma} phase. The compositional characteristics of the {sigma} phase which

  16. Non parametric denoising methods based on wavelets: Application to electron microscopy images in low exposure time

    International Nuclear Information System (INIS)

    Soumia, Sid Ahmed; Messali, Zoubeida; Ouahabi, Abdeldjalil; Trepout, Sylvain; Messaoudi, Cedric; Marco, Sergio


    The 3D reconstruction of the Cryo-Transmission Electron Microscopy (Cryo-TEM) and Energy Filtering TEM images (EFTEM) hampered by the noisy nature of these images, so that their alignment becomes so difficult. This noise refers to the collision between the frozen hydrated biological samples and the electrons beam, where the specimen is exposed to the radiation with a high exposure time. This sensitivity to the electrons beam led specialists to obtain the specimen projection images at very low exposure time, which resulting the emergence of a new problem, an extremely low signal-to-noise ratio (SNR). This paper investigates the problem of TEM images denoising when they are acquired at very low exposure time. So, our main objective is to enhance the quality of TEM images to improve the alignment process which will in turn improve the three dimensional tomography reconstructions. We have done multiple tests on special TEM images acquired at different exposure time 0.5s, 0.2s, 0.1s and 1s (i.e. with different values of SNR)) and equipped by Golding beads for helping us in the assessment step. We herein, propose a structure to combine multiple noisy copies of the TEM images. The structure is based on four different denoising methods, to combine the multiple noisy TEM images copies. Namely, the four different methods are Soft, the Hard as Wavelet-Thresholding methods, Bilateral Filter as a non-linear technique able to maintain the edges neatly, and the Bayesian approach in the wavelet domain, in which context modeling is used to estimate the parameter for each coefficient. To ensure getting a high signal-to-noise ratio, we have guaranteed that we are using the appropriate wavelet family at the appropriate level. So we have chosen âĂIJsym8âĂİ wavelet at level 3 as the most appropriate parameter. Whereas, for the bilateral filtering many tests are done in order to determine the proper filter parameters represented by the size of the filter, the range parameter and the

  17. The application of aberration-corrected electron microscopy to the characterization of gold-based catalysts (United States)

    Herzing, Andrew A.

    Electron microscopy has long been used to study the morphology of heterogeneous catalysts. Recent advances in electron optics now allow for the correction of the inherent spherical aberration (Cs) produced by the objective lens in the scanning transmission electron microscope (STEM, resulting in a significantly improved spatial resolution as well as the ability to use a much larger probe-current than was previously possible. In this thesis, the combination of high-angle annular dark-field (HAADF) imaging and microanalysis by x-ray energy dispersive spectroscopy (XEDS) in an aberration-corrected STEM has been applied for the first time to the characterization of gold-based heterogeneous catalysts. Multi-variate statistical analysis (MSA) has been employed in order to further improve the STEM-XEDS spectrum image data acquired with this technique. In addition, supplemental analysis using electron-energy loss spectroscopy (EELS) and energy-filtered transmission electron microscopy (EFTEM) in an aberration-corrected instrument has also been attempted. These techniques have proven extremely valuable in providing complimentary information to more traditional catalyst characterization techniques such as x-ray photoelectron spectroscopy and x-ray diffraction in four specific problems relating to catalysis. Firstly, the atomic-scale resolution of Cs-corrected HAADF imaging has been utilized to study Au/FeOx catalysts in order to determine the size and structure of the Au clusters present on the support surface. It was discovered that, while both inactive and active catalysts for low-temperature CO oxidation contained large Au particles (> 5 nm) and individual Au atoms, the active catalyst also contained sub-nm clusters comprised of only a few Au atoms. Secondly, novel CeO2 support materials for Au and Au-Pd catalysts were synthesized by precipitation with supercritical CO2. These supports were found to produce significantly more active catalysts than those based on CeO2

  18. From the patient to the clinical mycology laboratory: how can we optimise microscopy and culture methods for mould identification? (United States)

    Vyzantiadis, Timoleon-Achilleas A; Johnson, Elizabeth M; Kibbler, Christopher C


    The identification of fungi relies mainly on morphological criteria. However, there is a need for robust and definitive phenotypic identification procedures in order to evaluate continuously evolving molecular methods. For the future, there is an emerging consensus that a combined (phenotypic and molecular) approach is more powerful for fungal identification, especially for moulds. Most of the procedures used for phenotypic identification are based on experience rather than comparative studies of effectiveness or performance and there is a need for standardisation among mycology laboratories. This review summarises and evaluates the evidence for the major existing phenotypic identification procedures for the predominant causes of opportunistic mould infection. We have concentrated mainly on Aspergillus, Fusarium and mucoraceous mould species, as these are the most important clinically and the ones for which there are the most molecular taxonomic data.

  19. Web-based virtual microscopy at the RWTH Aachen University: didactic concept, methods and analysis of acceptance by the students. (United States)

    Merk, Magdalene; Knuechel, Ruth; Perez-Bouza, Alberto


    Fundamental knowledge of microscopic anatomy and pathology has always been an essential part in medical education. The traditional didactic concept comprises theoretical and practical lessons using a light microscope and glass slides. High-speed Internet connections and technical improvement in whole-slide digital microscopy (commonly termed "virtual microscopy") provide a new and attractive approach for both teachers and students. High picture quality and unlimited temporal and spatial availability of histology samples from different fields are key advantages of web-based digital microscopy. In this report we discuss the technical requirements, system efficiency, optical resolution and didactic concept. Furthermore, we present a review of the experience gained in the course of one year based on an analysis of student acceptance. Three groups with a total of 192 students between the 3rd and 5th year of medical studies attending the practical courses of general and advanced histopathology had access to both glass-mounted and digitalized slides. Prior to exams, students were asked to answer an anonymous questionnaire. The results of the study reflect the high acceptance and intensive use of the web-based digital histology by students, thus encouraging the development of further Web-based learning strategies for the teaching of histology and pathology. 2010 Elsevier GmbH. All rights reserved.

  20. Experimental transmission electron microscopy studies and phenomenological model of bismuth-based superconducting compounds

    International Nuclear Information System (INIS)

    Elboussiri, Khalid


    The main part of this thesis is devoted to an experimental study by transmission electron microscopy of the different phases of the superconducting bismuth cuprates Bi_2Sr_2Ca_n_-_1Cu_nO_2_n_+_4. In high resolution electron microscopy, the two types of incommensurate modulation realized in these compounds have been observed. A model of structure has been proposed from which the simulated images obtained are consistent with observations. The medium resolution images correlated with the electron diffraction data have revealed existence of a multi-soliton regime with latent lock in phases of commensurate periods between 4b and 10b. At last, a description of different phases of these compounds as a result of superstructures from a disordered perovskite type structure is proposed (author) [fr

  1. Electron microscopy study of the deactivation of nickel based catalysts for bio oil hydrodeoxygenation

    DEFF Research Database (Denmark)

    Gardini, Diego; Mortensen, Peter Mølgaard; Carvalho, Hudson W. P.


    Hydrodeoxygenation (HDO) is proposed as an efficient way to remove oxygen in bio-oil, improving its quality as a more sustainable alternative to conventional fuels in terms of CO2 neutrality and relative short production cycle [1]. Ni and Ni-MoS2 nanoparticles supported on ZrO2 show potential...... as high-pressure (100 bar) catalysts for purification of bio-oil by HDO. However, the catalysts deactivate in presence of sulfur, chlorine and potassium species, which are all naturally occurring in real bio-oil. The deactivation mechanisms of the Ni/ZrO2 have been investigated through scanning...... transmission electron microscopy (STEM), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Catalytic testing has been performed using guaiacol in 1-octanol acting as a model compound for bio-oil. Addition of sulphur (0.3 vol% octanethiol) in the feed...

  2. Model-based traction force microscopy reveals differential tension in cellular actin bundles. (United States)

    Soiné, Jérôme R D; Brand, Christoph A; Stricker, Jonathan; Oakes, Patrick W; Gardel, Margaret L; Schwarz, Ulrich S


    Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.

  3. A Fast Global Fitting Algorithm for Fluorescence Lifetime Imaging Microscopy Based on Image Segmentation


    Pelet, S.; Previte, M.J.R.; Laiho, L.H.; So, P.T. C.


    Global fitting algorithms have been shown to improve effectively the accuracy and precision of the analysis of fluorescence lifetime imaging microscopy data. Global analysis performs better than unconstrained data fitting when prior information exists, such as the spatial invariance of the lifetimes of individual fluorescent species. The highly coupled nature of global analysis often results in a significantly slower convergence of the data fitting algorithm as compared with unconstrained ana...

  4. Challenges of microtome‐based serial block‐face scanning electron microscopy in neuroscience (United States)



    Summary Serial block‐face scanning electron microscopy (SBEM) is becoming increasingly popular for a wide range of applications in many disciplines from biology to material sciences. This review focuses on applications for circuit reconstruction in neuroscience, which is one of the major driving forces advancing SBEM. Neuronal circuit reconstruction poses exceptional challenges to volume EM in terms of resolution, field of view, acquisition time and sample preparation. Mapping the connections between neurons in the brain is crucial for understanding information flow and information processing in the brain. However, information on the connectivity between hundreds or even thousands of neurons densely packed in neuronal microcircuits is still largely missing. Volume EM techniques such as serial section TEM, automated tape‐collecting ultramicrotome, focused ion‐beam scanning electron microscopy and SBEM (microtome serial block‐face scanning electron microscopy) are the techniques that provide sufficient resolution to resolve ultrastructural details such as synapses and provides sufficient field of view for dense reconstruction of neuronal circuits. While volume EM techniques are advancing, they are generating large data sets on the terabyte scale that require new image processing workflows and analysis tools. In this review, we present the recent advances in SBEM for circuit reconstruction in neuroscience and an overview of existing image processing and analysis pipelines. PMID:25907464

  5. Diatom Valve Three-Dimensional Representation: A New Imaging Method Based on Combined Microscopies (United States)

    Ferrara, Maria Antonietta; De Tommasi, Edoardo; Coppola, Giuseppe; De Stefano, Luca; Rea, Ilaria; Dardano, Principia


    The frustule of diatoms, unicellular microalgae, shows very interesting photonic features, generally related to its complicated and quasi-periodic micro- and nano-structure. In order to simulate light propagation inside and through this natural structure, it is important to develop three-dimensional (3D) models for synthetic replica with high spatial resolution. In this paper, we present a new method that generates images of microscopic diatoms with high definition, by merging scanning electron microscopy and digital holography microscopy or atomic force microscopy data. Starting from two digital images, both acquired separately with standard characterization procedures, a high spatial resolution (Δz = λ/20, Δx = Δy ≅ 100 nm, at least) 3D model of the object has been generated. Then, the two sets of data have been processed by matrix formalism, using an original mathematical algorithm implemented on a commercially available software. The developed methodology could be also of broad interest in the design and fabrication of micro-opto-electro-mechanical systems. PMID:27690008

  6. Atom-probe field-ion microscopy investigation of CMSX-4 Ni-base superalloy laser beam welds

    International Nuclear Information System (INIS)

    Babu, S.S.; David, S.A.; Vitek, J.M.; Miller, M.K.


    CMSX-4 superalloy laser beam welds were investigated by transmission electron microscopy and atom probe field-ion microscopy (APFIM). The weld microstructure consisted of fine (10- to 50-nm) irregularly shaped γ' precipitates (0.65 to 0.75 volume fraction) within the γ matrix. APFIM compositions of the γ and γ' phases were found to be different from those in the base metal. Concentration profiles across the γ and γ' phases showed extensive variations of Cr, Co and Al concentrations as a function of distance within the γ phase. Calculated lattice misfits near the γ/γ' interface in the welds are positive values compared to the negative values for base metal. (orig.)

  7. Helium ion microscopy based wall thickness and surface roughness analysis of polymer foams obtained from high internal phase emulsion

    International Nuclear Information System (INIS)

    Rodenburg, C.; Viswanathan, P.; Jepson, M.A.E.; Liu, X.; Battaglia, G.


    Due to their wide range of applications, porous polymers obtained from high internal phase emulsions have been widely studied using scanning electron microscopy. However, due to their lack of electrical conductivity, quantitative information of wall thicknesses and surface roughness, which are of particular interest to tissue engineering, has not been obtained. Here, Helium Ion Microscopy is used to examine uncoated polymer foams and some very strong but unexpected contrast is observed, the origin of which is established here. Based on this analysis, a method for the measurement of wall thickness variations and wall roughness measurements has been developed, based on the modeling of Helium ion transmission. The results presented here indicate that within the walls of the void structure there exist small features with height variations of ∼30 nm and wall thickness variations from ∼100 nm to larger 340 nm in regions surrounding interconnecting windows within the structure. The suggested imaging method is applicable to other porous carbon based structures with wall thicknesses in the range of 40–340 nm. - Highlights: • The first helium ion microscopy image of uncoated structures formed from HIPEs is presented. • Unusually high contrast features that change with accelerating voltage are observed. • The origin of the observed contrast is determined to be mass thickness contrast. • A new method for quantitative wall thickness variation/roughness measurements is demonstrated

  8. Helium ion microscopy based wall thickness and surface roughness analysis of polymer foams obtained from high internal phase emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Rodenburg, C., E-mail: [Department of Materials Science and Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD (United Kingdom); Viswanathan, P. [Department of Biomedical Sciences, University of Sheffield, Firth Court, Western Bank Sheffield, Sheffield S10 2 TN (United Kingdom); Jepson, M.A.E. [Department of Materials, Loughborough University, Loughborough, Leicestershire LE11 3TU (United Kingdom); Liu, X. [Carl Zeiss Microscopy GmbH, Carl-Zeiss-Strasse 22, 73447 Oberkochen (Germany); Battaglia, G. [Department of Chemistry University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom); The MRC/UCL Centre for Medical Molecular Virology, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)


    Due to their wide range of applications, porous polymers obtained from high internal phase emulsions have been widely studied using scanning electron microscopy. However, due to their lack of electrical conductivity, quantitative information of wall thicknesses and surface roughness, which are of particular interest to tissue engineering, has not been obtained. Here, Helium Ion Microscopy is used to examine uncoated polymer foams and some very strong but unexpected contrast is observed, the origin of which is established here. Based on this analysis, a method for the measurement of wall thickness variations and wall roughness measurements has been developed, based on the modeling of Helium ion transmission. The results presented here indicate that within the walls of the void structure there exist small features with height variations of ∼30 nm and wall thickness variations from ∼100 nm to larger 340 nm in regions surrounding interconnecting windows within the structure. The suggested imaging method is applicable to other porous carbon based structures with wall thicknesses in the range of 40–340 nm. - Highlights: • The first helium ion microscopy image of uncoated structures formed from HIPEs is presented. • Unusually high contrast features that change with accelerating voltage are observed. • The origin of the observed contrast is determined to be mass thickness contrast. • A new method for quantitative wall thickness variation/roughness measurements is demonstrated.

  9. PREFACE: 6th Workshop on Infrared Spectroscopy and Microscopy with Accelerator-Based Sources (WIRMS11) (United States)

    Lupi, Stefano; Perucchi, Andrea


    This volume of Journal of Physics: Conference Series is dedicated to a subset of papers related to the work presented at the 6th edition of the international Workshop on Infrared Spectroscopy and Microscopy with Accelerator-Based Sources (WIRMS), held in Trieste, Italy, September 4-8 2011. Previous editions of the conference were held in Porquerolles (France), Lake Tahoe (USA), Rathen (Germany), Awaji (Japan), and Banff (Canada). This edition was organized and chaired by Stefano Lupi (Roma La Sapienza) and co-chaired by Andrea Perucchi (Elettra), with the support of the Italian Synchrotron Light Laboratory ELETTRA, which was honored to host the WIRMS workshop in its tenth anniversary. The 6th WIRMS edition addressed several different topics, ranging from biochemistry to strongly correlated materials, from geology to conservation science, and from forensics to the study of cometary dusts. Representatives from the infrared scientific programs at synchrotron light sources and free-electron-laser facilities. This edition was attended by 88 participants, including representatives from the infrared scientific programs at synchrotron light sources and free-electron-laser facilities, who enjoyed the stimulating scientific presentations, several detailed discussions, and the beautiful weather and scenery of the Trieste gulf. Participants came from 16 different nations and four continents, including many young scientists, six of which were supported by the organizers. There were 45 scientific talks divided in 11 sessions: Facilities, Microspectroscopy (I, II, III), Time-Resolved Spectroscopies, Extreme Conditions, Condensed Matter, Near-Field, Imaging, THz Techniques and High-Resolution Spectroscopy. 37 posters were also presented at two very lively evening poster sessions. We would like to use the opportunity of writing this preface to thank all the participants of the workshop for the very high level of their scientific contribution and for the very friendly atmosphere

  10. Monolithically Integrated, Mechanically Resilient Carbon-Based Probes for Scanning Probe Microscopy (United States)

    Kaul, Anupama B.; Megerian, Krikor G.; Jennings, Andrew T.; Greer, Julia R.


    Scanning probe microscopy (SPM) is an important tool for performing measurements at the nanoscale in imaging bacteria or proteins in biology, as well as in the electronics industry. An essential element of SPM is a sharp, stable tip that possesses a small radius of curvature to enhance spatial resolution. Existing techniques for forming such tips are not ideal. High-aspect-ratio, monolithically integrated, as-grown carbon nanofibers (CNFs) have been formed that show promise for SPM applications by overcoming the limitations present in wet chemical and separate substrate etching processes.

  11. Polythiophenes and fullerene derivatives based donor-acceptor system: topography by atomic force microscopy

    International Nuclear Information System (INIS)

    Marcakova, M. L.; Repovsky, D.; Cik, G.; Velic, D.


    The goal of this work is to examine the surface of a polythiophene/fullerene film in order to understand the structure. In this work polythiophene is used as electron donor and fullerene-derivative is used as electron acceptor. Atomic force microscopy (AFM), is an ideal method to study surfaces and nanostructures. Surfaces of fullerene C60 , fullerene-derivates PCBM, polythiophene P12 and a mixture of P12 and PCBM are characterized. In all samples, the average roughness, the arithmetical value of divergence from the high of the surface, is determined concluding that P12 and PCBM mix together well and form a film with specific topography. (authors)

  12. Colocalization coefficients evaluating the distribution of molecular targets in microscopy methods based on pointed patterns

    Czech Academy of Sciences Publication Activity Database

    Pastorek, Lukáš; Sobol, Margaryta; Hozák, Pavel


    Roč. 146, č. 4 (2016), s. 391-406 ISSN 0948-6143 R&D Projects: GA TA ČR(CZ) TE01020118; GA ČR GA15-08738S; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LM2015062 Grant - others:Human Frontier Science Program(FR) RGP0017/2013 Institutional support: RVO:68378050 Keywords : Colocalization * Quantitative analysis * Pointed patterns * Transmission electron microscopy * Manders' coefficients * Immunohistochemistry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.553, year: 2016

  13. Mapping of Proteomic Composition on the Surfaces of Bacillus spores by Atomic Force Microscopy-based Immunolabeling

    Energy Technology Data Exchange (ETDEWEB)

    Plomp, M; Malkin, A J


    Atomic force microscopy provides a unique capability to image high-resolution architecture and structural dynamics of pathogens (e.g. viruses, bacteria and bacterial spores) at near molecular resolution in native conditions. Further development of atomic force microscopy in order to enable the correlation of pathogen protein surface structures with specific gene products is essential to understand the mechanisms of the pathogen life cycle. We have applied an AFM-based immunolabeling technique for the proteomic mapping of macromolecular structures through the visualization of the binding of antibodies, conjugated with nanogold particles, to specific epitopes on Bacillus spore surfaces. This information is generated while simultaneously acquiring the surface morphology of the pathogen. The immunospecificity of this labeling method was established through the utilization of specific polyclonal and monoclonal antibodies that target spore coat and exosporium epitopes of Bacillus atrophaeus and Bacillus anthracis spores.

  14. 3D imaging of cement-based materials at submicron resolution by combining laser scanning confocal microscopy with serial sectioning. (United States)

    Yio, M H N; Mac, M J; Wong, H S; Buenfeld, N R


    In this paper, we present a new method to reconstruct large volumes of nontransparent porous materials at submicron resolution. The proposed method combines fluorescence laser scanning confocal microscopy with serial sectioning to produce a series of overlapping confocal z-stacks, which are then aligned and stitched based on phase correlation. The method can be extended in the XY plane to further increase the overall image volume. Resolution of the reconstructed image volume does not degrade with increase in sample size. We have used the method to image cementitious materials, hardened cement paste and concrete and the results obtained show that the method is reliable. Possible applications of the method such as three-dimensional characterization of the pores and microcracks in hardened concrete, three-dimensional particle shape characterization of cementitious materials and three-dimensional characterization of other porous materials such as rocks and bioceramics are discussed. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  15. Microscopy based studies on the interaction of bio-based silver nanoparticles with Bombyx mori Nuclear Polyhedrosis virus. (United States)

    Tamilselvan, Selvaraj; Ashokkumar, Thirunavukkarasu; Govindaraju, Kasivelu


    In the present investigation, silver nanoparticles (AgNPs) interactions with Bombyx mori Nuclear Polyhedrosis virus (BmNPV) were characterized using High-Resolution Scanning Electron Microscopy (HR-SEM), Energy Dispersive X-ray Analysis (EDAX), Transmission Electron Microscopy (TEM), Atomic Force Microcopy (AFM) and Confocal Microscope (CM). HR-SEM study reveals that the biosynthesized AgNPs have interacted with BmNPV and were found on the surface. TEM micrographs of normal and viral polyhedra treated with AgNPs showed that the nanoparticles were accumulated in the membrane and it was noted that some of the AgNPs successfully penetrated the membrane by reaching the capsid of BmNPV. AFM and confocal microscopy studies reveal that the disruption in the shell membrane tends to lose its stability due to exposure of AgNPs to BmNPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Adaptive platform for fluorescence microscopy-based high-content screening (United States)

    Geisbauer, Matthias; Röder, Thorsten; Chen, Yang; Knoll, Alois; Uhl, Rainer


    Fluorescence microscopy has become a widely used tool for the study of medically relevant intra- and intercellular processes. Extracting meaningful information out of a bulk of acquired images is usually performed during a separate post-processing task. Thus capturing raw data results in an unnecessary huge number of images, whereas usually only a few images really show the particular information that is searched for. Here we propose a novel automated high-content microscope system, which enables experiments to be carried out with only a minimum of human interaction. It facilitates a huge speed-increase for cell biology research and its applications compared to the widely performed workflows. Our fluorescence microscopy system can automatically execute application-dependent data processing algorithms during the actual experiment. They are used for image contrast enhancement, cell segmentation and/or cell property evaluation. On-the-fly retrieved information is used to reduce data and concomitantly control the experiment process in real-time. Resulting in a closed loop of perception and action the system can greatly decrease the amount of stored data on one hand and increases the relative valuable data content on the other hand. We demonstrate our approach by addressing the problem of automatically finding cells with a particular combination of labeled receptors and then selectively stimulate them with antagonists or agonists. The results are then compared against the results of traditional, static systems.

  17. Systematic study of alginate-based microcapsules by micropipette aspiration and confocal fluorescence microscopy. (United States)

    Kleinberger, Rachelle M; Burke, Nicholas A D; Dalnoki-Veress, Kari; Stöver, Harald D H


    Micropipette aspiration and confocal fluorescence microscopy were used to study the structure and mechanical properties of calcium alginate hydrogel beads (A beads), as well as A beads that were additionally coated with poly-L-lysine (P) and sodium alginate (A) to form, respectively, AP and APA hydrogels. A beads were found to continue curing for up to 500 h during storage in saline, due to residual calcium chloride carried over from the gelling bath. In subsequent saline washes, micropipette aspiration proved to be a sensitive indicator of gel weakening and calcium loss. Aspiration tests were used to compare capsule stiffness before and after citrate extraction of calcium. They showed that the initial gel strength is largely due to the calcium alginate gel cores, while the long term strength is solely due to the poly-L-lysine-alginate polyelectrolyte complex (PEC) shells. Confocal fluorescence microscopy showed that calcium chloride exposure after PLL deposition led to PLL redistribution into the hydrogel bead, resulting in thicker but more diffuse and weaker PEC shells. Adding a final alginate coating to form APA capsules did not significantly change the PEC membrane thickness and stiffness, but did speed the loss of calcium from the bead core. © 2013.

  18. Observer Performance in the Use of Digital and Optical Microscopy for the Interpretation of Tissue-Based Biomarkers

    Directory of Open Access Journals (Sweden)

    Marios A. Gavrielides


    Full Text Available Background. We conducted a validation study of digital pathology for the quantitative assessment of tissue-based biomarkers with immunohistochemistry. Objective.\tTo examine observer agreement as a function of viewing modality (digital versus optical microscopy, whole slide versus tissue microarray (TMA review, biomarker type (HER2 incorporating membranous staining and Ki-67 with nuclear staining, and data type (continuous and categorical. Methods.\tEight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67 and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97 cores, using digital and optical microscopy. Results. Results showed relatively high overall interobserver and intermodality agreement, with different patterns specific to biomarker type. For HER2, there was better interobserver agreement for optical compared to digital microscopy for whole slides as well as better interobserver and intermodality agreement for TMAs. For Ki-67, those patterns were not observed. Conclusions. The differences in agreement patterns when examining different biomarkers and different scoring methods and reviewing whole slides compared to TMA stress the need for validation studies focused on specific pathology tasks to eliminate sources of variability that might dilute findings. The statistical uncertainty observed in our analyses calls for adequate sampling for each individual task rather than pooling cases.

  19. Deep-depletion physics-based analytical model for scanning capacitance microscopy carrier profile extraction

    International Nuclear Information System (INIS)

    Wong, K. M.; Chim, W. K.


    An approach for fast and accurate carrier profiling using deep-depletion analytical modeling of scanning capacitance microscopy (SCM) measurements is shown for an ultrashallow p-n junction with a junction depth of less than 30 nm and a profile steepness of about 3 nm per decade change in carrier concentration. In addition, the analytical model is also used to extract the SCM dopant profiles of three other p-n junction samples with different junction depths and profile steepnesses. The deep-depletion effect arises from rapid changes in the bias applied between the sample and probe tip during SCM measurements. The extracted carrier profile from the model agrees reasonably well with the more accurate carrier profile from inverse modeling and the dopant profile from secondary ion mass spectroscopy measurements

  20. Memory-effect based deconvolution microscopy for super-resolution imaging through scattering media (United States)

    Edrei, Eitan; Scarcelli, Giuliano


    High-resolution imaging through turbid media is a fundamental challenge of optical sciences that has attracted a lot of attention in recent years for its wide range of potential applications. Here, we demonstrate that the resolution of imaging systems looking behind a highly scattering medium can be improved below the diffraction-limit. To achieve this, we demonstrate a novel microscopy technique enabled by the optical memory effect that uses a deconvolution image processing and thus it does not require iterative focusing, scanning or phase retrieval procedures. We show that this newly established ability of direct imaging through turbid media provides fundamental and practical advantages such as three-dimensional refocusing and unambiguous object reconstruction.

  1. High-resolution TEM microscopy study of the creep behaviour of carbon-based cathode materials

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei, E-mail: [College of Materials Science and Engineering, Henan University of Science and Technology, Luoyang 471023 (China); Collaborative Innovation Center of Nonferrous Metals Henan Province, Luoyang 471023 (China); Chen, Weijie [College of Materials Science and Engineering, Henan University of Science and Technology, Luoyang 471023 (China); Collaborative Innovation Center of Nonferrous Metals Henan Province, Luoyang 471023 (China); Gu, Wanduo [Collaborative Innovation Center of Nonferrous Metals Henan Province, Luoyang 471023 (China)


    Creep is in close relationship with the materials deterioration and deformation of the cathodes in aluminum reduction cells. The purpose of this work is to obtain the creep mechanism of the carbon cathode for aluminum electrolysis. A modified Rapoport equipment was used for measuring the creep strain of the semi-graphitic cathodes during aluminum electrolysis with CR=2.5 and at temperature of 945 ℃. The arrangement of carbon atom has been studied after hexagonal graphite converting into rhombohedral graphite during aluminum electrolysis by XRD and high-resolution transmission electron microscopy (HRTEM). The creep deformation of the carbon cathode has a close relationship with the mobile dislocation walls. These results will be helpful in controlling the cathode quality and its performance in aluminum reduction cells.

  2. Distinction of heterogeneity on Au nanostructured surface based on phase contrast imaging of atomic force microscopy

    International Nuclear Information System (INIS)

    Jung, Mi; Choi, Jeong-Woo


    The discrimination of the heterogeneity of different materials on nanostructured surfaces has attracted a great deal of interest in biotechnology as well as nanotechnology. Phase imaging through tapping mode of atomic force microscopy (TMAFM) can be used to distinguish the heterogeneity on a nanostructured surface. Nanostructures were fabricated using anodic aluminum oxide (AAO). An 11-mercaptoundecanoic acid (11-MUA) layer adsorbed onto the Au nanodots through self-assembly to improve the bio-compatibility. The Au nanostructures that were modified with 11-MUA and the concave surfaces were investigated using the TMAFM phase images to compare the heterogeneous and homogeneous nanostructured surfaces. Although the topography and phase images were taken simultaneously, the images were different. Therefore, the contrast in the TMAFM phase images revealed the different compositional materials on the heterogeneous nanostructure surface.

  3. Specialized probes based on hydroxyapatite calcium for heart tissues research by atomic force microscopy

    International Nuclear Information System (INIS)

    Zhukov, Mikhail; Golubok, Alexander; Gulyaev, Nikolai


    The new specialized AFM-probes with hydroxyapatite structures for atomic force microscopy of heart tissues calcification were created and studied. A process of probe fabrication is demonstrated. The adhesive forces between specialized hydroxyapatite probe and endothelium/subendothelial layers were investigated. It was found that the adhesion forces are significantly higher for the subendothelial layers. We consider that it is connected with the formation and localization of hydroxyapatite in the area of subendothelial layers of heart tissues. In addition, the roughness analysis and structure visualization of the endothelial surface of the heart tissue were carried out. The results show high efficiency of created specialized probes at study a calcinations process of the aortic heart tissues.

  4. Laboratory source based full-field x-ray microscopy at 9 keV

    Energy Technology Data Exchange (ETDEWEB)

    Fella, C.; Balles, A.; Wiest, W. [Lehrstuhl für Röntgenmikroskopie, Julius-Maximilians-Universität, 97074 Würzburg (Germany); Zabler, S.; Hanke, R. [Lehrstuhl für Röntgenmikroskopie, Julius-Maximilians-Universität, 97074 Würzburg (Germany); Fraunhofer Development Center X-Ray Technology (EZRT), Flugplatzstrasse 75, 90768 Fürth (Germany)


    In the past decade, hard x-ray transmission microscopy experienced tremendous developments. With the avail-ability of efficient Fresnel zone plates, even set-ups utilizing laboratory sources were developed [1]. In order to improve the performance of these x-ray microscopes, novel approaches to fabricate optical elements [2] and brighter x-ray tubes [3] are promising candidates. We are currently building a laboratory transmission x-ray microscope for 9.25 keV, using an electron impact liquid-metal-jet anode source. Up to now, the further elements of our setup are: a polycapillary condenser, a tungsten zone plate, and a scintillator which is optically coupled to a CMOS camera. However, further variations in terms of optical elements are intended. Here we present the current status of our work, as well as first experimental results.

  5. Korean Clinic Based Outcome Measure Studies

    Directory of Open Access Journals (Sweden)

    Jongbae Park


    Full Text Available Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented briefly here including 1 Quality of Life of liver cancer patients after 8 Constitutional acupuncture; 2 Developing a Korean version of Measuring yourself Medical Outcome profile (MYMOP; and 3 Survey on 5 Shu points: a pilot In the first study, we have included 4 primary or secondary liver cancer patients collecting their diagnostic X-ray film and clinical data f개m their hospital, and asked them to fill in the European Organization Research and Treatment of Cancer, Quality of Life Questionnaire before the commencement of the treatment. The acupuncture treatment is set up format but not disclosed yet. The translation and developing a Korean version of outcome measures that is Korean clinician friendly has been sought for MYMOP is one of the most appropriate one. The permission was granted, the translation into Korean was done, then back translated into English only based on the Korean translation by the researcher who is bilingual in both languages. The back translation was compared by the original developer of MYMOP and confirmed usable. In order to test the existence of acupoints and meridians through popular forms of Korean acupuncture regimes, we aim at collecting opinions from 101 Korean clinicians that have used those forms. The questions asked include most effective symptoms, 5 Shu points, points those are least likely to use due to either adverse events or the lack of effectiveness, theoretical reasons for the above proposals, proposing outcome measures

  6. Clinical evaluation based on cost-effectiveness

    International Nuclear Information System (INIS)

    Inoue, Takehiro; Inoue, Toshihiko


    We carried out two Phase III clinical trials using high dose rate (HDR) remote afterloading brachytherapy unit. We evaluated the clinical results based not only on the medical but also the economical standpoint. The first trial is the Phase III trial for cervical cancer treated with HDR or medium dose rate (MDR) intracavitary radiotherapy. The second one is the Phase III trial for tongue cancer treated with HDR or low dose rate (LDR) interstitial radiation. For cervical cancer, the survival rate of patients treated with HDR brachytherapy is the some as for LDR brachytherapy. The average total cost of treatment for the HDR group was 1.47 million yen, while that for the MDR group was 1.58 million yen. The average total admission days was 63. For tongue cancer, the local control rate of the HDR group is almost the same as that of the LDR groups. The average total cost for the HDR group was 780 thousand yen, and that for the LDR group was 830 thousand yen. The average total admission days was 34. According to the cost-effectiveness, HDR brachytherapy for cervical cancer has the same result as MDR, and HDR brachytherapy for tongue cancer has the same result as LDR. However, HDR can be treated without admission for patients who live near the hospital. HDR can be applied for these patients with less expense. We must be aware of not only the medical results but also the cost-effectiveness. (author)

  7. Characterization of printed pigment-based inks on ink-jet media using cross-sectional electron microscopy

    International Nuclear Information System (INIS)

    Almeida, P. de; Pataki, T.; Peeters, D.; Roost, C. van


    This paper reports on the microscopic assessment of representative specimen cross-sections prepared by microtomy and ultramicrotomy with emphasis in structure-property information using optical, scanning and transmission electron microscopy, namely, the absolute optical density δ, the measured effective printing coverage C-tilde, the averaged pigment-based ink layer thickness t-bar, and the morphology at 100% nominal printing coverage. This work shows that for different test patches printed at the same nominal printing coverage a number of different printing schemes yield a pre-defined absolute optical density δ which basically depends on the measured effective printing coverage C-tilde and the type of pigment-based inks used (spectral absorptivity m≠∞) and therefore on the averaged pigment-based ink layer thickness t-bar. A method for estimating the spectral absorptivity m is presented which combines the absolute optical density δ of the test patch and the averaged pigment-based ink layer thickness t-bar as measured from cross-sectional electron microscopy

  8. GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method (United States)

    Kim, Byungyeon; Park, Byungjun; Lee, Seungrag; Won, Youngjae


    We demonstrated GPU accelerated real-time confocal fluorescence lifetime imaging microscopy (FLIM) based on the analog mean-delay (AMD) method. Our algorithm was verified for various fluorescence lifetimes and photon numbers. The GPU processing time was faster than the physical scanning time for images up to 800 × 800, and more than 149 times faster than a single core CPU. The frame rate of our system was demonstrated to be 13 fps for a 200 × 200 pixel image when observing maize vascular tissue. This system can be utilized for observing dynamic biological reactions, medical diagnosis, and real-time industrial inspection. PMID:28018724

  9. Annotating Evidence Based Clinical Guidelines : A Lightweight Ontology

    NARCIS (Netherlands)

    Hoekstra, R.; de Waard, A.; Vdovjak, R.; Paschke, A.; Burger, A.; Romano, P.; Marshall, M.S.; Splendiani, A.


    This paper describes a lightweight ontology for representing annotations of declarative evidence based clinical guidelines. We present the motivation and requirements for this representation, based on an analysis of several guidelines. The ontology provides the means to connect clinical questions

  10. StatSTEM: An efficient approach for accurate and precise model-based quantification of atomic resolution electron microscopy images

    Energy Technology Data Exchange (ETDEWEB)

    De Backer, A.; Bos, K.H.W. van den [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium); Van den Broek, W. [AG Strukturforschung/Elektronenmikroskopie, Institut für Physik, Humboldt-Universität zu Berlin, Newtonstraße 15, 12489 Berlin (Germany); Sijbers, J. [iMinds-Vision Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); Van Aert, S., E-mail: [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)


    An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighbouring columns, enabling the analysis of a large field of view. For this algorithm, the accuracy and precision with which measurements for the atomic column positions and scattering cross-sections from annular dark field (ADF) STEM images can be estimated, has been investigated. The highest attainable precision is reached even for low dose images. Furthermore, the advantages of the model-based approach taking into account overlap between neighbouring columns are highlighted. This is done for the estimation of the distance between two neighbouring columns as a function of their distance and for the estimation of the scattering cross-section which is compared to the integrated intensity from a Voronoi cell. To provide end-users this well-established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. - Highlights: • An efficient model-based method for quantitative electron microscopy is introduced. • Images are modelled as a superposition of 2D Gaussian peaks. • Overlap between neighbouring columns is taken into account. • Structure parameters can be obtained with the highest precision and accuracy. • StatSTEM, auser friendly program (GNU public license) is developed.

  11. Nanoscale characterization of local structures and defects in photonic crystals using synchrotron-based transmission soft X-ray microscopy (United States)

    Nho, Hyun Woo; Kalegowda, Yogesh; Shin, Hyun-Joon; Yoon, Tae Hyun


    For the structural characterization of the polystyrene (PS)-based photonic crystals (PCs), fast and direct imaging capabilities of full field transmission X-ray microscopy (TXM) were demonstrated at soft X-ray energy. PS-based PCs were prepared on an O2-plasma treated Si3N4 window and their local structures and defects were investigated using this label-free TXM technique with an image acquisition speed of ~10 sec/frame and marginal radiation damage. Micro-domains of face-centered cubic (FCC (111)) and hexagonal close-packed (HCP (0001)) structures were dominantly found in PS-based PCs, while point and line defects, FCC (100), and 12-fold symmetry structures were also identified as minor components. Additionally, in situ observation capability for hydrated samples and 3D tomographic reconstruction of TXM images were also demonstrated. This soft X-ray full field TXM technique with faster image acquisition speed, in situ observation, and 3D tomography capability can be complementally used with the other X-ray microscopic techniques (i.e., scanning transmission X-ray microscopy, STXM) as well as conventional characterization methods (e.g., electron microscopic and optical/fluorescence microscopic techniques) for clearer structure identification of self-assembled PCs and better understanding of the relationship between their structures and resultant optical properties. PMID:27087141

  12. Micromorphology of cactus-pear (Opuntia ficus-indica (L.) Mill) cladodes based on scanning microscopies. (United States)

    Ben Salem-Fnayou, Asma; Zemni, Hassène; Nefzaoui, Ali; Ghorbel, Abdelwahed


    Cladode ultrastructural features of two prickly and two spineless Opuntia ficus-indica cultivars were examined using environmental scanning electron and atomic force microscopies. Observations focused on cladode as well as spine and glochid surface micromorphologies. Prickly cultivars were characterized by abundant cracked epicuticular wax deposits covering the cladode surface, with an amorphous structure as observed by AFM, while less abundant waxy plates were observed by ESEM on spineless cultivar cladodes. Further AFM observations allowed a rough granular and crystalloid epicuticular wax structure to be distinguished in spineless cultivars. Regarding spine micromorphology, prickly cultivars had strong persistent spines, observed by ESEM as a compact arrangement of oblong epidermal cells with a rough granular structure. However, deciduous spines in spineless cultivars had a broken transversely fissured epidermis covering a parallel arrangement of fibres. Through AFM, the deciduous spine surface presented an irregular hilly and smooth microrelief while persistent spines exhibited rough helical filamentous prints. ESEM and AFM studies of cladode surfaces from prickly and spineless cactus pear cultivars revealed valuable micro-morphological details that ought to be extended to a large number of O. ficus-indica cultivars. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Evidence Based Studies in Clinical Transfusion Medicine

    NARCIS (Netherlands)

    A.J.G. Jansen (Gerard)


    textabstractAfter the introduction of blood component therapy in the 1960s, more and more attention is given to clinical transfusion medicine. Although blood transfusion is an important treatment in different clinical settings, there are still lack of much randomized clinical trials. Nowadays

  14. Transmission electron microscopy investigations of the CdSe based quantum structures

    International Nuclear Information System (INIS)

    Roventa, E.


    In this work, the structural morphology of the active region of the ZnSe laser diode: quaternary CdZnSSe quantum well or CdSe quantum dots embedded in CdSe/ZnSSe superlattices is investigated using Transmission Electron Microscopy. The conventional as well as high resolution imaging studies indicated that the degradation of the ZnSe laser diodes is connected with the formation of extended defects in the optical active region leading to a local strain relaxation of the quantum well. Furthermore the outdiffusion of Cd from the quantum well occurs predominantly where the defects are located. The chemical composition and ordering phenomena in CdSe/ZnSSe supperlattices were also investigated, employing a series of five-fold structures with different spacer layer thickness and a ten-fold structure. The composition in the CdSe/ZnSSe superlattice was determined to a certain extent using different techniques. Generally, the encountered difficulties regarding the accuracy of the obtained values are correlated with the complexity of the investigated system and with the available experimental methods used. Regarding the alignment of the dots, experimental results support a strain driven ordering process, in which the strain fields from buried dots lead to heterogeneous nucleation conditions for the dots in the subsequently deposited layers. An increased ordering with subsequent stacking of the dot layers is was also found. An anisotropy of the lateral alignment of the CdSe dots was also observed in two different left angle 110 right angle zone axes. The similar plan-view images shows that the preferential alignment of the dots does not follow low-index crystallographic directions. However, it is assumed that this is attributed to the anisotropic elastic strain distribution combined with surface diffusion. (orig.)

  15. Transmission electron microscopy investigations of the CdSe based quantum structures

    Energy Technology Data Exchange (ETDEWEB)

    Roventa, E.


    In this work, the structural morphology of the active region of the ZnSe laser diode: quaternary CdZnSSe quantum well or CdSe quantum dots embedded in CdSe/ZnSSe superlattices is investigated using Transmission Electron Microscopy. The conventional as well as high resolution imaging studies indicated that the degradation of the ZnSe laser diodes is connected with the formation of extended defects in the optical active region leading to a local strain relaxation of the quantum well. Furthermore the outdiffusion of Cd from the quantum well occurs predominantly where the defects are located. The chemical composition and ordering phenomena in CdSe/ZnSSe supperlattices were also investigated, employing a series of five-fold structures with different spacer layer thickness and a ten-fold structure. The composition in the CdSe/ZnSSe superlattice was determined to a certain extent using different techniques. Generally, the encountered difficulties regarding the accuracy of the obtained values are correlated with the complexity of the investigated system and with the available experimental methods used. Regarding the alignment of the dots, experimental results support a strain driven ordering process, in which the strain fields from buried dots lead to heterogeneous nucleation conditions for the dots in the subsequently deposited layers. An increased ordering with subsequent stacking of the dot layers is was also found. An anisotropy of the lateral alignment of the CdSe dots was also observed in two different left angle 110 right angle zone axes. The similar plan-view images shows that the preferential alignment of the dots does not follow low-index crystallographic directions. However, it is assumed that this is attributed to the anisotropic elastic strain distribution combined with surface diffusion. (orig.)

  16. Characterization of oral precancerous lesions based on higher-harmonic generation microscopy (United States)

    Lin, Chen-Yu; Lin, Chih-Feng; Sun, Chi-Kuang


    It is generally accepted that oral cancer arises in the presence of oral precancerous lesions. However, the clinical courses of these lesions are quite unpredictable, and a fundamental enigma remains that when and how these lesions turn to malignant growth. Characterization of these potentially malignant lesions is thus important and could serve as early indicators of this neoplastic transformation process, potentially facilitates the treatment outcome and improves the survival rate. Higher harmonic generation microscope (HGM), providing images with a leaving photodamages in the tissues, was used for this purpose. Oral cavity biopsies were obtained from 18 patients with clinical suspected oral precancerous lesions scheduled for surgical biopsy. HGM images were compared with histological images to determine the results. By visualization of subtle cellular and morphological changes, the preliminary result of this HGM image discloses excellent consistency with traditional histolopathology studies, without the need for fixation, sectioning and staining. More specifically speaking, the keratin thickness was found to be increased comparing with normal adjacent controls. In some cases, variations in cell size, nuclear size and increased nuclear/cytoplasmic ratio, and increased size of nucleoli were identified, indicating different stages of malignant transformation. These results together indicated that HGM provides the capability to characterize features of oral precancerous lesions as well as oral cancer progression, and holds the greatest potential as an ideal tool for clinical screening and surveillance of suspicious oral lesions.

  17. Volumetric label-free imaging and 3D reconstruction of mammalian cochlea based on two-photon excitation fluorescence microscopy

    International Nuclear Information System (INIS)

    Zhang, Xianzeng; Zhan, Zhenlin; Xie, Shusen; Geng, Yang; Ye, Qing


    The visualization of the delicate structure and spatial relationship of intracochlear sensory cells has relied on the laborious procedures of tissue excision, fixation, sectioning and staining for light and electron microscopy. Confocal microscopy is advantageous for its high resolution and deep penetration depth, yet disadvantageous due to the necessity of exogenous labeling. In this study, we present the volumetric imaging of rat cochlea without exogenous dyes using a near-infrared femtosecond laser as the excitation mechanism and endogenous two-photon excitation fluorescence (TPEF) as the contrast mechanism. We find that TPEF exhibits strong contrast, allowing cellular and even subcellular resolution imaging of the cochlea, differentiating cell types, visualizing delicate structures and the radial nerve fiber. Our results further demonstrate that 3D reconstruction rendered with z-stacks of optical sections enables better revealment of fine structures and spatial relationships, and easily performed morphometric analysis. The TPEF-based optical biopsy technique provides great potential for new and sensitive diagnostic tools for hearing loss or hearing disorders, especially when combined with fiber-based microendoscopy. (paper)

  18. 3D imaging of hematoxylin and eosin stained thick tissues with a sub-femtoliter resolution by using Cr:forsterite-laser-based nonlinear microscopy (Conference Presentation) (United States)

    Kao, Chien-Ting; Wei, Ming-Liang; Liao, Yi-Hua; Sun, Chi-Kuang


    Intraoperative assessment of excision tissues during cancer surgery is clinically important. The assessment is used to be guided by the examination for residual tumor with frozen pathology, while it is time consuming for preparation and is with low accuracy for diagnosis. Recently, reflection confocal microscopy (RCM) and nonlinear microscopy (NLM) were demonstrated to be promising methods for surgical border assessment. Intraoperative RCM imaging may enable detection of residual tumor directly on skin cancers patients during Mohs surgery. The assessment of benign and malignant breast pathologies in fresh surgical specimens was demonstrated by NLM. Without using hematoxylin and eosin (H and E) that are common dyes for histopathological diagnosis, RCM was proposed to image in vivo by using aluminum chloride for nuclear contrast on surgical wounds directly, while NLM was proposed to detect two photon fluorescence nuclear contrast from acrdine orange staining. In this paper, we propose and demonstrate 3D imaging of H and E stained thick tissues with a sub-femtoliter resolution by using Cr:forsterite-laser-based NLM. With a 1260 nm femtosecond Cr:forsterite laser as the excitation source, the hematoxylin will strongly enhance the third-harmonic generation (THG) signals, while eosin will illuminate strong fluorescence under three photon absorption. Compared with previous works, the 1260 nm excitation light provide high penetration and low photodamage to the exercised tissues so that the possibility to perform other follow-up examination will be preserved. The THG and three-photon process provides high nonlinearity so that the super resolution in 3D is now possible. The staining and the contrast of the imaging is also fully compatible with the current clinical standard on frozen pathology thus facilitate the rapid intraoperative assessment of excision tissues. This work is sponsored by National Health Research Institutes and supported by National Taiwan University

  19. Transmission electron microscopy characterization of laser-clad iron-based alloy on Al-Si alloy

    International Nuclear Information System (INIS)

    Mei, Z.; Wang, W.Y.; Wang, A.H.


    Microstructure characterization is important for controlling the quality of laser cladding. In the present work, a detailed microstructure characterization by transmission electron microscopy was carried out on the iron-based alloy laser-clad on Al-Si alloy and an unambiguous identification of phases in the coating was accomplished. It was found that there is austenite, Cr 7 C 3 and Cr 23 C 6 in the clad region; α-Al, NiAl 3 , Fe 2 Al 5 and FeAl 2 in the interface region; and α-Al and silicon in the heat-affected region. A brief discussion was given for their existence based on both kinetic and thermodynamic principles

  20. A High Precision Laser-Based Autofocus Method Using Biased Image Plane for Microscopy

    Directory of Open Access Journals (Sweden)

    Chao-Chen Gu


    Full Text Available This study designs and accomplishes a high precision and robust laser-based autofocusing system, in which a biased image plane is applied. In accordance to the designed optics, a cluster-based circle fitting algorithm is proposed to calculate the radius of the detecting spot from the reflected laser beam as an essential factor to obtain the defocus value. The experiment conduct on the experiment device achieved novel performance of high precision and robustness. Furthermore, the low demand of assembly accuracy makes the proposed method a low-cost and realizable solution for autofocusing technique.

  1. Note: Tormenta: An open source Python-powered control software for camera based optical microscopy. (United States)

    Barabas, Federico M; Masullo, Luciano A; Stefani, Fernando D


    Until recently, PC control and synchronization of scientific instruments was only possible through closed-source expensive frameworks like National Instruments' LabVIEW. Nowadays, efficient cost-free alternatives are available in the context of a continuously growing community of open-source software developers. Here, we report on Tormenta, a modular open-source software for the control of camera-based optical microscopes. Tormenta is built on Python, works on multiple operating systems, and includes some key features for fluorescence nanoscopy based on single molecule localization.

  2. Coherent anti-Stokes Raman scattering microscopy with a photonic crystal fiber based light source

    DEFF Research Database (Denmark)

    Paulsen, H.N.; Hilligsøe, Karen Marie; Thøgersen, J.


    A coherent anti-Stokes Raman scattering microscope based on a Ti:sapphire femtosecond oscillator and a photonic crystal fiber is demonstrated. The nonlinear response of the fiber is used to generate the additional wavelength needed in the Raman process. The applicability of the setup is demonstra......A coherent anti-Stokes Raman scattering microscope based on a Ti:sapphire femtosecond oscillator and a photonic crystal fiber is demonstrated. The nonlinear response of the fiber is used to generate the additional wavelength needed in the Raman process. The applicability of the setup...

  3. Clinical librarians as facilitators of nurses' evidence-based practice. (United States)

    Määttä, Sylvia; Wallmyr, Gudrun


    The aim of this study was to explore nurses' and ward-based clinical librarians' reflections on ward-based clinical librarians as facilitators for nurses' use of evidences-based practice. Nurses' use of evidence-based practice is reported to be weak. Studies have suggested that clinical librarians may promote evidence-based practice. To date, little is known about clinical librarians participating nurses in the wards. A descriptive, qualitative design was adopted for the study. In 2007, 16 nurses who had been attended by a clinical librarian in the wards were interviewed in focus groups. Two clinical librarians were interviewed by individual interviews. In the analysis, a content analysis was used. Three themes were generated from the interviews with nurses: 'The grip of everyday work', 'To articulate clinical nursing issues' and 'The clinical librarians at a catalyst'. The nurses experienced the grip of everyday work as a hindrance and had difficulties to articulate and formulate relevant nursing issues. In such a state, the nurses found the clinical librarian presence in the ward as enhancing the awareness of and the use of evidence-based practice. Three themes emerged from the analysis with the librarians. They felt as outsiders, had new knowledge and acquired a new role as ward-based clinical librarians. Facilitation is needed if nurses' evidence-based practice is going to increase. The combined use of nurses and clinical librarians' knowledge and skills can be optimised. To achieve this, nurses' skills in consuming and implementing evidence ought to be strengthened. The fusion of the information and knowledge management skill of the ward-based clinical librarian and the clinical expertise of the nurses can be of value. With such a collaborative model, nurse and ward-based clinical librarian might join forces to increase the use of evidence-based practice. © 2010 Blackwell Publishing Ltd.

  4. A low-noise measurement system for scanning thermal microscopy resistive nanoprobes based on a transformer ratio-arm bridge (United States)

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


    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.

  5. Repeatability and reproducibility of intracellular molar concentration assessed by synchrotron-based x-ray fluorescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Merolle, L., E-mail:; Gianoncelli, A. [Elettra - Sincrotrone Trieste, 34149 Basovizza, Trieste (Italy); Malucelli, E., E-mail:; Cappadone, C.; Farruggia, G.; Sargenti, A.; Procopio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40127 (Italy); Fratini, M. [Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Piazza del Viminale 1, 00184 Roma Italy (Italy); Department of Science, Roma Tre University, Via della Vasca Navale 84, I-00146 Rome (Italy); Notargiacomo, A. [Institute for Photonics and Nanotechnology, Consiglio Nazionale delle Richerche, 00156 Rome (Italy); Lombardo, M. [Department of Chemistry “G. Ciamician”, University of Bologna, Bologna 40126 (Italy); Lagomarsino, S. [Institute of Chemical-Physical Processes, Sapienza University of Rome, 00185 Rome (Italy); National Institute of Biostructures and Biosystems, 00136 Rome (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40127 (Italy); National Institute of Biostructures and Biosystems, 00136 Rome (Italy)


    Elemental analysis of biological sample can give information about content and distribution of elements essential for human life or trace elements whose absence is the cause of abnormal biological function or development. However, biological systems contain an ensemble of cells with heterogeneous chemistry and elemental content; therefore, accurate characterization of samples with high cellular heterogeneity may only be achieved by analyzing single cells. Powerful methods in molecular biology are abundant, among them X-Ray microscopy based on synchrotron light source has gaining increasing attention thanks to its extremely sensitivity. However, reproducibility and repeatability of these measurements is one of the major obstacles in achieving a statistical significance in single cells population analysis. In this study, we compared the elemental content of human colon adenocarcinoma cells obtained by three distinct accesses to synchrotron radiation light.

  6. Impact of thermal frequency drift on highest precision force microscopy using quartz-based force sensors at low temperatures

    Directory of Open Access Journals (Sweden)

    Florian Pielmeier


    Full Text Available In frequency modulation atomic force microscopy (FM-AFM the stability of the eigenfrequency of the force sensor is of key importance for highest precision force measurements. Here, we study the influence of temperature changes on the resonance frequency of force sensors made of quartz, in a temperature range from 4.8–48 K. The sensors are based on the qPlus and length extensional principle. The frequency variation with temperature T for all sensors is negative up to 30 K and on the order of 1 ppm/K, up to 13 K, where a distinct kink appears, it is linear. Furthermore, we characterize a new type of miniaturized qPlus sensor and confirm the theoretically predicted reduction in detector noise.

  7. The investigation of the light radiation caused polyethylene based materials deterioration by means of atomic force microscopy

    International Nuclear Information System (INIS)

    Sikora, A; Moroń, L; Wałecki, M; Kryla, P; Grabarek, A


    The impact of the environmental conditions on the materials used in various devices and constructions, in particular in electrotechnical applications, has an critical impact in terms of their reliability and utilization range in specific climatic conditions. Due to increasing utilitarian requirements, technological processes complexity and introducing new materials (for instance nanomaterials), advanced diagnostic techniques are desired. One of such techniques is atomic force microscopy (AFM), which allows to study the changes of the roughness and mechanical properties of the surface at the submicrometer scale, enabling the investigation of the degradation processes. In this work the deterioration of selected group of polyethylene based materials have been measured by means of AFM, as the samples were exposed to the simulated solar light and UV-C radiation. Such an analysis of the environmental conditions impact on the deterioration process using AFM methods for various versions of specific material was not presented before. (paper)

  8. Denoising of Microscopy Images: A Review of the State-of-the-Art, and a New Sparsity-Based Method. (United States)

    Meiniel, William; Olivo-Marin, Jean-Christophe; Angelini, Elsa D


    This paper reviews the state-of-the-art in denoising methods for biological microscopy images and introduces a new and original sparsity-based algorithm. The proposed method combines total variation (TV) spatial regularization, enhancement of low-frequency information, and aggregation of sparse estimators and is able to handle simple and complex types of noise (Gaussian, Poisson, and mixed), without any a priori model and with a single set of parameter values. An extended comparison is also presented, that evaluates the denoising performance of the thirteen (including ours) state-of-the-art denoising methods specifically designed to handle the different types of noises found in bioimaging. Quantitative and qualitative results on synthetic and real images show that the proposed method outperforms the other ones on the majority of the tested scenarios.

  9. The fractional Fourier transform as a simulation tool for lens-based X-ray microscopy

    DEFF Research Database (Denmark)

    Pedersen, Anders Filsøe; Simons, Hugh; Detlefs, Carsten


    The fractional Fourier transform (FrFT) is introduced as a tool for numerical simulations of X-ray wavefront propagation. By removing the strict sampling requirements encountered in typical Fourier optics, simulations using the FrFT can be carried out with much decreased detail, allowing...... the attenuation from the entire CRL using one or two effective apertures without loss of accuracy, greatly accelerating simulations involving CRLs. To demonstrate the applicability and accuracy of the FrFT, the imaging resolution of a CRL-based imaging system is estimated, and the FrFT approach is shown...

  10. Investigation of Amyloid Structures at Nanoscale via AFM based Dynamic Nanomechncial Microscopy

    DEFF Research Database (Denmark)

    Zhang, Shuai


    Amyloid structures are one important kind of protein aggregations. They are a group of stable misfolded species, other than native states, which have been found to accumulate as plaques on neuron cells. This behavior is considered to associate with tens of human neurodegenerative diseases...... summarized the main methodologies of DNM. I also utilized DNM to explore the path way of amyloid self-assembly, and the substrate effect to the conformation of amyloid structures. Furthermore, 2D peptide based material has also been characterized by DNM....

  11. The aqueous electrochemistry of carbon-based surfaces-investigation by scanning tunneling microscopy (United States)

    Mühl, T.; Myhra, S.


    Electro-oxidation of carbon-based materials will lead to conversion of the solid to CO2/CO at the anode, with H2 being produced at the cathode. Recent voltammetric investigations of carbon nano-tubes and single crystal graphite have shown that only edge sites and other defect sites are electrochemically active. Local oxidation of diamond-like carbon films (DLC) by an STM tip in moist air followed by imaging allows correlation of topographical change with electro-chemical conditions and surface reactivity. The results may have implications for lithographic processing of carbon surfaces, and may have relevance for electrochemical H2 production.

  12. [Research on WiFi-based wireless microscopy on a mobile phone and its application]. (United States)

    Hailan, Jin; Jing, Liu


    We proposed and realized a new device that acquires microscopic image wirelessly based on mobile phone and WiFi system. The mobile terminals could record, display and store the image from the far end via the wireless LAN. Using this system, a series of conceptual experiments on monitoring the microscopic images of common objects and liver cancer cells were successfully demonstrated. This system is expected to have important value in the experimental investigations on wirelessly monitoring the cell culture, and small insect etc.

  13. Arduino Due based tool to facilitate in vivo two-photon excitation microscopy. (United States)

    Artoni, Pietro; Landi, Silvia; Sato, Sebastian Sulis; Luin, Stefano; Ratto, Gian Michele


    Two-photon excitation spectroscopy is a powerful technique for the characterization of the optical properties of genetically encoded and synthetic fluorescent molecules. Excitation spectroscopy requires tuning the wavelength of the Ti:sapphire laser while carefully monitoring the delivered power. To assist laser tuning and the control of delivered power, we developed an Arduino Due based tool for the automatic acquisition of high quality spectra. This tool is portable, fast, affordable and precise. It allowed studying the impact of scattering and of blood absorption on two-photon excitation light. In this way, we determined the wavelength-dependent deformation of excitation spectra occurring in deep tissues in vivo.

  14. Note: Design of FPGA based system identification module with application to atomic force microscopy (United States)

    Ghosal, Sayan; Pradhan, Sourav; Salapaka, Murti


    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.

  15. Web-based volume slicer for 3D electron-microscopy data from EMDB. (United States)

    Salavert-Torres, José; Iudin, Andrii; Lagerstedt, Ingvar; Sanz-García, Eduardo; Kleywegt, Gerard J; Patwardhan, Ardan


    We describe the functionality and design of the Volume slicer - a web-based slice viewer for EMDB entries. This tool uniquely provides the facility to view slices from 3D EM reconstructions along the three orthogonal axes and to rapidly switch between them and navigate through the volume. We have employed multiple rounds of user-experience testing with members of the EM community to ensure that the interface is easy and intuitive to use and the information provided is relevant. The impetus to develop the Volume slicer has been calls from the EM community to provide web-based interactive visualisation of 2D slice data. This would be useful for quick initial checks of the quality of a reconstruction. Again in response to calls from the community, we plan to further develop the Volume slicer into a fully-fledged Volume browser that provides integrated visualisation of EMDB and PDB entries from the molecular to the cellular scale. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Quantitative phase microscopy for cellular dynamics based on transport of intensity equation. (United States)

    Li, Ying; Di, Jianglei; Ma, Chaojie; Zhang, Jiwei; Zhong, Jinzhan; Wang, Kaiqiang; Xi, Teli; Zhao, Jianlin


    We demonstrate a simple method for quantitative phase imaging of tiny transparent objects such as living cells based on the transport of intensity equation. The experiments are performed using an inverted bright field microscope upgraded with a flipping imaging module, which enables to simultaneously create two laterally separated images with unequal defocus distances. This add-on module does not include any lenses or gratings and is cost-effective and easy-to-alignment. The validity of this method is confirmed by the measurement of microlens array and human osteoblastic cells in culture, indicating its potential in the applications of dynamically measuring living cells and other transparent specimens in a quantitative, non-invasive and label-free manner.

  17. Intelligent tuning method of PID parameters based on iterative learning control for atomic force microscopy. (United States)

    Liu, Hui; Li, Yingzi; Zhang, Yingxu; Chen, Yifu; Song, Zihang; Wang, Zhenyu; Zhang, Suoxin; Qian, Jianqiang


    Proportional-integral-derivative (PID) parameters play a vital role in the imaging process of an atomic force microscope (AFM). Traditional parameter tuning methods require a lot of manpower and it is difficult to set PID parameters in unattended working environments. In this manuscript, an intelligent tuning method of PID parameters based on iterative learning control is proposed to self-adjust PID parameters of the AFM according to the sample topography. This method gets enough information about the output signals of PID controller and tracking error, which will be used to calculate the proper PID parameters, by repeated line scanning until convergence before normal scanning to learn the topography. Subsequently, the appropriate PID parameters are obtained by fitting method and then applied to the normal scanning process. The feasibility of the method is demonstrated by the convergence analysis. Simulations and experimental results indicate that the proposed method can intelligently tune PID parameters of the AFM for imaging different topographies and thus achieve good tracking performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Single Gold Nanoparticle-Based Colorimetric Detection of Picomolar Mercury Ion with Dark-Field Microscopy. (United States)

    Liu, Xiaojun; Wu, Zhangjian; Zhang, Qingquan; Zhao, Wenfeng; Zong, Chenghua; Gai, Hongwei


    Mercury severely damages the environment and human health, particularly when it accumulates in the food chain. Methods for the colorimetric detection of Hg(2+) have increasingly been developed over the past decade because of the progress in nanotechnology. However, the limits of detection (LODs) of these methods are mostly either comparable to or higher than the allowable maximum level (10 nM) in drinking water set by the US Environmental Protection Agency. In this study, we report a single Au nanoparticle (AuNP)-based colorimetric assay for Hg(2+) detection in solution. AuNPs modified with oligonucleotides were fixed on the slide. The fixed AuNPs bound to free AuNPs in the solution in the presence of Hg(2+) because of oligonucleotide hybridization. This process was accompanied by a color change from green to yellow as observed under an optical microscope. The ratio of changed color spots corresponded with Hg(2+) concentration. The LOD was determined as 1.4 pM, which may help guard against mercury accumulation. The proposed approach was applied to environmental samples with recoveries of 98.3 ± 7.7% and 110.0 ± 8.8% for Yuquan River and industrial wastewater, respectively.

  19. Ag/ZnO hybrid systems studied with scanning tunnelling microscopy-based luminescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Pascua, Leandro; Freund, Hans-Joachim [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin (Germany); Stavale, Fernando [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin (Germany); Centro Brasileiro de Pesquisas Físicas - CBPF/MCTI, Rua Xavier Sigaud 150, 22290-180 Rio de Janeiro (Brazil); Nilius, Niklas, E-mail: [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin (Germany); Institut für Physik, Carl von Ossietzky Universität Oldenburg, D-26111 Oldenburg (Germany)


    Coupled metal/oxide systems are prepared by depositing and embedding Ag nanoparticles into crystalline ZnO films grown on Au(111) supports. The morphology and optical properties of the compounds are investigated by topographic imaging and luminescence spectroscopy performed in a scanning tunnelling microscope (STM). The luminescence of bare ZnO is governed by the band-recombination and a Zn-vacancy related peak. After Ag deposition, two additional maxima are detected that are assigned to the in-plane and out-of-plane plasmon in Ag nanoparticles and have energies below and slightly above the oxide band-gap, respectively. Upon coating the particles with additional ZnO, the out-of-plane plasmon redshifts and loses intensity, indicating strong coupling to the oxide electronic system, while the in-plane mode broadens but remains detectable. The original situation can be restored by gently heating the sample, which drives the silver back to the surface. However, the optical response of pristine ZnO is not recovered even after silver evaporation at high temperature. Small discrepancies are explained with changes in the ZnO defect landscape, e.g., due to silver incorporation. Our experiments demonstrate how energy-transfer processes can be investigated in well-defined metal/oxide systems by means of STM-based spectroscopic techniques.

  20. Ag/ZnO hybrid systems studied with scanning tunnelling microscopy-based luminescence spectroscopy

    International Nuclear Information System (INIS)

    Pascua, Leandro; Freund, Hans-Joachim; Stavale, Fernando; Nilius, Niklas


    Coupled metal/oxide systems are prepared by depositing and embedding Ag nanoparticles into crystalline ZnO films grown on Au(111) supports. The morphology and optical properties of the compounds are investigated by topographic imaging and luminescence spectroscopy performed in a scanning tunnelling microscope (STM). The luminescence of bare ZnO is governed by the band-recombination and a Zn-vacancy related peak. After Ag deposition, two additional maxima are detected that are assigned to the in-plane and out-of-plane plasmon in Ag nanoparticles and have energies below and slightly above the oxide band-gap, respectively. Upon coating the particles with additional ZnO, the out-of-plane plasmon redshifts and loses intensity, indicating strong coupling to the oxide electronic system, while the in-plane mode broadens but remains detectable. The original situation can be restored by gently heating the sample, which drives the silver back to the surface. However, the optical response of pristine ZnO is not recovered even after silver evaporation at high temperature. Small discrepancies are explained with changes in the ZnO defect landscape, e.g., due to silver incorporation. Our experiments demonstrate how energy-transfer processes can be investigated in well-defined metal/oxide systems by means of STM-based spectroscopic techniques.

  1. Superpixel-based segmentation of muscle fibers in multi-channel microscopy. (United States)

    Nguyen, Binh P; Heemskerk, Hans; So, Peter T C; Tucker-Kellogg, Lisa


    Confetti fluorescence and other multi-color genetic labelling strategies are useful for observing stem cell regeneration and for other problems of cell lineage tracing. One difficulty of such strategies is segmenting the cell boundaries, which is a very different problem from segmenting color images from the real world. This paper addresses the difficulties and presents a superpixel-based framework for segmentation of regenerated muscle fibers in mice. We propose to integrate an edge detector into a superpixel algorithm and customize the method for multi-channel images. The enhanced superpixel method outperforms the original and another advanced superpixel algorithm in terms of both boundary recall and under-segmentation error. Our framework was applied to cross-section and lateral section images of regenerated muscle fibers from confetti-fluorescent mice. Compared with "ground-truth" segmentations, our framework yielded median Dice similarity coefficients of 0.92 and higher. Our segmentation framework is flexible and provides very good segmentations of multi-color muscle fibers. We anticipate our methods will be useful for segmenting a variety of tissues in confetti fluorecent mice and in mice with similar multi-color labels.

  2. Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images. (United States)

    Cheng, Jie; Zhou, Xiaobo; Miller, Eric L; Alvarez, Veronica A; Sabatini, Bernardo L; Wong, Stephen T C


    Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 μm/pixel instead of 0.08 μm/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the "necks" of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection.

  3. Identification by microscopy and MS-based electronic nose of a fraudulent addition to maize gluten

    Directory of Open Access Journals (Sweden)

    Frick G.


    Full Text Available Classical and chemometric methods have been used to detect falsified maize gluten products. Microscopic observations (numerous starch grains, seed envelopes and wheat bran fragments clearly showed the presence of atypical maize gluten particles in samples with otherwise normal crude protein levels (≥ 60% and the usual gold-yellow color. Chemical analyses in a few samples confirmed the presence of urea (19 to 174, melamine (0 to 20, and cyanuric acid (0 to 10 coping for the low levels of methionine (0 to 13 in incriminated products (genuine maize gluten methionine level ≥ 16 Furthermore, a fast technique (an electronic nose based on mass spectrometry detection also proved to be reliable for the identification of falsified maize gluten products: 100% correct classification of model and unknown samples was achieved with principal component analysis. As a consequence of these results, the Swiss feed-inspection authority blocked the import, or restricted the use, of 2,500 tons of the falsified products.

  4. Temporal focusing-based widefield multiphoton microscopy with spatially modulated illumination for biotissue imaging. (United States)

    Chang, Chia-Yuan; Lin, Cheng-Han; Lin, Chun-Yu; Sie, Yong-Da; Hu, Yvonne Yuling; Tsai, Sheng-Feng; Chen, Shean-Jen


    A developed temporal focusing-based multiphoton excitation microscope (TFMPEM) has a digital micromirror device (DMD) which is adopted not only as a blazed grating for light spatial dispersion but also for patterned illumination simultaneously. Herein, the TFMPEM has been extended to implement spatially modulated illumination at structured frequency and orientation to increase the beam coverage at the back-focal aperture of the objective lens. The axial excitation confinement (AEC) of TFMPEM can be condensed from 3.0 μm to 1.5 μm for a 50 % improvement. By using the TFMPEM with HiLo technique as two structured illuminations at the same spatial frequency but different orientation, reconstructed biotissue images according to the condensed AEC structured illumination are shown obviously superior in contrast and better scattering suppression. Picture: TPEF images of the eosin-stained mouse cerebellar cortex by conventional TFMPEM (left), and the TFMPEM with HiLo technique as 1.09 μm -1 spatially modulated illumination at 90° (center) and 0° (right) orientations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Synchrotron-based transmission x-ray microscopy for improved extraction in shale during hydraulic fracturing (United States)

    Kiss, Andrew M.; Jew, Adam D.; Joe-Wong, Claresta; Maher, Kate M.; Liu, Yijin; Brown, Gordon E.; Bargar, John


    Engineering topics which span a range of length and time scales present a unique challenge to researchers. Hydraulic fracturing (fracking) of oil shales is one of these challenges and provides an opportunity to use multiple research tools to thoroughly investigate a topic. Currently, the extraction efficiency from the shale is low but can be improved by carefully studying the processes at the micro- and nano-scale. Fracking fluid induces chemical changes in the shale which can have significant effects on the microstructure morphology, permeability, and chemical composition. These phenomena occur at different length and time scales which require different instrumentation to properly study. Using synchrotron-based techniques such as fluorescence tomography provide high sensitivity elemental mapping and an in situ micro-tomography system records morphological changes with time. In addition, the transmission X-ray microscope (TXM) at the Stanford Synchrotron Radiation Lightsource (SSRL) beamline 6-2 is utilized to collect a nano-scale three-dimensional representation of the sample morphology with elemental and chemical sensitivity. We present the study of a simplified model system, in which pyrite and quartz particles are mixed and exposed to oxidizing solution, to establish the basic understanding of the more complex geology-relevant oxidation reaction. The spatial distribution of the production of the oxidation reaction, ferrihydrite, is retrieved via full-field XANES tomography showing the reaction pathway. Further correlation between the high resolution TXM data and the high sensitivity micro-probe data provides insight into potential morphology changes which can decrease permeability and limit hydrocarbon recovery.

  6. Automated multiscale morphometry of muscle disease from second harmonic generation microscopy using tensor-based image processing. (United States)

    Garbe, Christoph S; Buttgereit, Andreas; Schürmann, Sebastian; Friedrich, Oliver


    Practically, all chronic diseases are characterized by tissue remodeling that alters organ and cellular function through changes to normal organ architecture. Some morphometric alterations become irreversible and account for disease progression even on cellular levels. Early diagnostics to categorize tissue alterations, as well as monitoring progression or remission of disturbed cytoarchitecture upon treatment in the same individual, are a new emerging field. They strongly challenge spatial resolution and require advanced imaging techniques and strategies for detecting morphological changes. We use a combined second harmonic generation (SHG) microscopy and automated image processing approach to quantify morphology in an animal model of inherited Duchenne muscular dystrophy (mdx mouse) with age. Multiphoton XYZ image stacks from tissue slices reveal vast morphological deviation in muscles from old mdx mice at different scales of cytoskeleton architecture: cell calibers are irregular, myofibrils within cells are twisted, and sarcomere lattice disruptions (detected as "verniers") are larger in number compared to samples from healthy mice. In young mdx mice, such alterations are only minor. The boundary-tensor approach, adapted and optimized for SHG data, is a suitable approach to allow quick quantitative morphometry in whole tissue slices. The overall detection performance of the automated algorithm compares very well with manual "by eye" detection, the latter being time consuming and prone to subjective errors. Our algorithm outperfoms manual detection by time with similar reliability. This approach will be an important prerequisite for the implementation of a clinical image databases to diagnose and monitor specific morphological alterations in chronic (muscle) diseases. © 2011 IEEE

  7. Electronic properties of dioctylterthiophene-based organic thin-film transistors: A Kelvin probe force microscopy study

    International Nuclear Information System (INIS)

    Afsharimani, N.; Nysten, B.


    It appeared in the past decades that semi-conducting organic liquid crystals could be used as the active layer in organic thin film transistors (OTFTs). They can be processed by simple methods such as inkjet printing, which paves the way to applications for cheap plastic electronics such as electronic tags, biosensors, and flexible screens. However, the measured field-effect mobility in these OTFTs is relatively low compared to inorganic devices. Generally, such low field-effect mobility values result from extrinsic effects such as grain boundaries or imperfect interfaces with source and drain electrodes. It has been shown that reducing the number of grain boundaries between the source and drain electrodes improves the field effect mobility. Therefore, it is important to understand the transport mechanisms by studying the local structure and electronic properties of organic thin films within the channel and at the interfaces with source and drain electrodes in order to improve the field-effect mobility in OTFTs. Kelvin probe force microscopy (KPFM) is an ideal tool for that purpose since it allows to simultaneously investigate the local structure and the electrical potential distribution in electronic devices. In this work, the structure and the electrical properties of OTFTs based on dioctylterthiophene (DOTT) were studied. The transistors were fabricated by spin-coating DOTT on the transistor structures with untreated and treated (silanized) channel silicon oxide. The potential profiles across the channel and at the metal-electrode interfaces were measured by KPFM. The effect of surface treatment on the electrical properties, charge trapping phenomenon and hysteresis effects is demonstrated and analyzed. - Highlights: • Kelvin probe force microscopy study of organic thin film transistors. • Cost and time savings by using solution processable molecules as active layers. • Smaller crystals and less charge trapping effects in silanized devices. • Decrement

  8. Mosaicing of single plane illumination microscopy images using groupwise registration and fast content-based image fusion (United States)

    Preibisch, Stephan; Rohlfing, Torsten; Hasak, Michael P.; Tomancak, Pavel


    Single Plane Illumination Microscopy (SPIM; Huisken et al., Nature 305(5686):1007-1009, 2004) is an emerging microscopic technique that enables live imaging of large biological specimens in their entirety. By imaging the living biological sample from multiple angles SPIM has the potential to achieve isotropic resolution throughout even relatively large biological specimens. For every angle, however, only a relatively shallow section of the specimen is imaged with high resolution, whereas deeper regions appear increasingly blurred. In order to produce a single, uniformly high resolution image, we propose here an image mosaicing algorithm that combines state of the art groupwise image registration for alignment with content-based image fusion to prevent degrading of the fused image due to regional blurring of the input images. For the registration stage, we introduce an application-specific groupwise transformation model that incorporates per-image as well as groupwise transformation parameters. We also propose a new fusion algorithm based on Gaussian filters, which is substantially faster than fusion based on local image entropy. We demonstrate the performance of our mosaicing method on data acquired from living embryos of the fruit fly, Drosophila, using four and eight angle acquisitions.

  9. Usefulness of problem-based learning in clinical nursing education ...

    African Journals Online (AJOL)

    Problem based learning (PBL) in clinical nursing is described as an effective learning strategy that can encourage students to become self-directed learners and to master clinical skills that can be transferable to service users. This study explores the usefulness of PBL in a nursing clinical setting from the nursing students' ...

  10. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    Directory of Open Access Journals (Sweden)

    Kampf Caroline


    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  11. Synchrotron-based X-ray Fluorescence Microscopy in Conjunction with Nanoindentation to Study Molecular-Scale Interactions of Phenol–Formaldehyde in Wood Cell Walls (United States)

    Joseph E. Jakes; Christopher G. Hunt; Daniel J. Yelle; Linda Lorenz; Kolby Hirth; Sophie-Charlotte Gleber; Stefan Vogt; Warren Grigsby; Charles R. Frihart


    Understanding and controlling molecular-scale interactions between adhesives and wood polymers are critical to accelerate the development of improved adhesives for advanced wood-based materials. The submicrometer resolution of synchrotron-based X-ray fluorescence microscopy (XFM) was found capable of mapping and quantifying infiltration of Br-labeled phenol−...

  12. Atomic force microscopy-based antibody recognition imaging of proteins in the pathological deposits in Pseudoexfoliation Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Creasey, Rhiannon [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Sharma, Shiwani [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Gibson, Christopher T. [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Craig, Jamie E. [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Ebner, Andreas [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Becker, Thomas [Nanochemistry Research Institute, Curtin University, GPO Box U1987, Perth, 6845 WA (Australia); Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Voelcker, Nicolas H., E-mail: [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia)


    The phenomenon of protein aggregation is of considerable interest to various disciplines, including the field of medicine. A range of disease pathologies are associated with this phenomenon. One of the ocular diseases hallmarked by protein aggregation is the Pseudoexfoliation (PEX) Syndrome. This condition is characterized by the deposition of insoluble proteinaceous material on the anterior human lens capsule. Genomic and proteomic analyses have revealed an association of specific genetic markers and various proteins, respectively, with PEX syndrome. However, the ultrastructure of the protein aggregates is poorly characterized. This study seeks to build capacity to determine the molecular nature of PEX aggregates on human lens capsules in their native state by AFM-based antibody recognition imaging. Lysyl oxidase-Like 1 (LOXL1), a protein identified as a component of PEX aggregates, is detected by an antibody-modified AFM probe. Topographical AFM images and antibody recognition images are obtained using three AFM-based techniques: TREC, phase and force-volume imaging. LOXL1 is found to be present on the lens capsule surface, and is localized around fibrous protein aggregates. Our evaluation shows that TREC imaging is best suited for human tissue imaging and holds significant potential for imaging of human disease tissues in their native state. -- Highlights: {yields} Atomic force microscopy techniques were applied to diseased human tissues. {yields} LOXL1 protein was detected on the small fibers of Pseudoexfoliation deposits. {yields} PicoTREC was the optimum technique for investigating protein aggregates.

  13. Focus measure method based on the modulus of the gradient of the color planes for digital microscopy (United States)

    Hurtado-Pérez, Román; Toxqui-Quitl, Carina; Padilla-Vivanco, Alfonso; Aguilar-Valdez, J. Félix; Ortega-Mendoza, Gabriel


    The modulus of the gradient of the color planes (MGC) is implemented to transform multichannel information to a grayscale image. This digital technique is used in two applications: (a) focus measurements during autofocusing (AF) process and (b) extending the depth of field (EDoF) by means of multifocus image fusion. In the first case, the MGC procedure is based on an edge detection technique and is implemented in over 15 focus metrics that are typically handled in digital microscopy. The MGC approach is tested on color images of histological sections for the selection of in-focus images. An appealing attribute of all the AF metrics working in the MGC space is their monotonic behavior even up to a magnification of 100×. An advantage of the MGC method is its computational simplicity and inherent parallelism. In the second application, a multifocus image fusion algorithm based on the MGC approach has been implemented on graphics processing units (GPUs). The resulting fused images are evaluated using a nonreference image quality metric. The proposed fusion method reveals a high-quality image independently of faulty illumination during the image acquisition. Finally, the three-dimensional visualization of the in-focus image is shown.

  14. Clinical oncology based upon radiation biology

    International Nuclear Information System (INIS)

    Hirata, Hideki


    This paper discussed the biological effects of radiation as physical energy, especially those of X-ray as electromagnetic radiation, by associating the position of clinical oncology with classical radiation cell biology as well as recent molecular biology. First, it described the physical and biological effects of radiation, cell death due to radiation and recovery, radiation effects at tissue level, and location information and dosage information in the radiotherapy of cancer. It also described the territories unresolved through radiation biology, such as low-dose high-sensitivity, bystander effects, etc. (A.O.)

  15. New ICPMS based strategies for clinical diagnosis

    International Nuclear Information System (INIS)

    Montes-Bayon, M.; Del Castillo, M.E.; Sanz-Medel, A.


    Full text: Glycosylation is the enzymatic process that links saccharides to produce glycans, either free or attached to proteins. This is an enzyme-directed site-specific process, as opposed to the chemical reaction of glycation which is the result of addition of a sugar molecule to a protein or lipid molecule without the controlling action of an enzyme. Both protein modifications, however, can be used as clinical biomarkers for a variety of disorders including chronic alcoholism, diabetes or congenital disorders of glycosylation. The potential of ICPMS as a tool in the diagnosis of such diseases will be illustrated in the presentation. (author)

  16. Introducing a performance-based objective clinical examination into ...

    African Journals Online (AJOL)

    Purpose: To describe how a formative Objective Structured Clinical Examination was applied to fourth year pharmacy students at a university in Northern Cyprus. Methods: A blueprint-guided performance-based objective clinical examination was implemented. Group-prepared case scenarios based on course objectives ...

  17. Evidence-based clinical guidelines for eating disorders : International comparison

    NARCIS (Netherlands)

    Hilbert, Anja; Hoek, Hans W.; Schmidt, Ricarda


    Purpose of review: The current systematic review sought to compare available evidence-based clinical treatment guidelines for all specific eating disorders. Recent findings: Nine evidence-based clinical treatment guidelines for eating disorders were located through a systematic search. The

  18. Workshop on the coupling of synchrotron radiation IR and X-rays with tip based scanning probe microscopies X-TIP

    Energy Technology Data Exchange (ETDEWEB)

    Comin, F.; Martinez-Criado, G.; Mundboth, K.; Susini, J. [European Synchrotron Radiation Facility (ESRF), 38 - Grenoble (France); Purans, J.; Sammelselg, V. [Tartu Univ. (Estonia); Chevrier, J.; Huant, S. [Universite Joseph-Fourier, Grenoble I, LEPES, 38 (France); Hamilton, B. [School of Electrical Engineering and Electronics, Manchester (United Kingdom); Saito, A. [Osaka Univ., RIKEN/SPring8 (Japan); Dhez, O. [OGG, INFM/CNR, 38 - Grenoble (France); Brocklesby, W.S. [Southampton Univ., Optoelectronics Research Centre (United Kingdom); Alvarez-Prado, L.M. [Ovieado, Dept. de Fisica (Spain); Kuzmin, A. [Institute of Solid State Physics - Riga (Latvia); Pailharey, D. [CRMC-N - CNRS, 13 - Marseille (France); Tonneau, D. [CRMCN - Faculte des sciences de Luminy, 13 - Marseille (France); Chretien, P. [Laboratoire de Genie Electrique de Paris, 75 - Paris (France); Cricenti, A. [ISM-CNR, Rome (Italy); DeWilde, Y. [ESPCI, 75 - Paris (France)


    The coupling of scanning probe microscopy (SPM) with synchrotron radiation is attracting increasing attention from nano-science community. By combining these 2 tools one can visualize, for example, the sample nano-structure prior to any X-ray characterization. Coupled with focusing devices or independently, SPM can provide spatial resolution below the optical limits. Furthermore, the possibility of employing SPM to manipulate nano-objects under X-ray beams is another exciting perspective. This document gathers the transparencies of 6 of the presentations made at the workshop: 1) the combination of atomic force microscopy and X-ray beam - experimental set-up and objectives; 2) the combination of scanning probe microscope and X-rays for detection of electrons; 3) towards soft X-ray scanning microscopy using tapered capillaries and laser-based high harmonic sources; 4) near-field magneto-optical microscopy; 5) near-field scanning optical microscopy - a brief overview -; and 6) from aperture-less near-field optical microscopy to infra-red near-field night vision. 4 posters entitled: 1) development of laboratory setup for X-ray/AFM experiments, 2) towards X-ray diffraction on single islands, 3) nano-XEOL using near-field detection, and 4) local collection with a STM tip of photoelectrons emitted by a surface irradiated by visible of UV laser beam, are included in the document.

  19. Workshop on the coupling of synchrotron radiation IR and X-rays with tip based scanning probe microscopies X-TIP

    International Nuclear Information System (INIS)

    Comin, F.; Martinez-Criado, G.; Mundboth, K.; Susini, J.; Purans, J.; Sammelselg, V.; Chevrier, J.; Huant, S.; Hamilton, B.; Saito, A.; Dhez, O.; Brocklesby, W.S.; Alvarez-Prado, L.M.; Kuzmin, A.; Pailharey, D.; Tonneau, D.; Chretien, P.; Cricenti, A.; DeWilde, Y.


    The coupling of scanning probe microscopy (SPM) with synchrotron radiation is attracting increasing attention from nano-science community. By combining these 2 tools one can visualize, for example, the sample nano-structure prior to any X-ray characterization. Coupled with focusing devices or independently, SPM can provide spatial resolution below the optical limits. Furthermore, the possibility of employing SPM to manipulate nano-objects under X-ray beams is another exciting perspective. This document gathers the transparencies of 6 of the presentations made at the workshop: 1) the combination of atomic force microscopy and X-ray beam - experimental set-up and objectives; 2) the combination of scanning probe microscope and X-rays for detection of electrons; 3) towards soft X-ray scanning microscopy using tapered capillaries and laser-based high harmonic sources; 4) near-field magneto-optical microscopy; 5) near-field scanning optical microscopy - a brief overview -; and 6) from aperture-less near-field optical microscopy to infra-red near-field night vision. 4 posters entitled: 1) development of laboratory setup for X-ray/AFM experiments, 2) towards X-ray diffraction on single islands, 3) nano-XEOL using near-field detection, and 4) local collection with a STM tip of photoelectrons emitted by a surface irradiated by visible of UV laser beam, are included in the document

  20. Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array. (United States)

    Navruz, Isa; Coskun, Ahmet F; Wong, Justin; Mohammad, Saqib; Tseng, Derek; Nagi, Richie; Phillips, Stephen; Ozcan, Aydogan


    We demonstrate a cellphone based contact microscopy platform, termed Contact Scope, which can image highly dense or connected samples in transmission mode. Weighing approximately 76 grams, this portable and compact microscope is installed on the existing camera unit of a cellphone using an opto-mechanical add-on, where planar samples of interest are placed in contact with the top facet of a tapered fiber-optic array. This glass-based tapered fiber array has ~9 fold higher density of fiber optic cables on its top facet compared to the bottom one and is illuminated by an incoherent light source, e.g., a simple light-emitting-diode (LED). The transmitted light pattern through the object is then sampled by this array of fiber optic cables, delivering a transmission image of the sample onto the other side of the taper, with ~3× magnification in each direction. This magnified image of the object, located at the bottom facet of the fiber array, is then projected onto the CMOS image sensor of the cellphone using two lenses. While keeping the sample and the cellphone camera at a fixed position, the fiber-optic array is then manually rotated with discrete angular increments of e.g., 1-2 degrees. At each angular position of the fiber-optic array, contact images are captured using the cellphone camera, creating a sequence of transmission images for the same sample. These multi-frame images are digitally fused together based on a shift-and-add algorithm through a custom-developed Android application running on the smart-phone, providing the final microscopic image of the sample, visualized through the screen of the phone. This final computation step improves the resolution and also removes spatial artefacts that arise due to non-uniform sampling of the transmission intensity at the fiber optic array surface. We validated the performance of this cellphone based Contact Scope by imaging resolution test charts and blood smears.

  1. Quantum Cascade Laser-Based Infrared Microscopy for Label-Free and Automated Cancer Classification in Tissue Sections. (United States)

    Kuepper, Claus; Kallenbach-Thieltges, Angela; Juette, Hendrik; Tannapfel, Andrea; Großerueschkamp, Frederik; Gerwert, Klaus


    A feasibility study using a quantum cascade laser-based infrared microscope for the rapid and label-free classification of colorectal cancer tissues is presented. Infrared imaging is a reliable, robust, automated, and operator-independent tissue classification method that has been used for differential classification of tissue thin sections identifying tumorous regions. However, long acquisition time by the so far used FT-IR-based microscopes hampered the clinical translation of this technique. Here, the used quantum cascade laser-based microscope provides now infrared images for precise tissue classification within few minutes. We analyzed 110 patients with UICC-Stage II and III colorectal cancer, showing 96% sensitivity and 100% specificity of this label-free method as compared to histopathology, the gold standard in routine clinical diagnostics. The main hurdle for the clinical translation of IR-Imaging is overcome now by the short acquisition time for high quality diagnostic images, which is in the same time range as frozen sections by pathologists.

  2. [A web-based integrated clinical database for laryngeal cancer]. (United States)

    E, Qimin; Liu, Jialin; Li, Yong; Liang, Chuanyu


    To establish an integrated database for laryngeal cancer, and to provide an information platform for laryngeal cancer in clinical and fundamental researches. This database also meet the needs of clinical and scientific use. Under the guidance of clinical expert, we have constructed a web-based integrated clinical database for laryngeal carcinoma on the basis of clinical data standards, Apache+PHP+MySQL technology, laryngeal cancer specialist characteristics and tumor genetic information. A Web-based integrated clinical database for laryngeal carcinoma had been developed. This database had a user-friendly interface and the data could be entered and queried conveniently. In addition, this system utilized the clinical data standards and exchanged information with existing electronic medical records system to avoid the Information Silo. Furthermore, the forms of database was integrated with laryngeal cancer specialist characteristics and tumor genetic information. The Web-based integrated clinical database for laryngeal carcinoma has comprehensive specialist information, strong expandability, high feasibility of technique and conforms to the clinical characteristics of laryngeal cancer specialties. Using the clinical data standards and structured handling clinical data, the database can be able to meet the needs of scientific research better and facilitate information exchange, and the information collected and input about the tumor sufferers are very informative. In addition, the user can utilize the Internet to realize the convenient, swift visit and manipulation on the database.

  3. Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells. (United States)

    Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph


    Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular

  4. Lipid Bilayer Membrane in a Silicon Based Micron Sized Cavity Accessed by Atomic Force Microscopy and Electrochemical Impedance Spectroscopy. (United States)

    Khan, Muhammad Shuja; Dosoky, Noura Sayed; Patel, Darayas; Weimer, Jeffrey; Williams, John Dalton


    Supported lipid bilayers (SLBs) are widely used in biophysical research to probe the functionality of biological membranes and to provide diagnoses in high throughput drug screening. Formation of SLBs at below phase transition temperature ( Tm ) has applications in nano-medicine research where low temperature profiles are required. Herein, we report the successful production of SLBs at above-as well as below-the Tm of the lipids in an anisotropically etched, silicon-based micro-cavity. The Si-based cavity walls exhibit controlled temperature which assist in the quick and stable formation of lipid bilayer membranes. Fusion of large unilamellar vesicles was monitored in real time in an aqueous environment inside the Si cavity using atomic force microscopy (AFM), and the lateral organization of the lipid molecules was characterized until the formation of the SLBs. The stability of SLBs produced was also characterized by recording the electrical resistance and the capacitance using electrochemical impedance spectroscopy (EIS). Analysis was done in the frequency regime of 10 -2 -10⁵ Hz at a signal voltage of 100 mV and giga-ohm sealed impedance was obtained continuously over four days. Finally, the cantilever tip in AFM was utilized to estimate the bilayer thickness and to calculate the rupture force at the interface of the tip and the SLB. We anticipate that a silicon-based, micron-sized cavity has the potential to produce highly-stable SLBs below their Tm . The membranes inside the Si cavity could last for several days and allow robust characterization using AFM or EIS. This could be an excellent platform for nanomedicine experiments that require low operating temperatures.


    Directory of Open Access Journals (Sweden)



    Full Text Available We demonstrate the feasibility of simultaneous multi-probe detection for an optical-resolution photoacoustic microscopy (OR-PAM system. OR-PAM has elicited the attention of biomedical imaging researchers because of its optical absorption contrast and high spatial resolution with great imaging depth. OR-PAM allows label-free and noninvasive imaging by maximizing the optical absorption of endogenous biomolecules. However, given the inadequate absorption of some biomolecules, detection sensitivity at the same incident intensity requires improvement. In this study, a modulated continuous wave with power density less than 3 mW/cm2 (1/4 of the ANSI safety limit excited the weak photoacoustic (PA signals of biological cells. A microcavity transducer is developed based on the bulk modulus of gas five orders of magnitude lower than that of solid; air pressure variation is inversely proportional to cavity volume at the same temperature increase. Considering that a PA wave expands in various directions, detecting PA signals from different positions and adding them together can increase detection sensitivity and signal-to-noise ratio. Therefore, we employ four detectors to acquire tiny PA signals simultaneously. Experimental results show that the developed OR-PAM system allows the label-free imaging of cells with weak optical absorption.

  6. Atomic structure of Mg-based metallic glass investigated with neutron diffraction, reverse Monte Carlo modeling and electron microscopy

    Directory of Open Access Journals (Sweden)

    Rafał Babilas


    Full Text Available The structure of a multicomponent metallic glass, Mg65Cu20Y10Ni5, was investigated by the combined methods of neutron diffraction (ND, reverse Monte Carlo modeling (RMC and high-resolution transmission electron microscopy (HRTEM. The RMC method, based on the results of ND measurements, was used to develop a realistic structure model of a quaternary alloy in a glassy state. The calculated model consists of a random packing structure of atoms in which some ordered regions can be indicated. The amorphous structure was also described by peak values of partial pair correlation functions and coordination numbers, which illustrated some types of cluster packing. The N = 9 clusters correspond to the tri-capped trigonal prisms, which are one of Bernal’s canonical clusters, and atomic clusters with N = 6 and N = 12 are suitable for octahedral and icosahedral atomic configurations. The nanocrystalline character of the alloy after annealing was also studied by HRTEM. The selected HRTEM images of the nanocrystalline regions were also processed by inverse Fourier transform analysis. The high-angle annular dark-field (HAADF technique was used to determine phase separation in the studied glass after heat treatment. The HAADF mode allows for the observation of randomly distributed, dark contrast regions of about 4–6 nm. The interplanar spacing identified for the orthorhombic Mg2Cu crystalline phase is similar to the value of the first coordination shell radius from the short-range order.

  7. A novel method for identifying a graph-based representation of 3-D microvascular networks from fluorescence microscopy image stacks. (United States)

    Almasi, Sepideh; Xu, Xiaoyin; Ben-Zvi, Ayal; Lacoste, Baptiste; Gu, Chenghua; Miller, Eric L


    A novel approach to determine the global topological structure of a microvasculature network from noisy and low-resolution fluorescence microscopy data that does not require the detailed segmentation of the vessel structure is proposed here. The method is most appropriate for problems where the tortuosity of the network is relatively low and proceeds by directly computing a piecewise linear approximation to the vasculature skeleton through the construction of a graph in three dimensions whose edges represent the skeletal approximation and vertices are located at Critical Points (CPs) on the microvasculature. The CPs are defined as vessel junctions or locations of relatively large curvature along the centerline of a vessel. Our method consists of two phases. First, we provide a CP detection technique that, for junctions in particular, does not require any a priori geometric information such as direction or degree. Second, connectivity between detected nodes is determined via the solution of a Binary Integer Program (BIP) whose variables determine whether a potential edge between nodes is or is not included in the final graph. The utility function in this problem reflects both intensity-based and structural information along the path connecting the two nodes. Qualitative and quantitative results confirm the usefulness and accuracy of this method. This approach provides a mean of correctly capturing the connectivity patterns in vessels that are missed by more traditional segmentation and binarization schemes because of imperfections in the images which manifest as dim or broken vessels. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. High efficiency and flexible working distance digital in-line holographic microscopy based on Fresnel zone plate

    International Nuclear Information System (INIS)

    Tian, Peng; Yang, Fan; Li, Fanxing; Hu, Song; Yan, Wei; Hua, Yilei


    Traditional digital in-line holography suffers from twin-image noise problems and extremely short working distances between the object and light source. Here, we propose lensless Fourier transform digital in-line holographic microscopy based on a single optical element. A Fresnel zone plate is used to split the incident light into two parts: one is scattered along the original direction, the other is gathered at a focal point and the sample is put behind the focus. The interference fringe pattern, formed by the two beams, is recorded digitally by a CCD camera. A novel reconstruction algorithm is proposed to present the object image. The proof-of-concept experiments demonstrate that the proposed technique can eliminate the twin-image noise problem, improving the image contrast with high efficiency, and increasing the flexibility of the working distance. Furthermore, a wide field of view and no contact make it a promising tool for the study of materials science, biology and microelectronics. (paper)

  9. Microscopy system of atomic force based on a digital optical reading unit and a buzzer-scanner

    International Nuclear Information System (INIS)

    Dabirian, R.; Loza M, D.; Wang, W. M.; Hwu, E. T.


    An astigmatic detection system (Ads) based on a compact disk/digital-versatile-disk (Cd-DVD) astigmatic optical pickup unit is presented. It can achieve a resolution better than 0.3 nm in detection of the vertical displacement and is able to detect the two-dimensional angular tilt of the object surface. Furthermore, a novel scanner design actuated by piezoelectric disk buzzers is presented. The scanner is composed of a quad-rod actuation structure and several piezoelectric disks. It can be driven directly with low-voltage and low-current sources, such as analogue outputs of a data acquisition card and enables a sufficient scanning range of up to μm. In addition, an economic, high-performance streamlined atomic force microscopy (AFM) was constructed, using the buzzer-scanner to move the sample relative to the probe, and using a Cd/DVD optical pickup unit to detect the mechanical resonance of a micro fabricated cantilever. The performance of the AFM is evaluated. The high sensitivity and high bandwidth of the detection system makes the equipment suitable for characterizing nano scale elements. An AFM using our detection system for detecting the deflection of micro fabricated cantilevers can resolve individual atomic steps on graphite surfaces. (Author)

  10. Image-based overlay and alignment metrology through optically opaque media with sub-surface probe microscopy (United States)

    van Es, Maarten H.; Mohtashami, Abbas; Piras, Daniele; Sadeghian, Hamed


    Nondestructive subsurface nanoimaging through optically opaque media is considered to be extremely challenging and is essential for several semiconductor metrology applications including overlay and alignment and buried void and defect characterization. The current key challenge in overlay and alignment is the measurement of targets that are covered by optically opaque layers. Moreover, with the device dimensions moving to the smaller nodes and the issue of the so-called loading effect causing offsets between between targets and product features, it is increasingly desirable to perform alignment and overlay on product features or so-called on-cell overlay, which requires higher lateral resolution than optical methods can provide. Our recently developed technique known as SubSurface Ultrasonic Resonance Force Microscopy (SSURFM) has shown the capability for high-resolution imaging of structures below a surface based on (visco-)elasticity of the constituent materials and as such is a promising technique to perform overlay and alignment with high resolution in upcoming production nodes. In this paper, we describe the developed SSURFM technique and the experimental results on imaging buried features through various layers and the ability to detect objects with resolution below 10 nm. In summary, the experimental results show that the SSURFM is a potential solution for on-cell overlay and alignment as well as detecting buried defects or voids and generally metrology through optically opaque layers.

  11. Determination of electrostatic force and its characteristics based on phase difference by amplitude modulation atomic force microscopy (United States)

    Wang, Kesheng; Cheng, Jia; Yao, Shiji; Lu, Yijia; Ji, Linhong; Xu, Dengfeng


    Electrostatic force measurement at the micro/nano scale is of great significance in science and engineering. In this paper, a reasonable way of applying voltage is put forward by taking an electrostatic chuck in a real integrated circuit manufacturing process as a sample, applying voltage in the probe and the sample electrode, respectively, and comparing the measurement effect of the probe oscillation phase difference by amplitude modulation atomic force microscopy. Based on the phase difference obtained from the experiment, the quantitative dependence of the absolute magnitude of the electrostatic force on the tip-sample distance and applied voltage is established by means of theoretical analysis and numerical simulation. The results show that the varying characteristics of the electrostatic force with the distance and voltage at the micro/nano scale are similar to those at the macroscopic scale. Electrostatic force gradually decays with increasing distance. Electrostatic force is basically proportional to the square of applied voltage. Meanwhile, the applicable conditions of the above laws are discussed. In addition, a comparison of the results in this paper with the results of the energy dissipation method shows the two are consistent in general. The error decreases with increasing distance, and the effect of voltage on the error is small.

  12. In situ electron microscopy studies of electromechanical behavior in metals at the nanoscale using a novel microdevice-based system

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Wonmo, E-mail:; Beniam, Iyoel; Qidwai, Siddiq M. [Naval Research Laboratory, Washington, DC 20375 (United States)


    Electrically assisted deformation (EAD) is an emerging technique to enhance formability of metals by applying an electric current through them. Despite its increasing importance in manufacturing applications, there is still an unresolved debate on the nature of the fundamental deformation mechanisms underlying EAD, mainly between electroplasticity (non-thermal effects) and resistive heating (thermal effects). This status is due to two critical challenges: (1) a lack of experimental techniques to directly observe fundamental mechanisms of material deformation during EAD, and (2) intrinsic coupling between electric current and Joule heating giving rise to unwanted thermally activated mechanisms. To overcome these challenges, we have developed a microdevice-based electromechanical testing system (MEMTS) to characterize nanoscale metal specimens in transmission electron microscopy (TEM). Our studies reveal that MEMTS eliminates the effect of Joule heating on material deformation, a critical advantage over macroscopic experiments, owing to its unique scale. For example, a negligible change in temperature (<0.02 °C) is predicted at ∼3500 A/mm{sup 2}. Utilizing the attractive features of MEMTS, we have directly investigated potential electron-dislocation interactions in single crystal copper (SCC) specimens that are simultaneously subjected to uniaxial loading and electric current density up to 5000 A/mm{sup 2}. Our in situ TEM studies indicate that for SCC, electroplasticity does not play a key role as no differences in dislocation activities, such as depinning and movement, are observed.

  13. Atomic force microscopy study of stacking modes of martensitic transformation in Fe-Mn-Si based shape memory alloys

    International Nuclear Information System (INIS)

    Liu, D.Z.; Kikuchi, T.; Kajiwara, S.; Shinya, N.


    Stacking modes of thermally induced and stress-induced martensitic transformation in Fe-28Mn-6Si-5Cr shape memory alloys have been studied using atomic force microscopy (AFM). It has been found that thermally induced martensite plates appear with the self-accommodated stacking form, in which all the three possible variants with different left angle 112 right angle shear directions in a {111} plane are activated and formed in parallel but at separate places; i.e. each plate corresponds to one variant. In addition, a plastic deformation band is always induced in austenite between two different variants. On the other hand, stress-induced martensite plates appear with the mono-partial stacking form, i.e. only single variant is activated in a {111} plane in a grain. The difference between stacking modes of thermally induced and stress-induced martensites makes them play a different role in contributing to shape memory effect in Fe-Mn-Si based shape memory alloys. (orig.)

  14. Direct observation of crosssectional potential distribution in GaN-based MIS structures by Kelvin-probe force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Masamitsu; Kikawa, Junjiroh [Research Organization of Science and Engineering, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577 (Japan); Fujishima, Tatsuya; Chikamatsu, Kentaro; Yamaguchi, Atsushi; Otake, Hirotaka [Research and Development Headquarters, ROHM Co., Ltd., 21 Saiin Mizosaki-Cho, Ukyo-ku, Kyoto 615-8585 (Japan); Nanishi, Yasushi [Department of Photonics, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577 (Japan)


    Cross-sectional potential distribution in GaN-based trench gate metal-insulator-semiconductor field-effect transistors (MISFET) at off- and operating-state has been investigated by using Kelvin-probe force microscopy to clarify the actual operating situation of trench gate MISFET. The potential distribution reflecting the wafer structure, n/p/n{sup -}/n{sup +}, is observed as shown in the right figure. At the off-state (the gate voltage is fixed to 0 V), it is found that the electric field at the internal p/n{sup -} interface become strong, on the contrary to that at top n/p interface is almost unchanged by the stepwise increase of the drain bias from 0 to 15 V. From the analysis of results obtained at operating state, we can confirm the situation how the channel forms by increasing the gate voltage. This information is useful for designing devices and improving their characteristics (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  15. Differential-interference-contrast digital in-line holography microscopy based on a single-optical-element. (United States)

    Zhang, Yuchao; Xie, Changqing


    Both digital in-line holography (DIH) and zone plate-based microscopy have received considerable interest as powerful imaging tools. However, the former suffers from a twin-image noise problem. The latter suffers from low efficiency and difficulty in fabrication. Here, we present an effective and efficient phase-contrast imaging approach, named differential-interference-contrast digital in-line holography (DIC-DIH), by using a single optical element to split the incident light into a plane wave and a converging spherical wave and generate a two-dimensional (2D) DIC effect simultaneously. Specifically, to improve image contrast, we present a new single optical element, termed 2D DIC compound photon sieves, by combining two overlaid binary gratings and a compound photon sieve through two logical XOR operations. The proof-of-concept experiments demonstrate that the proposed technique can eliminate the twin-image noise problem and improve image contrast with high efficiency. Additionally, we present an example of the phase-contrast imaging nonuniform thick photoresist development process.

  16. Light sheet-based fluorescence microscopy (LSFM) reduces phototoxic effects and provides new means for the modern life sciences (United States)

    Pampaloni, Francesco; Ansari, Nari; Girard, Philippe; Stelzer, Ernst H. K.


    Most optical technologies are applied to flat, basically two-dimensional cellular systems. However, physiological meaningful information relies on the morphology, the mechanical properties and the biochemistry of a cell's context. A cell requires the complex three-dimensional relationship to other cells. However, the observation of multi-cellular biological specimens remains a challenge. Specimens scatter and absorb light, thus, the delivery of the probing light and the collection of the signal light become inefficient; many endogenous biochemical compounds also absorb light and suffer degradation of some sort (photo-toxicity), which induces malfunction of a specimen. In conventional and confocal fluorescence microscopy, whenever a single plane, the entire specimen is illuminated. Recording stacks of images along the optical Z-axis thus illuminates the entire specimen once for each plane. Hence, cells are illuminated 10-20 and fish 100-300 times more often than they are observed. This can be avoided by changing the optical arrangement. The basic idea is to use light sheets, which are fed into the specimen from the side and overlap with the focal plane of a wide-field fluorescence microscope. In contrast to an epi-fluorescence arrangement, such an azimuthal fluorescence arrangement uses two independently operated lenses for illumination and detection. Optical sectioning and no photo-toxic damage or photo-bleaching outside a small volume close to the focal plane are intrinsic properties. Light sheet-based fluorescence microscopy (LSFM) takes advantage of modern camera technologies. LSFM can be operated with laser cutters and for fluorescence correlation spectroscopy. During the last few years, LSFM was used to record zebrafish development from the early 32-cell stage until late neurulation with sub-cellular resolution and short sampling periods (60-90 sec/stack). The recording speed was five 4-Megapixel large frames/sec with a dynamic range of 12-14 bit. We followed

  17. Porosity and permeability determination of organic-rich Posidonia shales based on 3-D analyses by FIB-SEM microscopy (United States)

    Grathoff, Georg H.; Peltz, Markus; Enzmann, Frieder; Kaufhold, Stephan


    The goal of this study is to better understand the porosity and permeability in shales to improve modelling fluid and gas flow related to shale diagenesis. Two samples (WIC and HAD) were investigated, both mid-Jurassic organic-rich Posidonia shales from Hils area, central Germany of different maturity (WIC R0 0.53 % and HAD R0 1.45 %). The method for image collection was focused ion beam (FIB) microscopy coupled with scanning electron microscopy (SEM). For image and data analysis Avizo and GeoDict was used. Porosity was calculated from segmented 3-D FIB based images and permeability was simulated by a Navier Stokes-Brinkman solver in the segmented images. Results show that the quantity and distribution of pore clusters and pores (≥ 40 nm) are similar. The largest pores are located within carbonates and clay minerals, whereas the smallest pores are within the matured organic matter. Orientation of the pores calculated as pore paths showed minor directional differences between the samples. Both samples have no continuous connectivity of pore clusters along the axes in the x, y, and z direction on the scale of 10 to 20 of micrometer, but do show connectivity on the micrometer scale. The volume of organic matter in the studied volume is representative of the total organic carbon (TOC) in the samples. Organic matter does show axis connectivity in the x, y, and z directions. With increasing maturity the porosity in organic matter increases from close to 0 to more than 5 %. These pores are small and in the large organic particles have little connection to the mineral matrix. Continuous pore size distributions are compared with mercury intrusion porosimetry (MIP) data. Differences between both methods are caused by resolution limits of the FIB-SEM and by the development of small pores during the maturation of the organic matter. Calculations show no permeability when only considering visible pores due to the lack of axis connectivity. Adding the organic matter with a

  18. Medical simulation-based education improves medicos' clinical skills. (United States)

    Wang, Zhaoming; Liu, Qiaoyu; Wang, Hai


    Clinical skill is an essential part of clinical medicine and plays quite an important role in bridging medicos and physicians. Due to the realities in China, traditional medical education is facing many challenges. There are few opportunities for students to practice their clinical skills and their dexterities are generally at a low level. Medical simulation-based education is a new teaching modality and helps to improve medicos' clinical skills to a large degree. Medical simulation-based education has many significant advantages and will be further developed and applied.

  19. Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution (United States)

    Yamashiro, Sawako; Watanabe, Naoki


    Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy. PMID:28684722

  20. Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution. (United States)

    Yamashiro, Sawako; Watanabe, Naoki


    Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy.

  1. Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials? (United States)

    Busquets, Joanna; Del Galdo, Francesco; Kissin, Eugene Y.


    Objectives. To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. Methods. Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. Results. The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 × 106 compared with 18.6 × 106 for the six normal skin samples (P < 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. Conclusions. CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease. PMID:20202926

  2. Image-Guided Cryoablation of the Spine in a Swine Model: Clinical, Radiological, and Pathological Findings with Light and Electron Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, Ricardo Miguel Costa de, E-mail:; Andrade, Celi Santos, E-mail:; Caldas, José Guilherme Mendes Pereira, E-mail: [Faculdade de Medicina da Universidade de São Paulo, Department of Radiology, Interventional Radiology Unit of the Instituto de Radiologia (Brazil); Tsunemi, Miriam Harumi, E-mail: [Universidade Estadual Paulista Júlio de Mesquita Filho, Department of Biostatistics, Biosciences Institute (Brazil); Ferreira, Lorraine Braga, E-mail:; Arana-Chavez, Victor Elias, E-mail: [Faculdade de Odontologia da Universidade de São Paulo, Department of Oral Pathology (Brazil); Cury, Patrícia Maluf, E-mail: [Faculdade de Medicina de São José do Rio Preto, Department of Pathology and Forensic Medicine (Brazil)


    PurposeThis study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body.MethodsThe institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO{sub 2}) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia.ResultsCBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO{sub 2} epidural injection were successful in all procedures. No major complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson’s correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed.ConclusionsCBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.

  3. Image-Guided Cryoablation of the Spine in a Swine Model: Clinical, Radiological, and Pathological Findings with Light and Electron Microscopy

    International Nuclear Information System (INIS)

    Freitas, Ricardo Miguel Costa de; Andrade, Celi Santos; Caldas, José Guilherme Mendes Pereira; Tsunemi, Miriam Harumi; Ferreira, Lorraine Braga; Arana-Chavez, Victor Elias; Cury, Patrícia Maluf


    PurposeThis study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body.MethodsThe institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO 2 ) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia.ResultsCBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO 2 epidural injection were successful in all procedures. No major complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson’s correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed.ConclusionsCBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers

  4. Fatigue crack initiation in nickel-based superalloys studied by microstructure-based FE modeling and scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Fried M.


    Full Text Available In this work stage I crack initiation in polycrystalline nickel-based superalloys is investigated by analyzing anisotropic mechanical properties, local stress concentrations and plastic deformation on the microstructural length scale. The grain structure in the gauge section of fatigue specimens was characterized by EBSD. Based on the measured data, a microstructure-based FE model could be established to simulate the strain and stress distribution in the specimens during the first loading cycle of a fatigue test. The results were in fairly good agreement with experimentally measured local strains. Furthermore, the onset of plastic deformation was predicted by identifying shear stress maxima in the microstructure, presumably leading to activation of slip systems. Measurement of plastic deformation and observation of slip traces in the respective regions of the microstructure confirmed the predicted slip activity. The close relation between micro-plasticity, formation of slip traces and stage I crack initiation was demonstrated by SEM surface analyses of fatigued specimens and an in-situ fatigue test in a large chamber SEM.

  5. Safety assessment in primary Mycobacterium tuberculosis smear microscopy centres in Blantyre Malawi: a facility based cross sectional survey. (United States)

    Majamanda, J; Ndhlovu, P; Shawa, I T


    Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is transmitted mainly through aerosolization of infected sputum which puts laboratory workers at risk in spite of the laboratory workers' risk of infection being at 3 to 9 times higher than the general public. Laboratory safety should therefore be prioritized and optimized to provide sufficient safety to laboratory workers. To assess the safety for the laboratory workers in TB primary microscopy centres in Blantyre urban. TB primary microscopy centers in Blantyre urban were assessed in aspects of equipment availability, facility layout, and work practice, using a standardized WHO/AFRO ISO 15189 checklist for the developing countries which sets the minimum safety score at ≥80%. Each center was graded according to the score it earned upon assessment. Only one (1) microscopy center out nine (9) reached the minimum safety requirement. Four (4) centers were awarded 1 star level, four (4) centers were awarded 2 star level and only one (1) center was awarded 3 star level. In Blantyre urban, 89% of the Tuberculosis microscopy centers are failing to provide the minimum safety to the laboratory workers. Government and other stake holders should be committed in addressing the safety challenges of TB microscopy centres in the country to ensure safety for the laboratory workers. It is recommended that the study be conducted at the regional or national level for both public and private laboratories in order to have a general picture of safety in Tb microscopy centres possibly across the country.

  6. Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies. (United States)

    Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku


    Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Bovine tuberculosis in South Darfur State, Sudan: an abattoir study based on microscopy and molecular detection methods. (United States)

    Asil, El Tigani A; El Sanousi, Sulieman M; Gameel, Ahmed; El Beir, Haytham; Fathelrahman, Maha; Terab, Nasir M; Muaz, Magzoub A; Hamid, Mohamed E


    Bovine tuberculosis (BTB) is a widespread zoonosis in developing countries but has received little attention in many sub-Saharan African countries including Sudan and particularly in some parts such as Darfur states. This study aimed to detect bovine tuberculosis among caseous materials of cattle slaughtered in abattoirs in South Darfur State, Sudan by using microscopic and PCR-based methods. The study was a cross-sectional abattoir-based study which examined a total of 6,680 bovine carcasses for caseous lesions in South Darfur State between 2007 and 2009. Collected specimens were examined for the presence of acid-fast bacilli (AFB) by using microscopic and culture techniques. Isolated mycobacteria were identified by selected conventional cultural and biochemical tests in comparison to a single tube multiplex PCR (m-PCR) assay which detect Mycobacterium bovis-specific 168-bp amplicons. Of the total 6,680 slaughtered cattle examined in South Darfur, 400 (6 %) showed caseations restricted to lymph nodes (86.8 %) or generalized (13.2 %). Bovine tuberculosis was diagnosed in 12 (0.18 %), bovine farcy in 59 (0.88 %), unidentified mycobacteria in 6 (0.09 %), and missed or contaminated cultures in 7 (0.1 %). Out of 18 cultures with nonbranching acid-fast rods, 12 amplified unique 168-bp sequence specific for M. bovis and subsequently confirmed as M. bovis. With the exception of the reference M. tuberculosis strains, none of the remaining AFB amplified the 337-bp amplicon specific for M. tuberculosis. It could be concluded that bovine tuberculosis is prevalent among cattle in South Darfur representing 4.5 % from all slaughtered cattle with caseous lesions. The study sustains microscopy as a useful and accessible technique for detecting AFB. m-PCR assay proved to be valuable for confirmation of BTB and its differentiation from other related mycobacteriosis, notably bovine farcy.

  8. Clinical dosimeter based on diamond detector

    International Nuclear Information System (INIS)

    Chervjakov, A.M.; Ljalina, L.I.; Ljutina, G.J.; Khrunov, V.S.; Martynov, S.S.; Popov, S.A.


    Full text: Diamond detectors have found application in the relative dosimetry and their parameters have been described elsewhere. Today, the exclusive producer of the diamond detector is the Institute of Physical and Technical Problems, Russia, and exclusive dealer is the PTW-Freiburg. The main features of the diamond detector are good long time stability, suitable range of the energy dependence for photon and electron beams in clinical use, independence of the measured date from temperature and pressure. The high sensitivity per volume unit of the diamond detector (1500 times higher than ionization chamber) allowed using detectors with very small volume (1-5 mm 3 ) and rather simple electronics for ionization current registration. The new dosimeter consists of the diamond detector itself, 40 m registration cable, pre-amplifier, micro-processor block for data handling and absorbed dose calculation using the calibration factor of diamond detector in terms of absorbed dose to water. Dosimeter has the possibility to work with PC using standard RS-232 interface. The main features of the dosimeter are as follows: the range of dose rate measurements for photon, electron and proton beams is within 0.01-1.0 Gy/s; the energy ranges for photons are 0.08-25 MeV, and 4-25 MeV for electrons, with energy dependence no more than ±2%; the main uncertainty of the dose measurements is within ±2%; the pre-irradiation dose for diamond detector is no more than 10 Gy; the sensitive volume of the used diamond detectors is within 1-5 mm 3 ; the weight of the dosimeter no more than 2 kg. The new dosimeter was evaluated at the Central Research Institute of Roentgenology and Radiology, St. Petersburg, Russia to verify its performance. The dosimeter was used as a reference instrument for dose measurements at Cobalt-60 unit, SL75-5 and SL-20 linear accelerators and the test results have shown that the device have met the specifications. It is planned to produce dosimeter as serial device by

  9. The 'grey area' between small cell and non-small cell lung carcinomas. Light and electron microscopy versus clinical data in 14 cases

    NARCIS (Netherlands)

    Mooi, W. J.; van Zandwijk, N.; Dingemans, K. P.; Koolen, M. G.; Wagenvoort, C. A.


    We studied 14 lung tumours which on light microscopy had posed difficulties on classification as either small cell or non-small cell carcinomas. The light and electron microscopical features were compared with patient follow-up data. Electron microscopy showed neuroendocrine granules in 12 cases,

  10. [Narrative-based medicine and clinical knowledge]. (United States)

    Saito, Seiji


    Narrative Based Medicine (NBM) can be defined as follows; a) It views the patient's illness as an unfolding story within the wider story of the patient's life and life-world; b) It acknowledges the patient as the narrator of the story and the subject of the tale; c) It recognizes that all medical theories, hypothesis and pathophysiologies as socially constructed narratives and accepts the coexistence of multiple different narratives; d) It regards the emergence of new stories from dialogue and discourse between patients and healthcare professionals as part of the treatment. Because psychiatry is the only area of specialist medicine where talking and listening are explicitly understood to be therapeutic, NBM can be adopted an effective perspective and method in psychiatry.

  11. Transmission electron microscopy study for investigating high-temperature reliability of Ti10W90-based and Ta-based diffusion barriers up to 600 C

    International Nuclear Information System (INIS)

    Budhiman, Nando; Schuermann, Ulrich; Kienle, Lorenz; Jensen, Bjoern; Chemnitz, Steffen; Wagner, Bernhard


    Abstractauthoren Transmission electron microscopy (TEM) analysis, including energy dispersive X-ray (EDX) (elemental mapping, line, and point measurements) and energy filtered TEM (EFTEM) methods, is applied to investigate the high temperature reliability, especially material diffusion, of two types of diffusion barriers: titanium-tungsten-based (Ti 10 W 90 -based) and tantalum-based (Ta-based), with nickel (Ni) layer on top. Both barriers were deposited as a form of stacked layers on sili-con (Si) wafers using the physical vapor deposition (PVD) technique. TEM analysis is performed on both barriers before and after annealing (at 600 C for 24 h inside a vacuum chamber). No diffusion of material into the Si substrate as observed. Additionally, only diffusion between the Ni and adjoining Ti 10 W 90 layers, and between Ni and adjoining Ta layers in the Ti 10 W 90 -based and Ta-based barriers, respectively, are observed due to annealing. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)


    Directory of Open Access Journals (Sweden)

    Angela Čuk


    Full Text Available Background. Evidence-based medicine employs systematic searching, evaluation and use of current research findings as the basis for clinical decision-making. However, there are some problems and uncertainties hindering introduction and spreading of the use of the method in clinical practice. Physicians often have no time for literature searching and for use of the method in practice. For certain questions in clinical practice there are no answers in medical literature. Most of the evidences in medical literature are only available in English. Introduction of the method is hampered also by the fact that clinical decision-making is complex and does not allow procedures prescribed in advance. Rigidity and universality of decisions resulting from the evidence may appear impersonal and may affect the relationship between the physician and the patient. Trends towards evidence based medicine are followed also by big multinational pharmaceutical corporations. They carry out large and expensive clinical trials using the results for promotional purposes. In this way, they get the competitive advantage and influence the objectivity of physicians’ clinical decision-making.Conclusions. With introduction of evidence based medicine into clinical practice physicians acquire new information and use a new form of continuing education by following new developments in their field. This way, new findings from medical literature get into clinical practice faster and more efficiently. In addition, physicians get more professional satisfaction and quality in clinical practice is higher.

  13. Semantically based clinical TCM telemedicine systems

    CERN Document Server

    Wong, Allan K Y; Lin, Wilfred W K; Dillon, Tharam S; Chang, Elizabeth J


    Recent years have seen the development of two significant trends namely: the adoption of some Traditional Chinese Medicine Practices into mainstream Allopathic Western Medicine and the advent of the internet and broad band networks leading to an increased interest in the use of Telemedicine to deliver medical services. In this book, we see the convergence of these two trends leading to a semantically-based TCM Telemedicine system that utilizes an ontology to provide sharable knowledge in the TCM realm to achieve this. The underpinning research required the development of a three-layer architecture and an Ontology of the TCM knowledge. As TCM knowledge like all medical knowledge is not frozen in time it was important to develop an approach that would allow evolution of the Ontology when new evidence became available. In order for the system to be practically grounded it was important to work with an industry partner PuraPharm Group/HerbMiners Informatics Limited. This partnership was initiated through Professo...

  14. Fluorescence confocal polarizing microscopy

    Indian Academy of Sciences (India)

    Much of the modern understanding of orientational order in liquid crystals (LCs) is based on polarizing microscopy (PM). A PM image bears only two-dimensional (2D) information, integrating the 3D pattern of optical birefringence over the path of light. Recently, we proposed a technique to image 3D director patterns by ...

  15. Thermally oxidized Inconel 600 and 690 nickel-based alloys characterizations by combination of global photoelectrochemistry and local near-field microscopy techniques (STM, STS, AFM, SKPFM) (United States)

    Mechehoud, F.; Benaioun, N. E.; Hakiki, N. E.; Khelil, A.; Simon, L.; Bubendorff, J. L.


    Thermally oxidized nickel-based alloys are studied by scanning tunnelling microscopy (STM), scanning tunnelling spectroscopy (STS), atomic force microscopy (AFM), scanning kelvin probe force microscopy (SKPFM) and photoelectro-chemical techniques as a function of oxidation time at a fixed temperature of 623 K. By photoelectrochemistry measurements we identify the formation of three oxides NiO, Fe2O3, Cr2O3 and determine the corresponding gap values. We use these values as parameter for imaging the surface at high bias voltage by STM allowing the spatial localization and identification of both NiO, Fe2O3 oxide phases using STS measurements. Associated to Kelvin probe measurements we show also that STS allow to distinguished NiO from Cr2O3 and confirm that the Cr2O3 is not visible at the surface and localized at the oxide/steel interface.

  16. Confocal scanning microscopy

    DEFF Research Database (Denmark)

    Bariani, Paolo

    This report is based on a metrological investigation on confocal microscopy technique carried out by Uffe Rolf Arlø Theilade and Paolo Bariani. The purpose of the experimental activity was twofold a metrological instrument characterization and application to assessment of rough PP injection moulded...... replicated topography. Confocal microscopy is seen to be a promising technique in metrology of microstructures. Some limitations with respect to surface metrology were found during the experiments. The experiments were carried out using a Zeiss LSM 5 Pascal microscope owned by the Danish Polymer Centre...

  17. Leakage radiation interference microscopy. (United States)

    Descrovi, Emiliano; Barakat, Elsie; Angelini, Angelo; Munzert, Peter; De Leo, Natascia; Boarino, Luca; Giorgis, Fabrizio; Herzig, Hans Peter


    We present a proof of principle for a new imaging technique combining leakage radiation microscopy with high-resolution interference microscopy. By using oil immersion optics it is demonstrated that amplitude and phase can be retrieved from optical fields, which are evanescent in air. This technique is illustratively applied for mapping a surface mode propagating onto a planar dielectric multilayer on a thin glass substrate. The surface mode propagation constant estimated after Fourier transformation of the measured complex field is well matched with an independent measurement based on back focal plane imaging.

  18. Addressing the future of clinical information systems--Web-based multilayer visualization. (United States)

    Poh, Chueh-Loo; Kitney, Richard I; Shrestha, Rasu B K


    This paper addresses some key issues relating to the development of new technology for clinical information systems (CIS) in relation to imaging and visualizing data. With the increasing importance of molecular and cellular biology, a new type of medicine, molecular based medicine, is now developing. This will significantly alter the way in which medicine is practiced. The view is presented that CIS will need to operate seamlessly across the Biological Continuum, i.e., the hierarchy of the human organism comprising systems, viscera, tissue, cells, proteins, and genes. We propose a multilayered visualization interface, which operates across the Biological Continuum, based on Web-based technology. A visualization interface package for two-dimensional and three-dimensional image data at the visceral and cellular levels is described. Two application examples are presented: 1) MR knee images, at the visceral level and 2) endothelial nuclei images, acquired from confocal laser microscopy, at the cellular level.

  19. SynapticDB, effective web-based management and sharing of data from serial section electron microscopy. (United States)

    Shi, Bitao; Bourne, Jennifer; Harris, Kristen M


    Serial section electron microscopy (ssEM) is rapidly expanding as a primary tool to investigate synaptic circuitry and plasticity. The ultrastructural images collected through ssEM are content rich and their comprehensive analysis is beyond the capacity of an individual laboratory. Hence, sharing ultrastructural data is becoming crucial to visualize, analyze, and discover the structural basis of synaptic circuitry and function in the brain. We devised a web-based management system called SynapticDB ( that catalogues, extracts, analyzes, and shares experimental data from ssEM. The management strategy involves a library with check-in, checkout and experimental tracking mechanisms. We developed a series of spreadsheet templates (MS Excel, Open Office spreadsheet, etc) that guide users in methods of data collection, structural identification, and quantitative analysis through ssEM. SynapticDB provides flexible access to complete templates, or to individual columns with instructional headers that can be selected to create user-defined templates. New templates can also be generated and uploaded. Research progress is tracked via experimental note management and dynamic PDF forms that allow new investigators to follow standard protocols and experienced researchers to expand the range of data collected and shared. The combined use of templates and tracking notes ensures that the supporting experimental information is populated into the database and associated with the appropriate ssEM images and analyses. We anticipate that SynapticDB will serve future meta-analyses towards new discoveries about the composition and circuitry of neurons and glia, and new understanding about structural plasticity during development, behavior, learning, memory, and neuropathology.

  20. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy. (United States)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei


    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

  1. Novel atomic force microscopy based biopanning for isolation of morphology specific reagents against TDP-43 variants in amyotrophic lateral sclerosis. (United States)

    Williams, Stephanie M; Venkataraman, Lalitha; Tian, Huilai; Khan, Galam; Harris, Brent T; Sierks, Michael R


    Because protein variants play critical roles in many diseases including TDP-43 in Amyotrophic Lateral Sclerosis (ALS), alpha-synuclein in Parkinson's disease and beta-amyloid and tau in Alzheimer's disease, it is critically important to develop morphology specific reagents that can selectively target these disease-specific protein variants to study the role of these variants in disease pathology and for potential diagnostic and therapeutic applications. We have developed novel atomic force microscopy (AFM) based biopanning techniques that enable isolation of reagents that selectively recognize disease-specific protein variants. There are two key phases involved in the process, the negative and positive panning phases. During the negative panning phase, phages that are reactive to off-target antigens are eliminated through multiple rounds of subtractive panning utilizing a series of carefully selected off-target antigens. A key feature in the negative panning phase is utilizing AFM imaging to monitor the process and confirm that all undesired phage particles are removed. For the positive panning phase, the target antigen of interest is fixed on a mica surface and bound phages are eluted and screened to identify phages that selectively bind the target antigen. The target protein variant does not need to be purified providing the appropriate negative panning controls have been used. Even target protein variants that are only present at very low concentrations in complex biological material can be utilized in the positive panning step. Through application of this technology, we acquired antibodies to protein variants of TDP-43 that are selectively found in human ALS brain tissue. We expect that this protocol should be applicable to generating reagents that selectively bind protein variants present in a wide variety of different biological processes and diseases.

  2. Concept-Based Learning in Clinical Experiences: Bringing Theory to Clinical Education for Deep Learning. (United States)

    Nielsen, Ann


    Concept-based learning is used increasingly in nursing education to support the organization, transfer, and retention of knowledge. Concept-based learning activities (CBLAs) have been used in clinical education to explore key aspects of the patient situation and principles of nursing care, without responsibility for total patient care. The nature of best practices in teaching and the resultant learning are not well understood. The purpose of this multiple-case study research was to explore and describe concept-based learning in the context of clinical education in inpatient settings. Four clinical groups (each a case) were observed while they used CBLAs in the clinical setting. Major findings include that concept-based learning fosters deep learning, connection of theory with practice, and clinical judgment. Strategies used to support learning, major teaching-learning foci, and preconditions for concept-based teaching and learning will be described. Concept-based learning is promising to support integration of theory with practice and clinical judgment through application experiences with patients. [J Nurs Educ. 2016;55(7):365-371.]. Copyright 2016, SLACK Incorporated.

  3. Experimental transmission electron microscopy studies and phenomenological model of bismuth-based superconducting compounds; Etudes experimentales par microscopie electronique en transmission et modele phenomenologique des composes supraconducteurs a base de bismuth

    Energy Technology Data Exchange (ETDEWEB)

    Elboussiri, Khalid


    The main part of this thesis is devoted to an experimental study by transmission electron microscopy of the different phases of the superconducting bismuth cuprates Bi{sub 2}Sr{sub 2}Ca{sub n-1}Cu{sub n}O{sub 2n+4}. In high resolution electron microscopy, the two types of incommensurate modulation realized in these compounds have been observed. A model of structure has been proposed from which the simulated images obtained are consistent with observations. The medium resolution images correlated with the electron diffraction data have revealed existence of a multi-soliton regime with latent lock in phases of commensurate periods between 4b and 10b. At last, a description of different phases of these compounds as a result of superstructures from a disordered perovskite type structure is proposed (author) [French] Le travail presente dans cette these consiste en une etude experimentale essentiellement par microscopie electronique en transmission des differentes phases supraconductrices presentes dans les composes appartenant a la famille des cuprates de bismuth Bi{sub 2}Sr{sub 2}Ca{sub n-1}Cu{sub n}O{sub 2n+4}. Les obsevations de microscopie electronique a haute resolution ont permis de mettre en evidence les differentes modulations incommensurables realisees dans ces composes. Un modele de structure est propose et a permis d'obtenir des images simulees compatibles avec les observations. D'autre part, les observations de microscopie electronique en moyenne resolution sur ces composes, combinees avec les resultats de diffraction electronique, ont montre l'existence d'un regime multisoliton associe a des phases de Lock-in latentes de parametres compris entre 4b et 10b. Enfin, une description des differentes phases de ces composes en terme de surstructures derivees de structure perovskite desordonnee est exposee. (auteur)

  4. Fast and compact optical-resolution photoacoustic microscopy using a water-proofing two-axis MEMS scanner, and a step forward to clinical applications (United States)

    Kim, Jin Young; Lee, Changho; Lim, Geunbae; Kim, Chulhong


    Optical-resolution photoacoustic microscopy (OR-PAM) is a novel microscopic tool to provide in vivo optically sensitive images in biomedical research. Conventional OR-PAM systems are typically slow and bulky because of the linear scanning stages with stepping motors. For practical purposes, however, fast imaging speed and small footprint are crucial. To address these issues, we have developed a real-time compact OR-PAM system equipped with a waterproof two-axis MEMS scanner. The OR-PAM system consists of key components such as an ultrasonic transducer with a bandwidth of 50 MHz, an opto-acoustic beam combiner (BC), and an MEMS scanner. These are all installed inside a small water tank, with dimensions of 30 mm × 90 mm × 30 mm along the x-, y-, and z-axes, respectively. A pulsed laser with a repetition rate of 50 kHz is confocally aligned with the photoacoustic (PA) waves in the BC to maximize the SNRs. The fast scanning ability of the MEMS scanner fully utilizes the A-scan speed of 50 kHz. For instance, the B- and C-scan imaging speeds are 125 Hz and 0.625 Hz, respectively, when the acquired PA maximum amplitude projection image has 200 × 200 pixels along the x- and y-axes, respectively. The measured lateral resolution of 3.6 μm and axial resolution of 27 μm are sufficient to resolve the small capillaries. Finally, we have successfully obtained in vivo PA images of iris microvasculatures in mice. This real-time and compact OR-PAM system is optimized to examine small animals in clinical studies.

  5. A data grid for imaging-based clinical trials (United States)

    Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.


    Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

  6. Revealing the Molecular Structure and the Transport Mechanism at the Base of Primary Cilia Using Superresolution STED Microscopy (United States)

    Yang, Tung-Lin

    The primary cilium is an organelle that serves as a signaling center of the cell and is involved in the hedgehog signaling, cAMP pathway, Wnt pathways, etc. Ciliary function relies on the transportation of molecules between the primary cilium and the cell, which is facilitated by intraflagellar transport (IFT). IFT88, one of the important IFT proteins in complex B, is known to play a role in the formation and maintenance of cilia in various types of organisms. The ciliary transition zone (TZ), which is part of the gating apparatus at the ciliary base, is home to a large number of ciliopathy molecules. Recent studies have identified important regulating elements for TZ gating in cilia. However, the architecture of the TZ region and its arrangement relative to intraflagellar transport (IFT) proteins remain largely unknown, hindering the mechanistic understanding of the regulation processes. One of the major challenges comes from the tiny volume at the ciliary base packed with numerous proteins, with the diameter of the TZ close to the diffraction limit of conventional microscopes. Using a series of stimulated emission depletion (STED) superresolution images mapped to electron microscopy images, we analyzed the structural organization of the ciliary base. Subdiffraction imaging of TZ components defines novel geometric distributions of RPGRIP1L, MKS1, CEP290, TCTN2 and TMEM67, shedding light on their roles in TZ structure, assembly, and function. We found TCTN2 at the outmost periphery of the TZ close to the ciliary membrane, with a 227+/-18 nm diameter. TMEM67 was adjacent to TCTN2, with a 205+/-20 nm diameter. RPGRIP1L was localized toward the axoneme at the same axial level as TCTN2 and TMEM67, with a 165+/-8 nm diameter. MKS1 was situated between TMEM67 and RPGRIP1L, with an 186+/-21 nm diameter. Surprisingly, CEP290 was localized at the proximal side of the TZ close to the distal end of the centrin-labeled basal body. The lateral width was unexpectedly close to

  7. Stratification of type 2 diabetes based on routine clinical markers

    DEFF Research Database (Denmark)

    Safai, Narges; Ali, Ashfaq; Rossing, Peter


    AIMS: We hypothesized that patients with dysregulated type 2 diabetes may be stratified based on routine clinical markers. METHODS: In this retrospective cohort study, diabetes related clinical measures including age at onset, diabetes duration, HbA1c, BMI, HOMA2-β, HOMA2-IR and GAD65...... autoantibodies, were used for sub-grouping patients by K-means clustering and for adjusting. Probability of diabetes complications (95% confidence interval), were calculated using logistic regression. RESULTS: Based on baseline data from patients with type 2 diabetes (n=2,290), the cluster analysis suggested up....... CONCLUSIONS: Patients with type 2 diabetes cluster into clinically relevant sub-groups based on routine clinical markers. The prevalence of diabetes complications seems to be sub-group specific. Our data suggests the need for a tailored strategy for the treatment of type 2 diabetes....

  8. Acid-base properties and the chemical imaging of surface-bound functional groups studied with scanning force microscopy

    NARCIS (Netherlands)

    van der Vegte, E.W.; Hadziioannou, G


    In this paper we present a scanning force microscopy (SFM) study on electrostatic and hydrogen-bonding interactions between chemically modified SFM probes and surface functional groups. pH-dependent adhesion force measurements in aqueous media between various ionizable functional groups showed a

  9. Structural changes in alginate-based microspheres exposed to in vivo environment as revealed by confocal Raman microscopy

    Czech Academy of Sciences Publication Activity Database

    Kroneková, Z.; Pelach, M.; Mazancová, P.; Uhelská, L.; Treľová, D.; Rázga, F.; Némethová, V.; Szalai, S.; Chorvát, D.; McGarrigle, J. J.; Omami, M.; Isa, D.; Ghani, S.; Majková, E.; Oberholzer, J.; Raus, Vladimír; Šiffalovič, P.; Lacík, I.


    Roč. 8, 26 January (2018), s. 1-12, č. článku 1637. ISSN 2045-2322 Institutional support: RVO:61389013 Keywords : confocal Raman microscopy * alginate * microcapsule Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.259, year: 2016

  10. The binding of cellulase variants to dislocations: a semi-quantitative analysis based on CLSM (confocal laser scanning microscopy) images

    DEFF Research Database (Denmark)

    Hidayat, Budi J.; Weisskopf, Carmen; Felby, Claus


    or slip planes. Here we study whether cellulases bind to dislocations to a higher extent than to the surrounding cell wall. The binding of fluorescently labelled cellobiohydrolases and endoglucanases to filter paper fibers was investigated using confocal laser scanning microscopy and a ratiometric method...

  11. An electron microscopy based method for the detection and quantification of nanomaterial number concentration in environmentally relevant media

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, A. [School of Geography, Earth and Environmental Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Lead, J.R., E-mail: [School of Geography, Earth and Environmental Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Center for Environmental Nanoscience and Risk, Department of Environmental Health Sciences, Arnold School of Public Health, University South Carolina, Columbia 29208, SC (United States); Baalousha, M., E-mail: [Center for Environmental Nanoscience and Risk, Department of Environmental Health Sciences, Arnold School of Public Health, University South Carolina, Columbia 29208, SC (United States)


    Improved detection and characterization of nanomaterials (NMs) in complex environmental media requires the development of novel sampling approaches to improve the detection limit to be close to environmentally realistic concentrations. Transmission electron microscopy (TEM) is an indispensable metrological tool in nanotechnology and environmental nanoscience due to its high spatial resolution and analytical capabilities when coupled to spectroscopic techniques. However, these capabilities are hampered by the conventional sample preparation methods, which suffer from low NM recovery. The current work presents a validated, fully quantitative sampling technique for TEM that overcomes conventional sample preparation shortcomings, and thus enables the use of TEM for measurement of particle number concentration and their detection in complex media at environmentally realistic concentrations. This sampling method is based on ultracentrifugation of NMs from suspension onto a poly-L-lysine (PLL) functionalized TEM grid, using active deposition (by ultracentrifugation) and retention (by PLL interactions with NM surface) of NMs on the substrate, enabling fully quantitative analysis. Similar analysis with AFM was satisfactory in simple media but the lack of chemical-selectivity of AFM limits its applicability for the detection of NMs in complex environmental samples. The sampling approach was validated using both citrate- and PVP-coated AuNMs in pure water, which demonstrated an even distribution of NM on the TEM grid and high NM recovery (80–100%) at environmentally relevant NM concentrations (ca. 0.20–100 μg L{sup −1}). The applicability of the sampling method to complex environmental samples was demonstrated by the quantification of particle number concentration of AuNMs in EPA soft water (with and without Suwannee River fulvic acid) and lake water. This sample preparation approach is also applicable to other types of NMs with some modifications (e.g. centrifugation

  12. An electron microscopy based method for the detection and quantification of nanomaterial number concentration in environmentally relevant media

    International Nuclear Information System (INIS)

    Prasad, A.; Lead, J.R.; Baalousha, M.


    Improved detection and characterization of nanomaterials (NMs) in complex environmental media requires the development of novel sampling approaches to improve the detection limit to be close to environmentally realistic concentrations. Transmission electron microscopy (TEM) is an indispensable metrological tool in nanotechnology and environmental nanoscience due to its high spatial resolution and analytical capabilities when coupled to spectroscopic techniques. However, these capabilities are hampered by the conventional sample preparation methods, which suffer from low NM recovery. The current work presents a validated, fully quantitative sampling technique for TEM that overcomes conventional sample preparation shortcomings, and thus enables the use of TEM for measurement of particle number concentration and their detection in complex media at environmentally realistic concentrations. This sampling method is based on ultracentrifugation of NMs from suspension onto a poly-L-lysine (PLL) functionalized TEM grid, using active deposition (by ultracentrifugation) and retention (by PLL interactions with NM surface) of NMs on the substrate, enabling fully quantitative analysis. Similar analysis with AFM was satisfactory in simple media but the lack of chemical-selectivity of AFM limits its applicability for the detection of NMs in complex environmental samples. The sampling approach was validated using both citrate- and PVP-coated AuNMs in pure water, which demonstrated an even distribution of NM on the TEM grid and high NM recovery (80–100%) at environmentally relevant NM concentrations (ca. 0.20–100 μg L"−"1). The applicability of the sampling method to complex environmental samples was demonstrated by the quantification of particle number concentration of AuNMs in EPA soft water (with and without Suwannee River fulvic acid) and lake water. This sample preparation approach is also applicable to other types of NMs with some modifications (e.g. centrifugation

  13. Evidence-based health care: its place within clinical governance. (United States)

    McSherry, R; Haddock, J

    This article explores the principles of evidence-based practice and its role in achieving quality improvements within the clinical governance framework advocated by the recent White Papers 'The New NHS: Modern, Dependable' (Department of Health (DoH), 1997) and 'A First Class Service: Quality in the New NHS' (DoH, 1998a). Within these White Papers there is an emphasis on improving quality of care, treatment and services through employing the principles of clinical governance. A major feature of clinical governance is guaranteeing quality to the public and the NHS, and ensuring that clinical, managerial and educational practice is based on scientific evidence. This article also examines what evidence-based practice is and what processes are required to promote effective healthcare interventions. The authors also look at how clinical governance relates to other methods/systems involved in clinical effectiveness. Finally, the importance for nurses and other healthcare professionals of familiarizing themselves with the development of critical appraisal skills, and their implications for developing evidence-based practice, is emphasized.

  14. Multiphoton Microscopy for Ophthalmic Imaging

    Directory of Open Access Journals (Sweden)

    Emily A. Gibson


    Full Text Available We review multiphoton microscopy (MPM including two-photon autofluorescence (2PAF, second harmonic generation (SHG, third harmonic generation (THG, fluorescence lifetime (FLIM, and coherent anti-Stokes Raman Scattering (CARS with relevance to clinical applications in ophthalmology. The different imaging modalities are discussed highlighting the particular strength that each has for functional tissue imaging. MPM is compared with current clinical ophthalmological imaging techniques such as reflectance confocal microscopy, optical coherence tomography, and fluorescence imaging. In addition, we discuss the future prospects for MPM in disease detection and clinical monitoring of disease progression, understanding fundamental disease mechanisms, and real-time monitoring of drug delivery.

  15. Automated Clinical Assessment from Smart home-based Behavior Data (United States)

    Dawadi, Prafulla Nath; Cook, Diane Joyce; Schmitter-Edgecombe, Maureen


    Smart home technologies offer potential benefits for assisting clinicians by automating health monitoring and well-being assessment. In this paper, we examine the actual benefits of smart home-based analysis by monitoring daily behaviour in the home and predicting standard clinical assessment scores of the residents. To accomplish this goal, we propose a Clinical Assessment using Activity Behavior (CAAB) approach to model a smart home resident’s daily behavior and predict the corresponding standard clinical assessment scores. CAAB uses statistical features that describe characteristics of a resident’s daily activity performance to train machine learning algorithms that predict the clinical assessment scores. We evaluate the performance of CAAB utilizing smart home sensor data collected from 18 smart homes over two years using prediction and classification-based experiments. In the prediction-based experiments, we obtain a statistically significant correlation (r = 0.72) between CAAB-predicted and clinician-provided cognitive assessment scores and a statistically significant correlation (r = 0.45) between CAAB-predicted and clinician-provided mobility scores. Similarly, for the classification-based experiments, we find CAAB has a classification accuracy of 72% while classifying cognitive assessment scores and 76% while classifying mobility scores. These prediction and classification results suggest that it is feasible to predict standard clinical scores using smart home sensor data and learning-based data analysis. PMID:26292348

  16. Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation. (United States)

    Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto


    Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

  17. A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy. (United States)

    Kijanka, M; van Donselaar, E G; Müller, W H; Dorresteijn, B; Popov-Čeleketić, D; El Khattabi, M; Verrips, C T; van Bergen En Henegouwen, P M P; Post, J A


    Immuno-electron microscopy is commonly performed with the use of antibodies. In the last decade the antibody fragment indicated as nanobody (VHH or single domain antibody) has found its way to different applications previously done with conventional antibodies. Nanobodies can be selected to bind with high affinity and specificity to different antigens. They are small (molecular weight ca. 15kDa) and are usually easy to produce in microorganisms. Here we have evaluated the feasibility of a nanobody binding to HER2 for application in immuno-electron microscopy. To obtain highest labeling efficiency combined with optimal specificity, different labeling conditions were analysed, which included nanobody concentration, fixation and blocking conditions. The obtained optimal protocol was applied for post-embedment labeling of Tokuyasu cryosections and for pre-embedment labeling of HER2 for fluorescence microscopy and both transmission and scanning electron microscopy. We show that formaldehyde fixation after incubation with the anti-HER2 nanobody, improves labeling intensity. Among all tested blocking agents the best results were obtained with a mixture of cold water fish gelatine and acetylated bovine serum albumin, which prevented a-specific interactions causing background labeling while preserving specific interactions at the same time. In conclusion, we have developed a nanobody-based protocol for immuno-gold labeling of HER2 for Tokuyasu cryosections in TEM as well as for pre-embedment gold labeling of cells for both TEM and SEM. Copyright © 2017. Published by Elsevier Inc.

  18. Efficient Imaging and Real-Time Display of Scanning Ion Conductance Microscopy Based on Block Compressive Sensing (United States)

    Li, Gongxin; Li, Peng; Wang, Yuechao; Wang, Wenxue; Xi, Ning; Liu, Lianqing


    Scanning Ion Conductance Microscopy (SICM) is one kind of Scanning Probe Microscopies (SPMs), and it is widely used in imaging soft samples for many distinctive advantages. However, the scanning speed of SICM is much slower than other SPMs. Compressive sensing (CS) could improve scanning speed tremendously by breaking through the Shannon sampling theorem, but it still requires too much time in image reconstruction. Block compressive sensing can be applied to SICM imaging to further reduce the reconstruction time of sparse signals, and it has another unique application that it can achieve the function of image real-time display in SICM imaging. In this article, a new method of dividing blocks and a new matrix arithmetic operation were proposed to build the block compressive sensing model, and several experiments were carried out to verify the superiority of block compressive sensing in reducing imaging time and real-time display in SICM imaging.

  19. Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study (United States)

    van Manen, Henk-Jan; van Apeldoorn, Aart A; Verrijk, Ruud; van Blitterswijk, Clemens A; Otto, Cees


    Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID:17722552

  20. Transmission Electron Microscopy of a CMSX-4 Ni-Base Superalloy Produced by Selective Electron Beam Melting

    Directory of Open Access Journals (Sweden)

    Alireza B. Parsa


    Full Text Available In this work, the microstructures of superalloy specimens produced using selective electron beam melting additive manufacturing were characterized. The materials were produced using a CMSX-4 powder. Two selective electron beam melting processing strategies, which result in higher and lower effective cooling rates, are described. Orientation imaging microscopy, scanning transmission electron microscopy and conventional high resolution transmission electron microscopy are used to investigate the microstructures. Our results suggest that selective electron beam melting processing results in near equilibrium microstructures, as far as γ′ volume fractions, the formation of small amounts of TCP phases and the partitioning behavior of the alloy elements are concerned. As expected, higher cooling rates result in smaller dendrite spacings, which are two orders of magnitude smaller than observed during conventional single crystal casting. During processing, columnar grains grow in <100> directions, which are rotated with respect to each other. There are coarse γ/γ′ microstructures in high angle boundary regions. Dislocation networks form low angle boundaries. A striking feature of the as processed selective electron beam melting specimens is their high dislocation density. From a fundamental point of view, this opens new possibilities for the investigation of elementary dislocation processes which accompany solidification.

  1. Nonlinear Near-Field Microwave Microscopy for RF Defect Localization in Nb-Based Superconducting Radio Frequency Cavities (United States)

    Tai, Tamin


    Niobium Superconducting Radio Frequency (SRF) cavities are very sensitive to localized defects that give rise to quenches at high accelerating gradients. In order to identify these defects via scanning microscopy, and to further understand the origins of the quench under high radio frequency excitation (1-3 GHz), a scanning probe with localized and up to ~ 200 mT RF magnetic field is required for low temperature microscopy to achieve sub-micron resolution. For this purpose, we developed a micro loop probe on silicon substrate with outer diameter 20 μ m and inner diameter 17 μ m and successfully fabricated it by lithography. The probe has been used to identify a signal arising from the nonlinear Meissner effect in a Nb thin film. In addition, a magnetic write head is another promising candidate to achieve this goal of understanding localized defect behavior under high RF magnetic field at low temperatures. We will discuss and compare both types of probe for nonlinear scanning microscopy and RF defect localization in superconductors. We acknowledge the support of DOE/HEP.

  2. Microcirculation in the murine liver: a computational fluid dynamic model based on 3D reconstruction from in vivo microscopy. (United States)

    Piergiovanni, Monica; Bianchi, Elena; Capitani, Giada; Li Piani, Irene; Ganzer, Lucia; Guidotti, Luca G; Iannacone, Matteo; Dubini, Gabriele


    The liver is organized in hexagonal functional units - termed lobules - characterized by a rather peculiar blood microcirculation, due to the presence of a tangled network of capillaries - termed sinusoids. A better understanding of the hemodynamics that governs liver microcirculation is relevant to clinical and biological studies aimed at improving our management of liver diseases and transplantation. Herein, we built a CFD model of a 3D sinusoidal network, based on in vivo images of a physiological mouse liver obtained with a 2-photon microscope. The CFD model was developed with Fluent 16.0 (ANSYS Inc., Canonsburg, PA), particular care was taken in imposing the correct boundary conditions representing a physiological state. To account for the remaining branches of the sinusoids, a lumped parameter model was used to prescribe the correct pressure at each outlet. The effect of an adhered cell on local hemodynamics is also investigated for different occlusion degrees. The model here proposed accurately reproduces the fluid dynamics in a portion of the sinusoidal network in mouse liver. Mean velocities and mass flow rates are in agreement with literature values from in vivo measurements. Our approach provides details on local phenomena, hardly described by other computational studies, either focused on the macroscopic hepatic vasculature or based on homogeneous porous medium model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Fickian-Based Empirical Approach for Diffusivity Determination in Hollow Alginate-Based Microfibers Using 2D Fluorescence Microscopy and Comparison with Theoretical Predictions

    Directory of Open Access Journals (Sweden)

    Maryam Mobed-Miremadi


    Full Text Available Hollow alginate microfibers (od = 1.3 mm, id = 0.9 mm, th = 400 µm, L = 3.5 cm comprised of 2% (w/v medium molecular weight alginate cross-linked with 0.9 M CaCl2 were fabricated to model outward diffusion capture by 2D fluorescent microscopy. A two-fold comparison of diffusivity determination based on real-time diffusion of Fluorescein isothiocyanate molecular weight (FITC MW markers was conducted using a proposed Fickian-based approach in conjunction with a previously established numerical model developed based on spectrophotometric data. Computed empirical/numerical (Dempiricial/Dnumerical diffusivities characterized by small standard deviations for the 4-, 70- and 500-kDa markers expressed in m2/s are (1.06 × 10−9 ± 1.96 × 10−10/(2.03 × 10−11, (5.89 × 10−11 ± 2.83 × 10−12/(4.6 × 10−12 and (4.89 × 10−12 ± 3.94 × 10−13/(1.27 × 10−12, respectively, with the discrimination between the computation techniques narrowing down as a function of MW. The use of the numerical approach is recommended for fluorescence-based measurements as the standard computational method for effective diffusivity determination until capture rates (minimum 12 fps for the 4-kDa marker and the use of linear instead of polynomial interpolating functions to model temporal intensity gradients have been proven to minimize the extent of systematic errors associated with the proposed empirical method.

  4. Heavy-ion microscopy

    International Nuclear Information System (INIS)

    Kraft, G.; Yang, T.C.H.; Richards, T.; Tobias, C.A.


    This chapter briefly describes the techniques of optical microscopy, scanning and transmission electron microscopy, soft x-ray microscopy and compares these latter techniques with heavy-ion microscopy. The resolution obtained with these various types of microscopy are compared and the influence of the etching procedure on total resolution is discussed. Several micrographs of mammalian cells are included

  5. A case-based assistant for clinical psychiatry expertise. (United States)

    Bichindaritz, I


    Case-based reasoning is an artificial intelligence methodology for the processing of empirical knowledge. Recent case-based reasoning systems also use theoretic knowledge about the domain to constrain the case-based reasoning. The organization of the memory is the key issue in case-based reasoning. The case-based assistant presented here has two structures in memory: cases and concepts. These memory structures permit it to be as skilled in problem-solving tasks, such as diagnosis and treatment planning, as in interpretive tasks, such as clinical research. A prototype applied to clinical work about eating disorders in psychiatry, reasoning from the alimentary questionnaires of these patients, is presented as an example of the system abilities.

  6. A predictive approach to selecting the size of a clinical trial, based on subjective clinical opinion. (United States)

    Spiegelhalter, D J; Freedman, L S


    The 'textbook' approach to determining sample size in a clinical trial has some fundamental weaknesses which we discuss. We describe a new predictive method which takes account of prior clinical opinion about the treatment difference. The method adopts the point of clinical equivalence (determined by interviewing the clinical participants) as the null hypothesis. Decision rules at the end of the study are based on whether the interval estimate of the treatment difference (classical or Bayesian) includes the null hypothesis. The prior distribution is used to predict the probabilities of making the decisions to use one or other treatment or to reserve final judgement. It is recommended that sample size be chosen to control the predicted probability of the last of these decisions. An example is given from a multi-centre trial of superficial bladder cancer.

  7. Are the MDS-UPDRS-based composite scores clinically applicable? (United States)

    Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert


    The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  8. Fresnel zone-plate based X-ray microscopy in Zernike phase contrast with sub-50 nm resolution at NSRL

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jie; Li Wenjie; Tian Jinping; Liu Longhua; Xiong Ying; Liu Gang; Wu Ziyu; Tian Yangchao [National Synchrotron Radiation Laboratory (China); Liu Yijin [School of Physics (China); Yue Zhengbo; Yu Hanqing [Laboratory of Environmental Engineering, School of Chemistry, University of Science and Technology of China, Hefei Anhui 230029 (China); Wang Chunru, E-mail: [Institute of Chemistry, Chinese Academy of Sciences, Beijing 10060 (China)


    A transmission X-ray microscope using Fresnel zone-plates (FZPs) has been installed at U7A beamline of National Synchrotron Radiation Laboratory (NSRL). The objective FZP with 45 nm outermost zone width delivers a sub-50 nm resolution. A gold phase ring with 2.5 {mu}m thickness and 4 {mu}m width was placed at the focal plane of the objective FZP at 8 keV to produce a negative Zernike phase contrast. A series of samples were used to test the performance of the Zernike phase contrast X-ray microscopy.

  9. Fresnel zone-plate based X-ray microscopy in Zernike phase contrast with sub-50 nm resolution at NSRL

    International Nuclear Information System (INIS)

    Chen Jie; Li Wenjie; Tian Jinping; Liu Longhua; Xiong Ying; Liu Gang; Wu Ziyu; Tian Yangchao; Liu Yijin; Yue Zhengbo; Yu Hanqing; Wang Chunru


    A transmission X-ray microscope using Fresnel zone-plates (FZPs) has been installed at U7A beamline of National Synchrotron Radiation Laboratory (NSRL). The objective FZP with 45 nm outermost zone width delivers a sub-50 nm resolution. A gold phase ring with 2.5 μm thickness and 4 μm width was placed at the focal plane of the objective FZP at 8 keV to produce a negative Zernike phase contrast. A series of samples were used to test the performance of the Zernike phase contrast X-ray microscopy.

  10. Statistical methods for mass spectrometry-based clinical proteomics

    NARCIS (Netherlands)

    Kakourou, A.


    The work presented in this thesis focuses on methods for the construction of diagnostic rules based on clinical mass spectrometry proteomic data. Mass spectrometry has become one of the key technologies for jointly measuring the expression of thousands of proteins in biological samples.

  11. From Paper Based Clinical Practice Guidelines to Declarative Workflow Management

    DEFF Research Database (Denmark)

    Lyng, Karen Marie; Hildebrandt, Thomas; Mukkamala, Raghava Rao


    We present a field study of oncology workflow, involving doctors, nurses and pharmacists at Danish hospitals and discuss the obstacles, enablers and challenges for the use of computer based clinical practice guidelines. Related to the CIGDec approach of Pesic and van der Aalst we then describe how...

  12. Evidence-Based Clinical Voice Assessment: A Systematic Review (United States)

    Roy, Nelson; Barkmeier-Kraemer, Julie; Eadie, Tanya; Sivasankar, M. Preeti; Mehta, Daryush; Paul, Diane; Hillman, Robert


    Purpose: To determine what research evidence exists to support the use of voice measures in the clinical assessment of patients with voice disorders. Method: The American Speech-Language-Hearing Association (ASHA) National Center for Evidence-Based Practice in Communication Disorders staff searched 29 databases for peer-reviewed English-language…

  13. The role of hypnotherapy in evidence-based clinical practice. (United States)

    Griffiths, M J


    The purpose of this review was to discuss the place of hypnotherapy in a modern medical world dominated by so-called evidence-based clinical practice. Hypnosis is an easily learned technique that is a valuable adjuvant to many medical, dental and psychological interventions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Investigation of (Fe,Co)NbB-Based Nanocrystalline Soft Magnetic Alloys by Lorentz Microscopy and Off-Axis Electron Holography. (United States)

    Zheng, Changlin; Kirmse, Holm; Long, Jianguo; Laughlin, David E; McHenry, Michael E; Neumann, Wolfgang


    The relationship between microstructure and magnetic properties of a (Fe,Co)NbB-based nanocrystalline soft magnetic alloy was investigated by analytical transmission electron microscopy (TEM). The microstructures of (Fe0.5Co0.5)80Nb4B13Ge2Cu1 nanocrystalline alloys annealed at different temperatures were characterized by TEM and electron diffraction. The magnetic structures were analyzed by Lorentz microscopy and off-axis electron holography, including quantitative measurement of domain wall width, induction, and in situ magnetic domain imaging. The results indicate that the magnetic domain structure and particularly the dynamical magnetization behavior of the alloys strongly depend on the microstructure of the nanocrystalline alloys. Smaller grain size and random orientation of the fine particles decrease the magneto-crystalline anisotropy and suggests better soft magnetic properties which may be explained by the anisotropy model of Herzer.

  15. Augment clinical measurement using a constraint-based esophageal model (United States)

    Kou, Wenjun; Acharya, Shashank; Kahrilas, Peter; Patankar, Neelesh; Pandolfino, John


    Quantifying the mechanical properties of the esophageal wall is crucial to understanding impairments of trans-esophageal flow characteristic of several esophageal diseases. However, these data are unavailable owing to technological limitations of current clinical diagnostic instruments that instead display esophageal luminal cross sectional area based on intraluminal impedance change. In this work, we developed an esophageal model to predict bolus flow and the wall property based on clinical measurements. The model used the constraint-based immersed-boundary method developed previously by our group. Specifically, we first approximate the time-dependent wall geometry based on impedance planimetry data on luminal cross sectional area. We then fed these along with pressure data into the model and computed wall tension based on simulated pressure and flow fields, and the material property based on the strain-stress relationship. As examples, we applied this model to augment FLIP (Functional Luminal Imaging Probe) measurements in three clinical cases: a normal subject, achalasia, and eosinophilic esophagitis (EoE). Our findings suggest that the wall stiffness was greatest in the EoE case, followed by the achalasia case, and then the normal. This is supported by NIH Grant R01 DK56033 and R01 DK079902.

  16. Transmission electron microscopy studies of HfO{sub 2} thin films grown by chloride-based atomic layer deposition

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, D.R.G. [Institute of Materials and Engineering Science, ANSTO, PMB 1, Menai, NSW 2234 (Australia)]. E-mail:; Aidla, A. [Institute of Physics, University of Tartu, Taehe 4, EE-51010 Tartu (Estonia); Aarik, J. [Institute of Physics, University of Tartu, Taehe 4, EE-51010 Tartu (Estonia)


    Detailed transmission electron microscopy characterization of HfO{sub 2} films deposited on Si(1 0 0) using atomic layer deposition has been carried out. The influence of deposition temperature has been investigated. At 226 deg. C, a predominantly quasi-amorphous film containing large grains of cubic HfO{sub 2} (a {sub 0} = 5.08 A) was formed. Grain morphology enabled the nucleation sites to be determined. Hot stage microscopy showed that both the cubic phase and the quasi-amorphous phase were very resistant to thermal modification up to 500 deg. C. These observations suggest that nucleation sites for the growth of the crystalline cubic phase form at the growing surface of the film, rather homogeneously within the film. The films grown at higher temperatures (300-750 deg. C) are crystalline and monoclinic. The principal effects of deposition temperature were on: grain size, which coarsens at the highest temperature; roughness with increases at the higher temperatures due to the prismatic faceting, and texture, with texturing being strongest at intermediate temperatures. Detailed interfacial characterization shows that interfacial layers of SiO{sub 2} form at low and high temperatures. However, at intermediate temperatures, interfaces devoid of SiO{sub 2} were formed.

  17. Signal-Characteristic analysis with respect to backing material of PVDF-based high-frequency ultrasound for photoacoustic microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Su; Chang, Jin Ho [Dept. of Electronic Engineering, Sogang University, Seoul (Korea, Republic of)


    Photoacoustic microscopy is capable of providing high-resolution molecular images, and its spatial resolution is typically determined by ultrasonic transducers used to receive the photoacoustic signals. Therefore, ultrasonic transducers for photoacoustic microscopy (PAM) should have a high operating frequency, broad bandwidth, and high signal-reception efficiency. Polyvinylidene fluoride (PVDF) is a suitable material. To take full advantage of this material, the selection of the backing material is crucial, as it influences the center frequency and bandwidth of the transducer. Therefore, we experimentally determined the most suitable backing material among EPO-TEK 301, E-Solder 3022, and RTV. For this, three PVDF high-frequency single-element transducers were fabricated with each backing material. The center frequency and -6 dB bandwidth of each transducer were ascertained by a pulse-echo test. The spatial resolution of each transducer was examined using wire-target images. The experimental results indicated that EPO-TEK 301 is the most suitable backing material for a PAM transducer. This material provides the highest signal magnitude and a reasonable bandwidth because a large portion of the energy propagates toward the front medium, and the PVDF resonates in the half-wave mode.

  18. Evidence-based integrative medicine in clinical veterinary oncology. (United States)

    Raditic, Donna M; Bartges, Joseph W


    Integrative medicine is the combined use of complementary and alternative medicine with conventional or traditional Western medicine systems. The demand for integrative veterinary medicine is growing, but evidence-based research on its efficacy is limited. In veterinary clinical oncology, such research could be translated to human medicine, because veterinary patients with spontaneous tumors are valuable translational models for human cancers. An overview of specific herbs, botanics, dietary supplements, and acupuncture evaluated in dogs, in vitro canine cells, and other relevant species both in vivo and in vitro is presented for their potential use as integrative therapies in veterinary clinical oncology. Published by Elsevier Inc.

  19. Simulated non-contact atomic force microscopy for GaAs surfaces based on real-space pseudopotentials

    International Nuclear Information System (INIS)

    Kim, Minjung; Chelikowsky, James R.


    We simulate non-contact atomic force microscopy (AFM) with a GaAs(1 1 0) surface using a real-space ab initio pseudopotential method. While most ab initio simulations include an explicit model for the AFM tip, our method does not introduce the tip modeling step. This approach results in a considerable reduction of computational work, and also provides complete AFM images, which can be directly compared to experiment. By analyzing tip-surface interaction forces in both our results and previous ab initio simulations, we find that our method provides very similar force profile to the pure Si tip results. We conclude that our method works well for systems in which the tip is not chemically active.

  20. Quantification of protein based on single-molecule counting by total internal reflection fluorescence microscopy with adsorption equilibrium

    International Nuclear Information System (INIS)

    Wang Lei; Xu Guang; Shi Zhikun; Jiang Wei; Jin Wenrui


    We developed a sensitive single-molecule imaging method for quantification of protein by total internal reflection fluorescence microscopy with adsorption equilibrium. In this method, the adsorption equilibrium of protein was achieved between solution and glass substrate. Then, fluorescence images of protein molecules in a evanescent wave field were taken by a highly sensitive electron multiplying charge coupled device. Finally, the number of fluorescent spots corresponding to the protein molecules in the images was counted. Alexa Fluor 488-labeled goat anti-rat IgG(H + L) was chosen as the model protein. The spot number showed an excellent linear relationship with protein concentration. The concentration linear range was 5.4 x 10 -11 to 8.1 x 10 -10 mol L -1

  1. Quantitative Method to Measure Thermal Conductivity of One-Dimensional Nanostructures Based on Scanning Thermal Wave Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyung Bae; Chung, Jae Hun; Hwang, Gwang Seok; Jung, Eui Han; Kwon, Oh Myoung [Korea University, Seoul (Korea, Republic of)


    We present a method to quantitatively measure the thermal conductivity of one-dimensional nanostructures by utilizing scanning thermal wave microscopy (STWM) at a nanoscale spatial resolution. In this paper, we explain the principle for measuring the thermal diffusivity of one-dimensional nanostructures using STWM and the theoretical analysis procedure for quantifying the thermal diffusivity. The SWTM measurement method obtains the thermal conductivity by measuring the thermal diffusivity, which has only a phase lag relative to the distance corresponding to the transferred thermal wave. It is not affected by the thermal contact resistances between the heat source and nanostructure and between the nanostructure and probe. Thus, the heat flux applied to the nanostructure is accurately obtained. The proposed method provides a very simple and quantitative measurement relative to conventional measurement techniques.

  2. Multiscale phase mapping of LiFePO4-based electrodes by transmission electron microscopy and electron forward scattering diffraction. (United States)

    Robert, Donatien; Douillard, Thierry; Boulineau, Adrien; Brunetti, Guillaume; Nowakowski, Pawel; Venet, Denis; Bayle-Guillemaud, Pascale; Cayron, Cyril


    LiFePO4 and FePO4 phase distributions of entire cross-sectioned electrodes with various Li content are investigated from nanoscale to mesoscale, by transmission electron microscopy and by the new electron forward scattering diffraction technique. The distributions of the fully delithiated (FePO4) or lithiated particles (LiFePO4) are mapped on large fields of view (>100 × 100 μm(2)). Heterogeneities in thin and thick electrodes are highlighted at different scales. At the nanoscale, the statistical analysis of 64 000 particles unambiguously shows that the small particles delithiate first. At the mesoscale, the phase maps reveal a core-shell mechanism at the scale of the agglomerates with a preferential pathway along the electrode porosities. At larger scale, lithiation occurs in thick electrodes "stratum by stratum" from the surface in contact with electrolyte toward the current collector.

  3. Quantitative Analysis of Rat Dorsal Root Ganglion Neurons Cultured on Microelectrode Arrays Based on Fluorescence Microscopy Image Processing. (United States)

    Mari, João Fernando; Saito, José Hiroki; Neves, Amanda Ferreira; Lotufo, Celina Monteiro da Cruz; Destro-Filho, João-Batista; Nicoletti, Maria do Carmo


    Microelectrode Arrays (MEA) are devices for long term electrophysiological recording of extracellular spontaneous or evocated activities on in vitro neuron culture. This work proposes and develops a framework for quantitative and morphological analysis of neuron cultures on MEAs, by processing their corresponding images, acquired by fluorescence microscopy. The neurons are segmented from the fluorescence channel images using a combination of segmentation by thresholding, watershed transform, and object classification. The positioning of microelectrodes is obtained from the transmitted light channel images using the circular Hough transform. The proposed method was applied to images of dissociated culture of rat dorsal root ganglion (DRG) neuronal cells. The morphological and topological quantitative analysis carried out produced information regarding the state of culture, such as population count, neuron-to-neuron and neuron-to-microelectrode distances, soma morphologies, neuron sizes, neuron and microelectrode spatial distributions. Most of the analysis of microscopy images taken from neuronal cultures on MEA only consider simple qualitative analysis. Also, the proposed framework aims to standardize the image processing and to compute quantitative useful measures for integrated image-signal studies and further computational simulations. As results show, the implemented microelectrode identification method is robust and so are the implemented neuron segmentation and classification one (with a correct segmentation rate up to 84%). The quantitative information retrieved by the method is highly relevant to assist the integrated signal-image study of recorded electrophysiological signals as well as the physical aspects of the neuron culture on MEA. Although the experiments deal with DRG cell images, cortical and hippocampal cell images could also be processed with small adjustments in the image processing parameter estimation.

  4. Clinical information system based on the medical smart card. (United States)

    Danon, Y L; Saiag, E


    Over the last 5 years Israel has implemented a nationwide health insurance plan covering the entire population of the country. We have developed a clinical information system based on electronic-chip health care medical smart cards. Health care cards are used in several European countries and chip smart cards have been successful in many sectors. Our project involves the community use of the MSC, thereby enabling health care professionals to skillfully employ card systems in the health care sector. This system can easily arrange electronic medical charts in clinics, facilitating the confidential sharing of personal health databases among health professionals. To develop an MSC applicable for daily use in the community and hospital system. The MSC project, currently underway in Israel and the USA, will aid in determining the costs, benefits and feasibility of the MSC. Successful implementation of the MSC in chosen clinics will promote a nationwide willingness to adopt this promising technology.

  5. Conducting Clinically Based Intimate Partner Violence Research: Safety Protocol Recommendations. (United States)

    Anderson, Jocelyn C; Glass, Nancy E; Campbell, Jacquelyn C

    Maintaining safety is of utmost importance during research involving participants who have experienced intimate partner violence (IPV). Limited guidance on safety protocols to protect participants is available, particularly information related to technology-based approaches to informed consent, data collection, and contacting participants during the course of a study. The purpose of the article is to provide details on the safety protocol developed and utilized with women receiving care at an urban HIV clinic and who were taking part in an observational study of IPV, mental health symptoms, and substance abuse and their relationship to HIV treatment adherence. The protocol presents the technological strategies to promote safety and allow autonomy in participant decision-making throughout the research process, including Voice over Internet Protocol telephone numbers, and tablet-based eligibility screening and data collection. Protocols for management of participants at risk for suicide and/or intimate partner homicide that included automated high-risk messaging to participants and research staff and facilitated disclosure of risk to clinical staff based on participant preferences are discussed. Use of technology and partnership with clinic staff helped to provide an environment where research regarding IPV could be conducted without undue burden or risk to participants. Utilizing tablet-based survey administration provided multiple practical and safety benefits for participants. Most women who screened into high-risk categories for suicide or intimate partner homicide did not choose to have their results shared with their healthcare providers, indicating the importance of allowing participants control over information sharing whenever possible.

  6. [Evidence-based aspects of clinical mastitis treatment]. (United States)

    Mansion-de Vries, E M; Hoedemaker, M; Krömker, V


    Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence-based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i.   e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents.

  7. Clinical intuition versus statistics: different modes of tacit knowledge in clinical epidemiology and evidence-based medicine. (United States)

    Braude, Hillel D


    Despite its phenomenal success since its inception in the early nineteen-nineties, the evidence-based medicine movement has not succeeded in shaking off an epistemological critique derived from the experiential or tacit dimensions of clinical reasoning about particular individuals. This critique claims that the evidence-based medicine model does not take account of tacit knowing as developed by the philosopher Michael Polanyi. However, the epistemology of evidence-based medicine is premised on the elimination of the tacit dimension from clinical judgment. This is demonstrated through analyzing the dichotomy between clinical and statistical intuition in evidence-based medicine's epistemology of clinical reasoning. I argue that clinical epidemiology presents a more nuanced epistemological model for the application of statistical epidemiology to the clinical context. Polanyi's theory of tacit knowing is compatible with the model of clinical reasoning associated with clinical epidemiology, but not evidence-based medicine.

  8. Simulation-based medical education in clinical skills laboratory. (United States)

    Akaike, Masashi; Fukutomi, Miki; Nagamune, Masami; Fujimoto, Akiko; Tsuji, Akiko; Ishida, Kazuko; Iwata, Takashi


    Clinical skills laboratories have been established in medical institutions as facilities for simulation-based medical education (SBME). SBME is believed to be superior to the traditional style of medical education from the viewpoint of the active and adult learning theories. SBME can provide a learning cycle of debriefing and feedback for learners as well as evaluation of procedures and competency. SBME offers both learners and patients a safe environment for practice and error. In a full-environment simulation, learners can obtain not only technical skills but also non-technical skills, such as leadership, team work, communication, situation awareness, decision-making, and awareness of personal limitations. SBME is also effective for integration of clinical medicine and basic medicine. In addition, technology-enhanced simulation training is associated with beneficial effects for outcomes of knowledge, skills, behaviors, and patient-related outcomes. To perform SBME, effectively, not only simulators including high-fidelity mannequin-type simulators or virtual-reality simulators but also full-time faculties and instructors as professionals of SBME are essential in a clinical skills laboratory for SBME. Clinical skills laboratory is expected to become an integrated medical education center to achieve continuing professional development, integrated learning of basic and clinical medicine, and citizens' participation and cooperation in medical education.

  9. Non-Rigid Contour-Based Registration of Cell Nuclei in 2-D Live Cell Microscopy Images Using a Dynamic Elasticity Model. (United States)

    Sorokin, Dmitry V; Peterlik, Igor; Tektonidis, Marco; Rohr, Karl; Matula, Pavel


    The analysis of the pure motion of subnuclear structures without influence of the cell nucleus motion and deformation is essential in live cell imaging. In this paper, we propose a 2-D contour-based image registration approach for compensation of nucleus motion and deformation in fluorescence microscopy time-lapse sequences. The proposed approach extends our previous approach, which uses a static elasticity model to register cell images. Compared with that scheme, the new approach employs a dynamic elasticity model for the forward simulation of nucleus motion and deformation based on the motion of its contours. The contour matching process is embedded as a constraint into the system of equations describing the elastic behavior of the nucleus. This results in better performance in terms of the registration accuracy. Our approach was successfully applied to real live cell microscopy image sequences of different types of cells including image data that was specifically designed and acquired for evaluation of cell image registration methods. An experimental comparison with the existing contour-based registration methods and an intensity-based registration method has been performed. We also studied the dependence of the results on the choice of method parameters.

  10. Calcium silicate-based cements: composition, properties, and clinical applications. (United States)

    Dawood, Alaa E; Parashos, Peter; Wong, Rebecca H K; Reynolds, Eric C; Manton, David J


    Mineral trioxide aggregate (MTA) is a calcium silicate-based cement (CSC) commonly used in endodontic procedures involving pulpal regeneration and hard tissue repair, such as pulp capping, pulpotomy, apexogenesis, apexification, perforation repair, and root-end filling. Despite the superior laboratory and clinical performance of MTA in comparison with previous endodontic repair cements, such as Ca(OH) 2 , MTA has poor handling properties and a long setting time. New CSC have been commercially launched and marketed to overcome the limitations of MTA. The aim of the present review was to explore the available literature on new CSC products, and to give evidence-based recommendations for the clinical use of these materials. Within the limitations of the available data in the literature regarding the properties and performance of the new CSC, the newer products could be promising alternatives to MTA; however, further research is required to support this assumption. © 2015 Wiley Publishing Asia Pty Ltd.

  11. Syndromic Panel-Based Testing in Clinical Microbiology. (United States)

    Ramanan, Poornima; Bryson, Alexandra L; Binnicker, Matthew J; Pritt, Bobbi S; Patel, Robin


    The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation. Copyright © 2017 American Society for Microbiology.

  12. Fractographic features of glass-ceramic and zirconia-based dental restorations fractured during clinical function. (United States)

    Oilo, Marit; Hardang, Anne D; Ulsund, Amanda H; Gjerdet, Nils R


    Fractures during clinical function have been reported as the major concern associated with all-ceramic dental restorations. The aim of this study was to analyze the fracture features of glass-ceramic and zirconia-based restorations fractured during clinical use. Twenty-seven crowns and onlays were supplied by dentists and dental technicians with information about type of cement and time in function, if available. Fourteen lithium disilicate glass-ceramic restorations and 13 zirconia-based restorations were retrieved and analyzed. Fractographic features were examined using optical microscopy to determine crack initiation and crack propagation of the restorations. The material comprised fractured restorations from one canine, 10 incisors, four premolars, and 11 molars. One crown was not categorized because of difficulty in orientation of the fragments. The results revealed that all core and veneer fractures initiated in the cervical margin and usually from the approximal area close to the most coronally placed curvature of the margin. Three cases of occlusal chipping were found. The margin of dental all-ceramic single-tooth restorations was the area of fracture origin. The fracture features were similar for zirconia, glass-ceramic, and alumina single-tooth restorations. Design features seem to be of great importance for fracture initiation. © 2014 Eur J Oral Sci.

  13. A quality assessment tool for markup-based clinical guidelines. (United States)

    Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan


    We introduce a tool for quality assessment of procedural and declarative knowledge. We developed this tool for evaluating the specification of mark-up-based clinical GLs. Using this graphical tool, the expert physician and knowledge engineer collaborate to perform scoring, using pre-defined scoring scale, each of the knowledge roles of the mark-ups, comparing it to a gold standard. The tool enables scoring the mark-ups simultaneously at different sites by different users at different locations.

  14. Statistical model based gender prediction for targeted NGS clinical panels

    Directory of Open Access Journals (Sweden)

    Palani Kannan Kandavel


    The reference test dataset are being used to test the model. The sensitivity on predicting the gender has been increased from the current “genotype composition in ChrX” based approach. In addition, the prediction score given by the model can be used to evaluate the quality of clinical dataset. The higher prediction score towards its respective gender indicates the higher quality of sequenced data.

  15. The use of atomic force microscopy as an important technique to analyze the dispersion of nanometric fillers and morphology in nanocomposites and polymer blends based on elastomers

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, Fabiula Danielli Bastos de; Scuracchio, Carlos Henrique, E-mail: [Universidade Federal do ABC (CECS/UFABC), Santo Andre, SP (Brazil). Centro de Engenharia, Modelagem e Ciencias Sociais Aplicadas


    AFM has been recognized as one of the most powerful tools for the analysis of surface morphologies because it creates three-dimensional images at angstrom and nano scale. This technique has been exhaustively used in the analyses of dispersion of nanometric components in nanocomposites and in polymer blends, because of the easiness of sample preparation and lower equipment maintenance costs compared to electron microscopy. In this review, contributions using AFM are described, with emphasis on the dispersion of nanofillers in polymeric matrices. It is aimed to show the importance of technical analysis for nanocomposites and polymer blends based on elastomers. (author)

  16. Examination of biogenic selenium-containing nanosystems based on polyelectrolyte complexes by atomic force, Kelvin probe force and electron microscopy methods

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanova, T. E., E-mail:; Vylegzhanina, M. E.; Valueva, S. V.; Volkov, A. Ya.; Kutin, A. A. [Institute of Macromolecular Compounds RAS, 199004 Bolshoy Pr., 31, St.-Petersburg (Russian Federation); Temiryazeva, M. P.; Temiryazev, A. G. [Kotel’nikov Institute of Radio Engineering and Electronics (Fryazino Branch) Russian Academy of Sciences, Fryazino, Moscow region, 141190 (Russian Federation)


    The morphology and electrical properties of biogenic selenium-containing nanosystems based on polyelectrolyte complexes (PECs) were examined using AFM, Kelvin Probe Force and electron microscopy methods. It has been found, that prepared nanostructures significantly differed in their morphological types and parameters. In particular, multilayers capsules can be produced via varying synthesis conditions, especially, the selenium–PEC mass ratio ν. At the “special point” (ν = 0.1), filled and hollow nano- and microcapsules are formed in the system. The multilayer character of the capsules walls is visible in the phase images. Kelvin Probe Force images showed the inhomogeneity of potential distribution in capsules and outside them.

  17. Electrochemistry and in situ scanning tunnelling microscopy of pure and redox-marked DNA- and UNA-based oligonucleotides on Au(111)-electrode surfaces

    DEFF Research Database (Denmark)

    Hansen, Allan Glargaard; Salvatore, Princia; Karlsen, K.


    the strongest and in accord with multiple site Ru-attachment. In situ STM disclosed molecular scale features in varying coverage on addition of the metal ions. The Ru-derivatives showed a bias voltage dependent broad maximum in the tunnelling current–overpotential correlation which could be correlated......We have studied adsorption and electrochemical electron transfer of several 13- and 15-base DNA and UNA (unlocked nucleic acids) oligonucleotides (ONs) linked to Au(111)-electrode surfaces via a 50-C6-SH group using cyclic voltammetry (CV) and scanning tunnelling microscopy in aqueous buffer under...

  18. Acid-base equilibrium: The best clinical approach


    Aristizábal-Salazar, Raúl E; Calvo-Torres, L. Felipe; Valencia-Arango, Luis Alfonso; Montoya-Canon, Mauricio; Barbosa-Gantiva, Oscar; Hincapié-Baena, Vanessa


    Acid-base balance disorders can be found in a primary or secondary form in patients with a disease process such as Diabetes Mellitus or acute renal failure, among others. The objective of this article is to explain and guide the correlation ship between the clinical findings in the patient and the parameters of arterial blood gases in a simple and precise manner, in order to make the correct acid-base balance diagnosis and adequate therapeutic interventions. A non-systematic review of the sci...

  19. Correlated Light Microscopy and Electron Microscopy

    NARCIS (Netherlands)

    Sjollema, Klaas A.; Schnell, Ulrike; Kuipers, Jeroen; Kalicharan, Ruby; Giepmans, Ben N. G.; MullerReichert, T; Verkade, P


    Understanding where, when, and how biomolecules (inter)act is crucial to uncover fundamental mechanisms in cell biology. Recent developments in fluorescence light microscopy (FLM) allow protein imaging in living cells and at the near molecular level. However, fluorescence microscopy only reveals

  20. A non-contact, thermal noise based method for the calibration of lateral deflection sensitivity in atomic force microscopy

    International Nuclear Information System (INIS)

    Mullin, Nic; Hobbs, Jamie K.


    Calibration of lateral forces and displacements has been a long standing problem in lateral force microscopies. Recently, it was shown by Wagner et al. that the thermal noise spectrum of the first torsional mode may be used to calibrate the deflection sensitivity of the detector. This method is quick, non-destructive and may be performed in situ in air or liquid. Here we make a full quantitative comparison of the lateral inverse optical lever sensitivity obtained by the lateral thermal noise method and the shape independent method developed by Anderson et al. We find that the thermal method provides accurate results for a wide variety of rectangular cantilevers, provided that the geometry of the cantilever is suitable for torsional stiffness calibration by the torsional Sader method, in-plane bending of the cantilever may be eliminated or accounted for and that any scaling of the lateral deflection signal between the measurement of the lateral thermal noise and the measurement of the lateral deflection is eliminated or corrected for. We also demonstrate that the thermal method may be used to characterize the linearity of the detector signal as a function of position, and find a deviation of less than 8% for the instrument used

  1. Synchrotron-based in situ soft X-ray microscopy of Ag corrosion in aqueous chloride solution

    International Nuclear Information System (INIS)

    Bozzini, B; D'Urzo, L; Gianoncelli, A; Kaulich, B; Kiskinova, M; Prasciolu, M; Tadjeddine, A


    In this paper we report an in situ X-ray microscopy study of a model metal electrochemistry system, incorporating faradaic reactivity: the anodic corrosion and cathodic electrodeposition of Ag in aqueous systems. The information at sub-μm scale about morpho-chemical evolution of the electrified interface, provided by this novel electroanalytical approach fosters fundamental understanding of important issues concerning material fabrication and stability, which are crucial in developing the next generation electrochemical technologies, such as fuel cells and biosensors. The key methodology challenge faced in this pilot electrochemical experiments is combining a three-electrode configuration and wet environment, which required metal electrodes suitable for transmitting soft X-rays and a sealed cell allowing working in high vacuum. This has been solved via lithographic fabrication route fabricating 75 nm thick Ag electrodes and using Si 3 N 4 membranes as X-ray windows and electrode support. Imaging in the STXM mode with phase contrast allowed us to monitor the corrosion morphologies and metal outgrowth features. Localised thickness variation and the build-up of reaction products of electron density different from that of the starting material have been detected with high sensitivity.

  2. Dual light-emitting diode-based multichannel microscopy for whole-slide multiplane, multispectral and phase imaging. (United States)

    Liao, Jun; Wang, Zhe; Zhang, Zibang; Bian, Zichao; Guo, Kaikai; Nambiar, Aparna; Jiang, Yutong; Jiang, Shaowei; Zhong, Jingang; Choma, Michael; Zheng, Guoan


    We report the development of a multichannel microscopy for whole-slide multiplane, multispectral and phase imaging. We use trinocular heads to split the beam path into 6 independent channels and employ a camera array for parallel data acquisition, achieving a maximum data throughput of approximately 1 gigapixel per second. To perform single-frame rapid autofocusing, we place 2 near-infrared light-emitting diodes (LEDs) at the back focal plane of the condenser lens to illuminate the sample from 2 different incident angles. A hot mirror is used to direct the near-infrared light to an autofocusing camera. For multiplane whole-slide imaging (WSI), we acquire 6 different focal planes of a thick specimen simultaneously. For multispectral WSI, we relay the 6 independent image planes to the same focal position and simultaneously acquire information at 6 spectral bands. For whole-slide phase imaging, we acquire images at 3 focal positions simultaneously and use the transport-of-intensity equation to recover the phase information. We also provide an open-source design to further increase the number of channels from 6 to 15. The reported platform provides a simple solution for multiplexed fluorescence imaging and multimodal WSI. Acquiring an instant focal stack without z-scanning may also enable fast 3-dimensional dynamic tracking of various biological samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Electrochemical force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kalinin, Sergei V.; Jesse, Stephen; Collins, Liam F.; Rodriguez, Brian J.


    A system and method for electrochemical force microscopy are provided. The system and method are based on a multidimensional detection scheme that is sensitive to forces experienced by a biased electrode in a solution. The multidimensional approach allows separation of fast processes, such as double layer charging, and charge relaxation, and slow processes, such as diffusion and faradaic reactions, as well as capturing the bias dependence of the response. The time-resolved and bias measurements can also allow probing both linear (small bias range) and non-linear (large bias range) electrochemical regimes and potentially the de-convolution of charge dynamics and diffusion processes from steric effects and electrochemical reactivity.

  4. Connecting clinical and actuarial prediction with rule-based methods. (United States)

    Fokkema, Marjolein; Smits, Niels; Kelderman, Henk; Penninx, Brenda W J H


    Meta-analyses comparing the accuracy of clinical versus actuarial prediction have shown actuarial methods to outperform clinical methods, on average. However, actuarial methods are still not widely used in clinical practice, and there has been a call for the development of actuarial prediction methods for clinical practice. We argue that rule-based methods may be more useful than the linear main effect models usually employed in prediction studies, from a data and decision analytic as well as a practical perspective. In addition, decision rules derived with rule-based methods can be represented as fast and frugal trees, which, unlike main effects models, can be used in a sequential fashion, reducing the number of cues that have to be evaluated before making a prediction. We illustrate the usability of rule-based methods by applying RuleFit, an algorithm for deriving decision rules for classification and regression problems, to a dataset on prediction of the course of depressive and anxiety disorders from Penninx et al. (2011). The RuleFit algorithm provided a model consisting of 2 simple decision rules, requiring evaluation of only 2 to 4 cues. Predictive accuracy of the 2-rule model was very similar to that of a logistic regression model incorporating 20 predictor variables, originally applied to the dataset. In addition, the 2-rule model required, on average, evaluation of only 3 cues. Therefore, the RuleFit algorithm appears to be a promising method for creating decision tools that are less time consuming and easier to apply in psychological practice, and with accuracy comparable to traditional actuarial methods. (c) 2015 APA, all rights reserved).

  5. Evidence-based clinical practice guidelines for chronic pancreatitis 2015. (United States)

    Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru


    Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

  6. Mixture-based gatekeeping procedures in adaptive clinical trials. (United States)

    Kordzakhia, George; Dmitrienko, Alex; Ishida, Eiji


    Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to "multivariate" multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.

  7. Deterministic versus evidence-based attitude towards clinical diagnosis. (United States)

    Soltani, Akbar; Moayyeri, Alireza


    Generally, two basic classes have been proposed for scientific explanation of events. Deductive reasoning emphasizes on reaching conclusions about a hypothesis based on verification of universal laws pertinent to that hypothesis, while inductive or probabilistic reasoning explains an event by calculation of some probabilities for that event to be related to a given hypothesis. Although both types of reasoning are used in clinical practice, evidence-based medicine stresses on the advantages of the second approach for most instances in medical decision making. While 'probabilistic or evidence-based' reasoning seems to involve more mathematical formulas at the first look, this attitude is more dynamic and less imprisoned by the rigidity of mathematics comparing with 'deterministic or mathematical attitude'. In the field of medical diagnosis, appreciation of uncertainty in clinical encounters and utilization of likelihood ratio as measure of accuracy seem to be the most important characteristics of evidence-based doctors. Other characteristics include use of series of tests for refining probability, changing diagnostic thresholds considering external evidences and nature of the disease, and attention to confidence intervals to estimate uncertainty of research-derived parameters.

  8. Clinical TVA-based studies: a general review

    Directory of Open Access Journals (Sweden)

    Thomas eHabekost


    Full Text Available In combination with whole report and partial report tasks, the Theory of Visual Attention (TVA can be used to estimate individual differences in five basic attentional parameters: The visual processing speed, the storage capacity of visual short-term memory, the perceptual threshold, the efficiency of top-down selectivity, and the spatial bias of attentional weighting. TVA-based assessment has been used in about 30 studies to investigate attentional deficits in a range of neurological and psychiatric conditions: (a neglect and simultanagnosia, (b reading disturbances, (c aging and neurodegenerative diseases, and most recently (d neurodevelopmental disorders. The article introduces TVA based assessment, discusses its methodology and psychometric properties, and reviews the progress made in each of the four research fields. The empirical results demonstrate the general usefulness of TVA-based assessment for many types of clinical neuropsychological research. The method’s most important qualities are cognitive specificity and theoretical grounding, but it is also characterized by good reliability and sensitivity to minor deficits. The review concludes by pointing to promising new areas for clinical TVA-based research.

  9. Labeling surface epitopes to identify Cryptosporidium life stages using a scanning electron microscopy-based immunogold approach. (United States)

    Edwards, Hanna; Thompson, R C Andrew; Koh, Wan H; Clode, Peta L


    The Apicomplexan parasite Cryptosporidium parvum is responsible for the widespread disease cryptosporidiosis, in both humans and livestock. The nature of C. parvum infection is far from understood and many questions remain in regard to host-parasite interactions, limiting successful treatment of the disease. To definitively identify a range of C. parvum stages in cell culture and to begin to investigate host cell interactions in some of the lesser known life stages, we have utilized a combined scanning electron microscopy and immunolabeling approach, correlating high resolution microstructural information with definitive immunogold labeling of Cryptosporidium stages. Several life cycle stages, including oocysts, merozoites I, trophozoites, gamonts and microgametocytes, were successfully immunolabeled in an in vitro model system. Developing oocysts were clearly immunolabeled, but this did not persist once excystation had occurred. Immunolabeling visualized on the host cell surface adjacent to invasive merozoites is likely to be indicative of receptor shedding, with merozoites also initiating host responses that manifested as abnormal microvilli on the host cell surface. Small sub-micron stages such as microgametocytes, which were impossible to identify as single entities without immunolabeling, were readily visualized and observed to attach to host cells via novel membranous projections. Epicellular parasites also expressed Cryptosporidium-derived epitopes within their encapsulating membrane. These data have allowed us to confidently identify a variety of C. parvum stages in cell culture at high resolution. With this, we provide new insight into C. parvum - host cell interactions and highlight future opportunities for investigating and targeting receptor-mediated interactions between Cryptosporidium life cycle stages and host cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Investigating local degradation and thermal stability of charged nickel-based cathode materials through real-time electron microscopy. (United States)

    Hwang, Sooyeon; Kim, Seung Min; Bak, Seong-Min; Cho, Byung-Won; Chung, Kyung Yoon; Lee, Jeong Yong; Chang, Wonyoung; Stach, Eric A


    In this work, we take advantage of in situ transmission electron microscopy (TEM) to investigate thermally induced decomposition of the surface of Li(x)Ni(0.8)Co(0.15)Al(0.05)O2 (NCA) cathode materials that have been subjected to different states of charge (SOC). While uncharged NCA is stable up to 400 °C, significant changes occur in charged NCA with increasing temperature. These include the development of surface porosity and changes in the oxygen K-edge electron energy loss spectra, with pre-edge peaks shifting to higher energy losses. These changes are closely related to O2 gas released from the structure, as well as to phase changes of NCA from the layered structure to the disordered spinel structure, and finally to the rock-salt structure. Although the temperatures where these changes initiate depend strongly on the state of charge, there also exist significant variations among particles with the same state of charge. Notably, when NCA is charged to x = 0.33 (the charge state that is the practical upper limit voltage in most applications), the surfaces of some particles undergo morphological and oxygen K-edge changes even at temperatures below 100 °C, a temperature that electronic devices containing lithium ion batteries (LIB) can possibly see during normal operation. Those particles that experience these changes are likely to be extremely unstable and may trigger thermal runaway at much lower temperatures than would be usually expected. These results demonstrate that in situ heating experiments are a unique tool not only to study the general thermal behavior of cathode materials but also to explore particle-to-particle variations, which are sometimes of critical importance in understanding the performance of the overall system.

  11. Clinical applications of MS-based protein quantification. (United States)

    Sabbagh, Bassel; Mindt, Sonani; Neumaier, Michael; Findeisen, Peter


    Mass spectrometry-based assays are increasingly important in clinical laboratory medicine and nowadays are already commonly used in several areas of routine diagnostics. These include therapeutic drug monitoring, toxicology, endocrinology, pediatrics, and microbiology. Accordingly, some of the most common analyses are therapeutic drug monitoring of immunosuppressants, vitamin D, steroids, newborn screening, and bacterial identification. However, MS-based quantification of peptides and proteins for routine diagnostic use is rather rare up to now despite excellent analytical specificity and good sensitivity. Here, we want to give an overview over current fit-for-purpose assays for MS-based protein quantification. Advantages as well as challenges of this approach will be discussed with focus on feasibility for routine diagnostic use. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Microsphere imaging with confocal microscopy and two photon microscopy

    International Nuclear Information System (INIS)

    Chun, Hyung Su; An, Kyung Won; Lee, Jai Hyung


    We have acquired images of polystyrene and fused-silica microsphere by using conventional optical microscopy, confocal microscopy and two-photon microscopy, and performed comparative analysis of these images. Different from conventional optical microscopy, confocal and two-photon microscopy had good optical sectioning capability. In addition, confocal microscopy and two-photon microscopy had better lateral resolution than conventional optical microscopy. These results are attributed to confocality and nonlinearity of confocal microscopy and two photon microscopy, respectively.

  13. Synchrotron based x-ray fluorescence microscopy confirms copper in the corrosion products of metals in contact with treated wood (United States)

    Samuel L. Zelinka; Joseph E. Jakes; Grant T. Kirker; David Vine; Stefan Vogt


    Copper based waterborne wood preservatives are frequently used to extend the service life of wood products when subjected to frequent moisture exposure. While these copper based treatments protect the wood from fungal decay and insect attack, they increase the corrosion of metals embedded or in contact with the treated wood. Previous research has shown the most...

  14. An internet-based teaching file on clinical nuclear medicine

    International Nuclear Information System (INIS)

    Jiang Zhong; Wu Jinchang


    Objective: The goal of this project was to develop an internet-based interactive digital teaching file on nuclide imaging in clinical nuclear medicine, with the capability of access to internet. Methods: On the basis of academic teaching contents in nuclear medicine textbook for undergraduates who major in nuclear medicine, Frontpage 2000, HTML language, and JavaScript language in some parts of the contents, were utilized in the internet-based teaching file developed in this study. Results: A practical and comprehensive teaching file was accomplished and may get access with acceptable speed to internet. Besides basic teaching contents of nuclide imagings, a large number of typical and rare clinical cases, questionnaire with answers and update data in the field of nuclear medicine were included in the file. Conclusion: This teaching file meets its goal of providing an easy-to-use and internet-based digital teaching file, characteristically with the contents instant and enriched, and with the modes diversified and colorful

  15. Designing topological defects in 2D materials using scanning probe microscopy and a self-healing mechanism: a density functional-based molecular dynamics study (United States)

    Popov, Igor; Đurišić, Ivana; Belić, Milivoj R.


    Engineering of materials at the atomic level is one of the most important aims of nanotechnology. The unprecedented ability of scanning probe microscopy to address individual atoms opened up the possibilities for nanomanipulation and nanolitography of surfaces and later on of two-dimensional materials. While the state-of-the-art scanning probe lithographic methods include, primarily, adsorption, desorption and repositioning of adatoms and molecules on substrates or tailoring nanoribbons by etching of trenches, the precise modification of the intrinsic atomic structure of materials is yet to be advanced. Here we introduce a new concept, scanning probe microscopy with a rotating tip, for engineering of the atomic structure of membranes based on two-dimensional materials. In order to indicate the viability of the concept, we present our theoretical research, which includes atomistic modeling, molecular dynamics simulations, Fourier analysis and electronic transport calculations. While stretching can be employed for fabrication of atomic chains only, our comprehensive molecular dynamics simulations indicate that nanomanipulation by scanning probe microscopy with a rotating tip is capable of assembling a wide range of topological defects in two-dimensional materials in a rather controllable and reproducible manner. We analyze two possibilities. In the first case the probe tip is retracted from the membrane while in the second case the tip is released beneath the membrane allowing graphene to freely relax and self-heal the pore made by the tip. The former approach with the tip rotation can be achieved experimentally by rotation of the sample, which is equivalent to rotation of the tip, whereas irradiation of the membrane by nanoclusters can be utilized for the latter approach. The latter one has the potential to yield a yet richer diversity of topological defects on account of a lesser determinacy. If successfully realized experimentally the concept proposed here could

  16. Electron microscopy for Engineers

    International Nuclear Information System (INIS)

    Jones, I P


    This paper reviews the application of (mainly) Transmission Electron Microscopy (TEM) in an engineering context. The first two sections are TEM and chemical in nature; the final three sections are more general and include aspects of Scanning Electron Microscopy (SEM).

  17. Evidence-based clinical guidelines in Kyrgyz Republic. (United States)

    Zurdinova, A A


    Improving quality of care in many countries is one of the priorities of health systems. At the same time one of the most important methods of improving quality of care is the widespread use of methods and principles of evidence-based medicine (EBM) [1]. The implementation of EBM in public health practice provides for the optimization of quality of care in terms of safety, efficacy and cost, one way of which is the use of clinical guidelines. Clinical guidelines developed with the use of EBM, provide an opportunity to use the latest and accurate information to optimize or neutralize impact on physician decision-making of subjective factors such as intuition, expertise, opinion of respected colleagues, recommendations of popular manuals and handbooks, etc. To assess and analyze the developed clinical guidelines (CG) and protocols (CP) in the Kyrgyz Republic in the period from 2008 to 2014 and evaluate their implementation in practical healthcare. Retrospective analysis of the developed clinical guidelines and protocols according to the approved methodology, interviewing leaders, questioning doctors and patients for their implementation. All participants gave informed consent for voluntary participation in the study. Within the framework of the National Program "Manas Taalimi" "Strategy for development of evidence-based medicine in the Kyrgyz Republic for 2006-2010" (MOH Order №490 from 09.04.06) was developed and approved for use. Its main purpose was to create a sustainable system of development, deployment and monitoring of the CG and CP and further promotion of EBM into practical health care, education and science. As a result, a number of documents ("Expert Council for assessing the quality of clinical guidelines/protocols", "AGREE instrument to assess the methodological content of clinical guidelines" [2], "The methodology of development and adaptation of clinical guidelines based on evidence-based medicine") were approved by the Order of the Ministry of

  18. Do evidence-based guidelines change clinical practice patterns?

    DEFF Research Database (Denmark)

    Kessel, Line; Erngaard, Ditte; Flesner, Per


    In 2013, the Danish Health and Medicines Authorities published a National Clinical Guideline on the treatment of age-related cataracts. The guideline provided evidence-based recommendations on the indication for cataract surgery, cataract surgery in patients with age-related macular degeneration......, on the use of toric intraocular lenses (IOLs) to correct preoperative corneal astigmatism, the use of intracameral and topical antibiotics to prevent endophthalmitis, choice of anti-inflammatory medication to control postoperative inflammation and prevent cystoid macular oedema, the use of immediate...

  19. Electron microscopy of surfaces

    International Nuclear Information System (INIS)

    Venables, J.A.


    Electron beam techniques used to study clean surfaces and surface processes on a microscopic scale are reviewed. Recent experimental examples and possible future developments are discussed. Special emphasis is given to (i) transmission diffraction and microscopy techniques, including atomic imaging; (ii) Auger microscopy on bulk and thin film samples; (iii) secondary electron microscopy, especially low energy secondaries for work-function imaging and photoelectron imaging; and (iv) reflection electron microscopy and diffraction. (orig.)

  20. Evidence-based clinical practice, [corrected] evidence-based medicine and the Cochrane collaboration. (United States)

    Gambrill, E


    Encouraging professionals in training and later to consider practice-related research findings when making important clinical decisions is an on-going concern. Evidenced-Based Medicine (EBM) and the Cochrane Collaboration (CC) provide a source of tools and ideas for doing so, as well as a roster of colleagues who share this interest. Evidenced-based medicine involves integrating clinical expertise with the best available external evidence from systematic research as well as considering the values and expectations of patients/clients. Advantage can be taken of educational formats developed in EBM, such as problem-based learning and critical-appraisal workshops in which participants learn how to ask key answerable questions related to important clinical practice questions (e.g., regarding effectiveness, accuracy of assessment measures, prediction, prevention, and quality of clinical practice guidelines) and to access and critically appraise related research. The Cochrane Collaboration is a world-wide network of centers that prepare, maintain, and disseminate high-quality systematic reviews on the efficacy of healthcare. These databases allow access to evidence related to clinical practice decisions. Forging reciprocal working relationships with those involved in EBM reciprocal and the CC should contribute to the pursuit of shared goals such as basing clinical decisions on the best-available evidence and involving clients as informed consumers.

  1. Dictionary of Microscopy (United States)

    Heath, Julian


    The past decade has seen huge advances in the application of microscopy in all areas of science. This welcome development in microscopy has been paralleled by an expansion of the vocabulary of technical terms used in microscopy: terms have been coined for new instruments and techniques and, as microscopes reach even higher resolution, the use of terms that relate to the optical and physical principles underpinning microscopy is now commonplace. The Dictionary of Microscopy was compiled to meet this challenge and provides concise definitions of over 2,500 terms used in the fields of light microscopy, electron microscopy, scanning probe microscopy, x-ray microscopy and related techniques. Written by Dr Julian P. Heath, Editor of Microscopy and Analysis, the dictionary is intended to provide easy navigation through the microscopy terminology and to be a first point of reference for definitions of new and established terms. The Dictionary of Microscopy is an essential, accessible resource for: students who are new to the field and are learning about microscopes equipment purchasers who want an explanation of the terms used in manufacturers' literature scientists who are considering using a new microscopical technique experienced microscopists as an aide mémoire or quick source of reference librarians, the press and marketing personnel who require definitions for technical reports.

  2. Hyperspectral light sheet microscopy (United States)

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan


    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos.

  3. Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice. (United States)

    Hajjaj, F M; Salek, M S; Basra, M K A; Finlay, A Y


    This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine.

  4. A fully-automated multiscale kernel graph cuts based particle localization scheme for temporal focusing two-photon microscopy (United States)

    Huang, Xia; Li, Chunqiang; Xiao, Chuan; Sun, Wenqing; Qian, Wei


    The temporal focusing two-photon microscope (TFM) is developed to perform depth resolved wide field fluorescence imaging by capturing frames sequentially. However, due to strong nonignorable noises and diffraction rings surrounding particles, further researches are extremely formidable without a precise particle localization technique. In this paper, we developed a fully-automated scheme to locate particles positions with high noise tolerance. Our scheme includes the following procedures: noise reduction using a hybrid Kalman filter method, particle segmentation based on a multiscale kernel graph cuts global and local segmentation algorithm, and a kinematic estimation based particle tracking method. Both isolated and partial-overlapped particles can be accurately identified with removal of unrelated pixels. Based on our quantitative analysis, 96.22% isolated particles and 84.19% partial-overlapped particles were successfully detected.

  5. Imaging of Pseudo Oil Base Mud in Environmental Scanning Electron Microscopy Imagerie des boues de forage à base d'huile de substitution par microscopie électronique à balayage ambiant

    Directory of Open Access Journals (Sweden)

    Tricart J. P.


    Full Text Available Characterizing pseudo oil base muds (POBM amounts to determining the relationships between the size distribution of droplets and stability of emulsions. Conventional scanning and transmission electron microscope (SEM and TEM have been used to investigate these problems. However, hydrated samples are difficult to handle using such techniques. The Environmental Scanning Electron Microscope (ESEM or Electroscan and the cryogenic techniques have opened the door to the study of wet and non-conductive specimens, and of various liquids or emulsions. ESEM with the cold stage allows us to directly visualize emulsions :- without any preparation or coating;- at different temperatures, by controlling the specimen temperature (between -180°C and -8O°C and pressure (between 400 and 1400 Pa. La caractérisation des boues de forage à base d'huile de substitution (POBM équivaut à définir la relation entre la répartition dimensionnelle des gouttelettes et la stabilité des émulsions. Les microscopes électroniques à balayage (SEM et à transmission (TEM classiques ont été utilisés pour étudier ces problèmes. Toutefois, les échantillons hydratés sont d'un traitement difficile à l'aide de ces techniques. Le microscope environnemental électronique à balayage (ESEM ou electroscan et les techniques cryogéniques ont ouvert la voie à l'étude de spécimens humides et non conducteurs, de liquides et d'émulsions divers. A froid, l'ESEM nous permet de visualiser des émulsions : - sans aucune préparation ou enrobage, - à différentes températures, en régulant la température (entre - 180°C et - 80°C et la pression (entre 400 et 1400 kPa du spécimen. Le présent document se propose de caractériser les boues à base d'huile de substitution et d'étudier : - l'homogénéité de la formulation et la procédure de préparation, - l'influence de la répartition dimensionnelle des gouttelettes sur la stabilité des émulsions.

  6. Spatiotemporal Ultrafast-Plasmon Control Based on Response Functions of Nanostructures Measured by Interferometric Cross-Correlation Microscopy

    Directory of Open Access Journals (Sweden)

    Kusaba Miyuki


    Full Text Available We demonstrate an electrical-field cross-correlation imaging technique to obtain a response function of localized plasmon generated by femtosecond laser pulses on gold nanostructures. Based on the measured response functions, we spatiotemporally control the plasmon by shaping the femtosecond excitation laser pulses.

  7. Interface properties of SrTiO3-based heterostructures studied by spectroscopy and high-resolution microscopy

    International Nuclear Information System (INIS)

    Pfaff, Florian Georg


    carrier concentration as well as the 2DES spatial extension can be observed for samples grown at very low oxygen pressures, which is related to the creation of oxygen vacancies in SrTiO 3 substrate. It is microscopically shown for the first time that sharp interfaces with a very low density of defects can also be grown at very low oxygen partial pressures. In addition, no significant effect of oxygen vacancies on specific structural properties is seen. Furthermore, a detailed analysis of the atomic spacing reveales a lattice distortion within the LaAlO 3 film which shows a significant dependence on the used growth parameters and, supported by density functional theory, points towards a complex interplay of electronic reconstruction, surface oxygen vacancies and lattice distortions as the driving mechanism for the 2DES formation. Beside the study of the structural properties of the interface in LaAlO 3 /SrTiO 3 heterostructures by means of transmission electron microscopy, the electronic structure of the 2DES is analyzed by resonant inelastic X-ray scattering (RIXS) measurements which show clear indications for localized charge carriers below the critical thickness for conductivity of four unit cells. Moreover, a Raman- and a fluorescence-like signal can be identified by excitation energy dependent RIXS and attributed to the electronic character of the intermediate state. Similar results are obtained on γ-Al 2 O 3 /SrTiO 3 heterostructures which fortifies this interpretation and could be a hint for a similar ground state in both heterostructures and interface magnetism also to be present in this system. By using resonant photoelectron spectroscopy the Ti 3d valence electrons can directly be observed and analyzed. Comparative measurements on LaAlO 3 /SrTiO 3 and γ-Al 2 O 3 /SrTiO 3 indicate the existence of different types of electronic states with Ti 3d character in both systems which can be attributed to mobile carriers forming the 2DES and carriers localized in states

  8. The nature of ancient Egyptian copper-containing carbon inks is revealed by synchrotron radiation based X-ray microscopy


    Christiansen , Thomas; Cotte , Marine; Loredo-Portales , René; Lindelof , Poul ,; Mortensen , Kell; Ryholt , Kim; Larsen , Sine


    International audience; For the first time it is shown that carbon black inks on ancient Egyptian papyri from different time periods and geographical regions contain copper. The inks have been investigated using synchrotron-based micro X-ray fluorescence (XRF) and micro X-ray absorption near-edge structure spectroscopy (XANES) at the European Synchrotron Radiation Facility (ESRF). The composition of the copper-containing carbon inks showed no significant differences that could be related to t...

  9. Comparison of confocal microscopy and two-photon microscopy in mouse cornea in vivo. (United States)

    Lee, Jun Ho; Lee, Seunghun; Gho, Yong Song; Song, In Seok; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean


    High-resolution imaging of the cornea is important for studying corneal diseases at cellular levels. Confocal microscopy (CM) has been widely used in the clinic, and two-photon microscopy (TPM) has recently been introduced in various pre-clinical studies. We compared the performance of CM and TPM in normal mouse corneas and neovascularized mouse corneas induced by suturing. Balb/C mice and C57BL/6 mice expressing green fluorescent protein (GFP) were used to compare modalities based on intrinsic contrast and extrinsic fluorescence contrast. CM based on reflection (CMR), CM based on fluorescence (CMF), and TPM based on intrinsic/extrinsic fluorescence and second harmonic generation (SHG) were compared by imaging the same sections of mouse corneas sequentially in vivo. In normal mouse corneas, CMR visualized corneal cell morphologies with some background noise, and CMF visualized GFP expressing corneal cells clearly. TPM visualized corneal cells and collagen in the stroma based on fluorescence and SHG, respectively. However, in neovascularized mouse corneas, CMR could not resolve cells deep inside the cornea due to high background noise from the effects of increased structural irregularity induced by suturing. CMF and TPM visualized cells and induced vasculature better than CMR because both collect signals from fluorescent cells only. Both CMF and TPM had signal decays with depth due to the structural irregularity, with CMF having faster signal decay than TPM. CMR, CMF, and TPM showed different degrees of image degradation in neovascularized mouse corneas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Stenostomum cf. leucops (Platyhelminthes in Thailand: a surface observation using scanning electron microscopy and phylogenetic analysis based on 18S ribosomal DNA sequences

    Directory of Open Access Journals (Sweden)

    Arin Ngamniyom


    Full Text Available The genus Stenostomum contains small turbellaria that are widely distributed in freshwater environments worldwide. However, there are only rare reports or studies of this genus from Thailand. Therefore, the objective of this study was to report S. cf. leucops in Thailand collected from Pathum Thani Province. The worm morphology and surface topography using scanning electron microscopy were determined. Moreover, the phylogenetic tree of S. cf. leucops was analysed with 17 flatworms based on the 18S ribosomal DNA sequences. The phylogenetic relationship shared a common ancestry of Catenulida species, and S. cf. leucops displayed a monophyletic pattern within Stenostomum spp. The results of the morphological and molecular data are discussed. These results may increase the knowledge of freshwater microturbellarians in Thailand.

  11. 3D Restoration Microscopy Improves Quantification of Enzyme-Labeled Fluorescence-Based Single-Cell Phosphatase Activity in Plankton


    Diaz-de-Quijano, Daniel; Palacios, Pilar; Hornák, Karel; Felip, Marisol


    The ELF or fluorescence-labeled enzyme activity (FLEA) technique is a culture-independent single-cell tool for assessing plankton enzyme activity in close-to-in situ conditions. We demonstrate that single-cell FLEA quantifications based on two-dimensional (2D) image analysis were biased by up to one order of magnitude relative to deconvolved 3D. This was basically attributed to out-of-focus light, and partially to object size. Nevertheless, if sufficient cells were measured (25-40 cells), bia...

  12. Etude des catalyseurs hétérogènes à base de Co en conditions réactives "réalistes" par microscopie électronique in-situ et opérando


    Dembélé , Kassiogé


    In this work, we studied cobalt catalysts used in producing hydrocarbons through the Fischer-Trospch synthesis process, in which their activation, operation and deactivation mechanisms are recorded using in-situ and environmental transmission electron microscopy. An operando methodology was developed by combining electron microscopy-based structural studies in an environmental cell and mass spectrometry analysis of the reacting gases. Using controlled-morphology nanocatalysts we have demonstr...

  13. Determining the structure-mechanics relationships of dense microtubule networks with confocal microscopy and magnetic tweezers-based microrheology. (United States)

    Yang, Yali; Valentine, Megan T


    The microtubule (MT) cytoskeleton is essential in maintaining the shape, strength, and organization of cells. Its spatiotemporal organization is fundamental for numerous dynamic biological processes, and mechanical stress within the MT cytoskeleton provides an important signaling mechanism in mitosis and neural development. This raises important questions about the relationships between structure and mechanics in complex MT structures. In vitro, reconstituted cytoskeletal networks provide a minimal model of cell mechanics while also providing a testing ground for the fundamental polymer physics of stiff polymer gels. Here, we describe our development and implementation of a broad tool kit to study structure-mechanics relationships in reconstituted MT networks, including protocols for the assembly of entangled and cross-linked MT networks, fluorescence imaging, microstructure characterization, construction and calibration of magnetic tweezers devices, and mechanical data collection and analysis. In particular, we present the design and assembly of three neodymium iron boron (NdFeB)-based magnetic tweezers devices optimized for use with MT networks: (1) high-force magnetic tweezers devices that enable the application of nano-Newton forces and possible meso- to macroscale materials characterization; (2) ring-shaped NdFeB-based magnetic tweezers devices that enable oscillatory microrheology measurements; and (3) portable magnetic tweezers devices that enable direct visualization of microscale deformation in soft materials under applied force. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Model Comparison for Breast Cancer Prognosis Based on Clinical Data.

    Directory of Open Access Journals (Sweden)

    Sabri Boughorbel

    Full Text Available We compared the performance of several prediction techniques for breast cancer prognosis, based on AU-ROC performance (Area Under ROC for different prognosis periods. The analyzed dataset contained 1,981 patients and from an initial 25 variables, the 11 most common clinical predictors were retained. We compared eight models from a wide spectrum of predictive models, namely; Generalized Linear Model (GLM, GLM-Net, Partial Least Square (PLS, Support Vector Machines (SVM, Random Forests (RF, Neural Networks, k-Nearest Neighbors (k-NN and Boosted Trees. In order to compare these models, paired t-test was applied on the model performance differences obtained from data resampling. Random Forests, Boosted Trees, Partial Least Square and GLMNet have superior overall performance, however they are only slightly higher than the other models. The comparative analysis also allowed us to define a relative variable importance as the average of variable importance from the different models. Two sets of variables are identified from this analysis. The first includes number of positive lymph nodes, tumor size, cancer grade and estrogen receptor, all has an important influence on model predictability. The second set incudes variables related to histological parameters and treatment types. The short term vs long term contribution of the clinical variables are also analyzed from the comparative models. From the various cancer treatment plans, the combination of Chemo/Radio therapy leads to the largest impact on cancer prognosis.

  15. Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers

    Directory of Open Access Journals (Sweden)

    Niina J. Ronkainen


    Full Text Available Nanotechnology has played a crucial role in the development of biosensors over the past decade. The development, testing, optimization, and validation of new biosensors has become a highly interdisciplinary effort involving experts in chemistry, biology, physics, engineering, and medicine. The sensitivity, the specificity and the reproducibility of biosensors have improved tremendously as a result of incorporating nanomaterials in their design. In general, nanomaterials-based electrochemical immunosensors amplify the sensitivity by facilitating greater loading of the larger sensing surface with biorecognition molecules as well as improving the electrochemical properties of the transducer. The most common types of nanomaterials and their properties will be described. In addition, the utilization of nanomaterials in immunosensors for biomarker detection will be discussed since these biosensors have enormous potential for a myriad of clinical uses. Electrochemical immunosensors provide a specific and simple analytical alternative as evidenced by their brief analysis times, inexpensive instrumentation, lower assay cost as well as good portability and amenability to miniaturization. The role nanomaterials play in biosensors, their ability to improve detection capabilities in low concentration analytes yielding clinically useful data and their impact on other biosensor performance properties will be discussed. Finally, the most common types of electroanalytical detection methods will be briefly touched upon.

  16. Organizing the public health-clinical health interface: theoretical bases. (United States)

    St-Pierre, Michèle; Reinharz, Daniel; Gauthier, Jacques-Bernard


    This article addresses the issue of the interface between public health and clinical health within the context of the search for networking approaches geared to a more integrated delivery of health services. The articulation of an operative interface is complicated by the fact that the definition of networking modalities involves complex intra- and interdisciplinary and intra- and interorganizational systems across which a new transversal dynamics of intervention practices and exchanges between service structures must be established. A better understanding of the situation is reached by shedding light on the rationale underlying the organizational methods that form the bases of the interface between these two sectors of activity. The Quebec experience demonstrates that neither the structural-functionalist approach, which emphasizes remodelling establishment structures and functions as determinants of integration, nor the structural-constructivist approach, which prioritizes distinct fields of practice in public health and clinical health, adequately serves the purpose of networking and integration. Consequently, a theoretical reframing is imperative. In this regard, structuration theory, which fosters the simultaneous study of methods of inter-structure coordination and inter-actor cooperation, paves the way for a better understanding of the situation and, in turn, to the emergence of new integration possibilities.

  17. Clinical advances of nanocarrier-based cancer therapy and diagnostics. (United States)

    Luque-Michel, Edurne; Imbuluzqueta, Edurne; Sebastián, Víctor; Blanco-Prieto, María J


    Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time. Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting. Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new 'targeted drugs', could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.

  18. Clinical results of proton beam therapy for skull base chordoma

    International Nuclear Information System (INIS)

    Igaki, Hiroshi; Tokuuye, Koichi; Okumura, Toshiyuki; Sugahara, Shinji; Kagei, Kenji; Hata, Masaharu; Ohara, Kiyoshi; Hashimoto, Takayuki; Tsuboi, Koji; Takano, Shingo; Matsumura, Akira; Akine, Yasuyuki


    Purpose: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. Methods and materials: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). Results: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. Conclusion: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy

  19. Live-cell Microscopy and Fluorescence-based Measurement of Luminal pH in Intracellular Organelles

    Directory of Open Access Journals (Sweden)

    Li Ma


    Full Text Available Luminal pH is an important functional feature of intracellular organelles. Acidification of the lumen of organelles such as endosomes, lysosomes, and the Golgi apparatus plays a critical role in fundamental cellular processes. As such, measurement of the luminal pH of these organelles has relevance to both basic research and translational research. At the same time, accurate measurement of intraorganellar pH in living cells can be challenging and may be a limiting hurdle for research in some areas. Here, we describe three powerful methods to measure rigorously the luminal pH of different intracellular organelles, focusing on endosomes, lysosomes, and the Golgi apparatus. The described methods are based on live imaging of pH-sensitive fluorescent probes and include: (1 A protocol based on quantitative, ratiometric measurement of endocytosis of pH-sensitive and pH-insensitive fluorescent conjugates of transferrin; (2 A protocol for the use of proteins tagged with a ratiometric variant of the pH-sensitive intrinsically fluorescent protein pHluorin; and (3 A protocol using the fluorescent dye LysoSensor™. We describe necessary reagents, key procedures, and methods and equipment for data acquisition and analysis. Examples of implementation of the protocols are provided for cultured cells derived from a cancer cell line and for primary cultures of mouse hippocampal neurons. In addition, we present strengths and weaknesses of the different described intraorganellar pH measurement methods. These protocols are likely to be of benefit to many researchers, from basic scientists to those conducting translational research with a focus on diseases in patient-derived cells.

  20. Efficiency investigation of an offshore deoiling hydrocyclone using real-time fluorescence- and microscopy-based monitors

    DEFF Research Database (Denmark)

    Hansen, Dennis S.; Bram, Mads Valentin; Yang, Zhenyu


    Offshore oil & gas production is facing an increasing challenge as the water fraction from the production wells rises over time. It is not uncommon that the extracted mixture contains a water-cut of more than 90%. The current North Sea discharge legislation states that the dispersed oil concentra......Offshore oil & gas production is facing an increasing challenge as the water fraction from the production wells rises over time. It is not uncommon that the extracted mixture contains a water-cut of more than 90%. The current North Sea discharge legislation states that the dispersed oil...... concentration in water must be less than 30 parts per million (ppm). Consequently, the discharge ports are sampled two times per day and analyzed using the OSPAR recommended GC-FID method. However, the variations of Oil-in-Water (OiW) concentration between sampling time points are unknown and could exceed...... the regulatory limits. This sampling method is commonly used since the current real-time OiW monitoring technology is still quite open and immature. This work focuses on experimental investigation of reliability and accuracy of selected real-time OiW measuring technologies based on two available commercial...

  1. Quantified abundance of magnetofossils at the Paleocene-Eocene boundary from synchrotron-based transmission X-ray microscopy. (United States)

    Wang, Huapei; Wang, Jun; Chen-Wiegart, Yu-Chen Karen; Kent, Dennis V


    The Paleocene-Eocene boundary (∼55.8 million years ago) is marked by an abrupt negative carbon isotope excursion (CIE) that coincides with an oxygen isotope decrease interpreted as the Paleocene-Eocene thermal maximum. Biogenic magnetite (Fe3O4) in the form of giant (micron-sized) spearhead-like and spindle-like magnetofossils, as well as nano-sized magnetotactic bacteria magnetosome chains, have been reported in clay-rich sediments in the New Jersey Atlantic Coastal Plain and were thought to account for the distinctive single-domain magnetic properties of these sediments. Uncalibrated strong field magnet extraction techniques have been typically used to provide material for scanning and transmission electron microscopic imaging of these magnetic particles, whose concentration in the natural sediment is thus difficult to quantify. In this study, we use a recently developed ultrahigh-resolution, synchrotron-based, full-field transmission X-ray microscope to study the iron-rich minerals within the clay sediment in their bulk state. We are able to estimate the total magnetization concentration of the giant biogenic magnetofossils to be only ∼10% of whole sediment. Along with previous rock magnetic studies on the CIE clay, we suggest that most of the magnetite in the clay occurs as isolated, near-equidimensional nanoparticles, a suggestion that points to a nonbiogenic origin, such as comet impact plume condensates in what may be very rapidly deposited CIE clays.

  2. New microscopy for nanoimaging

    CERN Document Server

    Kinjo, Y; Watanabe, M


    Two types of new microscopy, namely, X-ray contact microscopy (XRCM) in combination with atomic force microscopy (AFM) and X-ray projection microscopy (XRPM) using synchrotron radiation and zone plate optics were used to image the fine structures of human chromosomes. In the XRCM plus AFM system, location of X-ray images on a photoresist has become far easier than that with our previous method using transmission electron microscopy coupled with the replica method. In addition, the images obtained suggested that the conformation of chromatin fiber differs from the current textbook model regarding the architecture of a eukaryotic chromosome. X-ray images with high contrast of the specimens could be obtained with XRPM. The resolution of each microscopy was about 30 and 200-300 nm for XRCM plus AFM and XRPM, respectively. (author)

  3. Microscopy and Image Analysis. (United States)

    McNamara, George; Difilippantonio, Michael; Ried, Thomas; Bieber, Frederick R


    This unit provides an overview of light microscopy, including objectives, light sources, filters, film, and color photography for fluorescence microscopy and fluorescence in situ hybridization (FISH). We believe there are excellent opportunities for cytogeneticists, pathologists, and other biomedical readers, to take advantage of specimen optical clearing techniques and expansion microscopy-we briefly point to these new opportunities. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  4. CARS microscopy for imaging

    International Nuclear Information System (INIS)

    Arzumanyan Grigory; Voskanyan Karine


    Optical microscopy grows in its importance with the development of modern nanotechnology, biotechnology, methods of diagnostics and treatment of most dangerous diseases for mankind. There are several important goals of optical microscopy for biomedical studies among which the next three may be distinguished: fast imaging with high lateral spatial resolution, 3-D sectioning capability and high contrast for chemical selectivity. To meet these specific requirements, various types of both linear and nonlinear optical microscopy were elaborated. (authors)

  5. Fluorescence (Multiwave) Confocal Microscopy. (United States)

    Welzel, J; Kästle, Raphaela; Sattler, Elke C


    In addition to reflectance confocal microscopy, multiwave confocal microscopes with different laser wavelengths in combination with exogenous fluorophores allow fluorescence mode confocal microscopy in vivo and ex vivo. Fluorescence mode confocal microscopy improves the contrast between the epithelium and the surrounding soft tissue and allows the depiction of certain structures, like epithelial tumors, nerves, and glands. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Fabrication and characterization of a nanometer-sized optical fiber electrode based on selective chemical etching for scanning electrochemical/optical microscopy. (United States)

    Maruyama, Kenichi; Ohkawa, Hiroyuki; Ogawa, Sho; Ueda, Akio; Niwa, Osamu; Suzuki, Koji


    We have already reported a method for fabricating ultramicroelectrodes (Suzuki, K. JP Patent, 2004-45394, 2004). This method is based on the selective chemical etching of optical fibers. In this work, we undertake a detailed investigation involving a combination of etched optical fibers with various types of tapered tip (protruding-shape, double- (or pencil-) shape and triple-tapered electrode) and insulation with electrophoretic paint. Our goal is to establish a method for fabricating nanometer-sized optical fiber electrodes with high reproducibility. As a result, we realized pencil-shaped and triple-tapered electrodes that had radii in the nanometer range with high reproducibility. These nanometer-sized electrodes showed well-defined sigmoidal curves and stable diffusion-limited responses with cyclic voltammetry. The pencil-shaped optical fiber, which has a conical tip with a cone angle of 20 degrees , was effective for controlling the electrode radius. The pencil-shaped electrodes had higher reproducibility and smaller electrode radii (r(app) etched optical fiber electrodes. By using a pencil-shaped electrode with a 105-nm radius as a probe, we obtained simultaneous electrochemical and optical images of an implantable interdigitated array electrode. We achieved nanometer-scale resolution with a combination of scanning electrochemical microscopy SECM and optical microscopy. The resolution of the electrochemical and optical images indicated sizes of 300 and 930 nm, respectively. The neurites of living PC12 cells were also successfully imaged on a 1.6-microm scale by using the negative feedback mode of an SECM.

  7. Electron Microscopy Center (EMC) (United States)

    Federal Laboratory Consortium — The Electron Microscopy Center (EMC) at Argonne National Laboratory develops and maintains unique capabilities for electron beam characterization and applies those...

  8. Coherent light microscopy

    CERN Document Server

    Ferraro, Pietro; Zalevsky, Zeev


    This book deals with the latest achievements in the field of optical coherent microscopy. While many other books exist on microscopy and imaging, this book provides a unique resource dedicated solely to this subject. Similarly, many books describe applications of holography, interferometry and speckle to metrology but do not focus on their use for microscopy. The coherent light microscopy reference provided here does not focus on the experimental mechanics of such techniques but instead is meant to provide a users manual to illustrate the strengths and capabilities of developing techniques. Th

  9. Bridging fluorescence microscopy and electron microscopy

    NARCIS (Netherlands)

    Giepmans, Ben N. G.

    Development of new fluorescent probes and fluorescence microscopes has led to new ways to study cell biology. With the emergence of specialized microscopy units at most universities and research centers, the use of these techniques is well within reach for a broad research community. A major

  10. Clinical Holistic Medicine: Applied Consciousness-Based Medicine

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt


    Full Text Available Consciousness-based medicine is our term for a form of medical treatment that works by direct appeal to the consciousness of the patient, in contrast to modern biomedical treatment where drugs are used to affect body chemistry. With this concept, maybe we are (in a sense turning back to the “old medicine”, where the family physician was the all-concerned “old country doctor” who knew the child, the siblings, the parents, the family, and the village. In a series of papers on clinical holistic medicine, we would like to present the classic art of healing, where the physician works mostly with his hands, then show how the modern biomedical physician performs with biochemistry, and finally introduce consciousness-based medicine. Some of our questions will be: If you improve your quality of life, will you also improve your health? Will learning more about yourself bring more purpose in your life? Will finding someone to live with in a loving and mutually respectful relationship improve your health? Scientists and thinkers like Antonovsky, Frankl, Maslow, and Jung have pointed to love as a unique way to coherence in life, and thus to biological order and a better health. Several scientific studies have also suggested that patients who focus on improving their quality of life usually will not follow the general statistics for survival, since somehow other factors are at play, which sometimes you will find referred to as “exceptional”.

  11. Workplace-based clinical leadership training increases willingness to lead. (United States)

    MacPhail, Aleece; Young, Carmel; Ibrahim, Joseph Elias


    The purpose of this paper is to reflect upon a workplace-based, interdisciplinary clinical leadership training programme (CLP) to increase willingness to take on leadership roles in a large regional health-care centre in Victoria, Australia. Strengthening the leadership capacity of clinical staff is an advocated strategy for improving patient safety and quality of care. An interdisciplinary approach to leadership is increasingly emphasised in the literature; however, externally sourced training programmes are expensive and tend to target a single discipline. Appraisal of the first two years of CLP using multiple sourced feedback. A structured survey questionnaire with closed-ended questions graded using a five-point Likert scale was completed by participants of the 2012 programme. Participants from the 2011 programme were followed up for 18 months after completion of the programme to identify the uptake of new leadership roles. A reflective session was also completed by a senior executive staff that supported the implementation of the programme. Workplace-based CLP is a low-cost and multidisciplinary alternative to externally sourced leadership courses. The CLP significantly increased willingness to take on leadership roles. Most participants (93 per cent) reported that they were more willing to take on a leadership role within their team. Fewer were willing to lead at the level of department (79 per cent) or organisation (64 per cent). Five of the 11 participants from the 2011 programme had taken on a new leadership role 18 months later. Senior executive feedback was positive especially around the engagement and building of staff confidence. They considered that the CLP had sufficient merit to support continuation for at least another two years. Integrating health-care professionals into formal and informal leadership roles is essential to implement organisational change as part of the drive to improve the safety and quality of care for patients and service users

  12. Quantitative composition determination at the atomic level using model-based high-angle annular dark field scanning transmission electron microscopy

    International Nuclear Information System (INIS)

    Martinez, G.T.; Rosenauer, A.; De Backer, A.; Verbeeck, J.; Van Aert, S.


    High angle annular dark field scanning transmission electron microscopy (HAADF STEM) images provide sample information which is sensitive to the chemical composition. The image intensities indeed scale with the mean atomic number Z. To some extent, chemically different atomic column types can therefore be visually distinguished. However, in order to quantify the atomic column composition with high accuracy and precision, model-based methods are necessary. Therefore, an empirical incoherent parametric imaging model can be used of which the unknown parameters are determined using statistical parameter estimation theory (Van Aert et al., 2009, [1]). In this paper, it will be shown how this method can be combined with frozen lattice multislice simulations in order to evolve from a relative toward an absolute quantification of the composition of single atomic columns with mixed atom types. Furthermore, the validity of the model assumptions are explored and discussed. - Highlights: • A model-based method is extended from a relative toward an absolute quantification of chemical composition of single atomic columns from HAADF HRSTEM images. • The methodology combines statistical parameter estimation theory with frozen lattice multislice simulations to quantify chemical composition atomic column by atomic column. • Validity and limitations of this model-based method are explored and discussed. • Quantification results obtained for a complex structure show agreement with EDX refinement

  13. Connecting clinical and actuarial prediction with rule-based methods

    NARCIS (Netherlands)

    Fokkema, M.; Smits, N.; Kelderman, H.; Penninx, B.W.J.H.


    Meta-analyses comparing the accuracy of clinical versus actuarial prediction have shown actuarial methods to outperform clinical methods, on average. However, actuarial methods are still not widely used in clinical practice, and there has been a call for the development of actuarial prediction

  14. HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.

    Directory of Open Access Journals (Sweden)

    Daniel J Kyabayinze

    Full Text Available Intermittent screening and treatment (IST of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp, where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined.We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs targeting histidine-rich protein 2 (HRP2 and parasite lactate dehydrogenase (pLDH and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings.The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined.

  15. Building a web-based CAD server for clinical use, evaluation, and incremental learning. Implementation of analysis function based on execution result and clinical feedback

    International Nuclear Information System (INIS)

    Nomura, Yukihiro; Hayashi, Naoto; Masutani, Yoshitaka; Yoshikawa, Takeharu; Nemoto, Mitsutaka; Hanaoka, Shouhei; Maeda, Eriko; Ohtomo, Kuni; Miki, Soichiro


    Development of clinical image analysis software such as computer-assisted detection/diagnosis (CAD) involves a cycle of algorithm development, software implementation, clinical use, refinement of algorithm and software based on feedback. This cycle is expected to accelerate development of CAD software. We have been building a web-based CAD server that enables radiologists to use CAD software and to give feedback in clinical environment. The platform has been utilized in our hospital for 16 months, and more than 2,000 cases of feedback data have been accumulated. In this report, we introduce additional functions for performance evaluation based on executed results of CAD software and clinical feedback. (author)

  16. Enhanced Optoelectronic Performance of a Passivated Nanowire-Based Device: Key Information from Real-Space Imaging Using 4D Electron Microscopy

    KAUST Repository

    Khan, Jafar Iqbal


    Managing trap states and understanding their role in ultrafast charge-carrier dynamics, particularly at surface and interfaces, remains a major bottleneck preventing further advancements and commercial exploitation of nanowire (NW)-based devices. A key challenge is to selectively map such ultrafast dynamical processes on the surfaces of NWs, a capability so far out of reach of time-resolved laser techniques. Selective mapping of surface dynamics in real space and time can only be achieved by applying four-dimensional scanning ultrafast electron microscopy (4D S-UEM). Charge carrier dynamics are spatially and temporally visualized on the surface of InGaN NW arrays before and after surface passivation with octadecylthiol (ODT). The time-resolved secondary electron images clearly demonstrate that carrier recombination on the NW surface is significantly slowed down after ODT treatment. This observation is fully supported by enhancement of the performance of the light emitting device. Direct observation of surface dynamics provides a profound understanding of the photophysical mechanisms on materials\\' surfaces and enables the formulation of effective surface trap state management strategies for the next generation of high-performance NW-based optoelectronic devices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Transmission electron microscopy for elucidating the impact of silver-based treatments (ionic silver versus nanosilver-containing coating) on the model yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Despax, B; Saulou, C; Raynaud, P [Universite de Toulouse, UPS, INPT, LAPLACE, 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); Datas, L [Universite de Toulouse, UPS, INPT, CIRIMAT, 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); Mercier-Bonin, M [Universite de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, F-31077 Toulouse (France)


    After exposure to ionic silver or nanosilver-containing plasma coating, the same visual aspect of scanning transmission electron microscopy (STEM) images was observed for the model yeast Saccharomyces cerevisiae. The main common feature was the presence of electron-dense nodules all over the cell. However, high resolution TEM (HRTEM), STEM, energy dispersive x-ray microanalysis spectroscopy (EDS) and electron microdiffraction revealed some striking differences. Regarding ionic silver exposure, the formation of electron-dense nodules was related to the Ag{sup +} reactivity towards sulfur-containing compounds to form clusters with Ag{sub 2}S-like structures, together with the production of a few silver nanocrystals, mainly at the cell wall periphery. For nanosilver-based treatment, some sulfur-containing silver clusters preferentially located at the cell wall periphery were detected, together with nodules composed of silver, sulfur and phosphorus all over the cell. In both silver-based treatments, nitrogen and silver signals overlapped, confirming the affinity of silver entities for proteinaceous compounds. Moreover, in the case of nanosilver, interactions of silver with phosphorus-containing subcellular structures were indicated.

  18. Investigations on chloride-induced high temperature corrosion of iron-, nickel-, cobalt-base alloys by scanning electron microscopy and energy dispersive X-ray microspot analysis

    International Nuclear Information System (INIS)

    Ross, W.; Umland, F.


    The direct oxidation at 900 0 C in air and the corrosion of alloys in air after short exposure to chloride have been compared under identical conditions. Chloride destroys the original oxide layers by recristallisation and modifies the following scale growing in such a manner that no firmly sticking layers can be rebuilt. After a chloride induction therefore all other following corrosions will be enhanced. Experiments in a closed system, a so called transport furnace, showed that the chloride also acts as a gas phase carrier transporting firstly the oxide layer, under reducing conditions metals, too, as volatile chloro metal gas complexes in this case from hot to cold region of the furnace. Cobalt base alloys are less attacked than iron or nickel base alloys. As chloride is not found implicitly on the treated surface the identification of the chloride induced corrosion is difficult. However the scanning electron microscopy combined with quantitative energy dispersive X-ray analysis has been proved as an appropriate method for early detection. As the phenomena depend on the type of alloy, respectively, an illustration and interpretation catalogue is necessary. (orig.) [de

  19. Chemical compound-based direct reprogramming for future clinical applications (United States)

    Takeda, Yukimasa; Harada, Yoshinori; Yoshikawa, Toshikazu; Dai, Ping


    Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy. PMID:29739872

  20. Clinical dosimetry in photon radiotherapy. A Monte Carlo based investigation

    International Nuclear Information System (INIS)

    Wulff, Joerg


    Practical clinical dosimetry is a fundamental step within the radiation therapy process and aims at quantifying the absorbed radiation dose within a 1-2% uncertainty. To achieve this level of accuracy, corrections are needed for calibrated and air-filled ionization chambers, which are used for dose measurement. The procedures of correction are based on cavity theory of Spencer-Attix and are defined in current dosimetry protocols. Energy dependent corrections for deviations from calibration beams account for changed ionization chamber response in the treatment beam. The corrections applied are usually based on semi-analytical models or measurements and are generally hard to determine due to their magnitude of only a few percents or even less. Furthermore the corrections are defined for fixed geometrical reference-conditions and do not apply to non-reference conditions in modern radiotherapy applications. The stochastic Monte Carlo method for the simulation of radiation transport is becoming a valuable tool in the field of Medical Physics. As a suitable tool for calculation of these corrections with high accuracy the simulations enable the investigation of ionization chambers under various conditions. The aim of this work is the consistent investigation of ionization chamber dosimetry in photon radiation therapy with the use of Monte Carlo methods. Nowadays Monte Carlo systems exist, which enable the accurate calculation of ionization chamber response in principle. Still, their bare use for studies of this type is limited due to the long calculation times needed for a meaningful result with a small statistical uncertainty, inherent to every result of a Monte Carlo simulation. Besides heavy use of computer hardware, techniques methods of variance reduction to reduce the needed calculation time can be applied. Methods for increasing the efficiency in the results of simulation were developed and incorporated in a modern and established Monte Carlo simulation environment

  1. Limits to magnetic resonance microscopy

    International Nuclear Information System (INIS)

    Glover, Paul; Mansfield, Peter


    The last quarter of the twentieth century saw the development of magnetic resonance imaging (MRI) grow from a laboratory demonstration to a multi-billion dollar worldwide industry. There is a clinical body scanner in almost every hospital of the developed nations. The field of magnetic resonance microscopy (MRM), after mostly being abandoned by researchers in the first decade of MRI, has become an established branch of the science. This paper reviews the development of MRM over the last decade with an emphasis on the current state of the art. The fundamental principles of imaging and signal detection are examined to determine the physical principles which limit the available resolution. The limits are discussed with reference to liquid, solid and gas phase microscopy. In each area, the novel approaches employed by researchers to push back the limits of resolution are discussed. Although the limits to resolution are well known, the developments and applications of MRM have not reached their limit. (author)

  2. Monitoring additive manufacturing based products in clinical trials

    NARCIS (Netherlands)

    Marinakis, Yorgos; Harms, Rainer; Walsh, Steven Thomas


    Under U.S. federal regulation 31 CFR §312, medical interventions must report on a series of clinical trials phases before being submitted for approval for release to the U.S. market. Clinical trials are now being performed on medical interventions that were constructed through additive

  3. Teaching clinical reasoning: case-based and coached. (United States)

    Kassirer, Jerome P


    Optimal medical care is critically dependent on clinicians' skills to make the right diagnosis and to recommend the most appropriate therapy, and acquiring such reasoning skills is a key requirement at every level of medical education. Teaching clinical reasoning is grounded in several fundamental principles of educational theory. Adult learning theory posits that learning is best accomplished by repeated, deliberate exposure to real cases, that case examples should be selected for their reflection of multiple aspects of clinical reasoning, and that the participation of a coach augments the value of an educational experience. The theory proposes that memory of clinical medicine and clinical reasoning strategies is enhanced when errors in information, judgment, and reasoning are immediately pointed out and discussed. Rather than using cases artificially constructed from memory, real cases are greatly preferred because they often reflect the false leads, the polymorphisms of actual clinical material, and the misleading test results encountered in everyday practice. These concepts foster the teaching and learning of the diagnostic process, the complex trade-offs between the benefits and risks of diagnostic tests and treatments, and cognitive errors in clinical reasoning. The teaching of clinical reasoning need not and should not be delayed until students gain a full understanding of anatomy and pathophysiology. Concepts such as hypothesis generation, pattern recognition, context formulation, diagnostic test interpretation, differential diagnosis, and diagnostic verification provide both the language and the methods of clinical problem solving. Expertise is attainable even though the precise mechanisms of achieving it are not known.

  4. The Research of Clinical Decision Support System Based on Three-Layer Knowledge Base Model

    Directory of Open Access Journals (Sweden)

    Yicheng Jiang


    Full Text Available In many clinical decision support systems, a two-layer knowledge base model (disease-symptom of rule reasoning is used. This model often does not express knowledge very well since it simply infers disease from the presence of certain symptoms. In this study, we propose a three-layer knowledge base model (disease-symptom-property to utilize more useful information in inference. The system iteratively calculates the probability of patients who may suffer from diseases based on a multisymptom naive Bayes algorithm, in which the specificity of these disease symptoms is weighted by the estimation of the degree of contribution to diagnose the disease. It significantly reduces the dependencies between attributes to apply the naive Bayes algorithm more properly. Then, the online learning process for parameter optimization of the inference engine was completed. At last, our decision support system utilizing the three-layer model was formally evaluated by two experienced doctors. By comparisons between prediction results and clinical results, our system can provide effective clinical recommendations to doctors. Moreover, we found that the three-layer model can improve the accuracy of predictions compared with the two-layer model. In light of some of the limitations of this study, we also identify and discuss several areas that need continued improvement.

  5. Clinical use of Skype: a review of the evidence base. (United States)

    Armfield, Nigel R; Gray, Leonard C; Smith, Anthony C


    Skype is a popular and free software application that allows PCs and mobile devices to be used for video communication over the Internet. We reviewed the literature to determine whether the clinical use of Skype is supported by evidence. One small (n = 7) controlled clinical trial had assessed the effect of nursing communication using Skype on elderly patients with dementia and their carers. However, we were unable to identify any large, well-designed studies which had formally evaluated the safety, clinical effectiveness, security and privacy of Skype for the routine delivery of patient care. While there were many case reports and small studies, no firm evidence either in favour of, or against the use of Skype for clinical telehealth was found. The risks and benefits of using Skype for clinical purposes are not known.

  6. Analysis of degradation in nickel-based alloys using focused ion beam imaging and specimen preparation combined with analytical electron microscopy

    International Nuclear Information System (INIS)

    Phaneuf, M.W.; Botton, G.A.


    Focused ion beam (FIB) microscopes have become well-established in the semiconductor industry during the past decade, and are rapidly gaining attention in the field of materials science, both as a tool for producing site specific, parallel sided transmission electron microscope (TEM) specimens and as stand alone specimen preparation and imaging systems. FIB secondary electron imaging (SEI) of nickel-based alloys, such as commercially produced Alloy 600 (approximately Ni 15Cr 10Fe 0.5C), has been demonstrated to show a high degree of sensitivity to the presence of deformation in the alloy, and FIB secondary ion imaging (SII) is particularly useful for identifying the presence of grain boundary corrosion, as secondary ion yields from metallic specimens can increase by three orders of magnitude in the presence of oxygen. This 'oxygen enhanced yield', makes FIB SII ideal for detection of corrosion at grain boundaries down to thicknesses of only a few tens of nanometers. Historically, while TEM has been considered the tool of choice for high resolution chemical and crystallographic analysis of specimens, the technique has suffered from difficulties in producing suitable samples from site-specific areas with a high probability of success. The advent of FIB specimen preparation for TEM has largely changed that. FIB imaging can be combined with FIB 'nano-machining' techniques to produce site-specific, parallel sided TEM specimens well-suited to analytical electron microscopy (AEM) analyses in the TEM, including electron energy loss spectroscopy (EELS), energy dispersive x-ray spectroscopy (EDX) and electron diffraction. When combined with new FIB-based methodologies for surveying large areas to exactly select the regions of interest, such as crack tips or the maximum extent of penetration of intergranular attack (IGA), subsequent FIB TEM specimen preparation and TEM analysis unite to produce a powerful tool to study these phenomena. Examples of these applications of FIB

  7. Magnetic force microscopy : Quantitative issues in biomaterials

    NARCIS (Netherlands)

    Passeri, D.; Dong, C.; Reggente, M.; Angeloni, L.; Barteri, M.; Scaramuzzo, F.A.; De Angelis, F.; Marinelli, F.; Antonelli, F.; Rinaldi, F.; Marianecci, C.; Carafa, M.; Sorbo, A.; Sordi, D.; Arends, I.W.C.E.; Rossi, M.


    Magnetic force microscopy (MFM) is an atomic force microscopy (AFM) based technique in which an AFM tip with a magnetic coating is used to probe local magnetic fields with the typical AFM spatial resolution, thus allowing one to acquire images reflecting the local magnetic properties of the samples

  8. Confocal Raman microscopy

    CERN Document Server

    Dieing, Thomas; Hollricher, Olaf


    This second edition provides a cutting-edge overview of physical, technical and scientific aspects related to the widely used analytical method of confocal Raman microscopy. The book includes expanded background information and adds insights into how confocal Raman microscopy, especially 3D Raman imaging, can be integrated with other methods to produce a variety of correlative microscopy combinations. The benefits are then demonstrated and supported by numerous examples from the fields of materials science, 2D materials, the life sciences, pharmaceutical research and development, as well as the geosciences.

  9. Scanning transmission X-ray microscopy probe for in situ mechanism study of graphene-oxide-based resistive random access memory. (United States)

    Nho, Hyun Woo; Kim, Jong Yun; Wang, Jian; Shin, Hyun-Joon; Choi, Sung-Yool; Yoon, Tae Hyun


    Here, an in situ probe for scanning transmission X-ray microscopy (STXM) has been developed and applied to the study of the bipolar resistive switching (BRS) mechanism in an Al/graphene oxide (GO)/Al resistive random access memory (RRAM) device. To perform in situ STXM studies at the C K- and O K-edges, both the RRAM junctions and the I0 junction were fabricated on a single Si3N4 membrane to obtain local XANES spectra at these absorption edges with more delicate I0 normalization. Using this probe combined with the synchrotron-based STXM technique, it was possible to observe unique chemical changes involved in the BRS process of the Al/GO/Al RRAM device. Reversible oxidation and reduction of GO induced by the externally applied bias voltages were observed at the O K-edge XANES feature located at 538.2 eV, which strongly supported the oxygen ion drift model that was recently proposed from ex situ transmission electron microscope studies.

  10. Real-time deflection and friction force imaging by bimorph-based resonance-type high-speed scanning force microscopy in the contact mode. (United States)

    Cai, Wei; Fan, Haiyun; Zhao, Jianyong; Shang, Guangyi


    We report herein an alternative high-speed scanning force microscopy method in the contact mode based on a resonance-type piezoelectric bimorph scanner. The experimental setup, the modified optical beam deflection scheme suitable for smaller cantilevers, and a high-speed control program for simultaneous data capture are described in detail. The feature of the method is that the deflection and friction force images of the sample surface can be obtained simultaneously in real time. Images of various samples (e.g., a test grating, a thin gold film, and fluorine-doped tin oxide-coated glass slides) are acquired successfully. The imaging rate is 25 frames per second, and the average scan speed reaches a value of approximately 2.5 cm/s. The method combines the advantages of both observing the dynamic processes of the sample surface and monitoring the frictional properties on the nanometer scale. 07.79.Lh; 07.79.Sp; 68.37.Ps.

  11. Analysis of the dislocation content in a deformed Co-based superalloy by transmission electron microscopy and X-ray diffraction

    International Nuclear Information System (INIS)

    Breuer, D.; Klimanek, P.; Muehle, U.; Martin, U.


    The present paper compares the dislocation densities as determined in a Co-based superalloy (CoNi22Cr22W14) after creep and tensile deformation by Transmission Electron Microscopy (TEM) and X-ray profile analysis (XRD). After creep tests the dislocation densities obtained by both methods are in good agreement, which is the result of a nearly homogeneous dislocation distribution. The relationship between the dislocation density and the flow stress meets the Taylor equation. After tensile deformation the dislocation densities determined by TEM and XRD differ systematically from each other, but in both cases also a Taylor relationship can be obtained. The constant α of the dislocation interaction derived by TEM is much larger than in the creep tests and also than that of the XRD, which agrees well with the creep data. The difference between the TEM and the XRD results is the consequence of the dislocation cell structure much more developed in the tensile specimens, which leads to an underestimation of the dislocation density in TEM because of overweighting the cell interior. By fitting the Fourier coefficients of the X-ray diffraction line shapes with a bimodal distribution of the defect content (composite model), dislocation densities of the cell interior can be estimated that correspond well to the TEM data. (orig.)

  12. Methyldibromo glutaronitrile: clinical experience and exposure-based risk assessment. (United States)

    Zachariae, Claus; Rastogi, Suresh; Devantier, Charlotte; Menné, Torkil; Johansen, Jeanne Duus


    In the year 2000, the level of methyldibromo glutaronitrile (MDGN) allergy in dermatology clinics in Europe exceeded the level of allergies to all other preservatives, with a prevalence of 3.5%. In the present study, cases of primary sensitization and elicitation to MDGN due to cosmetic products were collected over an 8-month period at the Department of Dermatology, Gentofte University Hospital. The aim was to identify the products related to hand eczema, assess exposure to MDGN in these products and relate the findings to results from a newly developed updated risk assessment model for contact allergy. Out of 24 patients with a positive patch test to MDGN, 17 patients with hand eczema were identified. In 11 of these patients, cosmetic products used in relation to the onset of the disease were shown to contain MDGN (65%). In 8 of these 11 cases, primary sensitization was probable, 5 due to hand/body lotions and 3 due to lotions and/or liquid hand soap. Chemical analysis of 12 products showed that lotions contained 149-390 ppm of MDGN, liquid hand soap 144-399 ppm, a rinsing cream 293 ppm and shampoos 78-79 ppm. The shampoo exposure was not of certain relevance to the eczema. Applying the newly developed updated risk assessment model showed that the concentrations of MDGN in lotions of 149-390 ppm exceeded the calculated maximum acceptable exposure level for MDGN, which would be expected to lead to sensitization in consumers using such products, as seen in the current study. The present cases and updated exposure-based risk assessment process add to the evidence and need for re-defining safe-use concentrations of MDGN in cosmetic products.

  13. Multiphoton microscopy based cryo-imaging of inflated frozen human lung sections at -60°C in healthy and COPD lungs (United States)

    Abraham, Thomas; Kayra, Damian; Zhang, Angela; Suzuki, Masaru; McDonough, John; Elliott, W. M.; Cooper, Joel D.; Hogg, James C.


    Lung is a complex gas exchanger with interfacial area (where the gas exchange takes place) is about the size of a tennis court. Respiratory function is linked to the biomechanical stability of the gas exchange or alveolar regions which directly depends on the spatial distributions of the extracellular matrix fibers such fibrillar collagens and elastin fibers. It is very important to visualize and quantify these fibers at their native and inflated conditions to have correct morphometric information on differences between control and diseased states. This can be only achieved in the ex vivo states by imaging directly frozen lung specimens inflated to total lung capacity. Multiphoton microscopy, which uses ultra-short infrared laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from endogenously fluorescent proteins (e.g. elastin) and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens in fresh human lung tissues [J. Struct. Biol. (2010)171,189-196]. Here we report for the first time 3D image data obtained directly from thick frozen inflated lung specimens (~0.7- 1.0 millimeter thick) visualized at -60°C without prior fixation or staining in healthy and diseased states. Lung specimens donated for transplantation and released for research when no appropriate recipient was identified served as controls, and diseased lung specimens donated for research by patients receiving lung transplantation for very severe COPD (n=4) were prepared as previously described [N. Engl. J. Med. (2011) 201, 1567]. Lung slices evenly spaced between apex and base were examined using multiphoton microscopy while maintained at -60°C using a temperature controlled cold stage with a temperature resolution of 0.1°C. Infrared femto-second laser pulses tuned to 880nm, dry microscopic objectives, and non-de-scanned detectors/spectrophotometer located in the reflection geometry were

  14. 3D restoration microscopy improves quantification of enzyme-labeled fluorescence-based single-cell phosphatase activity in plankton. Cytometry Part A, 85A: 841–853

    Czech Academy of Sciences Publication Activity Database

    Diaz-de-Quijano, D.; Palacios, P.; Horňák, Karel; Felip, M.

    85A, č. 10 (2014), s. 841-853 ISSN 1552-4922 Institutional support: RVO:60077344 Keywords : 3D fluorescence microscopy * deconvolution * ELF phosphate * phosphatase activity * phytoplankton Subject RIV: EE - Microbiology, Virology Impact factor: 2.928, year: 2014

  15. Ultrafast scanning tunneling microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Botkin, D.A. [California Univ., Berkeley, CA (United States). Dept. of Physics]|[Lawrence Berkeley Lab., CA (United States)


    I have developed an ultrafast scanning tunneling microscope (USTM) based on uniting stroboscopic methods of ultrafast optics and scanned probe microscopy to obtain nanometer spatial resolution and sub-picosecond temporal resolution. USTM increases the achievable time resolution of a STM by more than 6 orders of magnitude; this should enable exploration of mesoscopic and nanometer size systems on time scales corresponding to the period or decay of fundamental excitations. USTM consists of a photoconductive switch with subpicosecond response time in series with the tip of a STM. An optical pulse from a modelocked laser activates the switch to create a gate for the tunneling current, while a second laser pulse on the sample initiates a dynamic process which affects the tunneling current. By sending a large sequence of identical pulse pairs and measuring the average tunnel current as a function of the relative time delay between the pulses in each pair, one can map the time evolution of the surface process. USTM was used to measure the broadband response of the STM`s atomic size tunnel barrier in frequencies from tens to hundreds of GHz. The USTM signal amplitude decays linearly with the tunnel junction conductance, so the spatial resolution of the time-resolved signal is comparable to that of a conventional STM. Geometrical capacitance of the junction does not appear to play an important role in the measurement, but a capacitive effect intimately related to tunneling contributes to the measured signals and may limit the ultimate resolution of the USTM.

  16. Analysis of quality data based on national clinical databases

    DEFF Research Database (Denmark)

    Utzon, Jan; Petri, A.L.; Christophersen, S.


    There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...... extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which...... is understandable to readers without specialised knowledge of statistics Udgivelsesdato: 2009/9/14...

  17. Analysis of quality data based on national clinical databases

    DEFF Research Database (Denmark)

    Utzon, Jan; Petri, A.L.; Christophersen, S.


    extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which......There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which...

  18. Development of a Primary Care-Based Clinic to Support Adults With a History of Childhood Cancer: The Tactic Clinic. (United States)

    Overholser, Linda S; Moss, Kerry M; Kilbourn, Kristin; Risendal, Betsy; Jones, Alison F; Greffe, Brian S; Garrington, Timothy; Leonardi-Warren, Kristin; Yamashita, Traci E; Kutner, Jean S


    Describe the development and evolution of a primary-care-based, multidisciplinary clinic to support the ongoing care of adult survivors of childhood cancer. A consultative clinic for adult survivors of childhood cancer has been developed that is located in an adult, academic internal medicine setting and is based on a long-term follow-up clinic model available at Children's Hospital Colorado. The clinic opened in July 2008. One hundred thirty-five patients have been seen as of April 2014. Referrals and clinic capacity have gradually increased over time, and a template has been developed in the electronic medical record to help facilitate completion of individualized care plan letters. A primary care-based, multidisciplinary consultative clinic for adults with a history of childhood cancer survivor is feasible and actively engages adult primary care resources to provide risk-based care for long-term pediatric cancer survivors. This model of care planning can help support adult survivors of pediatric cancer and their primary care providers in non-academic, community settings as well. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. International Multidisciplinary Microscopy Congress

    CERN Document Server

    Oral, Ahmet; Ozer, Mehmet; InterM; INTERM2013


    The International Multidisciplinary Microscopy Congress (INTERM2013) was organized on October 10-13, 2013. The aim of the congress was to bring together scientists from various branches to discuss the latest advances in the field of microscopy. The contents of the congress have been broadened to a more "interdisciplinary" scope, so as to allow all scientists working on related subjects to participate and present their work. These proceedings include 39 peer-reviewed technical papers, submitted by leading academic and research institutions from over 12 countries and representing some of the most cutting-edge research available. The 39 papers are grouped into the following sections: - Applications of Microscopy in the Physical Sciences - Applications of Microscopy in the Biological Sciences

  20. Stochastic Optical Reconstruction Microscopy (STORM). (United States)

    Xu, Jianquan; Ma, Hongqiang; Liu, Yang


    Super-resolution (SR) fluorescence microscopy, a class of optical microscopy techniques at a spatial resolution below the diffraction limit, has revolutionized the way we study biology, as recognized by the Nobel Prize in Chemistry in 2014. Stochastic optical reconstruction microscopy (STORM), a widely used SR technique, is based on the principle of single molecule localization. STORM routinely achieves a spatial resolution of 20 to 30 nm, a ten-fold improvement compared to conventional optical microscopy. Among all SR techniques, STORM offers a high spatial resolution with simple optical instrumentation and standard organic fluorescent dyes, but it is also prone to image artifacts and degraded image resolution due to improper sample preparation or imaging conditions. It requires careful optimization of all three aspects-sample preparation, image acquisition, and image reconstruction-to ensure a high-quality STORM image, which will be extensively discussed in this unit. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  1. Evidenced-based review of clinical studies on periodontics. (United States)


    Periodontal diseases have several implications for the practice of endodontics. First, advanced periodontitis often has direct implications for the long-term prognosis of the case and requires careful evaluation and coordinated treatment of both the periodontic and endodontic diseases. Second, the potential for functional interactions between odontogenic pathoses and marginal periodontitis requires careful collection of clinical observations and monitoring the outcome of various treatments. In this section, we provide an analysis of recent clinical studies in this area.

  2. Fungal keratitis - improving diagnostics by confocal microscopy

    DEFF Research Database (Denmark)

    Nielsen, Esben; Heegaard, S; Prause, J U


    Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological...... analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience...... with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12...

  3. A SOA-Based Platform to Support Clinical Data Sharing

    Directory of Open Access Journals (Sweden)

    R. Gazzarata


    Full Text Available The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions.

  4. Impact of clinical pharmacist-based parenteral nutrition service for bone marrow transplantation patients: a randomized clinical trial. (United States)

    Mousavi, Maryam; Hayatshahi, Alireza; Sarayani, Amir; Hadjibabaie, Molouk; Javadi, Mohammadreza; Torkamandi, Hassan; Gholami, Kheirollah; Ghavamzadeh, Ardeshir


    Parenteral nutrition (PN) is a well-documented supportive care which maintains the nutritional status of patients. Clinical pharmacists are often involved in providing PN services; however, few studies have investigated the effect of a clinical pharmacy-based PN service in resource-limited settings. We designed a randomized clinical trial to compare the clinical pharmacist-based PN service (intervention group) with the conventional method (control group) for adult patients undergoing hematopoietic stem cell transplantation in Shariati Hospital, Tehran, Iran (2011-2012). In the intervention group, the clinical pharmacists implemented standard guidelines of nutrition support. The conventional method was a routine nutrition support protocol which was pursued for all patients in the bone marrow transplantation wards. Main study outcomes included nutritional status (weight, albumin, total protein, pre-albumin, and nitrogen balance), length of hospital stay, time to engraftment, rate of graft versus host disease, and mortality rate. Patients were followed for 3 months. Fifty-nine patients were randomly allocated to a study group. The overall intake (oral and parenteral) in the control group was significantly lower than standard daily needed calories (P nutritional outcomes were either preserved or improved in the intervention group while the nutritional status in the control group was deteriorated (P values nutrition support service significantly improved nutritional status and clinical outcomes in comparison with the suboptimal conventional method. Future studies should assess the cost effectiveness of clinical pharmacists' PN services.

  5. Automated quantitative cytological analysis using portable microfluidic microscopy. (United States)

    Jagannadh, Veerendra Kalyan; Murthy, Rashmi Sreeramachandra; Srinivasan, Rajesh; Gorthi, Sai Siva


    In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Recognition and Evaluation of Clinical Section Headings in Clinical Documents Using Token-Based Formulation with Conditional Random Fields

    Directory of Open Access Journals (Sweden)

    Hong-Jie Dai


    Full Text Available Electronic health record (EHR is a digital data format that collects electronic health information about an individual patient or population. To enhance the meaningful use of EHRs, information extraction techniques have been developed to recognize clinical concepts mentioned in EHRs. Nevertheless, the clinical judgment of an EHR cannot be known solely based on the recognized concepts without considering its contextual information. In order to improve the readability and accessibility of EHRs, this work developed a section heading recognition system for clinical documents. In contrast to formulating the section heading recognition task as a sentence classification problem, this work proposed a token-based formulation with the conditional random field (CRF model. A standard section heading recognition corpus was compiled by annotators with clinical experience to evaluate the performance and compare it with sentence classification and dictionary-based approaches. The results of the experiments showed that the proposed method achieved a satisfactory F-score of 0.942, which outperformed the sentence-based approach and the best dictionary-based system by 0.087 and 0.096, respectively. One important advantage of our formulation over the sentence-based approach is that it presented an integrated solution without the need to develop additional heuristics rules for isolating the headings from the surrounding section contents.

  7. [Accreditation of clinical laboratories based on ISO standards]. (United States)

    Kawai, Tadashi


    International Organization for Standardization (ISO) have published two international standards (IS) to be used for accreditation of clinical laboratories; ISO/IEC 17025:1999 and ISO 15189:2003. Any laboratory accreditation body must satisfy the requirements stated in ISO/IEC Guide 58. In order to maintain the quality of the laboratory accreditation bodies worldwide, the International Laboratory Accreditation Cooperation (ILAC) has established the mutual recognition arrangement (MRA). In Japan, the International Accreditation Japan (IAJapan) and the Japan Accreditation Board for Conformity Assessment (JAB) are the members of the ILAC/MRA group. In 2003, the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the JAB have established the Development Committee of Clinical Laboratory Accreditation Program (CLAP), in order to establish the CLAP, probably starting in 2005.

  8. A case-based assistant for clinical psychiatry expertise.


    Bichindaritz, I.


    Case-based reasoning is an artificial intelligence methodology for the processing of empirical knowledge. Recent case-based reasoning systems also use theoretic knowledge about the domain to constrain the case-based reasoning. The organization of the memory is the key issue in case-based reasoning. The case-based assistant presented here has two structures in memory: cases and concepts. These memory structures permit it to be as skilled in problem-solving tasks, such as diagnosis and treatmen...

  9. Proximal design for a multimodality endoscope with multiphoton microscopy, optical coherence microscopy and visual modalities (United States)

    Kiekens, Kelli C.; Talarico, Olivia; Barton, Jennifer K.


    A multimodality endoscope system has been designed for early detection of ovarian cancer. Multiple illumination and detection systems must be integrated in a compact, stable, transportable configuration to meet the requirements of a clinical setting. The proximal configuration presented here supports visible light navigation with a large field of view and low resolution, high resolution multiphoton microscopy (MPM), and high resolution optical coherence microscopy (OCM). All modalities are integrated into a single optical system in the endoscope. The system requires two light sources: a green laser for visible light navigation and a compact fiber based femtosecond laser for MPM and OCM. Using an inline wavelength division multiplexer, the two sources are combined into a single mode fiber. To accomplish OCM, a fiber coupler is used to separate the femtosecond laser into a reference arm and signal arm. The reflected reference arm and the signal from the sample are interfered and wavelength separated by a reflection grating and detected using a linear array. The MPM signal is collimated and goes through a series of filters to separate the 2nd and 3rd harmonics as well as twophoton excitation florescence (2PEF) and 3PEF. Each signal is independently detected on a photo multiplier tube and amplified. The visible light is collected by multiple high numerical aperture fibers at the endoscope tip which are bundled into one SMA adapter at the proximal end and connected to a photodetector. This integrated system design is compact, efficient and meets both optical and mechanical requirements for clinical applications.

  10. Electron microscopy of GaAs-based structures with InAs and As quantum dots separated by an AlAs barrier

    International Nuclear Information System (INIS)

    Nevedomskiy, V. N.; Bert, N. A.; Chaldyshev, V. V.; Preobrazhenskiy, V. V.; Putyato, M. A.; Semyagin, B. R.


    Electron microscopy studies of GaAs-based structures grown by molecular beam epitaxy and containing arrays of semiconductor InAs quantum dots and metal As quantum dots are performed. The array of InAs quantum dots is formed by the Stranski-Krastanov mechanism and consists of vertically coupled pairs of quantum dots separated by a GaAs spacer 10 nm thick. To separate the arrays of semiconductor and metal quantum dots and to prevent diffusion-induced mixing, the array of InAs quantum dots is overgrown with an AlAs barrier layer 5 or 10 nm thick, after which a GaAs layer is grown at a comparatively low temperature (180°C). The array of As quantum dots is formed in an As-enriched layer of the low-temperature GaAs by means of post-growth annealing at 400–760°C for 15 min. It is established that the AlAs barrier layer has a surface profile corresponding to that of a subbarrier layer with InAs quantum dots. The presence of such a profile causes the formation of V-shaped structural defects upon subsequent overgrowth with the GaAs layer. Besides, it was obtained that AlAs layer is thinned over the InAs quantum dots tops. It is shown that the AlAs barrier layer in the regions between the InAs quantum dots effectively prevents the starting diffusion of excess As at annealing temperatures up to 600°C. However, the concentration of mechanical stresses and the reduced thickness of the AlAs barrier layer near the tops of the InAs quantum dots lead to local barrier breakthroughs and the diffusion of As quantum dots into the region of coupled pairs of InAs quantum dots at higher annealing temperatures

  11. Browser Based Platform in Maintaining Clinical Activities - Use of The iPads in Head and Neck Clinics (United States)

    Yang, W. Y.; Moore, J.; Quon, H.; Evans, K.; Sharabi, A.; Herman, J.; Hacker-Prietz, A.; McNutt, T.


    Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

  12. Browser based platform in maintaining clinical activities – use of the iPads in head and neck clinics

    International Nuclear Information System (INIS)

    Yang, W Y; Moore, J; Quon, H; Evans, K; Sharabi, A; Herman, J; Hacker-Prietz, A; McNutt, T


    Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

  13. A Semantic Web-based System for Managing Clinical Archetypes. (United States)

    Fernandez-Breis, Jesualdo Tomas; Menarguez-Tortosa, Marcos; Martinez-Costa, Catalina; Fernandez-Breis, Eneko; Herrero-Sempere, Jose; Moner, David; Sanchez, Jesus; Valencia-Garcia, Rafael; Robles, Montserrat


    Archetypes facilitate the sharing of clinical knowledge and therefore are a basic tool for achieving interoperability between healthcare information systems. In this paper, a Semantic Web System for Managing Archetypes is presented. This system allows for the semantic annotation of archetypes, as well for performing semantic searches. The current system is capable of working with both ISO13606 and OpenEHR archetypes.

  14. Evidence-Based Clinical Decision: Key to Improved Patients Care ...

    African Journals Online (AJOL)

    ... materials remain limited to mostly developed countries. There is need to adopt measures to further facilitate dissemination of current information of effective health to care providers and policymakers in resource-poor countries. This review is aimed at re-enforcing the need for applying best-evidence into clinical practice

  15. SSPM based radiation sensing: Preliminary laboratory and clinical results

    International Nuclear Information System (INIS)

    Konnoff, Daniel C.; Plant, Thomas K.; Shiner, Elizabeth


    Recent Solid State Photomultiplier (SSPM) technology has matured, reaching a performance level that is suitable for replacement of the ubiquitous photomultiplier tube in selected applications for environmental radiation monitoring, clinical dosimetry, and medical imaging purposes. The objective of this work is low signal level laboratory and high signal level clinical testing of the Hamamatsu MPPC (S10362-11-050C), Photonique SSPM (0810G1), and Voxtel SiPM (SQBF-EKAA/SQBF-EIOA) SSPMs coupled to different inorganic scintillator crystals (Prelude 420, BGO), inorganic doped glass scintillator material SiO 2 :Cu 2+ and organic BCF-12 plastic scintillating fibers, used as detector elements. Plastic Optical Fibers (POFs) and Glass Optical Fibers (GOFs) are used as signal conduits for laboratory and clinical testing. Further, reduction of electron-beam-generated Cerenkov light in optical fibers is facilitated by the inclusion of metalized air-core capillary tubing between the BCF-12 plastic scintillating fiber and the POF. In a clinical setting dose linearity, percent depth dose, and angular measurements for 6 MV/18 MV photon beams and 9 MeV electron beams are compared with and without the use of the air-core capillary tubing for BCF-12 plastic scintillating fiber. These same measurements are repeated for SiO 2 :Cu 2+ scintillator material without air-core capillary tubing.

  16. Robust tumor morphometry in multispectral fluorescence microscopy (United States)

    Tabesh, Ali; Vengrenyuk, Yevgen; Teverovskiy, Mikhail; Khan, Faisal M.; Sapir, Marina; Powell, Douglas; Mesa-Tejada, Ricardo; Donovan, Michael J.; Fernandez, Gerardo


    Morphological and architectural characteristics of primary tissue compartments, such as epithelial nuclei (EN) and cytoplasm, provide important cues for cancer diagnosis, prognosis, and therapeutic response prediction. We propose two feature sets for the robust quantification of these characteristics in multiplex immunofluorescence (IF) microscopy images of prostate biopsy specimens. To enable feature extraction, EN and cytoplasm regions were first segmented from the IF images. Then, feature sets consisting of the characteristics of the minimum spanning tree (MST) connecting the EN and the fractal dimension (FD) of gland boundaries were obtained from the segmented compartments. We demonstrated the utility of the proposed features in prostate cancer recurrence prediction on a multi-institution cohort of 1027 patients. Univariate analysis revealed that both FD and one of the MST features were highly effective for predicting cancer recurrence (p <= 0.0001). In multivariate analysis, an MST feature was selected for a model incorporating clinical and image features. The model achieved a concordance index (CI) of 0.73 on the validation set, which was significantly higher than the CI of 0.69 for the standard multivariate model based solely on clinical features currently used in clinical practice (p < 0.0001). The contributions of this work are twofold. First, it is the first demonstration of the utility of the proposed features in morphometric analysis of IF images. Second, this is the largest scale study of the efficacy and robustness of the proposed features in prostate cancer prognosis.

  17. Implementation outcomes of evidence-based quality improvement for depression in VA community based outpatient clinics

    Directory of Open Access Journals (Sweden)

    Fortney John


    Full Text Available Abstract Background Collaborative-care management is an evidence-based practice for improving depression outcomes in primary care. The Department of Veterans Affairs (VA has mandated the implementation of collaborative-care management in its satellite clinics, known as Community Based Outpatient Clinics (CBOCs. However, the organizational characteristics of CBOCs present added challenges to implementation. The objective of this study was to evaluate the effectiveness of evidence-based quality improvement (EBQI as a strategy to facilitate the adoption of collaborative-care management in CBOCs. Methods This nonrandomized, small-scale, multisite evaluation of EBQI was conducted at three VA Medical Centers and 11 of their affiliated CBOCs. The Plan phase of the EBQI process involved the localized tailoring of the collaborative-care management program to each CBOC. Researchers ensured that the adaptations were evidence based. Clinical and administrative staff were responsible for adapting the collaborative-care management program for local needs, priorities, preferences and resources. Plan-Do-Study-Act cycles were used to refine the program over time. The evaluation was based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance Framework and used data from multiple sources: administrative records, web-based decision-support systems, surveys, and key-informant interviews. Results Adoption: 69.0% (58/84 of primary care providers referred patients to the program. Reach: 9.0% (298/3,296 of primary care patients diagnosed with depression who were not already receiving specialty care were enrolled in the program. Fidelity: During baseline care manager encounters, education/activation was provided to 100% (298/298 of patients, barriers were assessed and addressed for 100% (298/298 of patients, and depression severity was monitored for 100% (298/298 of patients. Less than half (42.5%, 681/1603 of follow-up encounters during the acute

  18. Confocal Raman Microscopy

    CERN Document Server

    Dieing, Thomas; Toporski, Jan


    Confocal Raman Microscopy is a relatively new technique that allows chemical imaging without specific sample preparation. By integrating a sensitive Raman spectrometer within a state-of-the-art microscope, Raman microscopy with a spatial resolution down to 200nm laterally and 500nm vertically can be achieved using visible light excitation. Recent developments in detector and computer technology as well as optimized instrument design have reduced integration times of Raman spectra by orders of magnitude, so that complete images consisting of tens of thousands of Raman spectra can be acquired in seconds or minutes rather than hours, which used to be standard just one decade ago. The purpose of this book is to provide the reader a comprehensive overview of the rapidly developing field of Confocal Raman Microscopy and its applications.

  19. Problems of university-based scientists associated with clinical trials. (United States)

    Remington, R D


    University faculty members who participate in clinical trials face a number of difficulties in connection with this association. Publication opportunities are often limited, and individual scholarship is difficult to express and evaluate within the context of a cooperative trial. Merit increases, promotion, and the award of tenure will usually require evidence of scholarly achievement outside the trial setting. For this reason, it seems inadvisable to recommend that a young investigator devote a major portion of his scholarly and research time to such an activity. A possible exception may be a full-time appointment for 1 to 2 years. Nonetheless, cooperative clinical trials are an important investigative tool and they should continue to be associated with academic centers. If appropriate administrative arrangements can be made, it should be possible to solve the academic problems of the young investigator associated with such trials.

  20. Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool. (United States)

    Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio


    Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

  1. A comprehensive clinical competency-based assessment in periodontics. (United States)

    Shiloah, J; Scarbecz, M; Bland, P S; Hottel, T L


    Traditional periodontics clinical examinations in dental education frequently assess a narrow set of clinical skills and do not adequately assess the ability of students to independently manage a periodontal patient. As an alternative, the authors developed a comprehensive periodontics competency case experience (CCCE) for senior dental students and surveyed students regarding their experience with the CCCE. Students challenging the CCCE must treat a patient with moderate periodontitis and must independently decide when a state of periodontal and oral health has been achieved. Students are also required to conduct an oral presentation to periodontology faculty. Dental students who completed the CCCE had a favourable impression of the experience, compared with the traditional clinical examinations taken in the junior year. The majority of students rated all the components of the CCCE as 'somewhat' or 'very helpful'. About 72.4% of students felt that being able to work independently on the examination was very helpful for learning about the clinical management of patients with periodontal disease, followed by 'simulation of care in private practice' (65.5%), and oral photography experience (55.2%). The greatest difficulty reported by students was finding an acceptable patient. About 62.1% of students rated 'finding the right patient' as very difficult. Students reported having to screen a mean of 5.9 patients (SD: 4.5) to find a qualified patient. The results of the survey will be useful in improving the examination as an assessment tool in periodontal therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Resident evaluation of clinical teachers based on teachers' certification. (United States)

    Steiner, Ivan P; Yoon, Philip W; Kelly, Karen D; Diner, Barry M; Donoff, Michel G; Mackey, Duncan S; Rowe, Brian H


    To examine the influence of emergency medicine (EM) certification of clinical teaching faculty on evaluations provided by residents. A prospective cohort analysis was conducted of assessments between July 1994 and July 2000 on residents' evaluations of EM faculty at the University of Alberta, Edmonton, Canada. Resident- and faculty-related variables were entered anonymously using the validated evaluation tool (ER Scale). Credentialing and demographic information on EM faculty was supplemented by data obtained through a nine-question survey. Groups were compared using ANOVA. The 562 residents returned 705 (91%) valid evaluation sheets on 115 EM faculty members. The four domains of didactic teaching, clinical teaching, approachability, and helpfulness were assessed. The majority of ratings were in the very good or superb categories for each domain. Instructors with certification in EM had higher scores in didactic, clinical teaching compared with others, and teachers without national certification scored lower in the helpful and approachable categories (p certifications either through training or practice eligibility did not affect scores. Instructors under the age of 40 years had higher scores than the older age groups in three of four categories (p certification in EM, academic track, rotation year, and site are all correlated with better teaching performance.

  3. Assessment of microwave-based clinical waste decontamination unit. (United States)

    Hoffman, P N; Hanley, M J


    A clinical waste decontamination unit that used microwave-generated heat was assessed for operator safety and efficacy. Tests with loads artificially contaminated with aerosol-forming particles showed that no particles were detected outside the machine provided the seals and covers were correctly seated. Thermometric measurement of a self-generated steam decontamination cycle was used to determine the parameters needed to ensure heat disinfection of the waste reception hopper, prior to entry for maintenance or repair. Bacterial and thermometric test pieces were passed through the machine within a full load of clinical waste. These test pieces, designed to represent a worst case situation, were enclosed in aluminium foil to shield them from direct microwave energy. None of the 100 bacterial test pieces yielded growth on culture and all 100 thermal test pieces achieved temperatures in excess of 99 degrees C during their passage through the decontamination unit. It was concluded that this method may be used to render safe the bulk of of ward-generated clinical waste.

  4. Towards modeling of cardiac micro-structure with catheter-based confocal microscopy: a novel approach for dye delivery and tissue characterization. (United States)

    Lasher, Richard A; Hitchcock, Robert W; Sachse, Frank B


    This work presents a methodology for modeling of cardiac tissue micro-structure. The approach is based on catheter-based confocal imaging systems, which are emerging as tools for diagnosis in various clinical disciplines. A limitation of these systems is that a fluorescent marker must be available in sufficient concentration in the imaged region. We introduce a novel method for the local delivery of fluorescent markers to cardiac tissue based on a hydro-gel carrier brought into contact with the tissue surface. The method was tested with living rabbit cardiac tissue and applied to acquire three-dimensional image stacks with a standard inverted confocal microscope and two-dimensional images with a catheter-based confocal microscope. We processed these image stacks to obtain spatial models and quantitative data on tissue microstructure. Volumes of atrial and ventricular myocytes were 4901 +/- 1713 and 10 299 +/-3598 mum (3) (mean+/-sd), respectively. Atrial and ventricular myocyte volume fractions were 72.4 +/-4.7% and 79.7 +/- 2.9% (mean +/-sd), respectively. Atrial and ventricular myocyte density was 165 571 +/- 55 836 and 86 957 +/- 32 280 cells/mm (3) (mean+/-sd), respectively. These statistical data and spatial descriptions of tissue microstructure provide important input for modeling studies of cardiac tissue function. We propose that the described methodology can also be used to characterize diseased tissue and allows for personalized modeling of cardiac tissue.

  5. A service oriented approach for guidelines-based clinical decision support using BPMN. (United States)

    Rodriguez-Loya, Salvador; Aziz, Ayesha; Chatwin, Chris


    Evidence-based medical practice requires that clinical guidelines need to be documented in such a way that they represent a clinical workflow in its most accessible form. In order to optimize clinical processes to improve clinical outcomes, we propose a Service Oriented Architecture (SOA) based approach for implementing clinical guidelines that can be accessed from an Electronic Health Record (EHR) application with a Web Services enabled communication mechanism with the Enterprise Service Bus. We have used Business Process Modelling Notation (BPMN) for modelling and presenting the clinical pathway in the form of a workflow. The aim of this study is to produce spontaneous alerts in the healthcare workflow in the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). The use of BPMN as a tool to automate clinical guidelines has not been previously employed for providing Clinical Decision Support (CDS).

  6. A novel immuno-gold labeling protocol for nanobody-based detection of HER2 in breast cancer cells using immuno-electron microscopy

    NARCIS (Netherlands)

    Kijanka, M; van Donselaar, E G; Müller, W H; Dorresteijn, B; Popov-Celeketic, Dusan; El Khattabi, M; Verrips, C T; van Bergen En Henegouwen, P M P; Post, J A

    Immuno-electron microscopy is commonly performed with the use of antibodies. In the last decade the antibody fragment indicated as nanobody (VHH or single domain antibody) has found its way to different applications previously done with conventional antibodies. Nanobodies can be selected to bind

  7. Ballistic hole magnetic microscopy

    NARCIS (Netherlands)

    Haq, E.; Banerjee, T.; Siekman, M.H.; Lodder, J.C.; Jansen, R.


    A technique to study nanoscale spin transport of holes is presented: ballistic hole magnetic microscopy. The tip of a scanning tunneling microscope is used to inject hot electrons into a ferromagnetic heterostructure, where inelastic decay creates a distribution of electron-hole pairs.

  8. Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity (United States)

    Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.


    This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

  9. A Comparison of Urban School- and Community-Based Dental Clinics (United States)

    Larsen, Charles D.; Larsen, Michael D.; Handwerker, Lisa B.; Kim, Maile S.; Rosenthal, Murray


    Background: The objective of the study was to quantitatively compare school- and community-based dental clinics in New York City that provide dental services to children in need. It was hypothesized that the school-based clinics would perform better in terms of several measures. Methods: We reviewed billing and visit data derived from encounter…

  10. [Clinical neuropsychology in perspective: future challenges based on current developments]. (United States)

    Verdejo-García, Antonio; Tirapu-Ustárroz, Javier


    New lines of translational, interdisciplinary research are emerging among different fields of the neurosciences, which often point at clinical neuropsychology as the hinge discipline capable of linking the basic findings with their clinical implications and thereby endow them with some meaning for phenomenological experience. To establish the great lines of progress made in the fields of neuroscience and neuropsychology in recent years, so as to be able to foresee the strategic lines and priorities of neuroscience in the near future. To achieve this aim, the first step will be to identify the changes of paradigm that have taken place in the areas of neuroscience and psychology in the last two decades. The next step will be to propose new topics and fields of application that these changes in paradigm offer and demand from neuroscience. The false dichotomies of genes versus environment, mind versus brain, and reason versus emotion are considered, as are the new applications of neuropsychology to the understanding of psychopathological disorders, from the neurodegenerative to neurodevelopment, from 'dirty' drugs to cognitive and affective enhancers.

  11. Advanced Microscopy of Microbial Cells

    DEFF Research Database (Denmark)

    Haagensen, Janus Anders Juul; Regenberg, Birgitte; Sternberg, Claus


    microscopy, super-resolution optical microscopy (STED, SIM, PALM) as well as atomic force microscopy and Raman spectroscopy. Using examples of bistability in microbial populations as well as biofilm development and differentiation in bacterial and yeast consortia, we demonstrate the importance of microscopy...

  12. [The historical background and present development of evidence-based healthcare and clinical nursing]. (United States)

    Tsai, Jung-Mei


    Evidence-based healthcare (EBHC) emphasizes the integration of the best research evidence with patient values, specialist suggestions, and clinical circumstances during the process of clinical decision-making. EBHC is a recognized core competency in modern healthcare. Nursing is a professional discipline of empirical science that thrives in an environment marked by advances in knowledge and technology in medicine as well as in nursing. Clinical nurses must elevate their skills and professional qualifications, provide efficient and quality health services, and promote their proficiency in EBHC. The Institute of Medicine in the United States indicates that evidence-based research results often fail to disseminate efficiently to clinical decision makers. This problem highlights the importance of better promoting the evidence-based healthcare fundamentals and competencies to frontline clinical nurses. This article describes the historical background and present development of evidence-based healthcare from the perspective of modern clinical nursing in light of the importance of evidence-based healthcare in clinical nursing; describes the factors associated with evidence-based healthcare promotion; and suggests strategies and policies that may improve the promotion and application of EBHC in clinical settings. The authors hope that this paper provides a reference for efforts to improve clinical nursing in the realms of EBHC training, promotion, and application.

  13. Clinical and Community-Based Education in U.S. Dental Schools. (United States)

    Licari, Frank W; Evans, Caswell A


    This review of U.S. dental schools' clinical curricula suggests that the basic structure of clinical education has not changed significantly in the past 60 years, although important developments include the introduction of competency-based education and community-based clinical education. Most dental schools still have a two-year preclinical curriculum and a two-year clinical curriculum, and most schools still operate a large clinical facility where students receive the bulk of their clinical education and assessment for graduation. In those clinics, dental students are the main providers of patient treatment, with faculty serving in supervisory roles. In addition, a major portion of the entire dental curriculum continues to be dedicated to student education on the restoration of a single tooth or replacement of teeth. This article was written as part of the project "Advancing Dental Education in the 21 st Century."

  14. Quality and safety based management of radiological and clinical equipment

    International Nuclear Information System (INIS)

    Arora, S.; Saini, P.S.


    TQM (Total quality management) is the 'buzz' acronym expected in almost every aspect of industrial manufacturing, product development and services solicited by the outside agencies. The correct management of the many technological resources in health institutions in terms of efficiency, effectiveness and safety is a necessity in view of the criteria on which modern medicine is based. Almost all activities -be they diagnostic, therapeutic and rehabilitative - carried out within a modern hospital are based on widespread application of equipment and technology, the efficiency of which can directly influence the quality of service offered to the patient

  15. Polarized Light Microscopy (United States)

    Frandsen, Athela F.


    Polarized light microscopy (PLM) is a technique which employs the use of polarizing filters to obtain substantial optical property information about the material which is being observed. This information can be combined with other microscopy techniques to confirm or elucidate the identity of an unknown material, determine whether a particular contaminant is present (as with asbestos analysis), or to provide important information that can be used to refine a manufacturing or chemical process. PLM was the major microscopy technique in use for identification of materials for nearly a century since its introduction in 1834 by William Fox Talbot, as other techniques such as SEM (Scanning Electron Microscopy), FTIR (Fourier Transform Infrared spectroscopy), XPD (X-ray Powder Diffraction), and TEM (Transmission Electron Microscopy) had not yet been developed. Today, it is still the only technique approved by the Environmental Protection Agency (EPA) for asbestos analysis, and is often the technique first applied for identification of unknown materials. PLM uses different configurations in order to determine different material properties. With each configuration additional clues can be gathered, leading to a conclusion of material identity. With no polarizing filter, the microscope can be used just as a stereo optical microscope, and view qualities such as morphology, size, and number of phases. With a single polarizing filter (single polars), additional properties can be established, such as pleochroism, individual refractive indices, and dispersion staining. With two polarizing filters (crossed polars), even more can be deduced: isotropy vs. anisotropy, extinction angle, birefringence/degree of birefringence, sign of elongation, and anomalous polarization colors, among others. With the use of PLM many of these properties can be determined in a matter of seconds, even for those who are not highly trained. McCrone, a leader in the field of polarized light microscopy, often

  16. Personalized Clinical Diagnosis in Data Bases for Treatment Support in Phthisiology. (United States)

    Lugovkina, T K; Skornyakov, S N; Golubev, D N; Egorov, E A; Medvinsky, I D


    The decision-making is a key event in the clinical practice. The program products with clinical decision support models in electronic data-base as well as with fixed decision moments of the real clinical practice and treatment results are very actual instruments for improving phthisiological practice and may be useful in the severe cases caused by the resistant strains of Mycobacterium tuberculosis. The methodology for gathering and structuring of useful information (critical clinical signals for decisions) is described. Additional coding of clinical diagnosis characteristics was implemented for numeric reflection of the personal situations. The created methodology for systematization and coding Clinical Events allowed to improve the clinical decision models for better clinical results.

  17. Expert Systems Based Clinical Assessment and Tutorial Project. (United States)

    Papa, Frank; Shores, Jay

    This project at the Texas College of Osteopathic Medicine (Fort Worth) evaluated the use of an artificial-intelligence-derived measure, "Knowledge-Based Inference Tool" (KBIT), as the basis for assessing medical students' diagnostic capabilities and designing instruction to improve diagnostic skills. The instrument was designed to…

  18. From Paper Based Clinical Practice Guidelines to Declarative Workflow Management

    DEFF Research Database (Denmark)

    Lyng, Karen Marie; Hildebrandt, Thomas; Mukkamala, Raghava Rao


    a sub workflow can be described in a declarative workflow management system: the Resultmaker Online Consultant (ROC). The example demonstrates that declarative primitives allow to naturally extend the paper based flowchart to an executable model without introducing a complex cyclic control flow graph....

  19. Autecology and phylogeny of Coolia tropicalis and Coolia malayensis (Dinophyceae), with emphasis on taxonomy of C. tropicalis based on light microscopy, scanning electron microscopy and LSU rDNA(1). (United States)

    Mohammad-Noor, Normawaty; Moestrup, Øjvind; Lundholm, Nina; Fraga, Santiago; Adam, Aimimualiani; Holmes, Michael J; Saleh, Ejria


    Coolia is a widespread and ecologically important genus of benthic marine dinoflagellates found in tropical regions. Historically, there has been taxonomic confusion about the taxonomy and toxicity of this group. The goal of this study was to resolve morphological questions concerning Coolia tropicalis and determine the taxonomic identity of the Australian Coolia isolate which has been reported to produce cooliatoxins. To accomplish this, the morphology of tropical strains from Belize (the type locality of C. tropicalis), Malaysia, Indonesia, and Australia were examined and compared to published reports. The morphological analysis showed that C. tropicalis differs from the original description in that it has a slightly larger size (35-47 μm long by 30-45 μm wide versus 23-40 μm long by 25-39 μm wide), and the shape of fourth apical plate, and the length of Po plate (7.4-12 μm versus 7 μm). Based on both morphology and phylogenetic analysis using LSU D1- D3 rDNA sequences, the clones of C. tropicalis from Malaysia, Indonesia, and Belize were found to form a monophyletic clade within the genus. The strain producing cooliatoxin was found to be C. tropicalis, not Coolia monotis as originally assumed. To explore the factors influencing the growth of Coolia species, the growth rates of C. tropicalis and Coolia malayensis were determined at different temperatures and salinities. Both species tolerated a wide range of temperatures, but cannot survive at temperatures 35°C. C. monotis, the dominant species reported in the literature, probably does not produce toxins. © 2013 Phycological Society of America.

  20. Data and image transfer using mobile phones to strengthen microscopy-based diagnostic services in low and middle income country laboratories.

    Directory of Open Access Journals (Sweden)

    Coosje J Tuijn

    Full Text Available BACKGROUND: The emerging market of mobile phone technology and its use in the health sector is rapidly expanding and connecting even the most remote areas of world. Distributing diagnostic images over the mobile network for knowledge sharing, feedback or quality control is a logical innovation. OBJECTIVE: To determine the feasibility of using mobile phones for capturing microscopy images and transferring these to a central database for assessment, feedback and educational purposes. METHODS: A feasibility study was carried out in Uganda. Images of microscopy samples were taken using a prototype connector that could fix a variety of mobile phones to a microscope. An Information Technology (IT platform was set up for data transfer from a mobile phone to a website, including feedback by text messaging to the end user. RESULTS: Clear images were captured using mobile phone cameras of 2 megapixels (MP up to 5MP. Images were sent by mobile Internet to a website where they were visualized and feedback could be provided to the sender by means of text message. CONCLUSION: The process of capturing microscopy images on mobile phones, relaying them to a central review website and feeding back to the sender is feasible and of potential benefit in resource poor settings. Even though the system needs further optimization, it became evident from discussions with stakeholders that there is a demand for this type of technology.

  1. Electron microscopy in metallurgy

    International Nuclear Information System (INIS)

    Loretto, M.H.


    The aim of this paper is to review briefly the contribution which (TEM) transmission electron microscopy (including high voltage electron microscopy (HVEM)) has made to metallurgy. Since it is straightforward with modern electron microscopes to extract the crystallographic information which provides the basis for any interpretation, the major problem in most metallurgical work lies in assessing how the structure (which TEM has characterised) has arisen and which properties of the specimen can be understood in terms of this structure. Radiation damage, quenching, phase transformations, grain boundaries and plastic deformation have been the main fields in which TEM has contributed significantly. After briefly summarising the role of TEM in each field, examples of recent work will be used to indicate current TEM activity in physical metallurgy. (author)

  2. Second harmonic generation microscopy

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline; Brewer, Jonathan R.; Risbo, Jens


    Myofibers and collagen show non-linear optical properties enabling imaging using second harmonic generation (SHG) microscopy. The technique is evaluated for use as a tool for real-time studies of thermally induced changes in thin samples of unfixed and unstained pork. The forward and the backward...... scattered SHG light reveal complementary features of the structures of myofibers and collagen fibers. Upon heating the myofibers show no structural changes before reaching a temperature of 53 °C. At this temperature the SHG signal becomes extinct. The extinction of the SHG at 53 °C coincides with a low......-temperature endotherm peak observable in the differential scanning calorimetry (DSC) thermograms. DSC analysis of epimysium, the connective tissue layer that enfold skeletal muscles, produces one large endotherm starting at 57 °C and peaking at 59.5 °C. SHG microscopy of collagen fibers reveals a variability of thermal...


    Directory of Open Access Journals (Sweden)

    Bhavita Patel


    Full Text Available NTRODUCTION: Evidence - based medicine (EBM is defined as the „conscientious, explicit, and judicious use of current best evidence‟. It i s an important tool for lifelong learning in medicine, and medical students can develop the skills necessary to understand and use EBM. The teaching of EBM in Sumandeep Vidyapeeth is as part of Evidence Based Education System (EBES. The university has imp lemented the 16 hours of teaching with project work on Evidence Based Medicine in 1st MBBS and 2nd MBBS curriculum in addition to MBBS syllabus. AIMS & OBJECTIVES: This study was planned to take feedback from all the faculties those who are involved in Evi dence based Medicine teaching to evaluate their attitude and perception towards this innovative teaching method and to recommend improvements. MATERIAL & METHODS: A Descriptive, self - structured , pilot pretested questionnaire based cross sectional study was conducted in the year 2013 - 2014 among 40 faculties from 7 Departments like Anatomy, Physiology, Biochemistry, Microbiology, Pharmacology, Pathology and Forensic Medicine teaching Evidence Base d Medicine to students at S.B.K.S MI & RC, Sumandeep Vidyapeeth. Data was expressed as percentage. RESULTS: The response rate for the study was 75%. Almost 87% of faculties agreed that teaching EBM is a welcoming development during pre and para clinical ye ars. About 80% faculties agreed that it will help them in future clinical learning. 87% faculties agreed that literature and research searching improves their day to day teaching. About 77% of faculties have attended workshop and training held in Universit y and 83% of faculties agreed that they are interested in more learning and improving skills necessary to incorporate Evidence based medicine into their discipline. Barriers included shortage of time and need for training in teaching EBM. CONCLUSION: Facul ties of this University teaching Pre - clinical and Para - clinical medical students recognized

  4. Ontology-based data integration between clinical and research systems.

    Directory of Open Access Journals (Sweden)

    Sebastian Mate

    Full Text Available Data from the electronic medical record comprise numerous structured but uncoded elements, which are not linked to standard terminologies. Reuse of such data for secondary research purposes has gained in importance recently. However, the identification of relevant data elements and the creation of database jobs for extraction, transformation and loading (ETL are challenging: With current methods such as data warehousing, it is not feasible to efficiently maintain and reuse semantically complex data extraction and trans-formation routines. We present an ontology-supported approach to overcome this challenge by making use of abstraction: Instead of defining ETL procedures at the database level, we use ontologies to organize and describe the medical concepts of both the source system and the target system. Instead of using unique, specifically developed SQL statements or ETL jobs, we define declarative transformation rules within ontologies and illustrate how these constructs can then be used to automatically generate SQL code to perform the desired ETL procedures. This demonstrates how a suitable level of abstraction may not only aid the interpretation of clinical data, but can also foster the reutilization of methods for un-locking it.

  5. Evidence based exercise - clinical benefits of high intensity interval training. (United States)

    Shiraev, Tim; Barclay, Gabriella


    Aerobic exercise has a marked impact on cardiovascular disease risk. Benefits include improved serum lipid profiles, blood pressure and inflammatory markers as well as reduced risk of stroke, acute coronary syndrome and overall cardiovascular mortality. Most exercise programs prescribed for fat reduction involve continuous, moderate aerobic exercise, as per Australian Heart Foundation clinical guidelines. This article describes the benefits of exercise for patients with cardiovascular and metabolic disease and details the numerous benefits of high intensity interval training (HIIT) in particular. Aerobic exercise has numerous benefits for high-risk populations and such benefits, especially weight loss, are amplified with HIIT. High intensity interval training involves repeatedly exercising at a high intensity for 30 seconds to several minutes, separated by 1-5 minutes of recovery (either no or low intensity exercise). HIT is associated with increased patient compliance and improved cardiovascular and metabolic outcomes and is suitable for implementation in both healthy and 'at risk' populations. Importantly, as some types of exercise are contraindicated in certain patient populations and HIIT is a complex concept for those unfamiliar to exercise, some patients may require specific assessment or instruction before commencing a HIIT program.

  6. Preclinical and clinical development of siRNA-based therapeutics. (United States)

    Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L; Sood, Anil K; Lopez-Berestein, Gabriel


    The discovery of RNA interference, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Electron microscopy and diffraction

    International Nuclear Information System (INIS)

    Gjoennes, J.; Olsen, A.


    This report is a description of research activities and plans at the electron microscopy laboratorium, Physics Department, University of Oslo. Since the first electron microscope was installed in 1968, the research has covered inorganic structures, physical metallurgy, as well as theory of electron scattering and the development of methods in this field. The current plans involve efforts in the development of crystallographic and spectroscopic methods

  8. Visual-servoing optical microscopy (United States)

    Callahan, Daniel E.; Parvin, Bahram


    The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time: quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

  9. Clinical data warehousing for evidence based decision making. (United States)

    Narra, Lekha; Sahama, Tony; Stapleton, Peta


    Large volumes of heterogeneous health data silos pose a big challenge when exploring for information to allow for evidence based decision making and ensuring quality outcomes. In this paper, we present a proof of concept for adopting data warehousing technology to aggregate and analyse disparate health data in order to understand the impact various lifestyle factors on obesity. We present a practical model for data warehousing with detailed explanation which can be adopted similarly for studying various other health issues.

  10. Grid-based virtual clinic for medical diagnosis tutoring | Yatchou ...

    African Journals Online (AJOL)

    La réalisation visée est un outil collaboratif d\\'enseignement pour les médecins du terrain et les étudiants en médecine au sein d\\'une organisation virtuelle. The emerging grid-based technologies are increasingly adopted to enhance education and provide better learning services. This is characterized all over the world, ...

  11. Answering PICO Clinical Questions: a Semantic Graph-Based Approach


    Znaidi , Eya; Tamine , Lynda; Latiri , Chiraz


    International audience; In this paper, we tackle the issue related to the retrieval of the best evidence that fits with a PICO (Population, Intervention, Comparison and Outcome) question. We propose a new document ranking algorithm that relies on semantic based query expansion bounded by the local search context to better discard irrelevant documents. Experiments using a standard dataset including 423 PICO questions and more than 1,2 million of documents, show that our aproach is promising.

  12. Deep Learning Microscopy

    KAUST Repository

    Rivenson, Yair


    We demonstrate that a deep neural network can significantly improve optical microscopy, enhancing its spatial resolution over a large field-of-view and depth-of-field. After its training, the only input to this network is an image acquired using a regular optical microscope, without any changes to its design. We blindly tested this deep learning approach using various tissue samples that are imaged with low-resolution and wide-field systems, where the network rapidly outputs an image with remarkably better resolution, matching the performance of higher numerical aperture lenses, also significantly surpassing their limited field-of-view and depth-of-field. These results are transformative for various fields that use microscopy tools, including e.g., life sciences, where optical microscopy is considered as one of the most widely used and deployed techniques. Beyond such applications, our presented approach is broadly applicable to other imaging modalities, also spanning different parts of the electromagnetic spectrum, and can be used to design computational imagers that get better and better as they continue to image specimen and establish new transformations among different modes of imaging.

  13. Direct Microscopy: A Useful Tool to Diagnose Oral Candidiasis in Children and Adolescents. (United States)

    Marty, Mathieu; Bourrat, Emmanuelle; Vaysse, Frédéric; Bonner, Mark; Bailleul-Forestier, Isabelle


    Oral candidiasis is one of the most common opportunistic fungal infections of the oral cavity in human. Among children, this condition represents one of the most frequent affecting the mucosa. Although most diagnoses are made based on clinical signs and features, a microbiological analysis is sometimes necessary. We performed a literature review on the diagnosis of oral candidiasis to identify the techniques most commonly employed in routine clinical practice. A Medline-PubMed search covering the last 10 years was performed. Microbiological techniques were used in cases requiring confirmation of the clinical diagnosis. In such cases, direct microscopy was the method most commonly used for diagnosing candidiasis. Direct microscopy appears as the method of choice for confirming clinical diagnosis and could become a routine chair-side technique.

  14. Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China. (United States)

    Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian


    Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

  15. Plasmonics Enhanced Smartphone Fluorescence Microscopy

    KAUST Repository

    Wei, Qingshan; Acuna, Guillermo; Kim, Seungkyeum; Vietz, Carolin; Tseng, Derek; Chae, Jongjae; Shir, Daniel; Luo, Wei; Tinnefeld, Philip; Ozcan, Aydogan


    Smartphone fluorescence microscopy has various applications in point-of-care (POC) testing and diagnostics, ranging from e.g., quantification of immunoassays, detection of microorganisms, to sensing of viruses. An important need in smartphone-based microscopy and sensing techniques is to improve the detection sensitivity to enable quantification of extremely low concentrations of target molecules. Here, we demonstrate a general strategy to enhance the detection sensitivity of a smartphone-based fluorescence microscope by using surface-enhanced fluorescence (SEF) created by a thin metal-film. In this plasmonic design, the samples are placed on a silver-coated glass slide with a thin spacer, and excited by a laser-diode from the backside through a glass hemisphere, generating surface plasmon polaritons. We optimized this mobile SEF system by tuning the metal-film thickness, spacer distance, excitation angle and polarization, and achieved ~10-fold enhancement in fluorescence intensity compared to a bare glass substrate, which enabled us to image single fluorescent particles as small as 50 nm in diameter and single quantum-dots. Furthermore, we quantified the detection limit of this platform by using DNA origami-based brightness standards, demonstrating that ~80 fluorophores per diffraction-limited spot can be readily detected by our mobile microscope, which opens up new opportunities for POC diagnostics and sensing applications in resource-limited-settings.

  16. Plasmonics Enhanced Smartphone Fluorescence Microscopy

    KAUST Repository

    Wei, Qingshan


    Smartphone fluorescence microscopy has various applications in point-of-care (POC) testing and diagnostics, ranging from e.g., quantification of immunoassays, detection of microorganisms, to sensing of viruses. An important need in smartphone-based microscopy and sensing techniques is to improve the detection sensitivity to enable quantification of extremely low concentrations of target molecules. Here, we demonstrate a general strategy to enhance the detection sensitivity of a smartphone-based fluorescence microscope by using surface-enhanced fluorescence (SEF) created by a thin metal-film. In this plasmonic design, the samples are placed on a silver-coated glass slide with a thin spacer, and excited by a laser-diode from the backside through a glass hemisphere, generating surface plasmon polaritons. We optimized this mobile SEF system by tuning the metal-film thickness, spacer distance, excitation angle and polarization, and achieved ~10-fold enhancement in fluorescence intensity compared to a bare glass substrate, which enabled us to image single fluorescent particles as small as 50 nm in diameter and single quantum-dots. Furthermore, we quantified the detection limit of this platform by using DNA origami-based brightness standards, demonstrating that ~80 fluorophores per diffraction-limited spot can be readily detected by our mobile microscope, which opens up new opportunities for POC diagnostics and sensing applications in resource-limited-settings.

  17. A work-based learning approach for clinical support workers on mental health inpatient wards. (United States)

    Kemp, Philip; Gilding, Moorene; Seewooruttun, Khooseal; Walsh, Hannah


    Background With a rise in the number of unqualified staff providing health and social care, and reports raising concerns about the quality of care provided, there is a need to address the learning needs of clinical support workers. This article describes a qualitative evaluation of a service improvement project that involved a work-based learning approach for clinical support workers on mental health inpatient wards. Aim To investigate and identify insights in relation to the content and process of learning using a work-based learning approach for clinical support workers. Method This was a qualitative evaluation of a service improvement project involving 25 clinical support workers at the seven mental health inpatient units in South London and Maudsley NHS Foundation Trust. Three clinical skills tutors were appointed to develop, implement and evaluate the work-based learning approach. Four sources of data were used to evaluate this approach, including reflective journals, qualitative responses to questionnaires, three focus groups involving the clinical support workers and a group interview involving the clinical skills tutors. Data were analysed using thematic analysis. Findings The work-based learning approach was highly valued by the clinical support workers and enhanced learning in practice. Face-to-face learning in practice helped the clinical support workers to develop practice skills and reflective learning skills. Insights relating to the role of clinical support workers were also identified, including the benefits of face-to-face supervision in practice, particularly in relation to the interpersonal aspects of care. Conclusion A work-based learning approach has the potential to enhance care delivery by meeting the learning needs of clinical support workers and enabling them to apply learning to practice. Care providers should consider how the work-based learning approach can be used on a systematic, organisation-wide basis in the context of budgetary

  18. A Population-Based Clinical Trial of Irinotecan and Carboplatin

    Directory of Open Access Journals (Sweden)

    Derick Lau


    Full Text Available Purpose. Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci. We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin. Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limiting toxicity (DLT in 50 patients with solid tumors refractory to previous chemotherapy. The individual toxicity-limiting dose levels were analyzed for normal distribution using the method of Ryan-Joiner and subsequently used to determine a population-based maximum tolerated dose (pMTD. For comparison, a simulation study was performed using the method of modified Fibonacci. Results. The most common dose-limiting toxicities (DLTs included neutropenia (58%, thrombocytopenia (16%, and diarrhea (8%. The frequency of individual toxicity-limiting dose levels of 50 patients approximated a normal distribution. The dose levels associated with individual limiting toxicities ranged from level 1 (irinotecan 100 mg/m2 and carboplatin AUC = 4 mg/mL x min to level 8 (irinotecan 350 mg/m2 and carboplatin AUC = 6. The pMTD was determined to be dose level 3 (150 mg/m2 for irinotecan and AUC = 5 for carboplatin. In contrast, the MTD was determined to be dose level 4 (200 mg/m2 for irinotecan and AUC 5 for carboplatin by modified-Fibonacci simulation. Conclusions. The population-based design of phase I trial allows optimization of dose intensity and derivation of a pMTD. The pMTD has been applied in phase II trial of irinotecan and carboplatin in patients with small-cell lung cancer.

  19. A systematic literature review of evidence-based clinical practice for rare diseases

    DEFF Research Database (Denmark)

    Rath, Ana; Salamon, Valérie; Peixoto, Sandra


    diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes....... CONCLUSIONS: Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic...

  20. Technology-based strategies for promoting clinical reasoning skills in nursing education. (United States)

    Shellenbarger, Teresa; Robb, Meigan


    Faculty face the demand of preparing nursing students for the constantly changing health care environment. Effective use of online, classroom, and clinical conferencing opportunities helps to enhance nursing students' clinical reasoning capabilities needed for practice. The growth of technology creates an avenue for faculty to develop engaging learning opportunities. This article presents technology-based strategies such as electronic concept mapping, electronic case histories, and digital storytelling that can be used to facilitate clinical reasoning skills.

  1. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials. (United States)

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G


    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials.

  2. Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases. (United States)

    Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J


    We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Simulation-based education for building clinical teams

    Directory of Open Access Journals (Sweden)

    Marshall Stuart


    Full Text Available Failure to work as an effective team is commonly cited as a cause of adverse events and errors in emergency medicine. Until recently, individual knowledge and skills in managing emergencies were taught, without reference to the additional skills required to work as part of a team. Team training courses are now becoming commonplace, however their strategies and modes of delivery are varied. Just as different delivery methods of traditional education can result in different levels of retention and transfer to the real world, the same is true in team training of the material in different ways in traditional forms of education may lead to different levels of retention and transfer to the real world, the same is true in team training. As team training becomes more widespread, the effectiveness of different modes of delivery including the role of simulation-based education needs to be clearly understood. This review examines the basis of team working in emergency medicine, and the components of an effective emergency medical team. Lessons from other domains with more experience in team training are discussed, as well as the variations from these settings that can be observed in medical contexts. Methods and strategies for team training are listed, and experiences in other health care settings as well as emergency medicine are assessed. Finally, best practice guidelines for the development of team training programs in emergency medicine are presented.


    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr


    Full Text Available von Hippel-Lindau syndrome (VHL is a rare, genetic multi-system disorder characterized by the abnormal growth of tumors in certain parts of the body (angiomatosis. The tumors of the central nervous system (CNS are benign and are comprised of a nest of blood vessels and are called hemangioblastomas. Hemangioblastomas may develop in the brain, the retina of the eyes, and other areas of the nervous system. Other types of tumors develop in the adrenal glands, the kidneys, or the pancreas. Symptoms of VHL vary among patients and depend on the size and location of the tumors. Symptoms may include headaches, problems with balance and walking, dizziness, weakness of the limbs, vision problems, and high blood pressure. Cysts (fluid-filled sacs and/or tumors (benign or cancerous may develop around the hemangioblastomas and cause the symptoms listed above. Individuals with VHL are also at a higher risk than normal for certain types of cancer, especially kidney cancer. Based on the case of 30-year old patient with characteristics of von Hippel-Lindau syndrome as phakomatosis.

  5. Guidance for Researchers Developing and Conducting Clinical Trials in Practice-based Research Networks (PBRNs) (United States)

    Dolor, Rowena J.; Schmit, Kristine M.; Graham, Deborah G.; Fox, Chester H.; Baldwin, Laura Mae


    Background There is increased interest nationally in multicenter clinical trials to answer questions about clinical effectiveness, comparative effectiveness, and safety in real-world community settings. Primary care practice-based research networks (PBRNs), comprising community- and/or academically affiliated practices committed to improving medical care for a range of health problems, offer ideal settings for these trials, especially pragmatic clinical trials. However, many researchers are not familiar with working with PBRNs. Methods Experts in practice-based research identified solutions to challenges that researchers and PBRN personnel experience when collaborating on clinical trials in PBRNs. These were organized as frequently asked questions in a draft document presented at a 2013 Agency for Health care Research and Quality PBRN conference workshop, revised based on participant feedback, then shared with additional experts from the DARTNet Institute, Clinical Translational Science Award PBRN, and North American Primary Care Research Group PBRN workgroups for further input and modification. Results The “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice-Based Research Networks” offers guidance in the areas of recruiting and engaging practices, budgeting, project management, and communication, as well as templates and examples of tools important in developing and conducting clinical trials. Conclusion Ensuring the successful development and conduct of clinical trials in PBRNs requires a highly collaborative approach between academic research and PBRN teams. PMID:25381071

  6. How evidence based is the management of two common sports injuries in a sports injury clinic?


    Murray, I; Murray, S; MacKenzie, K; Coleman, S; Cullen, M


    Objectives: To examine the diagnosis and management of adults attending a sports injury clinic, to establish to what extent the management of the two most common injuries treated at this clinic is evidence based, and to explore factors that affect management.

  7. Clinical and Research Perspectives on Nonspeech Oral Motor Treatments and Evidence-Based Practice (United States)

    Muttiah, Nimisha; Georges, Katie; Brackenbury, Tim


    Purpose: Evidence-based practice (EBP) involves the incorporation of research evidence, clinical expertise, and client values in clinical decision making. One case in which these factors conflict is the use of nonspeech oral motor treatments (NSOMTs) for children with developmental speech sound disorders. Critical reviews of the research evidence…

  8. Population-Based Pediatric Reference Intervals in General Clinical Chemistry: A Swedish Survey. (United States)

    Ridefelt, Peter


    Very few high quality studies on pediatric reference intervals for general clinical chemistry and hematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. The Swedish survey included 701 healthy children. Reference intervals for general clinical chemistry and hematology were defined.

  9. Evaluation of Criteria-Based Clinical Audit in Improving Quality of ...

    African Journals Online (AJOL)


    ABSTRACT. Study evaluated criteria–based clinical audit in measuring and improving quality of obstetric care for five life-threatening obstetric complications: obstetric haemorrhage, eclampsia, genital tract infections, obstructed labor and uterine rupture. Clinical management of 65 patients was audited using a 'before.

  10. Students' Experiences of Clinic-Based Learning during a Final Year Veterinary Internship Programme (United States)

    Matthew, Susan M.; Taylor, Rosanne M.; Ellis, Robert A.


    This study investigated veterinary students' experiences of clinic-based learning (CBL) during a comprehensive final year internship programme. Open-ended surveys (n = 93) were used to gather qualitative data about students' conceptions of what is learned during CBL and their approaches to learning in clinics. Phenomenography was used for detailed…

  11. The Varied Circumstances Prompting Requests for Emergency Contraception at School-Based Clinics (United States)

    Sidebottom, Abbey; Harrison, Patricia A.; Amidon, Donna; Finnegan, Katie


    Background: Little is known about the circumstances that prompt teenagers to request emergency contraception (EC). This evaluation was designed to refine the EC clinical protocol and improve pregnancy prevention efforts in high school-based clinics by analyzing information on EC use and subsequent contraception use of EC patients. Methods: Sites…

  12. Competency-Based Assessment for Clinical Supervisors: Design-Based Research on a Web-Delivered Program (United States)

    Williams, Lauren Therese; Grealish, Laurie; Jamieson, Maggie


    Background Clinicians need to be supported by universities to use credible and defensible assessment practices during student placements. Web-based delivery of clinical education in student assessment offers professional development regardless of the geographical location of placement sites. Objective This paper explores the potential for a video-based constructivist Web-based program to support site supervisors in their assessments of student dietitians during clinical placements. Methods This project was undertaken as design-based research in two stages. Stage 1 describes the research consultation, development of the prototype, and formative feedback. In Stage 2, the program was pilot-tested and evaluated by a purposeful sample of nine clinical supervisors. Data generated as a result of user participation during the pilot test is reported. Users’ experiences with the program were also explored via interviews (six in a focus group and three individually). The interviews were transcribed verbatim and thematic analysis conducted from a pedagogical perspective using van Manen’s highlighting approach. Results This research succeeded in developing a Web-based program, “Feed our Future”, that increased supervisors’ confidence with their competency-based assessments of students on clinical placements. Three pedagogical themes emerged: constructivist design supports transformative Web-based learning; videos make abstract concepts tangible; and accessibility, usability, and pedagogy are interdependent. Conclusions Web-based programs, such as Feed our Future, offer a viable means for universities to support clinical supervisors in their assessment practices during clinical placements. A design-based research approach offers a practical process for such Web-based tool development, highlighting pedagogical barriers for planning purposes. PMID:25803172

  13. An ethnography of clinic "noise" in a community-based, promotora-centered mental health intervention. (United States)

    Getrich, Christina; Heying, Shirley; Willging, Cathleen; Waitzkin, Howard


    Community-based health interventions have emerged as a growing focus for anthropological research. The application of ethnographic approaches in clinical practice settings reveals that community-based interventions must grapple with "noise," or unanticipated factors such as patients' own perceptions of illness and treatment, primary care providers' non-adherence to guidelines-based treatment, the social dynamics of the clinic site itself, and incomplete understanding and acceptance of an intervention by a clinic's staff members. Such noise can influence the implementation and quality of treatment. Thus, identifying clinic-based noise is critical in assessments of fidelity to intervention protocols as well as outcomes of community-based interventions. This paper highlights findings from an evaluation of a mental health intervention focusing on the role of promotoras (briefly trained, non-professional community health workers) as mental health practitioners in two urban New Mexico, USA, community health centers. Our research identified three areas of clinic-based noise: the clinics' physical ability to "absorb" the intervention, the challenges of co-worker instability and interpersonal relationships, and balancing extra workplace demands. The findings demonstrate the value of ethnographic approaches in community-based intervention research.

  14. Fourier plane imaging microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dominguez, Daniel, E-mail:; Peralta, Luis Grave de [Department of Physics, Texas Tech University, Lubbock, Texas 79409 (United States); Nano Tech Center, Texas Tech University, Lubbock, Texas 79409 (United States); Alharbi, Nouf; Alhusain, Mdhaoui [Department of Physics, Texas Tech University, Lubbock, Texas 79409 (United States); Bernussi, Ayrton A. [Nano Tech Center, Texas Tech University, Lubbock, Texas 79409 (United States); Department of Electrical and Computer Engineering, Texas Tech University, Lubbock, Texas 79409 (United States)


    We show how the image of an unresolved photonic crystal can be reconstructed using a single Fourier plane (FP) image obtained with a second camera that was added to a traditional compound microscope. We discuss how Fourier plane imaging microscopy is an application of a remarkable property of the obtained FP images: they contain more information about the photonic crystals than the images recorded by the camera commonly placed at the real plane of the microscope. We argue that the experimental results support the hypothesis that surface waves, contributing to enhanced resolution abilities, were optically excited in the studied photonic crystals.

  15. Effects of conventional and problem-based learning on clinical and general competencies and career development

    NARCIS (Netherlands)

    Cohen-Schotanus, Janke; Muijtjens, Arno M. M.; Schonrock-Adema, Johanna; Geertsma, Jelle; van der Vleuten, Cees P. M.

    OBJECTIVE: To test hypotheses regarding the longitudinal effects of problem-based learning (PBL) and conventional learning relating to students' appreciation of the curriculum, self-assessment of general competencies, summative assessment of clinical competence and indicators of career development.

  16. Qualitative histologic evaluation of the tissue reaction to the polyurethane resin (ricinus communis - based biopolymer implantation assessed by light and scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    Gustavo Campos Belmonte


    Full Text Available The tissue reaction of bone tissue accessed by light microscopy and scanning electron microscopy (SEM images after polyurethane resin implantation is presented in this study. Twenty four male rabbits were used, divided into two groups of 12 animals each (experimental group and control group in which full-thickness cranial defect was surgically created. At 30 and 90 days post operation 6 animals of each group were euthanized and bone samples were removed for analysis. The microscopic results indicated no inflammatory foreign body reaction, a perfect union between the polymer and surgical bone bed surface, lack of bone resorption and presence of a thin layer of osteogenic material covering the polymer surface in contact with the surgical bone bed. The SEM images demonstrate the porosity of the resin, with diameters from 120 to 500 µm. This important feature of this polymer is associated with its osteoconductivity, allowing the bone growth inside it, improving the integration between the material and bone tissue. These results confirm that polyurethane resin derived from Ricinuscommunis is an excellent bone substitute for use in repair surgery for great bone losses.


    DEFF Research Database (Denmark)

    Bergholtz, Trine; Daugbjerg, Niels; Moestrup, Øjvind


    An undescribed species of the dinoflagellate genus Karlodinium J. Larsen (viz. K. armiger sp. nov.) is described from Alfacs Bay (Spain), using light and electron microscopy, pigment composition, and partial large subunit (LSU) rDNA sequence. The new species differs from the type species of Karlo......An undescribed species of the dinoflagellate genus Karlodinium J. Larsen (viz. K. armiger sp. nov.) is described from Alfacs Bay (Spain), using light and electron microscopy, pigment composition, and partial large subunit (LSU) rDNA sequence. The new species differs from the type species...... of Karlodinium (K. micrum (Leadbeater et Dodge) J. Larsen) by lacking rows of amphiesmal plugs, a feature presently considered to be a characteristic of Karlodinium. In K. armiger, an outer membrane is underlain by a complex system of cisternae and vacuoles. The pigment profile of K. armiger revealed...... sequence, differed in only 0.3% of 1438 bp. We consider the two taxa to belong to the same species. This necessitates a change of name for the most widely found species, K. micrum, to K. veneficum. The three genera Karlodinium, Takayama, and Karenia constitute a separate evolutionary lineage, for which...

  18. Medical subdomain classification of clinical notes using a machine learning-based natural language processing approach


    Weng, Wei-Hung; Wagholikar, Kavishwar B.; McCray, Alexa T.; Szolovits, Peter; Chueh, Henry C.


    Background The medical subdomain of a clinical note, such as cardiology or neurology, is useful content-derived metadata for developing machine learning downstream applications. To classify the medical subdomain of a note accurately, we have constructed a machine learning-based natural language processing (NLP) pipeline and developed medical subdomain classifiers based on the content of the note. Methods We constructed the pipeline using the clinical ...

  19. Difficulties of clinical radiodiagnosis of concomitant injuries of fornix and base of the skull

    International Nuclear Information System (INIS)

    Krutitskij, A.G.; Semisalov, S.Ya.


    Clinical radiological semiotics in 234 patients with injuries of fornix and base of the skull is studied. Among skull injuries the most critical are those of fornix and base of anterior parts of the skull. Severity of state doesn't exclude, but requires an obligatory X-ray examination, at least - review radiographs of the skull. When choosing the volume of surgical intervention the data on X-ray examination along with clinical pattern should be taken account of

  20. Clinical variability in dystrophic epidermolysis bullosa and findings with scanning electron microscopy Variabilidade clínica em epidermólise bolhosa distrófica e achados de microscopia eletrônica de varredura

    Directory of Open Access Journals (Sweden)

    Hiram Larangeira de Almeida Jr


    Full Text Available In dystrophic epidermolysis bullosa, the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane and its consequent loss. A 46 year-old female patient presented blisters with a pretibial distribution associated with nail dystrophy. Her two children had hyponychia and anonychia, which affected all toe nails and the thumb, forefinger and middle finger. DNA sequencing identified in exon 75 of COL7A1 gene a pathologic mutation: c.6235G>A (p.Gly2079Arg. Immunomapping of a blister demonstrated collagen IV (basal membrane in the blister roof and collagen VII in its floor, confirming dystrophic epidermolysis bullosa. Scanning electron microscopy of an inverted blister showed net-forming collagen attached to the blister roof . The variability found in this family has already been reported and confirms, on a clinical basis, the nail subtype as a dystrophic variant.Na epidermólise bolhosa distrófica, o defeito genético das fibrilas de ancoragem leva à clivagem abaixo da membrana basal com sua consequente perda. Uma paciente de 46 anos apresentava bolhas pré-tibiais associadas à distrofia ungueal. Seus dois filhos apresentavam hipo e anoníquia, afetando todas as unhas dos pododáctilos e dos primeiros, segundos e terceiros quirodáctilos. O sequenciamento de DNA identificou no exon 75 do gene COL7A1 uma mutação patológica: c.6235G>A (p.Gly2079Arg. O imunomapeamento identificou o colágeno IV no teto e colágeno VII no assoalho de uma bolha , confirmando o diagnóstico de epidermólise bolhosa distrófica. A microscopia eletrônica de varredura de um teto invertido de bolha demonstrou rede de colágeno aderida ao mesmo. A variabilidade clínica encontrada nessa família já foi escrita e confirma, que o subtipo ungueal das epidermólises bolhosas é uma forma distrófica.