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At least 73 records · Page 4Linked to original sources
PubMed2006

In vivo real-time vessel imaging and ex vivo 3D reconstruction of atherosclerotic plaque in apolipoprotein E-knockout mice using synchrotron radiation microscopy.

BACKGROUND: To examine the pathophysiology of atherosclerosis, imaging the vascular wall and pathology without tissue damage is required. We used the unmonochromatized synchrotron X-ray to acquire in vivo real-time and ex vivo images of atherosclerotic lesions in apo E-knockout mice without contrast agents or staining. METHODS: In the five apo E-knockout mice (apo E-/-, 12, 24, 32, 48, 62-week-old, 3 males) and age/sex matched five wild type mice on cow diets, we acquired in vivo real-time images of thoracic aorta without contrast agents and then, the central arterial trees were dissected intact. Ex vivo synchrotron images with tomographic reconstruction were done and compared with the corresponding pathology. RESULTS: For all living animals, in vivo real-time images of thoracic aorta could be acquired without contrast agents but could not identify the atherosclerotic lesions. Ex vivo images accurately determined aortic wall and atherosclerotic plaque without staining in comparison to histopathology according to the AHA classification (r=0.84, p<0.001). The volume rendered 3 D images of plaque showed central cholesterol clefts as matched with optical images. CONCLUSIONS: The combination of synchrotron enhanced X-ray microscopy and genetically engineered hyperlipidemic animals would be a useful tool to investigate the changes of advanced atherosclerotic lesions.

Animals↗
PubMed2003

Synchrotron radiation therapy of malignant brain glioma loaded with an iodinated contrast agent: first trial on rats bearing F98 gliomas.

PURPOSE: Enhancement of the radiation dose delivered to a brain tumor can be achieved by infusing an iodinated contrast agent to the patient and irradiating with kilovoltage X-rays in computed tomography (CT) mode. Synchrotron sources, providing monochromatic tunable intense beams, are ideal for this treatment. The aim of this study is to assess in vivo the efficiency of this novel radiotherapy modality, Synchrotron Radiation CT-Therapy. MATERIALS AND METHODS: Intracranial implantations of 10(5) F98 glioma cells were performed on 18 Fisher 344 rats. Six rats were untreated controls, six received radiotherapy alone (10 Gy in the tumor by single fraction tomographic irradiation at 50 keV), and six received the same radiotherapy treatment under a continuous infusion of iodinated contrast agent. RESULTS: The rats that received contrast agent during radiotherapy survived significantly longer than rats that received radiotherapy alone (p = 0.025). Mean survival times (mean +/- SD) were 12.3 +/- 0.8, 14.8 +/- 2.8, and 18.2 +/- 1.3 days; median survival times were 12.5, 15, and 18 days (untreated controls, irradiated without iodine, irradiated with iodine, respectively). The increase in life spans was 20% and 44% for the rats irradiated without or with iodine, respectively. CONCLUSIONS: This method of radiation dose enhancement in brain tumors with synchrotron radiation significantly increases survival and appears highly promising.

Algorithms↗
PubMed2005

Efficient use of synchrotron radiation for macromolecular diffraction data collection.

In recent years, number of X-ray synchrotron beam lines dedicated to collecting diffraction data from macromolecular crystals has exceeded 50. Indeed, today most protein and nucleic acid crystal structures are solved and refined based on the synchrotron data. Collecting diffraction data on a synchrotron beam line involves many technical points, but it is not a mere technicality. Even though the available hardware and software have become more advanced and user-friendly, it is always beneficial if the experimenter is aware of the problems involved in the data collection process and can make informed decisions leading to the highest possible quality of the acquired diffraction data. Various factors, important for the success of data collection experiments and their relevance for different kinds of applications, are discussed.

Computer Simulation↗
PubMed2006

New light for science: synchrotron radiation in structural medicine.

Macromolecular crystallography (MX) is a powerful method for obtaining detailed three-dimensional structural information about macromolecules. MX using synchrotron X-rays has contributed, significantly, to both fundamental and applied research, including the structure-based design of drugs to combat important diseases. New third-generation synchrotrons offer substantial improvements in terms of quality and brightness of the X-ray beams they produce. Important classes of macromolecules, such as membrane proteins (including many receptors) and macromolecular complexes, are difficult to obtain in quantity and to crystallise, which has hampered analysis by MX. Intensely bright X-rays from the latest synchrotrons will enable the use of extremely small crystals, and should usher in a period of rapid progress in resolving these previously refractory structures.

Antitubercular Agents↗
PubMed1998

Following the folding of RNA with time-resolved synchrotron X-ray footprinting.

The rapid mixing synchrotron X-ray footprinting technique described in this article allows nucleic acid folding and ligand binding reactions to be followed on a millisecond time resolution with single nucleotide resolution. In principle, the change in .OH protection of every nucleotide in a nucleic acid hundreds of nucleotides long can be monitored separately. In addition, a wide range of solution conditions are compatible with the radiolytic generation of .OH. These characteristics of synchrotron X-ray footprinting create opportunities for conducting thermodynamic and kinetic studies of nucleic acids that are both comprehensive and detailed. Kinetic footprinting studies of a number of systems have been initiated by the Center for Synchrotron Biosciences using this technique.

Flow Injection Analysis↗
PubMed1995

High-resolution macromolecular structure determination using CCD detectors and synchrotron radiation.

BACKGROUND: Synchrotron radiation sources have made impressive contributions to macromolecular crystallography. The delay in development of appropriate X-ray detectors has, however, been a significant limitation to their efficient use. New technologies, based on charge-coupled devices (CCDs), provide capabilities for faster, more accurate, automated data collection. RESULTS: A CCD-based X-ray detector has been developed for use in macromolecular crystallography and has been in operation for about one and a half years at the Cornell High Energy Synchrotron Source. It has been used for a variety of crystallographic projects, including a number of high-resolution structural studies. The statistical quality of the data, the detector's ease and efficiency of use, and the growing number of structural results illustrate the practical utility of this new detector system. CONCLUSIONS: The new detector has enhanced capabilities for measuring diffraction patterns from crystals of macromolecules, especially at high resolution, when the X-ray intensities are weak. The survey of results described here ranges from virus crystallography to weakly diffracting small-molecule structure determination and demonstrates the potential of CCD detectors when combined with synchrotron radiation sources.

Amino Acid Sequence↗
PubMed1999

Millisecond radiolytic modification of peptides by synchrotron X-rays identified by mass spectrometry.

Radiolysis of peptide and protein solutions with high-energy X-ray beams induces stable, covalent modifications of amino acid residues that are useful for synchrotron protein footprinting. A series of 5-14 amino acid residue peptides of varied sequences were selected to study their synchrotron radiolysis chemistry. Radiolyzed peptide products were detected within 10 ms of exposure to a white light synchrotron X-ray beam. Mass spectrometry techniques were used to characterize radiolytic modification to amino acids cysteine (Cys), methionine (Met), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), proline (Pro), histidine (His), and leucine (Leu). A reactivity order of Cys, Met >> Phe, Tyr, > Trp > Pro > His, Leu was determined under aerobic reaction conditions from MS/MS analysis of the radiolyzed peptide products. Radiolysis of peptides in 18O-labeled water under aerobic conditions revealed that oxygenated radical species from air and water both contribute to the modification of amino acid side chains. Cysteine and methionine side chains reacted with hydroxyl radicals generated from radiolysis of water as well as molecular oxygen. Phenylalanine and tyrosine residues were modified predominantly by hydroxyl radicals, and the source of modification of proline was exclusively through molecular oxygen.

Amino Acid Sequence↗
PubMed1999

Polymorph determination for the GP IIb/IIIa antagonist, roxifiban, using a combination of electron diffraction and synchrotron X-ray powder diffraction techniques.

Unit cell parameters of two polymorphs of roxifiban have been determined by a combination of transmission electron microscopy (TEM) single-crystal and synchrotron X-ray powder diffraction techniques. While it was difficult to differentiate the two forms by their standard X-ray diffraction patterns, the high-resolution synchrotron patterns clearly showed striking differences. Unit cells for the two forms required the use of cell parameters derived from TEM diffraction patterns. The two unit cells are, not surprisingly, very similar except for a doubling of one of the axes for form II. The combined use of TEM and synchrotron patterns appears to be a good general approach for characterizing complex (low-symmetry, large unit cell) polymorphs.

Amidines↗
PubMed2005

Synchrotron radiation circular dichroism spectroscopy of proteins and applications in structural and functional genomics.

The technique of Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy and its advantages over conventional circular dichroism spectroscopy are described in this tutorial review, as well as recent applications of the technique in structural and functional genomics. Circular dichroism (CD) spectroscopy is a well-established method in biological chemistry and structural biology, but its utility can be limited by the low flux of the light source in the far ultraviolet and vacuum ultraviolet wavelength regions in conventional CD instruments. The development of synchrotron radiation circular dichroism (SRCD), using the intense light of a synchrotron beam, has greatly expanded the utility of the method, especially as a tool for both structural and functional genomics. These applications take advantage of the enhanced features of SRCD relative to conventional CD: the ability to measure lower wavelength data containing more electronic transitions and hence more structural information, the higher signal-to-noise hence requiring smaller samples, the higher intensity enabling measurements in absorbing buffers and in the presence of lipids and detergents, and the ability to do faster measurements enabling high throughput and time-resolved spectroscopy.This article discusses recent developments in SRCD instrumentation, software, sample preparation and methods of analyses, with particular emphasis on their applications to the study of proteins. These advances have led to new applications in structural genomics (SG), including the potential for fold recognition as a means of target selection and the examination of membrane proteins, a class of proteins usually excluded from SG programmes. Other SG uses include detection of macromolecular interactions as a screen for complex formation, and examination of glycoproteins and sugar components. In functional genomics (FG) new applications include screening for ligand binding as a means of identifying function, and examination of structural differences in mutant proteins as a means of gaining insight into function.

Circular Dichroism↗
PubMed2005

X-Ray microanalytical techniques based on synchrotron radiation.

The development of 3rd generation synchrotron radiation sources like European Synchrotron Radiation Facility (ESRF) in parallel with recent advances in the technology of X-ray microfocusing elements like Kirkpatrick-Baez (KB) mirrors, diffractive (Fresnel zone plates, FZP) and refractive (compound refractive lenses, CRL) optics, makes it possible to use X-ray microscopy techniques with high energy X-rays (energy superior to 4 keV). Spectroscopy, imaging, tomography and diffraction studies of samples with hard X-rays at micrometre and sub-micrometre spatial resolutions are now possible. The concept of combining these techniques as a high-energy microscopy has been proposed and successfully realized at the ESRF beamlines. Therefore a short summary of X-ray microscopy techniques is presented first. The main emphasis will be put on those methods which aim to produce sub-micron and nanometre resolution. These methods fall into three broad categories: reflective, refractive and diffractive optics. The basic principles and recent achievements will be discussed for all optical devices. Recent applications of synchrotron based microanalytical techniques to characterise radioactive fuel particles (UO(2)) released from the Chernobyl reactor are reported.

Environmental Monitoring↗
PubMed1996

High-resolution confocal microscopy using synchrotron radiation.

A confocal scanning light microscope coupled to the Daresbury Synchrotron Radiation Source is described. The broad spectrum of synchrotron radiation and the application of achromatic quartz/CaF2 optics allows for confocal imaging over the wavelength range 200-700 nm. This includes UV light, which is particularly suitable for high-resolution imaging. The results of test measurements using 290-nm light indicate that a lateral resolution better than 100 nm is obtained. An additional advantage of the white synchrotron radiation is that the excitation wavelength can be chosen to match the absorption band of any fluorescent dye. The availability of UV light for confocal microscopy enables studies of naturally occurring fluorophores. The potential applications of the microscope are illustrated by the real-time imaging of hormone traffic using the naturally occurring oestrogen coumestrol. (The IUPAC name for coumestrol is 3,9-dihydroxy-6H-benzofurol[3,2-c][1]benzo-pyran-6-one (Chem. Abstr. Reg. No. 479-13-0). The trivial name will be used throughout this paper.

Animals↗
PubMed2000

Specific chemical and structural damage to proteins produced by synchrotron radiation.

Radiation damage is an inherent problem in x-ray crystallography. It usually is presumed to be nonspecific and manifested as a gradual decay in the overall quality of data obtained for a given crystal as data collection proceeds. Based on third-generation synchrotron x-ray data, collected at cryogenic temperatures, we show for the enzymes Torpedo californica acetylcholinesterase and hen egg white lysozyme that synchrotron radiation also can cause highly specific damage. Disulfide bridges break, and carboxyl groups of acidic residues lose their definition. Highly exposed carboxyls, and those in the active site of both enzymes, appear particularly susceptible. The catalytic triad residue, His-440, in acetylcholinesterase, also appears to be much more sensitive to radiation damage than other histidine residues. Our findings have direct practical implications for routine x-ray data collection at high-energy synchrotron sources. Furthermore, they provide a direct approach for studying the radiation chemistry of proteins and nucleic acids at a detailed, structural level and also may yield information concerning putative "weak links" in a given biological macromolecule, which may be of structural and functional significance.

Acetylcholinesterase↗
PubMed2000

Monte Carlo simulation of dose distributions from a synchrotron-produced microplanar beam array using the EGS4 code system.

Microbeam therapy is established as a general concept for brain tumour treatment. A synchrotron based x-ray source was chosen for experimental research into microbeam therapy, and therefore new simulations were essential for investigating the therapy parameters with a proper description of the synchrotron radiation characteristics. To design therapy parameters for tumour treatments, the newly upgraded LSCAT (Low energy SCATtering) package of the EGS4 Monte Carlo simulation code was adapted to develop an accurate self-written user code for calculating microbeam radiation dose profiles with a precision of 1 microm. LSCAT is highly suited to this purpose due to its ability to simulate low-energy x-ray transport with detailed photon interactions (including bound electron incoherent scattering functions, and linear polarized coherent scattering). The properties of the synchrotron x-ray microbeam, including its polarization, source spectrum and beam penumbra, were simulated by the new user codes. Two concentric spheres, an inner sphere, defined as a brain, and a surrounding sphere, defined as a skull, represented the phantom. The microbeam simulation was tested using a 3 x 3 cm array beam for small treatment areas and a 6 x 6 cm array for larger ones, with different therapy parameters, such as beam width and spacing. The results showed that the microbeam array retained an adequate peak-to-valley ratio, of five times at least, at tissue depths suitable for radiation therapy. Dose measurements taken at 1 microm resolution with an 'edge-on' MOSFET validated the basics of the user code for microplanar radiation therapy.

Brain Neoplasms↗
PubMed2005

Instrumentation for synchrotron-radiation macromolecular crystallography.

X-ray diffraction is an extremely important tool for structure determination of biological macromolecules, to the extent that currently around 85% of Protein Data Bank entries result from X-ray measurements. Many of these structure determinations use synchrotron radiation for data collection. This article aims to give synchrotron users an overview of the functioning of a synchrotron beamline and how the performance of various instruments combines to allow the collection of diffraction data.

Computer Simulation↗
PubMed1998

Integrated software for a macromolecular crystallography synchrotron beamline.

A package of software has been produced for the operation of the synchrotron beamline X12-C at the National Synchrotron Light Source at Brookhaven National Laboratory. Years of observing common user mistakes has enabled the production of software that reduces user errors significantly. Users of the beamline communicate with all the experimental apparatus, including both the data-collection equipment and the beamline components, including the monochromator, through an easy-to-use graphical user interface (GUI). Important features of the system are (1) its modularity, so that different underlying programs or different apparatus can be incorporated easily; (2) its ease of use, minimizing both user errors and training effort; and (3) that most of the experimental operations and parameters are logged automatically, again minimizing errors and facilitating more-or-less automatic reduction of the data. Features of the software are useful enough to have been incorporated into operations at other synchrotron beamlines.

Crystallography, X-Ray↗
PubMed2003

Comparison of intravenous coronary angiography using synchrotron radiation with selective coronary angiography.

Intravenous coronary angiography with synchrotron radiation is a novel and minimally invasive technique for coronary imaging. At the Hamburger Synchrotronstrahlungslabor HASYLAB at DESY, a dedicated angiography system has been developed, which has been shown to provide detailed images of coronary artery segments. For each scan, two monochromatic X-ray images below and above the K-edge of iodine were recorded simultaneously. The two images were subtracted logarithmically to produce a maximal contrast enhancement of the iodine. To date, the procedure has been carried out on 379 outpatients. No complications occurred during or after the angiographic procedure, and hospitalization was not required in any subject. The acceptance by patient is extremely high. Five outside reviewers, blinded as to the clinical data or prior angiographic interpretation, reviewed the images for the presence or absence of 70% or more occlusion of a vessel. They reached a sensitivity of 79% and a specificity of 99%. The study has demonstrated that the synchrotron method has satisfactory sensitivity and very high specificity for severe stenoses. The new method has several advantages over magnetic resonance imaging (MRI), electron beam computed tomography (EBCT), and multi-slice computed tomography (MSCT). Neither vascular calcification (CT) nor the presence of metal stents (MRI) impairs the evaluation of perfusion of segments of the coronary arteries. Furthermore, the spatial resolution is three or four times higher using synchrotron angiography, and problems due to respiratory motion are eliminated.

Adult↗
PubMed2006

Radiation damage to protein specimens from electron beam imaging and diffraction: a mini-review of anti-damage approaches, with special reference to synchrotron X-ray crystallography.

Recent research progress using X-ray cryo-crystallography with the photon beams from third-generation synchrotron sources has resulted in recognition that this intense radiation commonly damages protein samples even when they are held at 100 K. Other structural biologists examining thin protein crystals or single particle specimens encounter similar radiation damage problems during electron diffraction and imaging, but have developed some effective countermeasures. The aim of this concise review is to examine whether analogous approaches can be utilized to alleviate the X-ray radiation damage problem in synchrotron macromolecular crystallography. The critical discussion of this question is preceded by presentation of background material on modern technical procedures with electron beam instruments using 300-400 kV accelerating voltage, low-dose exposures for data recording, and protection of protein specimens by cryogenic cooling; these practical approaches to dealing with electron radiation damage currently permit best resolution levels of 6 A (0.6 nm) for single particle specimens, and of 1.9 A for two-dimensional membrane protein crystals. Final determination of the potential effectiveness and practical value of using such new or unconventional ideas will necessitate showing, by experimental testing, that these produce significantly improved protection of three-dimensional protein crystals during synchrotron X-ray diffraction.

Computer Simulation↗
PubMed2001

Design of synchrotron light source and its beamline dedicated to dual-energy x-ray computed tomography.

A synchrotron light source dedicated to medical applications has been designed at National Institute of Radiological Sciences. The storage ring, with circumference of 80 m, is designed for acceleration of 2.3 GeV and a stored current of 420 mA. It is equipped with two multipole wigglers to produce sufficient photon flux in a hard x-ray region required for medical applications. The purposes of the synchrotron light source are clinical performance of medical diagnoses clinically and research and development relating with medical applications. One of the most interesting applications for us is dual-energy x-ray computed tomography (CT). It gives the information about electron density of human tissue. The information plays an important role in advancing heavy-ion radiotherapy of cancers. Electron density can be derived from attenuation coefficients measured by different energy x rays. In this paper, a practical method of the dual-energy x-ray CT with synchrotron radiation is proposed with the theoretical consideration. The primitive experiment using monochromatic x rays emitted from radioisotopes proved the procedure of analysis mentioned here effective to derive electron densities from linear attenuation coefficients for two x rays of a different energy. The beamline dedicated to dual-energy x-ray CT is also proposed. It has a multipole wiggler as a light source and it mainly consists of a dual crystal monochromator and a rotating filter for attenuating photon flux of x rays and two-dimensional detector.

Equipment Design↗