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Sample records for macromolecular mri cas

  1. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetriaminepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-a, b-[N-(2-hydroxyethyl)-L- aspartamide] (PHEA) and poly-a, b-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.

  2. Implementation of fast macromolecular proton fraction mapping on 1.5 and 3 Tesla clinical MRI scanners: preliminary experience

    Science.gov (United States)

    Yarnykh, V.; Korostyshevskaya, A.

    2017-08-01

    Macromolecular proton fraction (MPF) is a biophysical parameter describing the amount of macromolecular protons involved into magnetization exchange with water protons in tissues. MPF represents a significant interest as a magnetic resonance imaging (MRI) biomarker of myelin for clinical applications. A recent fast MPF mapping method enabled clinical translation of MPF measurements due to time-efficient acquisition based on the single-point constrained fit algorithm. However, previous MPF mapping applications utilized only 3 Tesla MRI scanners and modified pulse sequences, which are not commonly available. This study aimed to test the feasibility of MPF mapping implementation on a 1.5 Tesla clinical scanner using standard manufacturer’s sequences and compare the performance of this method between 1.5 and 3 Tesla scanners. MPF mapping was implemented on 1.5 and 3 Tesla MRI units of one manufacturer with either optimized custom-written or standard product pulse sequences. Whole-brain three-dimensional MPF maps obtained from a single volunteer were compared between field strengths and implementation options. MPF maps demonstrated similar quality at both field strengths. MPF values in segmented brain tissues and specific anatomic regions appeared in close agreement. This experiment demonstrates the feasibility of fast MPF mapping using standard sequences on 1.5 T and 3 T clinical scanners.

  3. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  4. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  5. Separation and characterization of the two diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a common synthon in macromolecular MRI contrast agents: their water exchange and isomerization kinetics.

    Science.gov (United States)

    Burai, László; Tóth, Eva; Sour, Angélique; Merbach, André E

    2005-05-16

    Chiral, bifunctional poly(amino carboxylate) ligands are commonly used for the synthesis of macromolecular, Gd(III)-based MRI contrast agents, prepared in the objective of increasing relaxivity or delivering the paramagnetic Gd(III) to a specific site (targeting). Complex formation with such ligands results in two diastereomeric forms for the complex which can be separated by HPLC. We demonstrated that the diastereomer ratio for Ln(III) DTPA derivatives (approximately 60:40) remains constant throughout the lanthanide series, in contrast to Ln(III) EPTPA derivatives, where it varies as a function of the cation size with a maximum for the middle lanthanides (DTPA(5-) = diethylenetriaminepentaacetate; EPTPA(5-) = ethylenepropylenetriaminepentaacetate). The interconversion of the two diastereomers, studied by HPLC, is a proton-catalyzed process (k(obs) = k(1)[H(+)]). It is relatively fast for [Gd(EPTPA-bz-NH(2))(H(2)O)](2-) but slow enough for [Gd(DTPA-bz-NH(2))(H(2)O)](2-) to allow investigation of pure individual isomers (isomerization rate constants are k(1) = (3.03 +/- 0.07) x 10(4) and 11.6 +/- 0.5 s(-1) M(-1) for [Gd(EPTPA-bz-NH(2))(H(2)O)](2)(-) and [Gd(DTPA-bz-NH(2))(H(2)O)](2-), respectively). Individual water exchange rates have been determined for both diastereomers of [Gd(DTPA-bz-NH(2))(H(2)O)](2-) by a variable-temperature (17)O NMR study. Similarly to Ln(III) EPTPA derivatives, k(ex) values differ by a factor of 2 (k(ex)(298) = (5.7 +/- 0.2) x 10(6) and (3.1 +/- 0.1) x 10(6) s(-1)). This variance in the exchange rate has no consequence on the proton relaxivity of the two diastereomers, since it is solely limited by fast rotation. However, such difference in k(ex) will affect proton relaxivity when these diastereomers are linked to a slowly rotating macromolecule. Once the rotation is optimized, slow water exchange will limit relaxivity; thus, a factor of 2 in the exchange rate can lead to a remarkably different relaxivity for the diastereomer complexes

  6. MRI

    Science.gov (United States)

    MRI does not use ionizing radiation. No side effects from the magnetic fields and radio waves have been reported. The most common type of contrast (dye) used is gadolinium. It is very safe. Allergic reactions rarely ...

  7. Macromolecular Prodrugs of Ribavirin

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Hinton, Tracey M; Gajda, Paulina

    2017-01-01

    The requirement for new antiviral therapeutics is an ever present need. Particularly lacking are broad spectrum antivirals that have low toxicity. We develop such agents based on macromolecular prodrugs whereby both the polymer chain and the drug released from the polymer upon cell entry have ant...

  8. Macromolecular Crystallization in Microgravity

    Science.gov (United States)

    Snell, Edward H.; Helliwell, John R.

    2004-01-01

    The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural

  9. Macromolecular crystallization in microgravity

    Energy Technology Data Exchange (ETDEWEB)

    Snell, Edward H [Biophysics Group, NASA Marshall Space Flight Center, Code XD42, Huntsville, AL 35812 (United States); Helliwell, John R [Department of Chemistry, The University of Manchester, Manchester, M13 9PL (United Kingdom)

    2005-04-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  10. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    XU; Mianyi

    2001-01-01

    Chitosans with various degrees of deacetylation (D.D.), which were used as standard sample for FTIR determination, were prepared from completely deacetylated chitosan by homogeneous N-acetylation reaction. By combining four probable probe bands, i.e. 1655, 1560, 1380 and 1320 cm-1, eight probable reference bands, i.e. 3430, 2920, 2880, 1425, 1155, 1070, 1030 and 895 cm-1 and two baseline methods, the most suitable ratios Aprobe band/Areference band from IR spectra to determine the degree of acetylation of chitosan were evaluated from 48 combinations to be A1560/A2880, A1560/A2920 and A1655/A3430(A1560/A2880 is mostly recommended). The second baseline method, i.e. linking between adjacent two valleys, was better for measuring the absorbances of 1560 and 1655 cm-1 bands. The determination range of the D.D. (1%-100%) covered almost the whole range. The standard curves with A1560/A2880 and A1655/A3430 were also suitable for the determination of degree of substitution of other N-acylated chitosan, such as N-propionyl chitosan, N-butyryl chitosan and N-hexanoyl chitosan.

  11. Microgravity and Macromolecular Crystallography

    Science.gov (United States)

    Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

  12. CAS announces new academicians

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Twenty-nine prominent Chinese scientists have been elected as CAS Members and five of their colleagues from US, France and Russia as CAS Foreign Members in 2007. The announcement was made by CAS Vice President LI Jinghai at a press conference held on 27 December, 2007 in Beijing. CAS President LU Yongxiang was present at the meeting.

  13. Macromolecular architectures for organic photovoltaics.

    Science.gov (United States)

    Popere, Bhooshan C; Della Pelle, Andrea M; Poe, Ambata; Thayumanavan, S

    2012-03-28

    Research in the field of organic photovoltaics has gained considerable momentum in the last two decades owing to the need for developing low-cost and efficient energy harvesting systems. Elegant molecular architectures have been designed, synthesized and employed as active materials for photovoltaic devices thereby leading to a better molecular structure-device property relationship understanding. In this perspective, we outline new macromolecular scaffolds that have been designed within the purview of each of the three fundamental processes involving light harvesting, charge separation and charge transport.

  14. Emergent Property in Macromolecular Motion

    Institute of Scientific and Technical Information of China (English)

    吴嘉麟

    2003-01-01

    In this paper, the model of inverse cascade fractal super-blocks along one direction (in the positive or negative) in the 3-dimensional space is developed to describe the self-similar motion in macromolecular system. Microscopically the cohesive and dispersed states of the motion blocks are co-existent states with vastly different probability of occurrence.Experimental results and theoretical analysis show that the microscopic cohesive state energy and dispersed state energy of each motion block are respectively equal to the macroscopic glassy state energy kT8 and molten state energy kTm of the system. This singularity unveils topologically the nonintegrability, mathematically the anholonomy, and macroscopically the emergent property. This singularity also reveals that the glass, viscoelastic and melt states are three distinct emergent properties of macromolecular motion from a macroscopic viewpoint. The fractal concept of excluded volume is introduced to depict the random motion at various scales in the system. The Hausdorff dimensions of the excluded volune and the motion blocks are both found equal to 3/2.

  15. Data Mining of Macromolecular Structures.

    Science.gov (United States)

    van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

    2016-01-01

    The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

  16. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......, and gene regulation, at both transcriptional and translational levels. Udgivelsesdato: 1999-Jul...

  17. [CAS General Standards 2012

    Science.gov (United States)

    Council for the Advancement of Standards in Higher Education, 2011

    2011-01-01

    The mission of the Council for the Advancement of Standards in Higher Education (CAS) is to promote the improvement of programs and services to enhance the quality of student learning and development. CAS is a consortium of professional associations who work collaboratively to develop and promulgate standards and guidelines and to encourage…

  18. Analysis of Tagish Lake macromolecular organic material

    OpenAIRE

    Gilmour, I; Pearson, V. K.; Sephton, M.A.

    2001-01-01

    Macromolecular material is, by far, the major organic component of meteorites. Flash pyrolysis GCMS has been used to investigate this organic component in Tagish Lake. It is more condensed, less susbtituted than Murchson.

  19. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK.

  20. Macromolecular crowding: Macromolecules friend or foe.

    Science.gov (United States)

    Mittal, Shruti; Chowhan, Rimpy Kaur; Singh, Laishram Rajendrakumar

    2015-09-01

    Cellular interior is known to be densely crowded due to the presence of soluble and insoluble macromolecules, which altogether occupy ~40% of the total cellular volume. This results in altered biological properties of macromolecules. Macromolecular crowding is observed to have both positive and negative effects on protein folding, structure, stability and function. Significant data has been accumulated so far on both the aspects. However, most of the review articles so far have focused on the positive aspect of macromolecular crowding and not much attention has been paid on the deleterious aspect of crowding on macromolecules. In order to have a complete knowledge of the effect of macromolecular crowding on proteins and enzymes, it is important to look into both the aspects of crowding to determine its precise role under physiological conditions. To fill the gap in the understanding of the effect of macromolecular crowding on proteins and enzymes, this review article focuses on the deleterious influence of crowding on macromolecules. Macromolecular crowding is not always good but also has several deleterious effects on various macromolecular properties. Taken together, the properties of biological macromolecules in vivo appears to be finely regulated by the nature and level of the intracellular crowdedness in order to perform their biological functions appropriately. The information provided here gives an understanding of the role played by the nature and level of cellular crowdedness in intensifying and/or alleviating the burden of various proteopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Energy transfer in macromolecular arrays

    Science.gov (United States)

    Andrews, David L.; Jenkins, Robert D.

    2003-11-01

    Macromolecular systems comprised of many light-sensitive centres (the photosynthetic unit, dendrimers, and other highly symmetric multichromophore arrays) are important structures offering challenges to theoreticians and synthetic chemists alike. Here we outline novel photophysical interactions predicted and observed in such arrays. Using the tools of molecular quantum electrodynamics (QED) we present quantum amplitudes for a variety of higher-order resonance energy transfer (RET) schemes associated with well-known nonlinear optical effects such as two- and three-photon absorption. The initial analysis is extended to account for situations where the participant donor species are identical and exist in a highly symmetric environment, leading to the possible formation of excitons. It emerges from the QED theory that such excitons are closely associated with the higher-order RET processes. General results are interpreted by analyzing particular molecular architectures which offer interesting features such as rate enhancement or limitation and exciton pathway quenching. Applications in the areas of photosynthesis, molecular logic gates and low-intensity fluorescence energy transfer are predicted.

  2. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  3. Conference of CAS History Commission

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ The Commission of CAS History held its third conference on Oct. 31 in Beijing. CAS Vice-President Yang Bailing and Vice-Secretary of the CPC Leading Group at CAS Guo Chuanjie addressed the meeting, which was chaired by Guo Huadong, CAS vice secretary -general.

  4. Research Highlights of CAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ 1. Basic Research Basic research has always been one of the major tasks of CAS. Over the more than 50 years since its founding, CAS has gradually branched out to cover many fundamental fields of the natural sciences, such as mathematics, physics, chemistry, mechanics,astronomy, space science, life science, geoscience and environmental science - with nearly 10,000 research professionals and 117 open laboratories (including 50 key State laboratories). At present, there are 29 research institutes (including observatories) covering such fields as physical science, mathematics, mechanics and astronomy; with 31 open laboratories (nine key State laboratories, four State laboratories and 18 CAS open laboratories).

  5. Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

    Directory of Open Access Journals (Sweden)

    Yuka Miyake

    2015-12-01

    Full Text Available Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs, which showed longitudinal relaxivity (r1 values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer. In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T. In this study, the association constants (Ka of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA, measured and calculated with a quartz crystal microbalance (QCM in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

  6. Effects of macromolecular crowding on genetic networks.

    Science.gov (United States)

    Morelli, Marco J; Allen, Rosalind J; Wolde, Pieter Rein ten

    2011-12-21

    The intracellular environment is crowded with proteins, DNA, and other macromolecules. Under physiological conditions, macromolecular crowding can alter both molecular diffusion and the equilibria of bimolecular reactions and therefore is likely to have a significant effect on the function of biochemical networks. We propose a simple way to model the effects of macromolecular crowding on biochemical networks via an appropriate scaling of bimolecular association and dissociation rates. We use this approach, in combination with kinetic Monte Carlo simulations, to analyze the effects of crowding on a constitutively expressed gene, a repressed gene, and a model for the bacteriophage λ genetic switch, in the presence and absence of nonspecific binding of transcription factors to genomic DNA. Our results show that the effects of crowding are mainly caused by the shift of association-dissociation equilibria rather than the slowing down of protein diffusion, and that macromolecular crowding can have relevant and counterintuitive effects on biochemical network performance.

  7. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction...

  8. Asteroid named after CAS scientist

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ An asteroid has been named after CAS astronomy historian XI Zezong with the approval of the International Minor Planet Nomenclature Committee (IMPNC), announced China's National Astronomical Observatories at CAS (NAOC) on 17 August.

  9. Cas9 Functionally Opens Chromatin.

    Directory of Open Access Journals (Sweden)

    Amira A Barkal

    Full Text Available Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding.

  10. CRISPR-Cas

    NARCIS (Netherlands)

    Jackson, Simon A.; McKenzie, Rebecca E.; Fagerlund, Robert D.; Kieper, Sebastian N.; Fineran, Peter C.; Brouns, Stan J.J.

    2017-01-01

    Bacteria and archaea are engaged in a constant arms race to defend against the ever-present threats of viruses and invasion by mobile genetic elements. The most flexible weapons in the prokaryotic defense arsenal are the CRISPR-Cas adaptive immune systems. These systems are capable of selective

  11. Statistics of Multiscale Fluctuations in Macromolecular Systems

    CERN Document Server

    Yukalov, V I

    2012-01-01

    An approach is suggested for treating multiscale fluctuations in macromolecular systems. The emphasis is on the statistical properties of such fluctuations. The approach is illustrated by a macromolecular system with mesoscopic fluctuations between the states of atomic orbitals. Strong-orbital and weak-orbital couplings fluctuationally arise, being multiscale in space and time. Statistical properties of the system are obtained by averaging over the multiscale fluctuations. The existence of such multiscale fluctuations causes phase transitions between strong-coupling and weak-coupling states. These transitions are connected with structure and size transformations of macromolecules. An approach for treating density and size multiscale fluctuations by means of classical statistical mechanics is also advanced.

  12. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams.

  13. Growth and dissolution of macromolecular Markov chains

    CERN Document Server

    Gaspard, Pierre

    2016-01-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  14. Growth and Dissolution of Macromolecular Markov Chains

    Science.gov (United States)

    Gaspard, Pierre

    2016-07-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  15. Dextran: A promising macromolecular drug carrier

    Directory of Open Access Journals (Sweden)

    Dhaneshwar Suneela

    2006-01-01

    Full Text Available Over the past three decades intensive efforts have been made to design novel systems able to deliver the drug more effectively to the target site. The ongoing intense search for novel and innovative drug delivery systems is predominantly a consequence of the well-established fact that the conventional dosage forms are not sufficiently effective in conveying the drug compound to its site of action and once in the target area, in releasing the active agent over a desired period of time. The potential use of macromolecular prodrugs as a means of achieving targeted drug delivery has attracted considerable interest in recent years. Macromolecules such as antibodies, lipoproteins, lectins, proteins, polypeptides, polysaccharides, natural as well as synthetic polymers offer potential applicabilities as high molecular weight carriers for various therapeutically active compounds. Dextrans serve as one of the most promising macromolecular carrier candidates for a wide variety of therapeutic agents due to their excellent physico-chemical properties and physiological acceptance. The present contribution attempts to review various features of the dextran carrier like its source, structural and physico-chemical characteristics, pharmacokinetic fate and its applications as macromolecular carrier with special emphasis on dextran prodrugs.

  16. CAS information services for medicinal chemists.

    Science.gov (United States)

    Heyman, J J; Karasinskia, E H; Giles, P M

    1982-01-01

    In summary, the medicinal chemist has four new ways to access the information contained in the CAS database: CAS ONLINE, the only structure search system based on the entire CAS Registry database, and three printed services, CA SELECTS, BIOSIS/CAS SELECTS, and CAS Customer-Defined Information Services, which provide abstracts on specialized topics of interest.

  17. Recent CAS Achievements in Life Sciences

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Recent years have witnessed remarkable progress scored by CAS researchers along with the smooth development of the knowledge innovation program piloted at CAS. The follow-ings are just recent examples of CAS research achievements in life sciences.

  18. Cas1–Cas2 complex formation mediates spacer acquisition during CRISPR–Cas adaptive immunity

    OpenAIRE

    Nuñez, James K.; Kranzusch, Philip J.; Noeske, Jonas; Wright, Addison V.; Davies, Christopher W; Doudna, Jennifer A.

    2014-01-01

    The initial stage of CRISPR–Cas immunity involves the acquisition of foreign DNA spacer segments into the host genomic CRISPR locus. The nucleases Cas1 and Cas2 are the only proteins conserved amongst all CRISPR–Cas systems, yet the molecular functions of these proteins during immunity are unknown. Here we show that Cas1 and Cas2 from Escherichia coli form a stable complex that is essential for spacer acquisition and determine the 2.3-Å resolution crystal structure of the Cas1–Cas2 complex. M...

  19. Smoothing techniques for macromolecular global optimization

    Energy Technology Data Exchange (ETDEWEB)

    More, J.J.; Wu, Zhijun

    1995-09-01

    We study global optimization problems that arise in macromolecular modeling, and the solution of these problems via continuation and smoothing. Our results unify and extend the theory associated with the use of the Gaussian transform for smoothing. We show that the, Gaussian transform can be viewed as a special case of a generalized transform and that these generalized transforms share many of the properties of the Gaussian transform. We also show that the smoothing behavior of the generalized transform can be studied in terms of the Fourier transform and that these results indicate that the Gaussian transform has superior smoothing properties.

  20. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  1. Research Facility Development at CAS

    Institute of Scientific and Technical Information of China (English)

    Tian Dongsheng; Miao Yougui; Zhang Hongsong

    2005-01-01

    @@ This article gives an introductory account on the development of research facilities at the CAS over the past six years since the initiation of the Knowledge Innovation Program in 1998 and during the period of the national 10th Five-year Plan in particular. In addition, it expounds the key points for the future work at the CAS in this regard.

  2. Multiscale macromolecular simulation: role of evolving ensembles.

    Science.gov (United States)

    Singharoy, A; Joshi, H; Ortoleva, P J

    2012-10-22

    Multiscale analysis provides an algorithm for the efficient simulation of macromolecular assemblies. This algorithm involves the coevolution of a quasiequilibrium probability density of atomic configurations and the Langevin dynamics of spatial coarse-grained variables denoted order parameters (OPs) characterizing nanoscale system features. In practice, implementation of the probability density involves the generation of constant OP ensembles of atomic configurations. Such ensembles are used to construct thermal forces and diffusion factors that mediate the stochastic OP dynamics. Generation of all-atom ensembles at every Langevin time step is computationally expensive. Here, multiscale computation for macromolecular systems is made more efficient by a method that self-consistently folds in ensembles of all-atom configurations constructed in an earlier step, history, of the Langevin evolution. This procedure accounts for the temporal evolution of these ensembles, accurately providing thermal forces and diffusions. It is shown that efficiency and accuracy of the OP-based simulations is increased via the integration of this historical information. Accuracy improves with the square root of the number of historical timesteps included in the calculation. As a result, CPU usage can be decreased by a factor of 3-8 without loss of accuracy. The algorithm is implemented into our existing force-field based multiscale simulation platform and demonstrated via the structural dynamics of viral capsomers.

  3. Macromolecular recognition in the Protein Data Bank

    Energy Technology Data Exchange (ETDEWEB)

    Janin, Joël, E-mail: joel.janin@ibbmc.u-psud.fr [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Rodier, Francis [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Chakrabarti, Pinak [Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Bahadur, Ranjit P. [Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France)

    2007-01-01

    X-ray structures in the PDB illustrate both the specific recognition of two polypeptide chains in protein–protein complexes and dimeric proteins and their nonspecific interaction at crystal contacts. Crystal structures deposited in the Protein Data Bank illustrate the diversity of biological macromolecular recognition: transient interactions in protein–protein and protein–DNA complexes and permanent assemblies in homodimeric proteins. The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions. It is found that crystal-packing interfaces are usually much smaller; they bury fewer atoms and are less tightly packed than in specific assemblies. Standard-size interfaces burying 1200–2000 Å{sup 2} of protein surface occur in protease–inhibitor and antigen–antibody complexes that assemble with little or no conformation changes. Short-lived electron-transfer complexes have small interfaces; the larger size of the interfaces observed in complexes involved in signal transduction and homodimers correlates with the presence of conformation changes, often implicated in biological function. Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate. They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

  4. Rotation-Induced Macromolecular Spooling of DNA

    Directory of Open Access Journals (Sweden)

    Tyler N. Shendruk

    2017-07-01

    Full Text Available Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  5. Rotation-Induced Macromolecular Spooling of DNA

    Science.gov (United States)

    Shendruk, Tyler N.; Sean, David; Berard, Daniel J.; Wolf, Julian; Dragoman, Justin; Battat, Sophie; Slater, Gary W.; Leslie, Sabrina R.

    2017-07-01

    Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  6. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular st

  7. The role of macromolecular stability in desiccation tolerance.

    NARCIS (Netherlands)

    Wolkers, W.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular structures

  8. Chest MRI

    Science.gov (United States)

    Nuclear magnetic resonance - chest; Magnetic resonance imaging - chest; NMR - chest; MRI of the thorax; Thoracic MRI ... healthy enough to filter the contrast. During the MRI, the person who operates the machine will watch ...

  9. CAS School in Germany

    CERN Multimedia

    CERN Accelerator School

    The CERN Accelerator School (CAS), the Helmholtz Centre for Heavy Ion Research GmbH (GSI) and the Technische Universität Darmstadt (TU Darmstadt) jointly organised a course on General Accelerator Physics, at intermediate level, at TU Darmstadt from 27 September to 9 October 2009.   Participants in the CERN Accelerator School in Darmstadt, Germany. The Intermediate-level course followed established practice, with lectures on core topics in the mornings and specialised courses in the afternoons. The latter provided "hands-on" education and experience in the three selected topics: "RF Measurement Techniques", "Beam Instrumentation and Diagnostics" and "Optics Design and Correction". These proved to be highly successful, with participants choosing one course and following the topic throughout the school. Guided studies, tutorials, seminars and a poster session completed the programme. A visit to GSI and the F...

  10. Dual nuclease activity of a Cas2 protein in CRISPR-Cas subtype I-B of Leptospira interrogans.

    Science.gov (United States)

    Dixit, Bhuvan; Ghosh, Karukriti Kaushik; Fernandes, Gary; Kumar, Pankaj; Gogoi, Prerana; Kumar, Manish

    2016-04-01

    Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 carries a set of cas genes associated with CRISPR-Cas subtype I-B. Herein, we report for the first time active transcription of a set of cas genes (cas1 to cas8) of L. interrogans where cas4, cas1, cas2 and cas6, cas3, cas8, cas7, cas5 are clustered together in two independent operons. As an initial step toward comprehensive understanding of CRISPR-Cas system in spirochete, the biochemical study of one of the core Leptospira Cas2 proteins (Lep_Cas2) showed nuclease activity on both DNA and RNA in a nonspecific manner. Additionally, unlike other known Cas2 proteins, Lep_Cas2 showed metal-independent RNase activity and preferential activity on RNA over DNA. These results provide insight for understanding Cas2 diversity existing in the prokaryotic adaptive immune system.

  11. MRI and low back pain

    Science.gov (United States)

    Backache - MRI; Low back pain - MRI; Lumbar pain - MRI; Back strain - MRI; Lumbar radiculopathy - MRI; Herniated intervertebral disk - MRI; Prolapsed intervertebral disk - MRI; Slipped disk - MRI; Ruptured ...

  12. CAS Mathematician Receives Shaw Prize

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ WU Wentsun (WU Wenjun), a CAS Member from the Academy of Mathematics and System Sciences, has been honored with the 2006 Shaw Prize in Mathematical Sciences for his contributions to the new interdisciplinary field of mathematics and mechanization.

  13. Functional Sub-states by High-pressure Macromolecular Crystallography.

    Science.gov (United States)

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  14. Sequential recovery of macromolecular components of the nucleolus.

    Science.gov (United States)

    Bai, Baoyan; Laiho, Marikki

    2015-01-01

    The nucleolus is involved in a number of cellular processes of importance to cell physiology and pathology, including cell stress responses and malignancies. Studies of macromolecular composition of the nucleolus depend critically on the efficient extraction and accurate quantification of all macromolecular components (e.g., DNA, RNA, and protein). We have developed a TRIzol-based method that efficiently and simultaneously isolates these three macromolecular constituents from the same sample of purified nucleoli. The recovered and solubilized protein can be accurately quantified by the bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis or by mass spectrometry. We have successfully applied this approach to extract and quantify the responses of all three macromolecular components in nucleoli after drug treatments of HeLa cells, and conducted RNA-Seq analysis of the nucleolar RNA.

  15. An upper limit for macromolecular crowding effects

    Directory of Open Access Journals (Sweden)

    Miklos Andrew C

    2011-05-01

    Full Text Available Abstract Background Solutions containing high macromolecule concentrations are predicted to affect a number of protein properties compared to those properties in dilute solution. In cells, these macromolecular crowders have a large range of sizes and can occupy 30% or more of the available volume. We chose to study the stability and ps-ns internal dynamics of a globular protein whose radius is ~2 nm when crowded by a synthetic microgel composed of poly(N-isopropylacrylamide-co-acrylic acid with particle radii of ~300 nm. Results Our studies revealed no change in protein rotational or ps-ns backbone dynamics and only mild (~0.5 kcal/mol at 37°C, pH 5.4 stabilization at a volume occupancy of 70%, which approaches the occupancy of closely packing spheres. The lack of change in rotational dynamics indicates the absence of strong crowder-protein interactions. Conclusions Our observations are explained by the large size discrepancy between the protein and crowders and by the internal structure of the microgels, which provide interstitial spaces and internal pores where the protein can exist in a dilute solution-like environment. In summary, microgels that interact weakly with proteins do not strongly influence protein dynamics or stability because these large microgels constitute an upper size limit on crowding effects.

  16. Macromolecular components of tomato fruit pectin.

    Science.gov (United States)

    Fishman, M L; Gross, K C; Gillespie, D T; Sondey, S M

    1989-10-01

    Chelate and alkaline-soluble pectin extracted from cell walls of pericarp tissue from mature green, turning, and red ripe (Lycopersicon esculentum Mill.) fruit (cv. Rutgers), were studied by high-performance size-exclusion chromatography. Computer-aided curve fitting of the chromatograms to a series of Gaussian-shaped components revealed that pectin from all fractions was composed of a linear combination of five macromolecular-sized species. The relative sizes of these macromolecules as obtained from their radii of gyration were 1:2:4:8:16. Dialysis against 0.05 M NaCl induced partial dissociation of the biopolymers. Apparently, the weight fraction of smaller sized species increased at the expense of larger ones. Also, the dissociation produced low-molecular-weight fragments. Behavior in the presence of 0.05 M NaCl led to the conclusion that cell wall pectin acted as if it were an aggregated mosaic, held together at least partially through noncovalent interactions.

  17. The solvent component of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Weichenberger, Christian X. [European Academy of Bozen/Bolzano (EURAC), Viale Druso 1, Bozen/Bolzano, I-39100 Südtirol/Alto Adige (Italy); Afonine, Pavel V. [Lawrence Berkeley National Laboratory (LBNL), 1 Cyclotron Road, Mail Stop 64R0121, Berkeley, CA 94720 (United States); Kantardjieff, Katherine [California State University, San Marcos, CA 92078 (United States); Rupp, Bernhard, E-mail: br@hofkristallamt.org [k.-k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2015-04-30

    On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.

  18. MRI Scans

    Science.gov (United States)

    Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from ...

  19. Shoulder MRI

    Science.gov (United States)

    ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... that magnetic resonance imaging harms the fetus, pregnant women usually are advised not to have an MRI ...

  20. CAS Scientist Receives Trieste Science Prize

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ RAO Zihe, director of the CAS Institute of Biophysics and CAS Member, has been awarded the 2006Trieste Science Prize for "his worldclass contributions to structural biology and his studies of viruses responsible for human diseases."

  1. CAS to Address Water Eutrophication

    Institute of Scientific and Technical Information of China (English)

    Guo Haiyan; Zhao Baohua

    2002-01-01

    @@ At a meeting on April 5, the CAS authorities gave the green light to a proposal to carry out studies on the development and control of eutrophication on the middle and lower reaches of the Yangtze River. The five-year project,to cost 20 million yuan (about USS 2.4 million), will involve scientists from various CAS institutes, including the Nanjing Institute of Geography & Limnology, Wuhan Institute of Hydrobiology, Research Center for Eco-Environmental Sciences, Wuhan Institute of Botany, Institute of Chemistry, Institute of Geodesy & Geophysics, and Institute of Microbiology.

  2. CAS Academic Divisions in 2001

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ 1.Election of New Members In 2001, 56 scientists were elected new CAS members, including l0 in the Division of Mathematics & Physics, 10 in the Division of Chemistry, 12 in the Division of Biology, nine in the Division of Earth Sciences and 15 in the Division of Engineering Sciences.The average age of the new members is 60.4, and the youngest one is 38 years old. They are now working in nine provinces or municipalities, or governmental departments under the State Council, including 23 outstanding experts working for the CAS.

  3. Macromolecular networks and intelligence in microorganisms

    Directory of Open Access Journals (Sweden)

    Hans V Westerhoff

    2014-07-01

    Full Text Available Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of Information and Communication Technology (ICT: they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call intelligence. Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as human and brain out of the defining features of intelligence, all forms of life – from microbes to humans – exhibit some or all characteristics consistent with intelligence. We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.

  4. Macromolecular networks and intelligence in microorganisms

    Science.gov (United States)

    Westerhoff, Hans V.; Brooks, Aaron N.; Simeonidis, Evangelos; García-Contreras, Rodolfo; He, Fei; Boogerd, Fred C.; Jackson, Victoria J.; Goncharuk, Valeri; Kolodkin, Alexey

    2014-01-01

    Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence.” Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence,” all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence.” We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo. PMID:25101076

  5. Macromolecular Topography Leaps into the Digital Age

    Science.gov (United States)

    Lovelace, J.; Bellamy, H.; Snell, E. H.; Borgstahl, G.

    2003-01-01

    A low-cost, real-time digital topography system is under development which will replace x-ray film and nuclear emulsion plates. The imaging system is based on an inexpensive surveillance camera that offers a 1000x1000 array of 8 im square pixels, anti-blooming circuitry, and very quick read out. Currently, the system directly converts x-rays to an image with no phosphor. The system is small and light and can be easily adapted to work with other crystallographic equipment. Preliminary images have been acquired of cubic insulin at the NSLS x26c beam line. NSLS x26c was configured for unfocused monochromatic radiation. Six reflections were collected with stills spaced from 0.002 to 0.001 degrees apart across the entire oscillation range that the reflections were in diffracting condition. All of the reflections were rotated to the vertical to reduce Lorentz and beam related effects. This particular CCD is designed for short exposure applications (much less than 1 sec) and so has a relatively high dark current leading to noisy raw images. The images are processed to remove background and other system noise with a multi-step approach including the use of wavelets, histogram, and mean window filtering. After processing, animations were constructed with the corresponding reflection profile to show the diffraction of the crystal volume vs. the oscillation angle as well as composite images showing the parts of the crystal with the strongest diffraction for each reflection. The final goal is to correlate features seen in reflection profiles captured with fine phi slicing to those seen in the topography images. With this development macromolecular topography finally comes into the digital age.

  6. CAS Announces Academicians Elected in 2009

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Thirty five Chinese scientists and six of their colleagues from Canada,France and the United States were elected into CAS in 2009.The announcement was made by CAS President LU Yongxiang at a press conference held on December 4,2009,in Beijing.CAS Vice President LI Jinghai read the list of the new Members.

  7. CAS Headquarters Steps Up Efficiency Efforts

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ As part of China's S&T system reform and national Knowledge Innovation Program (KIP) spearheaded by CAS, an effort to downsize the administration at the CAS headquarters has made significant progress,Vice President Yang Bailing announced at a conference for position-engagement at the CAS headquarters on Nov. 4 in Beijing.

  8. Macromolecular Antioxidants and Dietary Fiber in Edible Seaweeds.

    Science.gov (United States)

    Sanz-Pintos, Nerea; Pérez-Jiménez, Jara; Buschmann, Alejandro H; Vergara-Salinas, José Rodrigo; Pérez-Correa, José Ricardo; Saura-Calixto, Fulgencio

    2017-02-01

    Seaweeds are rich in different bioactive compounds with potential uses in drugs, cosmetics and the food industry. The objective of this study was to analyze macromolecular antioxidants or nonextractable polyphenols, in several edible seaweed species collected in Chile (Gracilaria chilensis, Callophyllis concepcionensis, Macrocystis pyrifera, Scytosyphon lomentaria, Ulva sp. and Enteromorpha compressa), including their 1st HPLC characterization. Macromolecular antioxidants are commonly ignored in studies of bioactive compounds. They are associated with insoluble dietary fiber and exhibit significant biological activity, with specific features that are different from those of both dietary fiber and extractable polyphenols. We also evaluated extractable polyphenols and dietary fiber, given their relationship with macromolecular antioxidants. Our results show that macromolecular antioxidants are a major polyphenol fraction (averaging 42% to total polyphenol content), with hydroxycinnamic acids, hydroxybenzoic acids and flavonols being the main constituents. This fraction also showed remarkable antioxidant capacity, as determined by 2 complementary assays. The dietary fiber content was over 50% of dry weight, with some samples exhibiting the target proportionality between soluble and insoluble dietary fiber for adequate nutrition. Overall, our data show that seaweed could be an important source of commonly ignored macromolecular antioxidants. © 2017 Institute of Food Technologists®.

  9. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  10. High-resolution three-dimensional quantitative map of the macromolecular proton fraction distribution in the normal rat brain

    Directory of Open Access Journals (Sweden)

    Anna V. Naumova

    2017-02-01

    Full Text Available The presented dataset provides a normative high-resolution three-dimensional (3D macromolecular proton fraction (MPF map of the healthy rat brain in vivo and source images used for its reconstruction. The images were acquired using the protocol described elsewhere (Naumova, et al. High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields. Neuroimage (2016 doi: 10.1016/j.neuroimage.2016.09.036. The map was reconstructed from three source images with different contrast weightings (proton density, T1, and magnetization transfer using the single-point algorithm with a synthetic reference image. Source images were acquired from a living animal on an 11.7 T small animal MRI scanner with isotropic spatial resolution of 170 µm3 and total acquisition time about 1.5 h. The 3D dataset can be used for multiple purposes including interactive viewing of rat brain anatomy, measurements of reference MPF values in various brain structures, and development of image processing techniques for the rodent brain segmentation. It also can serve as a gold standard image for implementation and optimization of rodent brain MRI protocols.

  11. Macromolecular crystallography beamline X25 at the NSLS.

    Science.gov (United States)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L; Dvorak, Joseph; Flaks, Leon; Lamarra, Steven; Myers, Stuart F; Orville, Allen M; Robinson, Howard H; Roessler, Christian G; Schneider, Dieter K; Shea-McCarthy, Grace; Skinner, John M; Skinner, Michael; Soares, Alexei S; Sweet, Robert M; Berman, Lonny E

    2014-05-01

    Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community.

  12. Synthetic Approaches to Heterocyclic Ligands for Gd-Based MRI Contrast Agents

    Directory of Open Access Journals (Sweden)

    Paloma Ballesteros

    2007-08-01

    Full Text Available Magnetic Resonance Imaging (MRI methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs, capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

  13. Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells "in vitro" and correlating with progression "in vivo".

    Science.gov (United States)

    Perico, Maria Elisa; Grasso, Silvia; Brunelli, Matteo; Martignoni, Guido; Munari, Enrico; Moiso, Enrico; Fracasso, Giulio; Cestari, Tiziana; Naim, Hassan Y; Bronte, Vincenzo; Colombatti, Marco; Ramarli, Dunia

    2016-11-08

    The expression of Prostate Specific-Membrane Antigen (PSMA) increases in high-grade prostate carcinoma envisaging a role in growth and progression. We show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT and MAPK pathways thus promoting proliferation and survival. PSMA activity was dependent on the assembly of a macromolecular complex including filamin A, beta1 integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and Y1173 EGF-independent residues. Silencing or blocking experiments with drugs demonstrated that all the complex components were required for full PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that p130CAS and EGFR exerted a major role. All PSMA complex components were found assembled in multiple samples of two high-grade prostate carcinomas and associated with EGFR phosphorylation at Y1086. The expression of p130CAS and pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS 5+5. Patients with Gleason Score ≤5 resulted negative whereas those with GS≥5 expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases, respectively.Collectively, our results demonstrate for the first time that PSMA recruits a functionally active complex which is present in high-grade patients. In addition, two components of this complex, p130CAS and the novel pEGFRY1086, correlate with progression in castration-resistant patients and could be therefore useful in therapeutic or surveillance strategies of these patients.

  14. Generating triangulated macromolecular surfaces by Euclidean Distance Transform.

    Directory of Open Access Journals (Sweden)

    Dong Xu

    Full Text Available Macromolecular surfaces are fundamental representations of their three-dimensional geometric shape. Accurate calculation of protein surfaces is of critical importance in the protein structural and functional studies including ligand-protein docking and virtual screening. In contrast to analytical or parametric representation of macromolecular surfaces, triangulated mesh surfaces have been proved to be easy to describe, visualize and manipulate by computer programs. Here, we develop a new algorithm of EDTSurf for generating three major macromolecular surfaces of van der Waals surface, solvent-accessible surface and molecular surface, using the technique of fast Euclidean Distance Transform (EDT. The triangulated surfaces are constructed directly from volumetric solids by a Vertex-Connected Marching Cube algorithm that forms triangles from grid points. Compared to the analytical result, the relative error of the surface calculations by EDTSurf is <2-4% depending on the grid resolution, which is 1.5-4 times lower than the methods in the literature; and yet, the algorithm is faster and costs less computer memory than the comparative methods. The improvements in both accuracy and speed of the macromolecular surface determination should make EDTSurf a useful tool for the detailed study of protein docking and structure predictions. Both source code and the executable program of EDTSurf are freely available at http://zhang.bioinformatics.ku.edu/EDTSurf.

  15. Two-center-multipole expansion method: application to macromolecular systems

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Yakubovich, Alexander V.; Solov'yov, Andrey V.;

    2007-01-01

    We propose a theoretical method for the calculation of the interaction energy between macromolecular systems at large distances. The method provides a linear scaling of the computing time with the system size and is considered as an alternative to the well-known fast multipole method. Its...

  16. Genome modification by CRISPR/Cas9.

    Science.gov (United States)

    Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

    2014-12-01

    Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas)9-mediated genome modification enables us to edit the genomes of a variety of organisms rapidly and efficiently. The advantages of the CRISPR-Cas9 system have made it an increasingly popular genetic engineering tool for biological and therapeutic applications. Moreover, CRISPR-Cas9 has been employed to recruit functional domains that repress/activate gene expression or label specific genomic loci in living cells or organisms, in order to explore developmental mechanisms, gene expression regulation, and animal behavior. One major concern about this system is its specificity; although CRISPR-Cas9-mediated off-target mutation has been broadly studied, more efforts are required to further improve the specificity of CRISPR-Cas9. We will also discuss the potential applications of CRISPR-Cas9.

  17. Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9

    Directory of Open Access Journals (Sweden)

    Yan Feng

    2016-08-01

    Full Text Available The type II CRISPR/Cas9 system has been used widely for genome editing in zebrafish. However, the requirement for the 5′-NGG-3′ protospacer-adjacent motif (PAM of Cas9 from Streptococcus pyogenes (SpCas9 limits its targeting sequences. Here, we report that a Cas9 ortholog from Staphylococcus aureus (SaCas9, and its KKH variant, successfully induced targeted mutagenesis with high frequency in zebrafish. Confirming previous findings, the SpCas9 variant, VQR, can also induce targeted mutations in zebrafish. Bioinformatics analysis of these new Cas targets suggests that the number of available target sites in the zebrafish genome can be greatly expanded. Collectively, the expanded target repertoire of Cas9 in zebrafish should further facilitate the utility of this organism for genetic studies of vertebrate biology.

  18. Optimizing Decision Tree Attack on CAS Scheme

    Directory of Open Access Journals (Sweden)

    PERKOVIC, T.

    2016-05-01

    Full Text Available In this paper we show a successful side-channel timing attack on a well-known high-complexity cognitive authentication (CAS scheme. We exploit the weakness of CAS scheme that comes from the asymmetry of the virtual interface and graphical layout which results in nonuniform human behavior during the login procedure, leading to detectable variations in user's response times. We optimized a well-known probabilistic decision tree attack on CAS scheme by introducing this timing information into the attack. We show that the developed classifier could be used to significantly reduce the number of login sessions required to break the CAS scheme.

  19. MRI of the Prostate

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Prostate Magnetic resonance imaging (MRI) of the prostate ... limitations of MRI of the Prostate? What is MRI of the Prostate? Magnetic resonance imaging (MRI) is ...

  20. MRI zoo

    DEFF Research Database (Denmark)

    Laustsen, Christoffer

    The basic idea was to use MRI to produce a sequence of 3D gray scale image slices of various animals, subsequentlyimaged with a clinical CT system. For this purpose, these animals were used: toad, lungfish, python snake and a horseshoe crab. Each animal was sacrificed according to standard....... MRI was done using a Philips Achieva 1.5 T system and CT was performed using a Siemens Somatom system. Axial and sagittal slices were acquired using standard T1w and T2w MRI sequences, and visualization was made using the Mistar software (Apollo Imaging Technology, Melbourne, Australia). Images were...

  1. Pediatric MRI

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIH Study of Normal Brain Development is a longitudinal study using anatomical MRI, diffusion tensor imaging (DTI), and MR spectroscopy (MRS) to map pediatric...

  2. Knee MRI

    Science.gov (United States)

    ... air-conditioned and well-lit. Some scanners have music to help you pass the time. When the ... that magnetic resonance imaging harms the fetus, pregnant women usually are advised not to have an MRI ...

  3. Semiotic and discursive variables in cas-based didactical engineering

    DEFF Research Database (Denmark)

    Winsløw, Carl

    2003-01-01

    CAS, didactical engeneering, Maple, semiotics, undergraduate teaching, mathematics, education, didactics......CAS, didactical engeneering, Maple, semiotics, undergraduate teaching, mathematics, education, didactics...

  4. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.

    Science.gov (United States)

    Gemperle, Jakub; Hexnerová, Rozálie; Lepšík, Martin; Tesina, Petr; Dibus, Michal; Novotný, Marian; Brábek, Jan; Veverka, Václav; Rosel, Daniel

    2017-08-14

    CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.

  5. 51 CAS Members Elected in 2005

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Atotal of 51 prominent Chinese scientists were elected CAS members in 2005. The announce ment was made at a press conference held on Dec. 16 in Beijing. CAS President LU Yongxiang was present at the conference to give a briefing on the election and the new members.

  6. International Cooperation at CAS Since 1998

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Since 1998 when the Knowledge Innovation Program (KIP) was launched,the rapid development of CAS has offered great opportunities to forge international cooperation.Focusing on capacity building to effectively absorb global innovation resources and through organizing major innovative activities,CAS has increasingly expanded and intensified international partnerships.

  7. CAS paleoichthyologist gives Artedi Lecture in Sweden

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Prof. ZHANG Miman (CHANG Mee-mann), a CAS Member from the CAS Institute of Vertebrate Paleontology and Paleoanthropology, was invited to give a talk at the Artedi Lectures at the Royal Swedish Academy of Sciences in Stockholm, Sweden, on 5 December, 2008.

  8. CAS, Max Planck Society to Enhance Cooperation

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ According to a briefing issued by the CAS Bureau of In ternational Cooperation on May 8, 2004, CAS and the Max Planck Society (MPS) in Germany are considering to establish a multidisciplinary institute in Shanghai to conduct research into computational biology. The move is applauded as a fresh step in promoting Sino-German S&T cooperation.

  9. CAS, Sinopec forge all-round partnership

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ CAS and China Petroleum & Chemical Corporation (Sinopec), the 3nd largest oil refiner in the world, inked an agreement for comprehensive strategic cooperation on 23 January in Beijing. Sinopec President WANG Tianpu and CAS Vice President SHI Erwei were present to witness the event

  10. CAS Joins Asian Consortium of Science Academies

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ CAS formally became a member of the Association of Academies of Sciences in Asia (AASA) at the fourth general assembly of AASA from Sept. 23 to 25 in Tehran, Iran. A CAS delegation headed by Vice-President Yang Bailing attended the conference.

  11. CAS issues its 2008 Science & Society Series

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ CAS recently released its 2008 Science and Society Series consisting of three reports on scientific progress, high-tech advancement and sustainable development. Among them, the latter two were completed under the organization of the CAS Institute of Policy and Management.

  12. CAS Launches Website for Scientific Education

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ CAS member Wang Shouguan and SecretaryGeneral of the Ministry of Science and Technology Zhang Jing'an jointly push the button on August 26 in Beijing to launch a CAS website for scientific education (http ://www.fipse. cn/).

  13. Stochastic reaction–diffusion algorithms for macromolecular crowding

    Science.gov (United States)

    Sturrock, Marc

    2016-06-01

    Compartment-based (lattice-based) reaction–diffusion algorithms are often used for studying complex stochastic spatio-temporal processes inside cells. In this paper the influence of macromolecular crowding on stochastic reaction–diffusion simulations is investigated. Reaction–diffusion processes are considered on two different kinds of compartmental lattice, a cubic lattice and a hexagonal close packed lattice, and solved using two different algorithms, the stochastic simulation algorithm and the spatiocyte algorithm (Arjunan and Tomita 2010 Syst. Synth. Biol. 4, 35–53). Obstacles (modelling macromolecular crowding) are shown to have substantial effects on the mean squared displacement and average number of molecules in the domain but the nature of these effects is dependent on the choice of lattice, with the cubic lattice being more susceptible to the effects of the obstacles. Finally, improvements for both algorithms are presented.

  14. Controlled architecture for improved macromolecular memory within polymer networks.

    Science.gov (United States)

    DiPasquale, Stephen A; Byrne, Mark E

    2016-08-01

    This brief review analyzes recent developments in the field of living/controlled polymerization and the potential of this technique for creating imprinted polymers with highly structured architecture with macromolecular memory. As a result, it is possible to engineer polymers at the molecular level with increased homogeneity relating to enhanced template binding and transport. Only recently has living/controlled polymerization been exploited to decrease heterogeneity and substantially improve the efficiency of the imprinting process for both highly and weakly crosslinked imprinted polymers. Living polymerization can be utilized to create imprinted networks that are vastly more efficient than similar polymers produced using conventional free radical polymerization, and these improvements increase the role that macromolecular memory can play in the design and engineering of new drug delivery and sensing platforms.

  15. Isotope labeling for NMR studies of macromolecular structure and interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wright, P.E. [Scripps Research Institute, La Jolla, CA (United States)

    1994-12-01

    Implementation of biosynthetic methods for uniform or specific isotope labeling of proteins, coupled with the recent development of powerful heteronuclear multidimensional NMR methods, has led to a dramatic increase in the size and complexity of macromolecular systems that are now amenable to NMR structural analysis. In recent years, a new technology has emerged that combines uniform {sup 13}C, {sup 15}N labeling with heteronuclear multidimensional NMR methods to allow NMR structural studies of systems approaching 25 to 30 kDa in molecular weight. In addition, with the introduction of specific {sup 13}C and {sup 15}N labels into ligands, meaningful NMR studies of complexes of even higher molecular weight have become feasible. These advances usher in a new era in which the earlier, rather stringent molecular weight limitations have been greatly surpassed and NMR can begin to address many central biological problems that involve macromolecular structure, dynamics, and interactions.

  16. Temperature-dependent macromolecular X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Weik, Martin, E-mail: martin.weik@ibs.fr; Colletier, Jacques-Philippe [CEA, IBS, Laboratoire de Biophysique Moléculaire, F-38054 Grenoble (France); CNRS, UMR5075, F-38027 Grenoble (France); Université Joseph Fourier, F-38000 Grenoble (France)

    2010-04-01

    The dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. X-ray crystallography provides structural details of biological macromolecules. Whereas routine data are collected close to 100 K in order to mitigate radiation damage, more exotic temperature-controlled experiments in a broader temperature range from 15 K to room temperature can provide both dynamical and structural insights. Here, the dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. Experimental strategies of kinetic crystallography are discussed that have allowed the generation and trapping of macromolecular intermediate states by combining reaction initiation in the crystalline state with appropriate temperature profiles. A particular focus is on recruiting X-ray-induced changes for reaction initiation, thus unveiling useful aspects of radiation damage, which otherwise has to be minimized in macromolecular crystallography.

  17. Refinement of macromolecular structures against neutron data with SHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  18. The vibron dressing in α-helicoidal macromolecular chains

    Institute of Scientific and Technical Information of China (English)

    D.(C)evizovi(c); S.Galovi(c); A.Reshetnyak; Z.Ivi(c)

    2013-01-01

    We present a study of the physical properties of the vibrational excitation in α-helicoidal macromolecular chains,caused by the interaction with acoustical and optical phonon modes.The influence of the temperature and the basic system parameters on the vibron dressing have been analyzed by employing the simple mean-field approach based on the variational extension of the Lang-Firsov unitary transformation.The applied approach predicts a region in system parameter space where one has an abrupt transition from a partially dressed (light and mobile) to a fully dressed (immobile) vibron state.We found that the boundary of this region depends on system temperature and the type of bond among structural elements in the macromolecular chain.

  19. A macromolecular model for the endothelial surface layer

    Science.gov (United States)

    Harden, James; Danova-Okpetu, Darina; Grest, Gary

    2006-03-01

    The endothelial surface layer (ESL) is a micron-scale macromolecular lining of the luminal side of blood vessels composed of proteoglycans, glycoproteins, polysaccharides and associated plasma proteins all in dynamic equilibrium. It has numerous physiological roles including the regulation of blood flow and microvascular permeability, and active participation in mechanotransduction and stress regulation, coagulation, cell adhesion, and inflammatory response. The dynamic structure and the mechanical properties of the ESL are crucial for many of its physiological properties. We present a topological model for the ESL composed of three basic macromolecular elements: branched proteoglycans, linear polysaccharide chains, and small plasma proteins. The model was studied using non-equilibrium molecular dynamics simulations and compared with scaling theories for associating tethered polymers. We discuss the observed dynamical and mechanical properties of the ESL captured by this model, and the possible physical insight it provides into the physiological behavior of the ESL.

  20. A Strategy for the Development of Macromolecular Nonlinear Optical Materials

    Science.gov (United States)

    1990-01-01

    obsolete. SECURITY CLASSIFICATION OF THIS PAGE STRATEGY FOR THE DEVELOPMENT OF MACROMOLECULAR NONLINEAR OPTICAL MATERIALS Braja K. Mandala , Jan-Chan...materials is significantly different from the conventional inorganic NLO materials. The extent of second order (quadratic) NLO effect such as second...is a criterion of paramount importance for a large second order electro-optic effect in organic materials 8 ,9 . The most common approach to obtain

  1. Facilitating structure determination: workshop on robotics andautomation in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

    2006-03-28

    As part of the annual Advanced Light Source (ALS) andStanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting inOctober of this year, the macromolecular crystallography staff at bothsynchrotrons held a joint hands-on workshop to address automation issuesin crystal mounting and data collection at the beamline. This paperdescribes the ALS portion of the workshop, while the accompanying paperreviews the SSRL workshop.

  2. Single-particle cryo-electron microscopy of macromolecular assemblies

    OpenAIRE

    Cheng, Kimberley

    2009-01-01

    In this thesis, single-particle cryo-electron microscopy (cryo-EM) was used to study the structure of three macromolecular assemblies: the two hemocyanin isoforms from Rapana thomasiana, the Pyrococcus furiosus chaperonin, and the ribosome from Escherichia coli. Hemocyanins are large respiratory proteins in arthropods and molluscs. Most molluscan hemocyanins exist as two distinct isoforms composed of related polypeptides. In most species the two isoforms differ in terms of their oligomeric st...

  3. CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

    Science.gov (United States)

    Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

    2014-05-06

    In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

  4. In vitro enzymology of Cas9.

    Science.gov (United States)

    Anders, Carolin; Jinek, Martin

    2014-01-01

    Cas9 is a bacterial RNA-guided endonuclease that uses base pairing to recognize and cleave target DNAs with complementarity to the guide RNA. The programmable sequence specificity of Cas9 has been harnessed for genome editing and gene expression control in many organisms. Here, we describe protocols for the heterologous expression and purification of recombinant Cas9 protein and for in vitro transcription of guide RNAs. We describe in vitro reconstitution of the Cas9-guide RNA ribonucleoprotein complex and its use in endonuclease activity assays. The methods outlined here enable mechanistic characterization of the RNA-guided DNA cleavage activity of Cas9 and may assist in further development of the enzyme for genetic engineering applications.

  5. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  6. REFMAC5 for the refinement of macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Murshudov, Garib N., E-mail: garib@ysbl.york.ac.uk [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Skubák, Pavol [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Lebedev, Andrey A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Pannu, Navraj S. [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Steiner, Roberto A. [Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London (United Kingdom); Nicholls, Robert A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Winn, Martyn D. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Long, Fei; Vagin, Alexei A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom)

    2011-04-01

    The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described. This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement tools such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, ‘jelly-body’ restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback–Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.

  7. Macromolecular amplification of binding response in superaptamer hydrogels.

    Science.gov (United States)

    Bai, Wei; Gariano, Nicholas A; Spivak, David A

    2013-05-08

    It is becoming more important to detect ultralow concentrations of analytes for biomedical, environmental, and national security applications. Equally important is that new methods should be easy to use, inexpensive, portable, and if possible allow detection by the naked eye. By and large, detection of low concentrations of analytes cannot be achieved directly but requires signal amplification by catalysts, macromolecules, metal surfaces, or supramolecular aggregates. The rapidly progressing field of macromolecular signal amplification has been advanced using conjugated polymers, chirality in polymers, solvating polymers, and polymerization/depolymerization strategies. A new type of aptamer-based hydrogel with specific response to target proteins presented in this report demonstrates an additional category of macromolecular signal amplification. This superaptamer assembly provides the first example of using protein-specific aptamers to create volume-changing hydrogels with amplified response to the target protein. A remarkable aspect of these superaptamer hydrogels is that volume shrinking is visible to the naked eye down to femtomolar concentrations of protein. This extraordinary macromolecular amplification is attributed to a complex interplay between protein-aptamer supramolecular cross-links and the consequential reduction of excluded volume in the hydrogel. Specific recognition is even maintained in biological matrices such as urine and tears. Furthermore, the gels can be dried for long-term storage and regenerated for use without loss of activity. In practice, the ease of this biomarker detection method offers an alternative to traditional analytical techniques that require sophisticated instrumentation and highly trained personnel.

  8. Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine

    Science.gov (United States)

    Defoort, Jean-Philippe; Nardelli, Bernardetta; Huang, Wolin; Ho, David D.; Tam, James P.

    1992-05-01

    We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8^+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.

  9. A review of MRI evaluation of demyelination in cuprizone murine model

    Science.gov (United States)

    Krutenkova, E.; Pan, E.; Khodanovich, M.

    2015-11-01

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  10. A review of MRI evaluation of demyelination in cuprizone murine model

    Energy Technology Data Exchange (ETDEWEB)

    Krutenkova, E., E-mail: len--k@yandex.ru; Pan, E.; Khodanovich, M., E-mail: khodanovich@mail.tsu.ru [National Research Tomsk State University, Lenina pr., 36, Tomsk (Russian Federation)

    2015-11-17

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  11. CAS at the Cockcroft Institute

    CERN Multimedia

    2007-01-01

    The CERN Accelerator School (CAS) and the UK’s new centre for accelerator science, the Cockcroft Institute, jointly organised a course on General Accelerator Physics, at intermediate level, at the Cockcroft Institute, Daresbury, UK, from 16 to 28 September 2007. The venue took advantage of the excellent new facilities in the Institute and the existing infrastructure of the adjacent Daresbury Laboratory. The intermediate level course followed established practice, with lectures on core topics in the mornings and specialised courses in the afternoons. The latter provided "hands-on" education and experience in the three selected topics: "RF Measurements Techniques", "Beam Instrumentation and Diagnostics" and "Optics Design and Correction". These proved to be highly successful, with participants choosing one course and following the topic throughout the school. Guided studies, tutorials, seminars and a poster session completed the prog...

  12. MRI Artifacts

    Directory of Open Access Journals (Sweden)

    Abed Al Nasser Assi

    2009-12-01

    Full Text Available   "nMagnetic resonance imaging (MRI has become more and more frequently used in medical imaging diagnostic in recent years. Radiologists and technicians working at these systems are relatively often confronted with image artifacts related to the radiowave with strong magnetic in the scanner. Many artifacts may be corrected or modulated through an understanding of their cause. This requires familiarity with scanner design; theory of operation; and image acquisition. The purpose of this review article is to present the most relevant artifacts that arise in MRI scanner, to provide some physical background on the formation of artifacts, and to suggest strategies to reduce or avoid these artifacts. The most frequent artifacts that can occur during MRI scanning are Motion related artifacts; Para-magnetic artifacts; Phase Wrap artifacts; Frequency artifacts; Susceptibility artifacts; Clipping artefact; Chemical Shift artifact and "Zebra" artefact .    "n  

  13. Portable MRI

    Energy Technology Data Exchange (ETDEWEB)

    Espy, Michelle A. [Los Alamos National Laboratory

    2012-06-29

    This project proposes to: (1) provide the power of MRI to situations where it presently isn't available; (2) perform the engineering required to move from lab to a functional prototype; and (3) leverage significant existing infrastructure and capability in ultra-low field MRI. The reasons for doing this: (1) MRI is the most powerful tool for imaging soft-tissue (e.g. brain); (2) Billions don't have access due to cost or safety issues; (3) metal will heat/move in high magnetic fields; (4) Millions of cases of traumatic brain injury in US alone; (5) even more of non-traumatic brain injury; (6) (e.g. stroke, infection, chemical exposure); (7) Need for early diagnostic; (8) 'Signature' wound of recent conflicts; (9) 22% of injuries; (10) Implications for post-traumatic stress disorder; and (11) chronic traumatic encephalopathy.

  14. Assisting Students' Cognitive Strategies with the Use of CAS

    Science.gov (United States)

    Sarvari, Csaba; Lavicza, Zsolt; Klincsik, Mihaly

    2010-01-01

    This paper examines various cognitive strategies applied while CAS (Computer Algebra System) are used in undergraduate-level engineering mathematics teaching and learning. We posed some questions in relation to such CAS use: What kind of tools can CAS offer to enhance different cognitive strategies of students? How can the use of CAS widen the…

  15. Breast MRI scan

    Science.gov (United States)

    MRI - breast; Magnetic resonance imaging - breast; Breast cancer - MRI; Breast cancer screening - MRI ... radiologist) see some areas more clearly. During the MRI, the person who operates the machine will watch ...

  16. MRI Safety during Pregnancy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z MRI Safety During Pregnancy Magnetic resonance imaging (MRI) Illness ... during the exam? Contrast material MRI during pregnancy Magnetic resonance imaging (MRI) If you are pregnant and your doctor ...

  17. MRI (Magnetic Resonance Imaging)

    Science.gov (United States)

    ... and Procedures Medical Imaging MRI (Magnetic Resonance Imaging) MRI (Magnetic Resonance Imaging) Share Tweet Linkedin Pin it More sharing options ... usually given through an IV in the arm. MRI Research Programs at FDA Magnetic Resonance Imaging (MRI) ...

  18. MRI of the Chest

    Medline Plus

    Full Text Available ... the limitations of MRI of the Chest? What is MRI of the Chest? Magnetic resonance imaging (MRI) ... ray, CT and ultrasound. top of page How is the procedure performed? MRI examinations may be performed ...

  19. Nucleosomes Inhibit Cas9 Endonuclease Activity in Vitro.

    Science.gov (United States)

    Hinz, John M; Laughery, Marian F; Wyrick, John J

    2015-12-01

    During Cas9 genome editing in eukaryotic cells, the bacterial Cas9 enzyme cleaves DNA targets within chromatin. To understand how chromatin affects Cas9 targeting, we characterized Cas9 activity on nucleosome substrates in vitro. We find that Cas9 endonuclease activity is strongly inhibited when its target site is located within the nucleosome core. In contrast, the nucleosome structure does not affect Cas9 activity at a target site within the adjacent linker DNA. Analysis of target sites that partially overlap with the nucleosome edge indicates that the accessibility of the protospacer-adjacent motif (PAM) is the critical determinant of Cas9 activity on a nucleosome.

  20. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  1. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease

    Science.gov (United States)

    The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th...

  2. Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

    Science.gov (United States)

    Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A

    2015-03-12

    Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

  3. MRI zoo

    DEFF Research Database (Denmark)

    Laustsen, Christoffer

    The basic idea was to use MRI to produce a sequence of 3D gray scale image slices of various animals, subsequentlyimaged with a clinical CT system. For this purpose, these animals were used: toad, lungfish, python snake and a horseshoe crab. Each animal was sacrificed according to standard proced...

  4. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available BACKGROUND: Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins. METHODOLOGY/PRINCIPAL FINDINGS: As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l. CONCLUSIONS/SIGNIFICANCE: We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of

  5. CAS Readjusts Implementation of Its Talent Program

    Institute of Scientific and Technical Information of China (English)

    Guo Haiyan

    2002-01-01

    @@ CAS has decided to readjust the way of implementing its Century Program (or Hundred-Talents Program), to give more independence to research institutes in head hunting and guarantee the support for the Program recruits on a selective basis.

  6. CAS physicist receives Richard Geller Prize

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Dr. SUN Liangting from the CAS Institute of Modern Physics has been awarded the Richard Geller Prize for his outstanding contributions to the development of Electron Cyclotron Resonance (ECR) ion sources, especially an all-permanent magnetic one.

  7. AKRO/SF: Catch Accounting System (CAS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Catch Accounting System (CAS) creates total catch estimates for the groundfish fisheries in the Bering Sea/Aleutian Islands and Gulf of Alaska. Each year, quotas...

  8. CAS Scientists Develop China's First RFQ Accelerator

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ With the support of the National Program on Key Basic Research Projects (dubbed the "973Program"), researchers from the CAS Institute of High Energy Physics (IHEP) have developed the first high-power Radio Frequency Quadrupole (RFQ) accelerator in China.

  9. The new CAS-DIS digital ionosonde

    Directory of Open Access Journals (Sweden)

    Wang Shun

    2013-04-01

    Full Text Available A high quality digital ionosonde called the Chinese Academy of Sciences digital ionosonde (CAS-DIS has been developed for investigations of the ionosphere. Two important features are used for the CAS-DIS; first, the technique of analog down-conversion has been replaced by the new approach of digital down-conversion technology. Secondly, to solve the problem of large instantaneous receiving bandwidth in digital receivers, an analog narrowband tracking filter is used for the CAS-DIS. The center frequency of the filter tracks the carrier frequency transmitted in real-time, to ensure that the frequency components are filtered out of the effective bandwidth. This report describes the system architecture of the CAS-DIS, its main features, and its test results for ionosphere detection. 

  10. Heaviest yet LBO monocrystal grown at CAS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ After three years of hard work, a research team led by Prof. HU Zhanggui with the CAS Technical Institute of Physics and Chemistry has made breakthrough progress in the studies of lithium triborate (LBO), a nonlinear optical crystal.

  11. Bringing macromolecular machinery to life using 3D animation.

    Science.gov (United States)

    Iwasa, Janet H

    2015-04-01

    Over the past decade, there has been a rapid rise in the use of three-dimensional (3D) animation to depict molecular and cellular processes. Much of the growth in molecular animation has been in the educational arena, but increasingly, 3D animation software is finding its way into research laboratories. In this review, I will discuss a number of ways in which 3d animation software can play a valuable role in visualizing and communicating macromolecular structures and dynamics. I will also consider the challenges of using animation tools within the research sphere.

  12. BLOOD FLOW AND MACROMOLECULAR TRANSPORT IN CURVED BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    WEI Lan; WEN Gong-bi; TAN Wen-chang

    2006-01-01

    A numerical analysis of the steady/pulsatile flow and macromolecular (such as LDL and Albumin) transport in curved blood vessels was carried out. The computational results predict that the vortex of the secondary flow is time-dependent in the aortic arch.The concentration of macromolecule concentrates at the region of sharp curve, and the wall concentration at the outer part is higher than that at the inner part. Atherosclerosis and thrombosis are prone to develop in such regions with sharp flow.

  13. CRISPR-Cas: biology, mechanisms and relevance.

    Science.gov (United States)

    Hille, Frank; Charpentier, Emmanuelle

    2016-11-01

    Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes-termed spacers-into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent.This article is part of the themed issue 'The new bacteriology'.

  14. CRISPR-Cas: biology, mechanisms and relevance

    Science.gov (United States)

    Hille, Frank

    2016-01-01

    Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent. This article is part of the themed issue ‘The new bacteriology’. PMID:27672148

  15. CRISPR-Cas9 Structures and Mechanisms.

    Science.gov (United States)

    Jiang, Fuguo; Doudna, Jennifer A

    2017-05-22

    Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes. The use of CRISPR-Cas9 as an RNA-programmable DNA targeting and editing platform is simplified by a synthetic single-guide RNA (sgRNA) mimicking the natural dual trans-activating CRISPR RNA (tracrRNA)-CRISPR RNA (crRNA) structure. This review aims to provide an in-depth mechanistic and structural understanding of Cas9-mediated RNA-guided DNA targeting and cleavage. Molecular insights from biochemical and structural studies provide a framework for rational engineering aimed at altering catalytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for the development of Cas9-based therapies against genetic diseases.

  16. Identifying and visualizing macromolecular flexibility in structural biology

    Directory of Open Access Journals (Sweden)

    Martina Palamini

    2016-09-01

    Full Text Available Structural biology comprises a variety of tools to obtain atomic resolution data for the investigation of macromolecules. Conventional structural methodologies including crystallography, NMR and electron microscopy often do not provide sufficient details concerning flexibility and dynamics, even though these aspects are critical for the physiological functions of the systems under investigation. However, the increasing complexity of the molecules studied by structural biology (including large macromolecular assemblies, integral membrane proteins, intrinsically disordered systems, and folding intermediates continuously demands in-depth analyses of the roles of flexibility and conformational specificity involved in interactions with ligands and inhibitors. The intrinsic difficulties in capturing often subtle but critical molecular motions in biological systems have restrained the investigation of flexible molecules into a small niche of structural biology. Introduction of massive technological developments over the recent years, which include time-resolved studies, solution X-ray scattering, and new detectors for cryo-electron microscopy, have pushed the limits of structural investigation of flexible systems far beyond traditional approaches of NMR analysis. By integrating these modern methods with powerful biophysical and computational approaches such as generation of ensembles of molecular models and selective particle picking in electron microscopy, more feasible investigations of dynamic systems are now possible. Using some prominent examples from recent literature, we review how current structural biology methods can contribute useful data to accurately visualize flexibility in macromolecular structures and understand its important roles in regulation of biological processes.

  17. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  18. Critical review and perspective of macromolecularly imprinted polymers.

    Science.gov (United States)

    Kryscio, David R; Peppas, Nicholas A

    2012-02-01

    Molecular recognition is a fundamental and ubiquitous process that is the driving force behind life. Natural recognition elements - including antibodies, enzymes, nucleic acids, and cells - exploit non-covalent interactions to bind to their targets with exceptionally strong affinities. Due to this unparalleled proficiency, scientists have long sought to mimic natural recognition pathways. One promising approach is molecularly imprinted polymers (MIPs), which are fully synthetic systems formed via the crosslinking of organic polymers in the presence of a template molecule, which results in stereo-specific binding sites for this analyte of interest. Macromolecularly imprinted polymers, those synthesized in the presence of macromolecule templates (>1500 Da), are of particular importance because they open up the field for a whole new set of robust diagnostic tools. Although the specific recognition of small-molecular-weight analytes is now considered routine, extension of these efficacious procedures to the protein regime has, thus far, proved challenging. This paper reviews the main approaches employed, highlights studies of interest with an emphasis on recent work, and offers suggestions for future success in the field of macromolecularly imprinted polymers.

  19. The macromolecular crystallography facility at the advanced light source

    Science.gov (United States)

    Earnest, Thomas; Padmore, Howard; Cork, Carl; Behrsing, Rolf; Kim, Sung-Hou

    1996-10-01

    Synchrotron radiation offers several advantages over the use of rotating anode sources for biological crystallography, which allow for the collection of higher-resolution data, substantially more rapid data collection, phasing by multiwavelength anomalous diffraction (MAD) techniques, and time-resolved experiments using polychromatic radiation (Laue diffraction). The use of synchrotron radiation is often necessary to record useful data from crystals which diffract weakly or have very large unit cells. The high brightness and stability characteristics of the advanced light source (ALS) at Lawrence Berkeley National Laboratory, along with the low emittance and long straight sections to accommodate insertion devices present in third generation synchrotrons like the ALS, lead to several advantages in the field of macromolecular crystallography. We are presently constructing a macromolecular crystallography facility at the ALS which is optimized for user-friendliness and high-throughput data collection, with advanced capabilities for MAD and Laue experiments. The X-rays will be directed to three branchlines. A well-equipped support lab will be available for biochemistry, crystal mounting and sample storage, as well as computer hardware and software available, along with staff support, allowing for the complete processing of data on site.

  20. MMDB and VAST+: tracking structural similarities between macromolecular complexes.

    Science.gov (United States)

    Madej, Thomas; Lanczycki, Christopher J; Zhang, Dachuan; Thiessen, Paul A; Geer, Renata C; Marchler-Bauer, Aron; Bryant, Stephen H

    2014-01-01

    The computational detection of similarities between protein 3D structures has become an indispensable tool for the detection of homologous relationships, the classification of protein families and functional inference. Consequently, numerous algorithms have been developed that facilitate structure comparison, including rapid searches against a steadily growing collection of protein structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date archive of protein structure similarities computed with the Vector Alignment Search Tool (VAST). These similarities have been recorded on the level of single proteins and protein domains, comprising in excess of 1.5 billion pairwise alignments. Here we present VAST+, an extension to the existing VAST service, which summarizes and presents structural similarity on the level of biological assemblies or macromolecular complexes. VAST+ simplifies structure neighboring results and shows, for macromolecular complexes tracked in MMDB, lists of similar complexes ranked by the extent of similarity. VAST+ replaces the previous VAST service as the default presentation of structure neighboring data in NCBI's Entrez query and retrieval system. MMDB and VAST+ can be accessed via http://www.ncbi.nlm.nih.gov/Structure.

  1. Macromolecular Crowding Enhances Thermal Stability of Rabbit Muscle Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; HE Huawei; LI Sen

    2008-01-01

    The effect of dextran on the conformation (or secondary structure) and thermal stability of creatine kinase (CK) was studied using the far-ultraviolet (UV) circular dichroism (CD) spectra.The results showed that lower concentrations of dextran (less than 60 g/L) induced formation of the secondary CK structures.However,the secondary structure content of CK decreased when the dextran concentrations exceeded 60 g/L.Thermally induced transition curves were measured for CK in the presence of different concentrations of dextran by far-UV CD.The thermal transition curves were fitted to a two-state model by a nonlinear,least-squares method to obtain the transition temperature of the unfolding transition.An increase in the tran- sition temperature was observed with the increase of the dextran concentration.These observations qualita-tively accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.These findings imply that the effects of macromolecular crowding can have an important influence on our understanding of how protein folding oc-curs in vivo.

  2. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  3. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics.

    Science.gov (United States)

    Lönn, Peter; Kacsinta, Apollo D; Cui, Xian-Shu; Hamil, Alexander S; Kaulich, Manuel; Gogoi, Khirud; Dowdy, Steven F

    2016-09-08

    Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

  4. Battlefield MRI

    Energy Technology Data Exchange (ETDEWEB)

    Espy, Michelle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-06-01

    Magnetic Resonance Imaging is the best method for non-invasive imaging of soft tissue anatomy, saving countless lives each year. It is regarded as the gold standard for diagnosis of mild to moderate traumatic brain injuries. Furthermore, conventional MRI relies on very high, fixed strength magnetic fields (> 1.5 T) with parts-per-million homogeneity, which requires very large and expensive magnets.

  5. Fast Realistic MRI Simulations Based on Generalized Multi-Pool Exchange Tissue Model.

    Science.gov (United States)

    Liu, Fang; Velikina, Julia V; Block, Walter F; Kijowski, Richard; Samsonov, Alexey A

    2017-02-01

    We present MRiLab, a new comprehensive simulator for large-scale realistic MRI simulations on a regular PC equipped with a modern graphical processing unit (GPU). MRiLab combines realistic tissue modeling with numerical virtualization of an MRI system and scanning experiment to enable assessment of a broad range of MRI approaches including advanced quantitative MRI methods inferring microstructure on a sub-voxel level. A flexible representation of tissue microstructure is achieved in MRiLab by employing the generalized tissue model with multiple exchanging water and macromolecular proton pools rather than a system of independent proton isochromats typically used in previous simulators. The computational power needed for simulation of the biologically relevant tissue models in large 3D objects is gained using parallelized execution on GPU. Three simulated and one actual MRI experiments were performed to demonstrate the ability of the new simulator to accommodate a wide variety of voxel composition scenarios and demonstrate detrimental effects of simplified treatment of tissue micro-organization adapted in previous simulators. GPU execution allowed  ∼ 200× improvement in computational speed over standard CPU. As a cross-platform, open-source, extensible environment for customizing virtual MRI experiments, MRiLab streamlines the development of new MRI methods, especially those aiming to infer quantitatively tissue composition and microstructure.

  6. MRI of the Chest

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Chest Magnetic resonance imaging (MRI) of the chest ... limitations of MRI of the Chest? What is MRI of the Chest? Magnetic resonance imaging (MRI) is ...

  7. PROFESSOR TEJ PAL SINGH: THE LEGEND OF INDIAN MACROMOLECULAR CRYSTALLOGRAPHY

    Directory of Open Access Journals (Sweden)

    Md. Imtaiyaz Hassan

    2013-12-01

    Full Text Available Professor Tej Pal Singh, an internationally recognized Indian scientist par excellence, is one of the pioneers of Indian macromolecular crystallography. He is a person of significant and enduring accomplishments as a teacher, scientist, administrator and family man. He has developed various methods to crystallize wide varieties of proteins. He has successfully determined crystal structures of lactoferrin, phospholipase A2, lactoperoxidase, peptidoglycan recognition proteins, disintegrin, zinc-α2-glycoprotein and several others including various protein-ligand and protein-protein complexes. He has a remarkably high number of structural entries in protein data bank. He received most of the prestigious awards and honors by Indian Government. This article covers most of his research and other achievements which will be a source of inspiration for young scientific community, motivation for peers and joy for his fellow colleagues and friends.

  8. Identification of macromolecular complexes in cryoelectron tomograms of phantom cells

    Science.gov (United States)

    Frangakis, Achilleas S.; Böhm, Jochen; Förster, Friedrich; Nickell, Stephan; Nicastro, Daniela; Typke, Dieter; Hegerl, Reiner; Baumeister, Wolfgang

    2002-01-01

    Electron tomograms of intact frozen-hydrated cells are essentially three-dimensional images of the entire proteome of the cell, and they depict the whole network of macromolecular interactions. However, this information is not easily accessible because of the poor signal-to-noise ratio of the tomograms and the crowded nature of the cytoplasm. Here, we describe a template matching algorithm that is capable of detecting and identifying macromolecules in tomographic volumes in a fully automated manner. The algorithm is based on nonlinear cross correlation and incorporates elements of multivariate statistical analysis. Phantom cells, i.e., lipid vesicles filled with macromolecules, provide a realistic experimental scenario for an assessment of the fidelity of this approach. At the current resolution of ≈4 nm, macromolecules in the size range of 0.5–1 MDa can be identified with good fidelity. PMID:12391313

  9. Detecting stoichiometry of macromolecular complexes in live cells using FRET

    Science.gov (United States)

    Ben-Johny, Manu; Yue, Daniel N.; Yue, David T.

    2016-01-01

    The stoichiometry of macromolecular interactions is fundamental to cellular signalling yet challenging to detect from living cells. Fluorescence resonance energy transfer (FRET) is a powerful phenomenon for characterizing close-range interactions whereby a donor fluorophore transfers energy to a closely juxtaposed acceptor. Recognizing that FRET measured from the acceptor's perspective reports a related but distinct quantity versus the donor, we utilize the ratiometric comparison of the two to obtain the stoichiometry of a complex. Applying this principle to the long-standing controversy of calmodulin binding to ion channels, we find a surprising Ca2+-induced switch in calmodulin stoichiometry with Ca2+ channels—one calmodulin binds at basal cytosolic Ca2+ levels while two calmodulins interact following Ca2+ elevation. This feature is curiously absent for the related Na channels, also potently regulated by calmodulin. Overall, our assay adds to a burgeoning toolkit to pursue quantitative biochemistry of dynamic signalling complexes in living cells. PMID:27922011

  10. An analysis of fractal geometry of macromolecular gelation

    Institute of Scientific and Technical Information of China (English)

    左榘; 陈天红; 冉少峰; 何炳林; 董宝中; 生文君; 杨恒林

    1996-01-01

    With fractal geometry theory and based on experiments, an analysis of fractal geometry behavior of gelation of macromolecules was carried out. Using the cross-linking copolymerization of styrene-divinylbenzene (DVB) as an example, through the determinations of the evolution of the molecular weight, size and the dependence of scattering intensity on the angle of macromolecules by employing laser and synchrotron small angle X-ray scattering, respectively, this chemical reaction was described quantitatively, its fractal behavior was analyzed and the fractal dimension was also measured. By avoiding the complex theories on gelation, this approach is based on modern physical techniques and theories to perform the analysis of the behavior of fractal geometry of macromolecular gelation and thus is able to reveal the rules of this kind of complicated gelation more essentially and profoundly.

  11. Revealing the macromolecular targets of complex natural products

    Science.gov (United States)

    Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

  12. Macromolecularly "Caged" Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence.

    Science.gov (United States)

    Misra, Santosh K; Srivastava, Indrajit; Tripathi, Indu; Daza, Enrique; Ostadhossein, Fatemeh; Pan, Dipanjan

    2017-02-08

    Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.

  13. On macromolecular refinement at subatomic resolution withinteratomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Lunin, Vladimir Y.; Urzhumtsev, Alexandre

    2007-11-09

    A study of the accurate electron density distribution in molecular crystals at subatomic resolution, better than {approx} 1.0 {angstrom}, requires more detailed models than those based on independent spherical atoms. A tool conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8-1.0 {angstrom}, the number of experimental data is insufficient for the full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark datasets gave results comparable in quality with results of multipolar refinement and superior of those for conventional models. Applications to several datasets of both small- and macro-molecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  14. Protein Coevolution and Isoexpression in Yeast Macromolecular Complexes

    Directory of Open Access Journals (Sweden)

    Laurence Ettwiller

    2007-01-01

    Full Text Available Previous studies in the yeast Saccharomyces cerevisiae have shown that genes encoding subunits of macromolecular complexes have similar evolutionary rates (K and expression levels (E. Besides, it is known that the expression of a gene is a strong predictor of its rate of evolution (i.e., E and K are correlated. Here we show that intracomplex variation of subunit expression correlates with intracomplex variation of their evolutionary rates (using two different measures of dispersion. However, a similar trend was observed for randomized complexes. Therefore, using a mathematical transformation, we created new variables capturing intracomplex variation of both E and K. The values of these new compound variables were smaller for real complexes than for randomized ones. This shows that proteins in complexes tend to have closer expressivities (E and K's simultaneously than in the randomly grouped genes. We speculate about the possible implications of this finding.

  15. [Progress in researches on synthetic antimicrobial macromolecular polymers].

    Science.gov (United States)

    Wei, Gang; Yang, Lihua; Chu, Liangyin

    2010-08-01

    Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.

  16. Macromolecular Crystallization with Microfluidic Free-Interface Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Segelke, B

    2005-02-24

    Fluidigm released the Topaz 1.96 and 4.96 crystallization chips in the fall of 2004. Topaz 1.96 and 4.96 are the latest evolution of Fluidigm's microfluidics crystallization technologies that enable ultra low volume rapid screening for macromolecular crystallization. Topaz 1.96 and 4.96 are similar to each other but represent a major redesign of the Topaz system and have of substantially improved ease of automation and ease of use, improved efficiency and even further reduced amount of material needed. With the release of the new Topaz system, Fluidigm continues to set the standard in low volume crystallization screening which is having an increasing impact in the field of structural genomics, and structural biology more generally. In to the future we are likely to see further optimization and increased utility of the Topaz crystallization system, but we are also likely to see further innovation and the emergence of competing technologies.

  17. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  18. Extracting trends from two decades of microgravity macromolecular crystallization history

    Science.gov (United States)

    Judge, Russell A.; Snell, Edward H.; van der Woerd, Mark J.

    2005-01-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  19. Large-volume protein crystal growth for neutron macromolecular crystallography.

    Science.gov (United States)

    Ng, Joseph D; Baird, James K; Coates, Leighton; Garcia-Ruiz, Juan M; Hodge, Teresa A; Huang, Sijay

    2015-04-01

    Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

  20. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  1. Sacroillite tuberculeuse: à propos de deux cas

    Science.gov (United States)

    Diallo, Ismaël; Zabsonré, Joëlle Tiendrébéogo; Kambou, Bénilde Marie Ange Tiemtoré; Sondo, Apoline Kongnimissom; Sagna, Yempabou; Ouédraogo, Dieu-Donné

    2016-01-01

    La sacroiliite tuberculeuse est rare et de diagnostic difficile. Les auteurs rapportent deux cas. Il s'agissait dans le premier cas d'une patiente de 40 ans ayant une infection à VIH ; le diagnostic a été histologique après une biopsie chirurgicale. Le second cas a concerné un patient de 25 ans vivant en milieu carcéral chez qui le diagnostic a été établi sur la base des arguments cliniques, biologiques, radiologiques et l'efficacité du traitement ; l'intradermoréaction à la tuberculine était phlycténulaire. Le scanner a été indispensable au diagnostic lésionnel en montrant une érosion des berges et des abcès des parties molles. Le traitement a été médical et a fait appel aux antituberculeux. PMID:28292032

  2. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary [University of Oxford, South Parks Road, Oxford OX1 3QU (United Kingdom); Ravelli, Raimond B. G. [Maastricht University, PO Box 616, Maastricht 6200 MD (Netherlands); Carmichael, Ian [University of Notre Dame, Notre Dame, IN 46556 (United States); Kneale, Geoff; McGeehan, John E., E-mail: john.mcgeehan@port.ac.uk [University of Portsmouth, King Henry 1st Street, Portsmouth PO1 2DY (United Kingdom)

    2015-01-30

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N{sub 1}—C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.

  3. Knee MRI scan

    Science.gov (United States)

    MRI - knee ... radiologist see certain areas more clearly. During the MRI, the person who operates the machine will watch ... less anxious. Your provider may suggest an "open" MRI, in which the machine is not as close ...

  4. MRI of the Chest

    Medline Plus

    Full Text Available ... MRI of the Chest? What is MRI of the Chest? Magnetic resonance imaging (MRI) is a noninvasive ... of page What are some common uses of the procedure? MR imaging of the chest is performed ...

  5. Play the MRI Game

    Science.gov (United States)

    ... Teachers' Questionnaire MRI Play MRI the Magnetic Miracle Game About the game In the MRI imaging technique, strong magnets and ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  6. MRI of the Chest

    Medline Plus

    Full Text Available ... MRI of the Chest? What is MRI of the Chest? Magnetic resonance imaging (MRI) is a noninvasive ... of page What are some common uses of the procedure? MR imaging of the chest is performed ...

  7. MRI of the Chest

    Medline Plus

    Full Text Available ... You may resume your usual activities and normal diet immediately after the exam. On very rare occasions, ... Magnetic Resonance Imaging (MRI) Safety MRI Safety During Pregnancy Images related to Magnetic Resonance Imaging (MRI) - Chest ...

  8. CAS physicist receives Tate Medal from American Institute of Physics

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The American Institute of Physics (AIP) 2007 Tate Medal for Leadership in International Physics goes to Prof. YU Lu, a physicist from the CAS Institute of Physics and chair of the CAS Interdisciplinary Center for Theoretical Studies.

  9. CAS to Further Strengthen Cooperation with the EU

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ In light of the concept that scientific knowledge should serve humanity, CAS is open to the whole world and will further cooperate with the European Union in various fields, asserts CAS President Lu Yongxiang.

  10. CAS enacts rules to guide management of its institutes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ CAS issued Regulations for Comprehensive Administration of Research Institutes at the annual work conference opened on 24 March in Beijing. It is regarded as another cardinal document for CAS management after its Constitution, which was decreed in 2006.

  11. Evolution and classification of the CRISPR-Cas systems

    Science.gov (United States)

    S. Makarova, Kira; H. Haft, Daniel; Barrangou, Rodolphe; J. J. Brouns, Stan; Charpentier, Emmanuelle; Horvath, Philippe; Moineau, Sylvain; J. M. Mojica, Francisco; I. Wolf, Yuri; Yakunin, Alexander F.; van der Oost, John; V. Koonin, Eugene

    2012-01-01

    The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a `polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR–cas loci. PMID:21552286

  12. CNPC and CAS Sign Technological Cooperation Agreement

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ On August 16, 2006, China National Petroleum Corporation (CNPC) signed technological cooperation agreement with Chinese Academy of Sciences (CAS) at the Diaoyutai State Guesthouse in Beijing. Vice President of CNPC Zhou Jiping and Vice President of CAS Li Jiayang signed the agreement on behalf of both sides,marking a new era of unite brainstorm in petroleum technology. It will boost the development of petrochemical technology, especially the technology for the exploration and development of oil and gas field, engineering, oil refining and chemicals.

  13. CRISPR-Cas: Revolutionising genome engineering.

    Science.gov (United States)

    Nicholson, Samantha Anne; Pepper, Michael Sean

    2016-08-01

    The ability to permanently alter or repair the human genome has been the subject of a number of science fiction films, but with the recent advent of several customisable sequence-specific endonuclease technologies, genome engineering looks set to become a clinical reality in the near future. This article discusses recent advancements in the technology called 'clustered regularly interspaced palindromic repeat (CRISPR)-associated genes' (CRISPR-Cas), the potential of CRISPR-Cas to revolutionise molecular medicine, and the ethical and regulatory hurdles facing its application.

  14. CRISPR-Cas immunity in prokaryotes.

    Science.gov (United States)

    Marraffini, Luciano A

    2015-10-01

    Prokaryotic organisms are threatened by a large array of viruses and have developed numerous defence strategies. Among these, only clustered, regularly interspaced short palindromic repeat (CRISPR)-Cas systems provide adaptive immunity against foreign elements. Upon viral injection, a small sequence of the viral genome, known as a spacer, is integrated into the CRISPR locus to immunize the host cell. Spacers are transcribed into small RNA guides that direct the cleavage of the viral DNA by Cas nucleases. Immunization through spacer acquisition enables a unique form of evolution whereby a population not only rapidly acquires resistance to its predators but also passes this resistance mechanism vertically to its progeny.

  15. CAS scientists active in earthquake relief operation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Soon after the devastating earthquake taking place on last 12 May in Sichuan, the CAS leadership promptly mobilized its researchers to dedicate their expertise to the nationwide drive of the disaster's relief and reduction. A leading group was established to coordinate the Academy's efforts in this regard. All of the eight CAS institutions located in Sichuan were organized to do everything possible to reduce their losses to the minimum. At the same time, a trans-departmental and interdisciplinary taskforce was formed to provide a powerful S&T backing for the nationwide drive.

  16. Engineered CRISPR-Cas9 nucleases with altered PAM specificities.

    Science.gov (United States)

    Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Topkar, Ved V; Nguyen, Nhu T; Zheng, Zongli; Gonzales, Andrew P W; Li, Zhuyun; Peterson, Randall T; Yeh, Jing-Ruey Joanna; Aryee, Martin J; Joung, J Keith

    2015-07-23

    Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities.

  17. Animal MRI Core

    Data.gov (United States)

    Federal Laboratory Consortium — The Animal Magnetic Resonance Imaging (MRI) Core develops and optimizes MRI methods for cardiovascular imaging of mice and rats. The Core provides imaging expertise,...

  18. CAS Maps Out a Blueprint for Its Future Development

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ At the enlarged summer session of the Party's Leading Group at CAS held from July 25 to 29 in Beijing,the CAS leadership called for implementing the third-phase work of the Knowledge Innovation Program (KIP) through innovation and reform, so as to open up new prospects for CAS development in the years to come.

  19. CAS, Thai S&T ministry to further cooperation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Hosted by the CAS Bureau of International Cooperation, the Second CAS-Thai MOST Joint Workshop on S&T Cooperation was held on 28 and 29 June in Chengdu, capital of southwest China's Sichuan Province. More than 120 officials and scholars from Sichuan Provincial Government, CAS, and Thai Ministry of Science and Technology(MOST) were present at the meeting.

  20. Structural plasticity and in vivo activity of Cas1 from the type I-F CRISPR-Cas system.

    Science.gov (United States)

    Wilkinson, Max E; Nakatani, Yoshio; Staals, Raymond H J; Kieper, Sebastian N; Opel-Reading, Helen K; McKenzie, Rebecca E; Fineran, Peter C; Krause, Kurt L

    2016-04-15

    CRISPR-Cas systems are adaptive immune systems in prokaryotes that provide protection against viruses and other foreign DNA. In the adaptation stage, foreign DNA is integrated into CRISPR (clustered regularly interspaced short palindromic repeat) arrays as new spacers. These spacers are used in the interference stage to guide effector CRISPR associated (Cas) protein(s) to target complementary foreign invading DNA. Cas1 is the integrase enzyme that is central to the catalysis of spacer integration. There are many diverse types of CRISPR-Cas systems, including type I-F systems, which are typified by a unique Cas1-Cas2-3 adaptation complex. In the present study we characterize the Cas1 protein of the potato phytopathogen Pectobacterium atrosepticum, an important model organism for understanding spacer acquisition in type I-F CRISPR-Cas systems. We demonstrate by mutagenesis that Cas1 is essential for adaptation in vivo and requires a conserved aspartic acid residue. By X-ray crystallography, we show that although P. atrosepticum Cas1 adopts a fold conserved among other Cas1 proteins, it possesses remarkable asymmetry as a result of structural plasticity. In particular, we resolve for the first time a flexible, asymmetric loop that may be unique to type I-F Cas1 proteins, and we discuss the implications of these structural features for DNA binding and enzymatic activity.

  1. CRISPR-Cas9 gene editing

    NARCIS (Netherlands)

    Oude Blenke, Erik; Evers, Martijn J.W.; Mastrobattista, Enrico; Oost, van der John

    2016-01-01

    The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with

  2. CRISPR-Cas9 gene editing

    NARCIS (Netherlands)

    Oude Blenke, Erik; Evers, Martijn J.W.; Mastrobattista, Enrico; Oost, van der John

    2016-01-01

    The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with

  3. CAS scores progress in MIS development

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A CAS initiative to upgrade its management information system (MIS) is making landmark progress. The first-phase development of the Academia Resource Planning (ARP), a major MIS project at the Academy, passed the acceptance check by a 17-strong panel of experts on 23 January 2007 in Beijing.

  4. CAS expert receives Tribology Gold Medal

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Prof. XUE Qunji, a senior expert in tribology from the CAS Lanzhou Institute of Chemical Physics (L1CP) and member of the Chinese Academy of Engineering, received the Tribology Gold Medalfor 2011 on February 27, 2012 in Beijing. As one of the world's most outstanding and influential tribologists in the last forty years, Prof.

  5. CAS researchers find a new mineral

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Mineralogists from the CAS Guangzhou Institute of Geochemistry (GIG) recently discovered Xieite, a chromium-iron oxide in its natural state. It has been authorized as a new mineral by Commission on New Minerals Nomenclature and Classification under the International Mineralogical Association (CNMNC-IMA).

  6. Using the CAS Standards in Assessment Projects

    Science.gov (United States)

    Dean, Laura A.

    2013-01-01

    This chapter provides an overview of the use of professional standards of practice in assessment and of the Council for the Advancement of Standards in Higher Education (CAS). It outlines a model for conducting program self-studies and discusses the importance of implementing change based on assessment results.

  7. Boosting plant immunity with CRISPR/Cas

    OpenAIRE

    Chaparro-Garcia, Angela; Kamoun, Sophien; Nekrasov, Vladimir

    2015-01-01

    CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method.See related Research: http://www.genomebiology.com/2015/16/1/238.

  8. Boosting plant immunity with CRISPR/Cas.

    Science.gov (United States)

    Chaparro-Garcia, Angela; Kamoun, Sophien; Nekrasov, Vladimir

    2015-11-19

    CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method.See related Research: http://www.genomebiology.com/2015/16/1/238.

  9. Controlling UCAVs by JTACs in CAS missions

    Science.gov (United States)

    Kumaş, A. E.

    2014-06-01

    By means of evolving technology, capabilities of UAVs (Unmanned Aerial Vehicle)s are increasing rapidly. This development provides UAVs to be used in many different areas. One of these areas is CAS (Close Air Support) mission. UAVs have several advantages compared to manned aircraft, however there are also some problematic areas. The remote controlling of these vehicles from thousands of nautical miles away via satellite may lead to various problems both ethical and tactical aspects. Therefore, CAS missions require a good level of ALI (Air-Land Integration), a high SA (situational awareness) and precision engagement. In fact, there is an aware friendly element in the target area in CAS missions, unlike the other UAV operations. This element is an Airman called JTAC (Joint Terminal Attack Controller). Unlike the JTAC, UAV operators are too far away from target area and use the limited FOV (Field of View) provided by camera and some other sensor data. In this study, target area situational awareness of a UAV operator and a JTAC, in a high-risk mission for friendly ground forces and civilians such as CAS, are compared. As a result of this comparison, answer to the question who should control the UCAV (Unmanned Combat Aerial Vehicle) in which circumstances is sought. A literature review is made in UAV and CAS fields and recent air operations are examined. The control of UCAV by the JTAC is assessed by SWOT analysis and as a result it is deduced that both control methods can be used in different situations within the framework of the ROE (Rules Of Engagement) is reached.

  10. Macromolecular crowding for tailoring tissue-derived fibrillated matrices.

    Science.gov (United States)

    Magno, Valentina; Friedrichs, Jens; Weber, Heather M; Prewitz, Marina C; Tsurkan, Mikhail V; Werner, Carsten

    2017-06-01

    Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials characteristics only. In this work, we demonstrate how macromolecular crowding (MMC) - the supplementation of matrix reconstitution media with synthetic or natural macromolecules in ways to create excluded volume effects (EVE) - can be employed for tailoring important structural and biophysical characteristics of kidney-derived fibrillated matrices. Porcine kidneys were decellularized, ground and the obtained extracellular matrix (ECM) preparations were reconstituted under varied MMC conditions. We show that MMC strongly influences the fibrillogenesis kinetics and impacts the architecture and the elastic modulus of the reconstituted matrices, with diameters and relative alignment of fibrils increasing at elevated concentrations of the crowding agent Ficoll400, a nonionic synthetic polymer of sucrose. Furthermore, we demonstrate how MMC modulates the distribution of key ECM molecules within the reconstituted matrix scaffolds. As a proof of concept, we compared different variants of kidney-derived fibrillated matrices in cell culture experiments referring to specific requirements of kidney tissue engineering approaches. The results revealed that MMC-tailored matrices support the morphogenesis of human umbilical vein endothelial cells (HUVECs) into capillary networks and of murine kidney stem cells (KSCs) into highly branched aggregates. The established methodology is concluded to provide generally applicable new options for tailoring tissue-specific multiphasic matrices in vitro. Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials

  11. Naturally Occurring Off-Switches for CRISPR-Cas9.

    Science.gov (United States)

    Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J; Maxwell, Karen L; Davidson, Alan R

    2016-12-15

    CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. NMR RELAXIVITY AND IMAGING OF NEUTRAL MACROMOLECULAR POLYESTER GADOLINIUM (Ⅲ) COMPLEXES

    Institute of Scientific and Technical Information of China (English)

    Kai-chao Yu; Hong-bing Hu; Mai-li Liu; Han-zhen Yuan; Chao-hui Ye; Ren-xi Zhuo

    1999-01-01

    Five neutral macromolecular polyester gadolinium (Ⅲ) complexes with pendant hydrophobic alkyl and aromatic functional groups were prepared. The longitudinal relaxation rates of these complexes were measured. One of these Gd (Ⅲ) complexes was chosen for the acute toxicity test and T1-weighted imaging measurement. Preliminary results showed that. compared with Gd-DTPA, the neutral macromolecular gadolinium (Ⅲ) complexes provide higher T1 relaxivity enhancement and longer function duration.

  13. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function.

    Science.gov (United States)

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-04-28

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.

  14. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2011-07-01

    Full Text Available Abstract Background The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III. Results A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs containing a distinct form of the RNA Recognition Motif (RRM domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes. Conclusions Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure

  15. A versatile microparticle-based immunoaggregation assay for macromolecular biomarker detection and quantification.

    Directory of Open Access Journals (Sweden)

    Haiyan Wu

    Full Text Available The rapid, sensitive and low-cost detection of macromolecular biomarkers is critical in clinical diagnostics, environmental monitoring, research, etc. Conventional assay methods usually require bulky, expensive and designated instruments and relative long assay time. For hospitals and laboratories that lack immediate access to analytical instruments, fast and low-cost assay methods for the detection of macromolecular biomarkers are urgently needed. In this work, we developed a versatile microparticle (MP-based immunoaggregation method for the detection and quantification of macromolecular biomarkers. Antibodies (Abs were firstly conjugated to MP through streptavidin-biotin interaction; the addition of macromolecular biomarkers caused the aggregation of Ab-MPs, which were subsequently detected by an optical microscope or optical particle sizer. The invisible nanometer-scale macromolecular biomarkers caused detectable change of micrometer-scale particle size distributions. Goat anti-rabbit immunoglobulin and human ferritin were used as model biomarkers to demonstrate MP-based immunoaggregation assay in PBS and 10% FBS to mimic real biomarker assay in the complex medium. It was found that both the number ratio and the volume ratio of Ab-MP aggregates caused by biomarker to all particles were directly correlated to the biomarker concentration. In addition, we found that the detection range could be tuned by adjusting the Ab-MP concentration. We envision that this novel MP-based immunoaggregation assay can be combined with multiple detection methods to detect and quantify macromolecular biomarkers at the nanogram per milliliter level.

  16. JBluIce-EPICS control system for macromolecular crystallography.

    Energy Technology Data Exchange (ETDEWEB)

    Stepanov, S.; Makarov, O.; Hilgart, M.; Pothineni, S.; Urakhchin, A.; Devarapalli, S.; Yoder, D.; Becker, M.; Ogata, C.; Sanishvili, R.; Nagarajan, V.; Smith, J. L.; Fischetti, R. F. (Biosciences Division); (Univ. of Michigan)

    2011-01-01

    The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline component. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallographic experiments, especially in the field of microcrystallography.

  17. Patch-clamp detection of macromolecular translocation along nuclear pores

    Directory of Open Access Journals (Sweden)

    Bustamante J.O.

    1998-01-01

    Full Text Available The present paper reviews the application of patch-clamp principles to the detection and measurement of macromolecular translocation along the nuclear pores. We demonstrate that the tight-seal 'gigaseal' between the pipette tip and the nuclear membrane is possible in the presence of fully operational nuclear pores. We show that the ability to form a gigaseal in nucleus-attached configurations does not mean that only the activity of channels from the outer membrane of the nuclear envelope can be detected. Instead, we show that, in the presence of fully operational nuclear pores, it is likely that the large-conductance ion channel activity recorded derives from the nuclear pores. We conclude the technical section with the suggestion that the best way to demonstrate that the nuclear pores are responsible for ion channel activity is by showing with fluorescence microscopy the nuclear translocation of ions and small molecules and the exclusion of the same from the cisterna enclosed by the two membranes of the envelope. Since transcription factors and mRNAs, two major groups of nuclear macromolecules, use nuclear pores to enter and exit the nucleus and play essential roles in the control of gene activity and expression, this review should be useful to cell and molecular biologists interested in understanding how patch-clamp can be used to quantitate the translocation of such macromolecules into and out of the nucleus

  18. Timely deposition of macromolecular structures is necessary for peer review

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Soueidan, Hayssam; Wessels, Lodewyk F. A. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Perrakis, Anastassis, E-mail: a.perrakis@nki.nl [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature.

  19. Synchrotron radiation macromolecular crystallography: science and spin-offs

    Directory of Open Access Journals (Sweden)

    John R. Helliwell

    2015-03-01

    Full Text Available A current overview of synchrotron radiation (SR in macromolecular crystallography (MX instrumentation, methods and applications is presented. Automation has been and remains a central development in the last decade, as have the rise of remote access and of industrial service provision. Results include a high number of Protein Data Bank depositions, with an increasing emphasis on the successful use of microcrystals. One future emphasis involves pushing the frontiers of using higher and lower photon energies. With the advent of X-ray free-electron lasers, closely linked to SR developments, the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules is anticipated, as well as the opening up of femtosecond time-resolved diffraction structural studies. At SR sources, a very high-throughput assessment for the best crystal samples and the ability to tackle just a few micron and sub-micron crystals will become widespread. With higher speeds and larger detectors, diffraction data volumes are becoming long-term storage and archiving issues; the implications for today and the future are discussed. Together with the rise of the storage ring to its current pre-eminence in MX data provision, the growing tendency of central facility sites to offer other centralized facilities complementary to crystallography, such as cryo-electron microscopy and NMR, is a welcome development.

  20. New concepts and applications in the macromolecular chemistry of fullerenes.

    Science.gov (United States)

    Giacalone, Francesco; Martín, Nazario

    2010-10-08

    A new classification on the different types of fullerene-containing polymers is presented according to their different properties and applications they exhibit in a variety of fields. Because of their interest and novelty, water-soluble and biodegradable C(60)-polymers are discussed first, followed by polyfullerene-based membranes where unprecedented supramolecular structures are presented. Next are compounds that involve hybrid materials formed from fullerenes and other components such as silica, DNA, and carbon nanotubes (CNTs) where the most recent advances have been achieved. A most relevant topic is still that of C(60)-based donor-acceptor (D-A) polymers. Since their application in photovoltaics D-A polymers are among the most realistic applications of fullerenes in the so-called molecular electronics. The most relevant aspects in these covalently connected fullerene/polymer hybrids as well as new concepts to improve energy conversion efficiencies are presented.The last topics disccused relate to supramolecular aspects that are in involved in C(60)-polymer systems and in the self-assembly of C(60)-macromolecular structures, which open a new scenario for organizing, by means of non-covalent interactions, new supramolecular structures at the nano- and micrometric scale, in which the combination of the hydrofobicity of fullerenes with the versatility of the noncovalent chemistry afford new and spectacular superstructures.

  1. Macromolecular metallurgy of binary mesocrystals via designed multiblock terpolymers.

    Science.gov (United States)

    Xie, Nan; Liu, Meijiao; Deng, Hanlin; Li, Weihua; Qiu, Feng; Shi, An-Chang

    2014-02-26

    Self-assembling block copolymers provide access to the fabrication of various ordered phases. In particular, the ordered spherical phases can be used to engineer soft mesocrystals with domain size at the 5-100 nm scales. Simple block copolymers, such as diblock copolymers, form a limited number of mesocrystals. However multiblock copolymers are capable to form more complex mesocrystals. We demonstrate that designed B1AB2CB3 multiblock terpolymers, in which the A- and C-blocks form spherical domains and the packing of these spheres can be controlled by changing the lengths of the middle and terminal B-blocks, self-assemble into various binary mesocrystals with space group symmetries of a large number of binary ionic crystals, including NaCl, CsCl, ZnS, α-BN, AlB2, CaF2, TiO2, ReO3, Li3Bi, Nb3Sn(A15), and α-Al2O3. This approach can be generalized to other terpolymers as well as to tetrapolymers to obtain ternary mesocrystals. Our study provides a new concept of macromolecular metallurgy for producing crystal phases in a mesoscale and thus makes multiblock copolymers a robust platform for the engineering of functional materials.

  2. Macromolecular Powder Diffraction: Ready for genuine biological problems.

    Science.gov (United States)

    Karavassili, Fotini; Margiolaki, Irene

    2016-01-01

    Knowledge of 3D structures of biological molecules plays a major role in both understanding important processes of life and developing pharmaceuticals. Among several methods available for structure determination, macromolecular X-ray powder diffraction (XRPD) has transformed over the past decade from an impossible dream to a respectable method. XRPD can be employed in biosciences for various purposes such as observing phase transitions, characterizing bulk pharmaceuticals, determining structures via the molecular replacement method, detecting ligands in protein-ligand complexes, as well as combining micro-sized single crystal crystallographic data and powder diffraction data. Studies using synchrotron and laboratory sources in some standard configuration setups are reported in this review, including their respective advantages and disadvantages. Methods presented here provide an alternative, complementary set of tools to resolve structural problems. A variety of already existing software packages for powder diffraction data processing and analysis, some of which have been adapted to large unit cell studies, are briefly described. This review aims to provide necessary elements of theory and current methods, along with practical explanations, available software packages and highlighted case studies.

  3. Canadian macromolecular crystallography facility: a suite of fully automated beamlines.

    Science.gov (United States)

    Grochulski, Pawel; Fodje, Michel; Labiuk, Shaunivan; Gorin, James; Janzen, Kathryn; Berg, Russ

    2012-06-01

    The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.

  4. CAS Introduction to Accelerator Physics in Bulgaria

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The CERN Accelerator School (CAS) and the Institute for Nuclear Research & Nuclear Energy (INRNE – Bulgarian Academy of Sciences) jointly organised a course on Introduction to Accelerators, at the Grand Hotel Varna, Bulgaria, from 19 September to 1 October, 2010.   CERN Accelerator School group photo. The course was extremely well attended with 109 participants representing 34 different nationalities, coming from countries as far away as Australia, Canada and Vietnam. The intensive programme comprised 39 lectures, 3 seminars, 4 tutorials where the students were split into three groups, a poster session where students could present their own work, and 7 hours of guided and private study. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and excellent quality of their lectures. For the first time at CAS, the CERN Director-General, Rolf Heuer, visited the school and presented a seminar entitled...

  5. CAS - Great success for the DSP course

    CERN Multimedia

    2007-01-01

    The CERN Accelerator School (CAS) and the Uppsala University jointly organized a specialized school on "Digital Signal Processing" in Sigtuna, Sweden from 1-9 June, 2007. This course was a "première" in many ways: firstly the topic had never been addressed by CAS, and secondly the structure of the course differed from the usual specialized courses in the sense that it was composed of 32 hours of theoretical lectures in the mornings and 16 hours "hands-on" courses in the afternoons. The latter, which have been designed by CERN experts, had some logistic implications in transporting computers and circuit boards (DSP and FPGA) to Sweden. The principle of this new approach was extremely well received by the accelerator community and 97 participants representing 23 different nationalities (80% of the participants originating from the CERN Member States) attended the course. As illustrated by the very positive feedback received from th...

  6. Efficient Mitochondrial Genome Editing by CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Areum Jo

    2015-01-01

    Full Text Available The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9 system has been widely used for nuclear DNA editing to generate mutations or correct specific disease alleles. Despite its flexible application, it has not been determined if CRISPR/Cas9, originally identified as a bacterial defense system against virus, can be targeted to mitochondria for mtDNA editing. Here, we show that regular FLAG-Cas9 can localize to mitochondria to edit mitochondrial DNA with sgRNAs targeting specific loci of the mitochondrial genome. Expression of FLAG-Cas9 together with gRNA targeting Cox1 and Cox3 leads to cleavage of the specific mtDNA loci. In addition, we observed disruption of mitochondrial protein homeostasis following mtDNA truncation or cleavage by CRISPR/Cas9. To overcome nonspecific distribution of FLAG-Cas9, we also created a mitochondria-targeted Cas9 (mitoCas9. This new version of Cas9 localizes only to mitochondria; together with expression of gRNA targeting mtDNA, there is specific cleavage of mtDNA. MitoCas9-induced reduction of mtDNA and its transcription leads to mitochondrial membrane potential disruption and cell growth inhibition. This mitoCas9 could be applied to edit mtDNA together with gRNA expression vectors without affecting genomic DNA. In this brief study, we demonstrate that mtDNA editing is possible using CRISPR/Cas9. Moreover, our development of mitoCas9 with specific localization to the mitochondria should facilitate its application for mitochondrial genome editing.

  7. Annotation and Classification of CRISPR-Cas Systems.

    Science.gov (United States)

    Makarova, Kira S; Koonin, Eugene V

    2015-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is represented in most archaea and many bacteria. Among the currently known prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented complexity and diversity. Classification of CRISPR-Cas variants that would capture their evolutionary relationships to the maximum possible extent is essential for comparative genomic and functional characterization of this theoretically and practically important system of adaptive immunity. To this end, a multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified. Comparative genomic analysis of the CRISPR-Cas systems in new archaeal and bacterial genomes performed over the 3 years elapsed since the development of this classification makes it clear that new types and subtypes of CRISPR-Cas need to be introduced. Moreover, this classification system captures only part of the complexity of CRISPR-Cas organization and evolution, due to the intrinsic modularity and evolutionary mobility of these immunity systems, resulting in numerous recombinant variants. Moreover, most of the cas genes evolve rapidly, complicating the family assignment for many Cas proteins and the use of family profiles for the recognition of CRISPR-Cas subtype signatures. Further progress in the comparative analysis of CRISPR-Cas systems requires integration of the most sensitive sequence comparison tools, protein structure comparison, and refined approaches for comparison of gene neighborhoods.

  8. Breaking-Cas-interactive design of guide RNAs for CRISPR-Cas experiments for ENSEMBL genomes.

    Science.gov (United States)

    Oliveros, Juan C; Franch, Mònica; Tabas-Madrid, Daniel; San-León, David; Montoliu, Lluis; Cubas, Pilar; Pazos, Florencio

    2016-07-08

    The CRISPR/Cas technology is enabling targeted genome editing in multiple organisms with unprecedented accuracy and specificity by using RNA-guided nucleases. A critical point when planning a CRISPR/Cas experiment is the design of the guide RNA (gRNA), which directs the nuclease and associated machinery to the desired genomic location. This gRNA has to fulfil the requirements of the nuclease and lack homology with other genome sites that could lead to off-target effects. Here we introduce the Breaking-Cas system for the design of gRNAs for CRISPR/Cas experiments, including those based in the Cas9 nuclease as well as others recently introduced. The server has unique features not available in other tools, including the possibility of using all eukaryotic genomes available in ENSEMBL (currently around 700), placing variable PAM sequences at 5' or 3' and setting the guide RNA length and the scores per nucleotides. It can be freely accessed at: http://bioinfogp.cnb.csic.es/tools/breakingcas, and the code is available upon request.

  9. Prospects of CAS/MPS Cooperation

    Institute of Scientific and Technical Information of China (English)

    Mu Rongping

    2004-01-01

    @@ In the next 20 years, collaboration between the Chinese Academy of Sciences (CAS) and the Max Planck Society for the Advancement of Science (MPS) will meet with great strategic opportunities. We should seek the chance to innovatively improve our cooperation. This could include further improvement of the mechanisms,expansion of areas, actively seeking new patterns, and strengthening our research on science and technology foresight.

  10. CAS Wildlife Conservationist Receives Whitley Award

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Prof. JIANG Zhigang of the CAS Institute of Zoology has been honored with the 2006 Whitley Award by Whitley Fund for Nature, a UK registered charity offering a wide range of awards to outstanding nature conservation leaders around the world.Jiang is chosen for the award in recognition of his ecosystem approach to conservation of the Przewalski's Gazelle in pastoral areas around Qinghai Lake in northwest China's Qinghai-Tibet Plateau.

  11. CAS overseas talent programs pay off

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ With an objective to establish a highly innovative research contingent,CAS has Iaunched a number of talent-recruitment and training schemes sinece the initiation of its Knowledge Innovation Program in 1998,namely,Engaging Outstanding Overseas Talents,Overseas Review Experts,Overseas Supervisors for Doctoral Candidates,Fund for Overseas Outstanding Scholars,Academic Seminars,Einstein Visiting Professorship,and Research Fellowship for International Young Researchers.

  12. A Sweeping Reshuffle at CAS Institutes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Reorganization of CAS institutes was conducted over the past four years. For example, with the merger of the former Institute of Mathematics,Institute of Applied Mathematics, Institute of Systems Science and Institute of Computational Mathematics & Scientific/Engineering Computing, an Academy of Mathematics & System Sciences was formed. In the Shanghai area, the eight former biological institutes was regrouped into four institutes and one center,which formed the newly established Shanghai Institutes for Biological Sciences.

  13. MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems.

    Directory of Open Access Journals (Sweden)

    Sophie S Abby

    Full Text Available Biologists often wish to use their knowledge on a few experimental models of a given molecular system to identify homologs in genomic data. We developed a generic tool for this purpose.Macromolecular System Finder (MacSyFinder provides a flexible framework to model the properties of molecular systems (cellular machinery or pathway including their components, evolutionary associations with other systems and genetic architecture. Modelled features also include functional analogs, and the multiple uses of a same component by different systems. Models are used to search for molecular systems in complete genomes or in unstructured data like metagenomes. The components of the systems are searched by sequence similarity using Hidden Markov model (HMM protein profiles. The assignment of hits to a given system is decided based on compliance with the content and organization of the system model. A graphical interface, MacSyView, facilitates the analysis of the results by showing overviews of component content and genomic context. To exemplify the use of MacSyFinder we built models to detect and class CRISPR-Cas systems following a previously established classification. We show that MacSyFinder allows to easily define an accurate "Cas-finder" using publicly available protein profiles.MacSyFinder is a standalone application implemented in Python. It requires Python 2.7, Hmmer and makeblastdb (version 2.2.28 or higher. It is freely available with its source code under a GPLv3 license at https://github.com/gem-pasteur/macsyfinder. It is compatible with all platforms supporting Python and Hmmer/makeblastdb. The "Cas-finder" (models and HMM profiles is distributed as a compressed tarball archive as Supporting Information.

  14. DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions.

    Science.gov (United States)

    Kuang, Xingyan; Dhroso, Andi; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

    2016-01-01

    Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction's mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein-protein interactions or protein-DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1,040,000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43,000 RNA-mediated interactions, and ∼12,000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network

  15. Non-contact luminescence lifetime cryothermometry for macromolecular crystallography.

    Science.gov (United States)

    Mykhaylyk, V B; Wagner, A; Kraus, H

    2017-05-01

    Temperature is a very important parameter when aiming to minimize radiation damage to biological samples during experiments that utilize intense ionizing radiation. A novel technique for remote, non-contact, in situ monitoring of the protein crystal temperature has been developed for the new I23 beamline at the Diamond Light Source, a facility dedicated to macromolecular crystallography (MX) with long-wavelength X-rays. The temperature is derived from the temperature-dependent decay time constant of luminescence from a minuscule scintillation sensor (luminescence lifetime thermometry is presented, the features of the detection method and the choice of temperature sensor are discussed, and it is demonstrated how the temperature monitoring system was integrated within the viewing system of the endstation used for the visualization of protein crystals. The thermometry system was characterized using a Bi4Ge3O12 crystal scintillator that exhibits good responsivity of the decay time constant as a function of temperature over a wide range (8-270 K). The scintillation sensor was calibrated and the uncertainty of the temperature measurements over the primary operation temperature range of the beamline (30-150 K) was assessed to be ±1.6 K. It has been shown that the temperature of the sample holder, measured using the luminescence sensor, agrees well with the expected value. The technique was applied to characterize the thermal performance of different sample mounts that have been used in MX experiments at the I23 beamline. The thickness of the mount is shown to have the greatest impact upon the temperature distribution across the sample mount. Altogether, these tests and findings demonstrate the usefulness of the thermometry system in highlighting the challenges that remain to be addressed for the in-vacuum MX experiment to become a reliable and indispensable tool for structural biology.

  16. A Compact X-Ray System for Macromolecular Crystallography. 5

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  17. A Compact X-Ray System for Macromolecular Crystallography

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  18. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein.

    Science.gov (United States)

    Tang, Lichun; Zeng, Yanting; Du, Hongzi; Gong, Mengmeng; Peng, Jin; Zhang, Buxi; Lei, Ming; Zhao, Fang; Wang, Weihua; Li, Xiaowei; Liu, Jianqiao

    2017-03-01

    Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

  19. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  20. CRISPR-Cas adaptive immune systems of the sulfolobales

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Erdmann, Susanne;

    2015-01-01

    The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive......, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel...... mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed....

  1. CRISPR-Cas9 Based Engineering of Actinomycetal Genomes

    DEFF Research Database (Denmark)

    Tong, Yaojun; Charusanti, Pep; Zhang, Lixin

    2015-01-01

    . To facilitate the genetic manipulation of actinomycetes, we developed a highly efficient CRISPR-Cas9 system to delete gene(s) or gene cluster(s), implement precise gene replacements, and reversibly control gene expression in actinomycetes. We demonstrate our system by targeting two genes, actIORF1 (SCO5087......) and actVB (SCO5092), from the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2). Our CRISPR-Cas9 system successfully inactivated the targeted genes. When no templates for homology-directed repair (HDR) were present, the site-specific DNA double-strand breaks (DSBs) introduced by Cas9....... Moreover, we developed a system to efficiently and reversibly control expression of target genes, deemed CRISPRi, based on a catalytically dead variant of Cas9 (dCas9). The CRISPR-Cas9 based system described here comprises a powerful and broadly applicable set of tools to manipulate actinomycetal genomes....

  2. CRISPR/Cas9: Transcending the Reality of Genome Editing

    Directory of Open Access Journals (Sweden)

    Sergiu Chira

    2017-06-01

    Full Text Available With the expansion of the microbiology field of research, a new genome editing tool arises from the biology of bacteria that holds the promise of achieving precise modifications in the genome with a simplicity and versatility that surpasses previous genome editing methods. This new technique, commonly named CRISPR/Cas9, led to a rapid expansion of the biomedical field; more specifically, cancer characterization and modeling have benefitted greatly from the genome editing capabilities of CRISPR/Cas9. In this paper, we briefly summarize recent improvements in CRISPR/Cas9 design meant to overcome the limitations that have arisen from the nuclease activity of Cas9 and the influence of this technology in cancer research. In addition, we present challenges that might impede the clinical applicability of CRISPR/Cas9 for cancer therapy and highlight future directions for designing CRISPR/Cas9 delivery systems that might prove useful for cancer therapeutics.

  3. Advances in therapeutic CRISPR/Cas9 genome editing.

    Science.gov (United States)

    Savić, Nataša; Schwank, Gerald

    2016-02-01

    Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Coaching and engaging. Developing teaching with CAS in High School

    DEFF Research Database (Denmark)

    Bang, Henrik Peter; Grønbæk, Niels; Larsen, Claus Richard

    The extensive use of CAS at upper secondary school in Denmark provides a laboratory for research on the development of standards for CAS teaching. The poster focuses on action research into teachers developing lessons and student activities in an ongoing collaboration between university and high...... schools on use of CAS in mathematics teaching. Coaches1 mediate design processes, reflection and documentation, and enable sharing. We discuss coaching as a valuable part of action research, and how to draw findings from the collaboration....

  5. CAS Announces Its Action Plan for Revitalizing Northeast China

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ A conference of the CAS leading group for the revitalization of northeast China with science and technology was held on Sept. 1 and 2 in Changchun, capital of northeast China's Jilin Province. Chaired by CAS Vice President Shi Erwei, the meeting focused on the implementation of a CAS action plan for retrieving China's northeast, an old industrial base and once the industrialization locomotive of the country.

  6. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... the limitations of MRI of the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) ... ray, CT and ultrasound. top of page How is the procedure performed? MRI examinations may be performed ...

  7. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... Site Index A-Z Magnetic Resonance Imaging (MRI) - Head Magnetic resonance imaging (MRI) of the head uses ... of the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) is a noninvasive medical ...

  8. Impairments in Brain Perfusion, Metabolites, Functional Connectivity, and Cognition in Severe Asymptomatic Carotid Stenosis Patients: An Integrated MRI Study

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2017-01-01

    Full Text Available Carotid artery stenosis without transient ischemic attack (TIA or stroke is considered as “asymptomatic.” However, recent studies have demonstrated that these asymptomatic carotid artery stenosis (aCAS patients had cognitive impairment in tests of executive function, psychomotor speed, and memory, indicating that “asymptomatic” carotid stenosis may not be truly asymptomatic. In this study, when 19 aCAS patients compared with 24 healthy controls, aCAS patients showed significantly poorer performance on global cognition, memory, and executive function. By utilizing an integrated MRI including pulsed arterial spin labeling (pASL MRI, Proton MR Spectroscopy (MRS, and resting-state functional MRI (R-fMRI, we also found that aCAS patients suffered decreased cerebral blood flow (CBF mainly in the Left Frontal Gyrus and had decreased NAA/Cr ratio in the left hippocampus and decreased connectivity to the posterior cingulate cortex (PCC in the anterior part of default mode network (DMN.

  9. Abdominal MRI scan

    Science.gov (United States)

    Nuclear magnetic resonance - abdomen; NMR - abdomen; Magnetic resonance imaging - abdomen; MRI of the abdomen ... radiologist see certain areas more clearly. During the MRI, the person who operates the machine will watch ...

  10. MRI of the Chest

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    Full Text Available ... about pregnancy and MRI. If you have claustrophobia (fear of enclosed spaces) or anxiety, you may want ... projectiles within the MRI scanner room and may cause you and/or others nearby harm. These items ...

  11. MRI of the Chest

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    Full Text Available ... internal body structures. MRI does not use ionizing radiation (x-rays). Detailed MR images allow physicians to ... tomography (CT) scans, MRI does not utilize ionizing radiation. Instead, radiofrequency pulses re-align hydrogen atoms that ...

  12. MRI of the Chest

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    Full Text Available ... clearer and more detailed than with other imaging methods. This detail makes MRI an invaluable tool in ... might be obscured by bone with other imaging methods. The contrast material used in MRI exams is ...

  13. MRI of the Chest

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    Full Text Available ... conditions. MRI uses a powerful magnetic field, radio frequency pulses and a computer to produce detailed pictures ... with claustrophobia. Newer open MRI units provide very high quality images for many types of exams. Older ...

  14. MRI of the Chest

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    Full Text Available ... or headphones during the exam. MRI scanners are air-conditioned and well-lit. Music may be played ... the limitations of MRI of the Chest? High-quality images are assured only if you are able ...

  15. MRI of the Chest

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    Full Text Available ... clearer and more detailed than with other imaging methods. This detail makes MRI an invaluable tool in ... might be obscured by bone with other imaging methods. The contrast material used in MRI exams is ...

  16. MRI of the Chest

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    Full Text Available ... have this exam in the first trimester of pregnancy unless the potential benefit from the MRI exam ... See the Safety page for more information about pregnancy and MRI. If you have claustrophobia (fear of ...

  17. MRI of the Chest

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    Full Text Available ... top of page What are the benefits vs. risks? Benefits MRI is a noninvasive imaging technique that ... risking the side effects of conventional (catheter) angiography . Risks The MRI examination poses almost no risk to ...

  18. MRI of the Chest

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    Full Text Available ... or potentially pose a risk, depending on their nature and the strength of the MRI magnet. Many ... of the body being studied. If a contrast material will be used in the MRI exam, a ...

  19. MRI of the Chest

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    Full Text Available ... is done because a potential abnormality needs further evaluation with additional views or a special imaging technique. ... MRI an invaluable tool in early diagnosis and evaluation of cardiovascular conditions. MRI has proven valuable in ...

  20. MRI of the Chest

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    Full Text Available ... MRI. If you have claustrophobia (fear of enclosed spaces) or anxiety, you may want to ask your ... or headphones during the exam. MRI scanners are air-conditioned and well-lit. Music may be played ...

  1. MRI of the Chest

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    Full Text Available ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Chest Magnetic resonance imaging (MRI) of ... Although there is no reason to believe that magnetic resonance imaging harms the fetus, pregnant women usually are ...

  2. MRI of the Chest

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    Full Text Available ... claustrophobia. Newer open MRI units provide very high quality images for many types of exams; however, older ... MRI units may not provide this same image quality. Certain types of exams cannot be performed using ...

  3. MRI of the Chest

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    Full Text Available ... is done because a potential abnormality needs further evaluation with additional views or a special imaging technique. ... MRI an invaluable tool in early diagnosis and evaluation of cardiovascular conditions. MRI has proven valuable in ...

  4. MRI of the Chest

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    Full Text Available ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... that magnetic resonance imaging harms the fetus, pregnant women usually are advised not to have an MRI ...

  5. MRI of the Chest

    Science.gov (United States)

    ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... that magnetic resonance imaging harms the fetus, pregnant women usually are advised not to have an MRI ...

  6. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography

    Directory of Open Access Journals (Sweden)

    Julian C.-H. Chen

    2017-01-01

    Full Text Available The Protein Crystallography Station (PCS, located at the Los Alamos Neutron Scattering Center (LANSCE, was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER for 13 years (2002–2014. The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallography in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  7. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography.

    Science.gov (United States)

    Chen, Julian C-H; Unkefer, Clifford J

    2017-01-01

    The Protein Crystallography Station (PCS), located at the Los Alamos Neutron Scattering Center (LANSCE), was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER) for 13 years (2002-2014). The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallo-graphy in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  8. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed.

  9. Comprehensive model for simultaneous MRI determination of perfusion and permeability using a blood-pool agent in rats rhabdomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Bazelaire, Cedric de [Saint Louis Hospital, Radiology Department, Paris (France); Siauve, Nathalie; Fournier, Laure; Clement, Olivier; Kerviler, Eric de; Cuenod, Charles Andre [George Pompidou European Hospital, Radiology Department, Paris (France); Frouin, Frederique [INSERM U494, Faculte de Medecine Pitie-Salpetriere, Paris (France); Robert, Philippe [Guerbet Laboratoire Guerbet, Recherche et Developpement, Paris (France)

    2005-12-01

    To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/{alpha} 13 ms/1.2 ms/60 ) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume V{sub distribution}, volume transfer constant K{sup trans}, rate constant of influx k{sub pe}, and initial extraction (fraction) E. Tumor perfusion was F=43{+-}29 ml.min{sup -1}.100 g{sup -1}. The permeability study allowed the measurement of k{sub pe}=0.37{+-}0.12 min{sup -1} and K{sup trans}=0.01{+-}0.0031 min{sup -1}. The blood volume could be assimilated to the distribution volume (V{sub distribution}=2.9{+-}1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34{+-}1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization. (orig.)

  10. Ectopia cordis thoracique sporadique: description clinique d'un cas

    Science.gov (United States)

    Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Katamea, Tina; Lubala, Nina; Munkana, Arthur Ndundula; Kabuya, Maguy Sangaji; Monga, Joséphine Kalenga; Luboya, Oscar Numbi

    2012-01-01

    Nous décrivons un cas d'ectopia cordis, une malformation cardiaque congénitale extrêmement rare dans laquelle le coeur est partiellement ou complètement situé en dehors des limites de la cage thoracique. Dans le cas que nous décrivons, elle est thoracique et isolée. Ce cas a été diagnostiqué en salle de naissance au Katanga, au sud de la République Démocratique du Congo. Il s'agit du premier cas documenté chez un nouveau-né Congolais. PMID:23346276

  11. CRISPR-Cas9-guided Genome Engineering in C. elegans

    Science.gov (United States)

    Kim, Hyun-Min; Colaiácovo, Monica P.

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is successfully being used for efficient and targeted genome editing in various organisms including the nematode C. elegans. Recent studies developed various CRISPR-Cas9 approaches to enhance genome engineering via two major DNA double-strand break repair pathways: non-homologous end joining and homologous recombination. Here we describe a protocol for Cas9-mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning and injection methods required for delivering Cas9, sgRNAs and repair template DNA into the C. elegans germline. PMID:27366893

  12. Control of gene expression by CRISPR-Cas systems

    Science.gov (United States)

    2013-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. PMID:24273648

  13. The 6th Meeting of CAS Board of Executive Directors

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The 6th meeting of the board of executive directors of China Association for Standardization (CAS) (the 2nd chairman meeting in 2005) was held in Beijing on January 19th, 2006. The attendees were Mr. Li Zhonghai, President of CAS, who presided over the meeting, Ms. Li Rui and Mr. Li Chuntian, Advisers of CAS, Sun Xiaokang and Shi Baoquan, Vice Directors of SAC (Standardization Administration of China), Jiao Yunqi, President of CNIS (China National Institute of Standardization), Zhang Jianquan, Director of SPC (the Standards Press of China), over 20executive directors and some CAS officers.

  14. MRI in acute poliomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L. [Imaging Department, The Schneider Children`s Medical Centre of Israel, Kaplan Street, Petah Tiqva 49202 (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Dagan, O. [The Intensive Care Unit, The Schneider Children`s Medical Centre of Israel, Beilinson Medical Campus, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Grunebaum, M. [Imaging Department, The Schneider Children`s Medical Centre of Israel, Kaplan Street, Petah Tiqva 49202 (Israel)]|[Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    1996-05-01

    MRI can be used in the diagnosis of anterior horn infection and for assessing the extent of disease. There are no specific MRI signs to differentiate between the various possible pathogens. This is demonstrated in the present case of poliomyelitis, in which MRI of the spine played an important role in establishing the diagnosis. (orig.). With 1 fig.

  15. MRI of the Chest

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    Full Text Available ... field of the MRI unit, metal and electronic items are not allowed in the exam room. In addition to affecting the MRI images, ... damaged pins, hairpins, metal zippers and similar metallic items, which can distort ... In most cases, an MRI exam is safe for patients with metal implants, except ...

  16. fMRI Neuroinformatics

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Christensen, Mark Schram; Madsen, Kristoffer M.

    2006-01-01

    Functional magnetic resonance imaging (fMRI) generates vast amounts of data. The handling, processing, and analysis of fMRI data would be inconceivable without computer-based methods. fMRI neuroinformatics is concerned with research, development, and operation of these methods. Reconstruction...

  17. Synthesis and characterization of miktoarm star copolymer of styrene and butadiene using multifunctional macromolecular initiator

    Institute of Scientific and Technical Information of China (English)

    Hai Yan Zhang; Xing Ying Zhang

    2009-01-01

    A new kind of multifunctional macromolecular initiator with Sn-C bonds and polydiene arms was synthesized by living anionic polymerization.At first,polydiene-stannum chloride(PD-SnCl3)was prepared by the reaction of n-butyl-Li(n-BuLi),stannic chloride(SnCl4)and diene.Then PD-SnCl3 was used to react with the dilithium initiator to prepare the multifunctional organic macromolecular initiators.The result suggested that the initiators had a remarkable yield by GPC,nearly 90%.By using these multifunctional macromolecular initiators,styrene and butadiene were effectively polymerized via anionic polymerization,which gave birth to novel miktoarm star copolymers.The relative molecular weight and polydispersity index,microstructure contents,copolymerization components,glass transition temperature(Tg)and morphology of the miktoarm star copolymers were investigated by GPC-UV,1H NMR,DSC and TEM,respectively.

  18. Use of Site-Specifically Tethered Chemical Nucleases to Study Macromolecular Reactions

    Directory of Open Access Journals (Sweden)

    Mukherjee Srabani

    2003-01-01

    Full Text Available During a complex macromolecular reaction multiple changes in molecular conformation and interactions with ligands may occur. X-ray crystallography may provide only a limited set of snapshots of these changes. Solution methods can augment such structural information to provide a more complete picture of a macromolecular reaction. We analyzed the changes in protein conformation and protein:nucleic acid interactions which occur during transcription initiation by using a chemical nuclease tethered to cysteines introduced site-specifically into the RNA polymerase of bacteriophage T7 (T7 RNAP. Changes in cleavage patterns as the polymerase steps through transcription reveal a series of structural transitions which mediate transcription initiation. Cleavage by tethered chemical nucleases is seen to be a powerful method for revealing the conformational dynamics of macromolecular reactions, and has certain advantages over cross-linking or energy transfer approaches.

  19. New CRISPR–Cas systems from uncultivated microbes

    Science.gov (United States)

    Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

    2016-12-01

    CRISPR–Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR–Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR–Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR–Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR–Cas system. In bacteria, we discovered two previously unknown systems, CRISPR–CasX and CRISPR–CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

  20. Recent Advances in Genome Editing Using CRISPR/Cas9.

    Science.gov (United States)

    Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding.

  1. Recent Advances in Genome Editing Using CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Yuduan eDing

    2016-05-01

    Full Text Available AbstractThe CRISPR (clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-associated nuclease 9 system is a versatile tool for genome engineering that uses a guide RNA (gRNA to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding.

  2. New CRISPR-Cas systems from uncultivated microbes

    Science.gov (United States)

    Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

    2017-02-01

    CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

  3. Macromolecular Hydrogen Sulfide Donors Trigger Spatiotemporally Confined Changes in Cell Signaling.

    Science.gov (United States)

    Ercole, Francesca; Mansfeld, Friederike M; Kavallaris, Maria; Whittaker, Michael R; Quinn, John F; Halls, Michelle L; Davis, Thomas P

    2016-01-11

    Hydrogen sulfide (H2S) is involved in a myriad of cell signaling processes that trigger physiological events ranging from vasodilation to cell proliferation. Moreover, disturbances to H2S signaling have been associated with numerous pathologies. As such, the ability to release H2S in a cellular environment and stimulate signaling events is of considerable interest. Herein we report the synthesis of macromolecular H2S donors capable of stimulating cell signaling pathways in both the cytosol and at the cell membrane. Specifically, copolymers having pendent oligo(ethylene glycol) and benzonitrile groups were synthesized, and the benzonitrile groups were subsequently transformed into primary aryl thioamide groups via thionation using sodium hydrosulfide. These thioamide moieties could be incorporated into a hydrophilic copolymer or a block copolymer (i.e., into either the hydrophilic or hydrophobic domain). An electrochemical sensor was used to demonstrate release of H2S under simulated physiological conditions. Subsequent treatment of HEK293 cells with a macromolecular H2S donor elicited a slow and sustained increase in cytosolic ERK signaling, as monitored using a FRET-based biosensor. The macromolecular donor was also shown to induce a small, fast and sustained increase in plasma membrane-localized PKC activity immediately following addition to cells. Studies using an H2S-selective fluorescent probe in live cells confirmed release of H2S from the macromolecular donor over physiologically relevant time scales consistent with the signaling observations. Taken together, these results demonstrate that by using macromolecular H2S donors it is possible to trigger spatiotemporally confined cell signaling events. Moreover, the localized nature of the observed signaling suggests that macromolecular donor design may provide an approach for selectively stimulating certain cellular biochemical pathways.

  4. The Joint Structural Biology Group beam lines at the ESRF: Modern macromolecular crystallography

    CERN Document Server

    Mitchell, E P

    2001-01-01

    Macromolecular crystallography has evolved considerably over the last decade. Data sets in under an hour are now possible on high throughput beam lines leading to electron density and, possibly, initial models calculated on-site. There are five beam lines currently dedicated to macromolecular crystallography: the ID14 complex and BM-14 (soon to be superseded by ID-29). These lines handle over five hundred projects every six months and demand is increasing. Automated sample handling, alignment and data management protocols will be required to work efficiently with this demanding load. Projects developing these themes are underway within the JSBG.

  5. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  6. THE STEADY/PULSATILE FLOW AND MACROMOLECULAR TRANSPORT IN T-BIFURCATION BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    李丁; 温功碧

    2003-01-01

    A numerical analysis of the steady and pulsatile, macromolecular( such as lowdensity lipopotein ( LDL ), Albumin ) transport in T-bifurcation was proposed. Theinfluence of Reynolds number and mass flow ratio etc. parameters on the velocity field andmass transport were calculated. The computational results predict that the blood flow factorsaffect the macromolecular distribution and the transport across the wall, it shows thathemodynamic play an important role in the process of atherosclerosis . The LDL and Albuminconcentration on the wall varies most greatly in flow bifurcation area where the wall shearstress varies greatly at the branching vessel and the atherosclerosis often appears there.

  7. Accounting for large amplitude protein deformation during in silico macromolecular docking.

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-02-22

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  8. Influence of protein crowder size on hydration structure and dynamics in macromolecular crowding

    Science.gov (United States)

    Wang, Po-hung; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2017-03-01

    We investigate the effects of protein crowder sizes on hydration structure and dynamics in macromolecular crowded systems by all-atom MD simulations. The crowded systems consisting of only small proteins showed larger total surface areas than those of large proteins at the same volume fractions. As a result, more water molecules were trapped within the hydration shells, slowing down water diffusion. The simulation results suggest that the protein crowder size is another factor to determine the effect of macromolecular crowding and to explain the experimental kinetic data of proteins and DNAs in the presence of crowding agents.

  9. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-01-01

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success. PMID:21541061

  10. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Directory of Open Access Journals (Sweden)

    Chantal Prévost

    2011-02-01

    Full Text Available Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  11. Phase Sensitive X-Ray Diffraction Imaging of Defects in Biological Macromolecular Crystals

    Science.gov (United States)

    Hu, Z. W.; Lai, B.; Chu, Y. S.; Cai, Z.; Mancini, D. C.; Thomas, B. R.; Chernov, A. A.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Characterization of defects and/or disorder in biological macromolecular crystals presents much greater challenges than in conventional small-molecule crystals. The lack of sufficient contrast of defects is often a limiting factor in x-ray diffraction topography of protein crystals. This has seriously hampered efforts to understand mechanisms and origins of formation of imperfections, and the role of defects as essential entities in the bulk of macromolecular crystals. In this report, we employ a phase sensitive x-ray diffraction imaging approach for augmenting the contrast of defects in protein crystals.

  12. Poly(isophthalic acid)(ethylene oxide) as a Macromolecular Modulator for Metal-Organic Polyhedra.

    Science.gov (United States)

    Chen, Teng-Hao; Wang, Le; Trueblood, Jonathan V; Grassian, Vicki H; Cohen, Seth M

    2016-08-03

    A new strategy was developed by using a polymer ligand, poly(isophthalic acid)(ethylene oxide), to modulate the growth of metal-organic polyhedra (MOP) crystals. This macromolecular modulator can effectively control the crystal habit of several different Cu24L24 (L = isophthalic acid derivatives) MOPs. The polymer also directed the formation of MOP structures under reaction conditions that only produce metal-organic frameworks in the absence of modulator. Moreover, the polymer also enabled the deposition of MOP crystals on glass surfaces. This macromolecular modulator strategy provides an innovative approach to control the morphology and assembly of MOP particles.

  13. Effect of macromolecular crowding on the rate of diffusion-limited enzymatic reaction

    Indian Academy of Sciences (India)

    Manish Agrawal; S B Santra; Rajat Anand; Rajaram Swaminathan

    2008-08-01

    The cytoplasm of a living cell is crowded with several macromolecules of different shapes and sizes. Molecular diffusion in such a medium becomes anomalous due to the presence of macromolecules and diffusivity is expected to decrease with increase in macromolecular crowding. Moreover, many cellular processes are dependent on molecular diffusion in the cell cytosol. The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some of the experimental observations.

  14. CRISPR/Cas9 based genome editing of Penicillium chrysogenum

    NARCIS (Netherlands)

    Pohl, Carsten; Kiel, Jan A K W; Driessen, Arnold J M; Bovenberg, Roel A L; Nygård, Yvonne

    2016-01-01

    CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially rel

  15. CAS Scientists Find New Anti-SARS Compounds

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Scientists from the CAS Shanghai Institute of Materia Medica (SIMM) and the National Center for Drug Screening (NCDS) have identified several novel compounds that could be potential weapons to combat the SARS epidemic. This was announced at a news briefing held by the CAS Shanghai Institutes for Biological Sciences on June 19 in Shanghai.

  16. First International Student Obtains His PhD at CAS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Mr. Ghulam Rasul, the first international student formally enrolled by the Graduate University of CAS (GUCAS) has received his PhD degree this summer after having passed his dissertation defense on May 21 at the CAS Institute of Atmospheric Physics (IAP).

  17. CAS issues its 2007 prizes for outstanding achievements

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ One individual and three research groups have been honored with the prestigious CAS Awards for Outstanding S&T Achievements in 2007. CAS President LU Yongxiang conferred the awards on the laureates at the Academy's annual work conference opened on 24 March in Beijing.

  18. CAS Scientist Awarded Tyler Prize for Environment Achievement

    Institute of Scientific and Technical Information of China (English)

    Guo Haiyan; Zhao Baohua

    2002-01-01

    @@ Prof. Liu Dongsheng (Tungsheng Liu), a CAS member and professor at CAS Institute of Geology and Geophysics, has been awarded the 2002 Tyler Prize for Environment Achievement. He shared a cash prize of $200,000 with the other laureate, Dr. Wallace S. Broecker from Columbia University, the US, and received a gold Tyler Prize medallion on April 12.

  19. CAS, Shanghai, Pasteur to Jointly Set Up a New Institute

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ An agreement for jointly establishing the CAS Institut Pasteur of Shanghai was signed on August 30 in east China's Shanghai Municipality. Representatives from the collaborative partners, including Shanghai Vice Mayor Yan Junqi, CAS Vice President Chen Zhu and President of Institut Pasteur Philippe Kourilsky witnessed the signing ceremony.

  20. Reaction to Indispensable Manual Calculation Skills in a CAS Environment.

    Science.gov (United States)

    Monaghan, John

    2001-01-01

    Reacts to an article published in a previous issue of this journal on the effects of graphing calculators and computer algebra systems (CAS) on students' manual calculation and algebraic manipulation skills. Considers the contribution made by Jean-Baptiste Lagrange to thinking about the role of CAS in teaching algebra. (ASK)

  1. CAS conducts ex-post evaluation on research projects

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Under the auspices of the CAS Center for Project Supervision and Evaluation, a panel of experts recently conducted an ex-post evaluation on a research project entitled "the electrical system for an electric vehicle." The appraisal is the first of its kind in project management at CAS.

  2. Recent Progress in CRISPR/Cas9 Technology.

    Science.gov (United States)

    Mei, Yue; Wang, Yan; Chen, Huiqian; Sun, Zhong Sheng; Ju, Xing-Da

    2016-02-20

    The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, a simple and efficient tool for genome editing, has experienced rapid progress in its technology and applicability in the past two years. Here, we review the recent advances in CRISPR/Cas9 technology and the ways that have been adopted to expand our capacity for precise genome manipulation. First, we introduce the mechanism of CRISPR/Cas9, including its biochemical and structural implications. Second, we highlight the latest improvements in the CRISPR/Cas9 system, especially Cas9 protein modifications for customization. Third, we review its current applications, in which the versatile CRISPR/Cas9 system was employed to edit the genome, epigenome, or RNA of various organisms. Although CRISPR/Cas9 allows convenient genome editing accompanied by many benefits, we should not ignore the significant ethical and biosafety concerns that it raises. Finally, we discuss the prospective applications and challenges of several promising techniques adapted from CRISPR/Cas9.

  3. Progress Scored in Management Information System at CAS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ CAS initiative to upgrade its management information system (MIS) is making significant progress. Recently, 116 CAS subordinates have completed their online trial operation of a MIS project at the Academy, called Academia Resource Planning (ARP), marking an important phased achievement of the initiative.

  4. Teaching Undergraduate Mathematics Using CAS Technology: Issues and Prospects

    Science.gov (United States)

    Tobin, Patrick C.; Weiss, Vida

    2016-01-01

    The use of handheld CAS technology in undergraduate mathematics courses in Australia is paradoxically shrinking under sustained disapproval or disdain from the professional mathematics community. Mathematics education specialists argue with their mathematics colleagues over a range of issues in course development and this use of CAS or even…

  5. Transformation of OODT CAS to Perform Larger Tasks

    Science.gov (United States)

    Mattmann, Chris; Freeborn, Dana; Crichton, Daniel; Hughes, John; Ramirez, Paul; Hardman, Sean; Woollard, David; Kelly, Sean

    2008-01-01

    A computer program denoted OODT CAS has been transformed to enable performance of larger tasks that involve greatly increased data volumes and increasingly intensive processing of data on heterogeneous, geographically dispersed computers. Prior to the transformation, OODT CAS (also alternatively denoted, simply, 'CAS') [wherein 'OODT' signifies 'Object-Oriented Data Technology' and 'CAS' signifies 'Catalog and Archive Service'] was a proven software component used to manage scientific data from spaceflight missions. In the transformation, CAS was split into two separate components representing its canonical capabilities: file management and workflow management. In addition, CAS was augmented by addition of a resource-management component. This third component enables CAS to manage heterogeneous computing by use of diverse resources, including high-performance clusters of computers, commodity computing hardware, and grid computing infrastructures. CAS is now more easily maintainable, evolvable, and reusable. These components can be used separately or, taking advantage of synergies, can be used together. Other elements of the transformation included addition of a separate Web presentation layer that supports distribution of data products via Really Simple Syndication (RSS) feeds, and provision for full Resource Description Framework (RDF) exports of metadata.

  6. Optimization of genome editing through CRISPR-Cas9 engineering.

    Science.gov (United States)

    Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F

    2016-04-01

    CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing.

  7. CRISPR-Cas9 Genome Engineering in Saccharomyces cerevisiae Cells.

    Science.gov (United States)

    Ryan, Owen W; Poddar, Snigdha; Cate, Jamie H D

    2016-06-01

    This protocol describes a method for CRISPR-Cas9-mediated genome editing that results in scarless and marker-free integrations of DNA into Saccharomyces cerevisiae genomes. DNA integration results from cotransforming (1) a single plasmid (pCAS) that coexpresses the Cas9 endonuclease and a uniquely engineered single guide RNA (sgRNA) expression cassette and (2) a linear DNA molecule that is used to repair the chromosomal DNA damage by homology-directed repair. For target specificity, the pCAS plasmid requires only a single cloning modification: replacing the 20-bp guide RNA sequence within the sgRNA cassette. This CRISPR-Cas9 protocol includes methods for (1) cloning the unique target sequence into pCAS, (2) assembly of the double-stranded DNA repair oligonucleotides, and (3) cotransformation of pCAS and linear repair DNA into yeast cells. The protocol is technically facile and requires no special equipment. It can be used in any S. cerevisiae strain, including industrial polyploid isolates. Therefore, this CRISPR-Cas9-based DNA integration protocol is achievable by virtually any yeast genetics and molecular biology laboratory.

  8. Engineering the Caenorhabditis elegans genome with CRISPR/Cas9

    NARCIS (Netherlands)

    Waaijers, Selma; Boxem, Mike

    2014-01-01

    The development in early 2013 of CRISPR/Cas9-based genome engineering promises to dramatically advance our ability to alter the genomes of model systems at will. A single, easily produced targeting RNA guides the Cas9 endonuclease to a specific DNA sequence where it creates a double strand break. Im

  9. Interference activity of a minimal Type I CRISPR-Cas system from Shewanella putrefaciens.

    Science.gov (United States)

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-10-15

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs.

  10. Interference activity of a minimal Type I CRISPR–Cas system from Shewanella putrefaciens

    Science.gov (United States)

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-01-01

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)–Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs. PMID:26350210

  11. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular crow

  12. A kinetic type extended model for dense gases and macromolecular fluids

    Directory of Open Access Journals (Sweden)

    M. Cristina Carrisi

    2005-05-01

    Full Text Available Extended thermodynamics is an important theory which is appreciated from mathematicians and physicists. Following its ideas and considering the macroscopic approach with suggestions from the kinetic one, we find in this paper, the solution of an interesting model: the model for dense gases and macromolecular fluids.

  13. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many...

  14. Isolation and chemical characterization of resistant macromolecular constituents in microalgae and marine sediments

    NARCIS (Netherlands)

    Gelin, F.

    1996-01-01

    The recognition of novel, insoluble and non-hydrolysable macromolecular constituents in protective tissues of fresh-water algae and higher plants has had a major impact on our understanding of the origin and fate of sedimentary organic matter (OM) in terrestrial and lacustrine deposits. The investig

  15. Researches, Publications and Achievements 2007-2011, Department of Macromolecular Science and Engineering

    OpenAIRE

    All teaching staffs at Department of Macromolecular Science and Engineering (19 members)

    2012-01-01

    Recent researches, publications and achievements are presented, which were made during these five years (2007-2011) by 19 members at Department of Macromolecular Science and Engineering. Listed publications include original papers, books, reviews and reports. Achievements such as invited lectures, patents, funds and financial supports, and awards are also listed.

  16. Synergy of DNA-bending nucleoid proteins and macromolecular crowd-condensing DNA

    NARCIS (Netherlands)

    Bessa Ramos, E.; Wintraecken, C.H.J.M.; Geerling, A.C.M.; Vries, de R.J.

    2007-01-01

    Many prokaryotic nucleoid proteins bend DNA and form extended helical protein-DNA fibers rather than condensed structures. On the other hand, it is known that such proteins (such as bacterial HU) strongly promote DNA condensation by macromolecular crowding. Using theoretical arguments, we show that

  17. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971-1980

    Directory of Open Access Journals (Sweden)

    Kunst, B.

    2008-07-01

    Full Text Available The postgraduate study of macromolecular sciences (PSMS was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technologicaldisciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The study comprised basic fields of macromolecular sciences: organic chemistry of synthetic macromolecules, physical chemistry of macromolecules, physics of macromolecules, biological macromolecules and polymer engineering with polymer application and processing, and teaching was performed in 29 lecture courses lead by 30 professors with their collaborators. PSMS ceased to exist with the change of legislation in Croatia in 1980, when the attitude prevailed to render back postgraduate studies to the university schools. During 9 years of existence of PSMS the MSci grade was awarded to 37 macromolecular experts. It was assessed that the PSMS some thirty years ago was an important example of modern postgraduate education as compared with the international postgraduate development. In concordance with the recent introduction of similar interdisciplinary studies in macromolecular sciences elsewhere in the world, the establishment of a modern interdisciplinary study in the field would be of importance for further development of these sciences in Croatia.

  18. Macromolecular Crowding Modulates Folding Mechanism of α/β Protein Apoflavodoxin

    Science.gov (United States)

    Homouz, D.; Stagg, L.; Wittungstafshede, P.; Cheung, M.

    2009-01-01

    Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.

  19. Hydropyrolysis: A new technique for the analysis of macromolecular material in meteorites

    Science.gov (United States)

    Sephton, Mark A.; Love, Gordon D.; Meredith, Will; Snape, Colin E.; Sun, Cheng-Gong; Watson, Jonathan S.

    2005-10-01

    The carbonaceous chondrite meteorites are fragments of asteroids that have remained relatively unprocessed since the formation of the Solar System 4.56 billion years ago. The major organic component in these meteorites is a macromolecular phase that is resistant to solvent extraction. The information contained within macromolecular material can be accessed by degradative techniques such as pyrolysis. Hydropyrolysis refers to pyrolysis assisted by high hydrogen gas pressures and a dispersed sulphided molybdenum catalyst. Hydropyrolysis of the Murchison macromolecular material successfully releases much greater quantities of hydrocarbons than traditional pyrolysis techniques (twofold greater than hydrous pyrolysis) including significant amounts of high molecular weight polyaromatic hydrocarbons (PAH) such as phenanthrene, carbazole, fluoranthene, pyrene, chrysene, perylene, benzoperylene and coronene units with varying degrees of alkylation. When hydropyrolysis products are collected using a silica trap immersed in liquid nitrogen, the technique enables the solubilisation and retention of compounds with a wide range of volatilities (i.e. benzene to coronene). This report describes the hydropyrolysis method and the information it can provide about meteorite macromolecular material constitution.

  20. MRI in psychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Mulert, Christoph [UKE, Hamburg (Germany). Psychiatry Neuroimaging Branch; Shenton, Martha E. (ed.) [Harvard Medical School, Boston, MA (United States). Dept. of Psychiatry and Radiology

    2014-07-01

    This is the first comprehensive textbook on the use of MRI in psychiatry covering imaging techniques, brain systems and a review of findings in different psychiatric disorders. The book is divided into three sections, the first of which covers in detail all the major MRI-based methodological approaches available today, including fMRI, EEG-fMRI, DTI, and MR spectroscopy. In addition, the role of MRI in imaging genetics and combined brain stimulation and imaging is carefully explained. The second section provides an overview of the different brain systems that are relevant for psychiatric disorders, including the systems for perception, emotion, cognition, and reward. The final part of the book presents the MRI findings that are obtained in all the major psychiatric disorders using the previously discussed techniques. Numerous carefully chosen images support the informative text, making this an ideal reference work for all practitioners and trainees with an interest in this flourishing field.

  1. CRISPR/Cas9系统的脱靶效应%Off-target of CRISPR/Cas9 System

    Institute of Scientific and Technical Information of China (English)

    尹珅; 贺桂芳; 赖方秾; 谢凤云; 马俊宇

    2016-01-01

    在细菌中发现的免疫系统CRISPR/Cas9,已经成为最有效的基因工程编辑工具,甚至大有希望可以治疗人类遗传性疾病。但是CRISPR/Cas9系统在使用时会产生严重的脱靶问题,导致假表型和错误的解释。提高与靶点结合的高效率,同时减少脱靶效应,将是今后CRISPR/Cas9技术的挑战。综述关注与CRISPR/Cas9脱靶效应相关的内容,总结了影响其靶点专一性的因素,减少CRISPR/Cas9脱靶效应的可行性方法和设计工具等,供大家学习讨论。%As an adaptive immune system discovered in bacteria,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)technology has been used as the most effective genome-editing tool. By now,CRISPR/Cas9 has shown a great promise in healing human genetic diseases,however,off-target is a critical issue while applying it. The off-target of CRISPR/Cas9 leads to the false phenotype and wrong interpretation. Optimization of on-target activity and minimizing off-target activity will be challenges while CRISPR/Cas9 is applied in the future. In this review,we focused on the off-target related issues,including factors involved in the target specificity,strategies and tools of minimizing the off-target of CRISPR/Cas9.

  2. Pilomatricome: étude de 22 cas

    Science.gov (United States)

    Nasreddine, Fatima Zahra; Hali, Fouzia; Chiheb, Soumiya

    2016-01-01

    Le pilomatricome est une tumeur cutanée fréquente et bénigne du follicule pileux chez l'enfant. C'est une tumeur annexielle souvent méconnue et confondue avec d'autres lésions cutanées. Les localisations habituelles sont la tête et le cou. Le but de ce travail est de rapporter une série de 22 cas comportant des formes inhabituelles colligées au service de dermatologie sur une période allant de Janvier 2006 jusqu'au Mai 2015. L’étude a concerné 16 femmes et 6 hommes. La moyenne d’âge était de 23,3 ans (4-80 ans). La localisation cervico faciale a été observée dans 12 cas, 2 patients avaient des localisations multiples, un garçon de 4ans avait une localisation au niveau fronto-temporal et une fillette de 14 ans avait une localisation au niveau du visage et de l'avant-bras, et un patient de 48 ans avait une localisation sous unguéale. L'aspect clinique était typique dans tous les cas avec des nodules sous cutanés de consistance pierreuse. Tous les patients ont bénéficié d'une exérèse des nodules sous anesthésie locale. L’étude histologique était en faveur d'un épithélioma momifié de Malherbe d'exérèse complète sans signes de malignité. Aucun patient n'a présenté de rechute. L'originalité de notre étude réside dans la présence de localisations exceptionnelles au niveau latéro-vertébral, des membres et sous-unguéale, l’âge de survenue inhabituel à 80 ans et la présence de localisations multiples signalées chez 2 enfants. PMID:27516819

  3. Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System.

    Science.gov (United States)

    Ka, Donghyun; Lee, Hasup; Jung, Yi-Deun; Kim, Kyunggon; Seok, Chaok; Suh, Nayoung; Bae, Euiyoung

    2016-01-01

    CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition during CRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S. pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems.

  4. [Temporomandibular joint: MRI diagnostics].

    Science.gov (United States)

    Kress, B; Schmitter, M

    2005-09-01

    MRI of the temporomandibular joint (TMJ) requires 1.5 T. The radiologist must be familiar with the anatomy and pathology of the TMJ. This review gives a description of MRI protocols for the TMJ, and MRI anatomy and pathology of the TMJ (open and closed mouth) by means of MR images and drawings. Diagnosing of the TMJ related diseases depends on standardized clinical and MR examinations. Therefore close interdisciplinary cooperation between dentist and radiologist is necessary.

  5. MRI brain imaging.

    Science.gov (United States)

    Skinner, Sarah

    2013-11-01

    General practitioners (GPs) are expected to be allowed to request MRI scans for adults for selected clinically appropriate indications from November 2013 as part of the expansion of Medicare-funded MRI services announced by the Federal Government in 2011. This article aims to give a brief overview of MRI brain imaging relevant to GPs, which will facilitate explanation of scan findings and management planning with their patients. Basic imaging techniques, common findings and terminology are presented using some illustrative case examples.

  6. Anchors for the Cosmic Distance Scale: the Cepheids U Sgr, CF Cas and CEab Cas

    CERN Document Server

    Majaess, D; Bidin, C Moni; Bonatto, C; Berdnikov, L; Balam, D; Moyano, M; Gallo, L; Turner, D; Lane, D; Gieren, W; Borissova, J; Kovtyukh, V; Beletsky, Y

    2013-01-01

    New and existing X-ray, UBVJHKsW(1-4), and spectroscopic observations were analyzed to constrain fundamental parameters for M25, NGC 7790, and dust along their sight-lines. The star clusters are of particular importance given they host the classical Cepheids U Sgr, CF Cas, and the visual binary Cepheids CEa and CEb Cas. Precise results from the multiband analysis, in tandem with a comprehensive determination of the Cepheids' period evolution (dP/dt) from ~140 years of observations, helped resolve concerns raised regarding the clusters and their key Cepheid constituents. Specifically, distances derived for members of M25 and NGC 7790 are 630+-25 pc and 3.40+-0.15 kpc, respectively.

  7. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Head Magnetic resonance imaging (MRI) of the head ... limitations of MRI of the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) is ...

  8. CRISPR/Cas9-mediated viral interference in plants

    KAUST Repository

    Ali, Zahir

    2015-11-11

    Background The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. Results In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. Conclusions These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

  9. CRISPR/Cas9 in Genome Editing and Beyond.

    Science.gov (United States)

    Wang, Haifeng; La Russa, Marie; Qi, Lei S

    2016-06-01

    The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.

  10. Chronic arsenic intoxication diagnostic score (CAsIDS).

    Science.gov (United States)

    Dani, Sergio Ulhoa; Walter, Gerhard Franz

    2017-08-31

    Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions. Copyright © 2017 John Wiley & Sons, Ltd.

  11. CRISPR/Cas9 Based Genome Editing of Penicillium chrysogenum.

    Science.gov (United States)

    Pohl, C; Kiel, J A K W; Driessen, A J M; Bovenberg, R A L; Nygård, Y

    2016-07-15

    CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. The developed CRISPR/Cas9 toolbox is highly flexible and allows editing of new targets with minimal cloning efforts. The Cas9 protein and the sgRNA can be either delivered during transformation, as preassembled CRISPR-Cas9 ribonucleoproteins (RNPs) or expressed from an AMA1 based plasmid within the cell. The direct delivery of the Cas9 protein with in vitro synthesized sgRNA to the cells allows for a transient method for genome engineering that may rapidly be applicable for other filamentous fungi. The expression of Cas9 from an AMA1 based vector was shown to be highly efficient for marker-free gene deletions.

  12. CAS Introduction to Accelerator Physics in Spain

    CERN Multimedia

    CERN Bulletin

    2012-01-01

    The CERN Accelerator School (CAS) and the University of Granada jointly organised a course called "Introduction to Accelerator Physics" in Granada, Spain, from 28 October to 9 November, 2012.   The course attracted over 200 applicants, of whom 139 were selected to attend. The students were of 25 different nationalities, coming from countries as far away as Australia, China, Guatemala and India. The intensive programme comprised 38 lectures, 3 seminars, 4 tutorials where the students were split into three groups, a poster session and 7 hours of guided and private study. Feedback from the students was very positive, praising the expertise of the lecturers, as well as the high standard and quality of their lectures. CERN's Director-General, Rolf Heuer, gave a public lecture at the Parque de las Ciencias entitled "The Large Hadron Collider: Unveiling the Universe". In addition to the academic programme, the students had the opportunity to visit the well...

  13. CAS course on Plasma Wake Acceleration

    CERN Multimedia

    CERN Accelerator School

    2015-01-01

    The CERN Accelerator School (CAS) recently organised a specialised course on Plasma Wake Acceleration, held at CERN, Geneva, Switzerland, from 23 to 29 November 2014.    Following a number of introductory lectures on laser and plasma physics, as well as an overview of conventional accelerators and their limitations, the course covered a large number of aspects of plasma wake acceleration schemes: the creation of plasma by high power lasers or particle beams, a description of the plasma creation process through simulations and the characteristics of the accelerated particle beams, including results of the latest achievements. Lectures on beam diagnostics, the applications of plasma accelerated beams, and topical seminars completed the programme.  The course was very successful, with 109 students of 26 nationalities attending; most participants coming from European counties, but also from the US, Israel, India, South Korea, Russia and Ukraine. Feedback from the participants was...

  14. CAS Accelerator Physics (Ion Sources) in Slovakia

    CERN Multimedia

    CAS School

    2012-01-01

    The CERN Accelerator School (CAS) and the Slovak University of Technology jointly organised a specialised course on ion sources, held at the Hotel Senec, Senec, Slovakia, from 29 May to 8 June, 2012.   Following some background lectures on accelerator physics and the fundamental processes of atomic and plasma physics, the course covered a wide range of topics related to ion sources and highlighted the latest developments in the field. Realistic case studies and topical seminars completed the programme. The school was very successful, with 69 participants representing 25 nationalities. Feedback from the participants was extremely positive, reflecting the high standard of the lectures. The case studies were performed with great enthusiasm and produced some excellent results. In addition to the academic programme, the participants were able to take part in a one-day excursion consisting of a guided tour of Bratislava and free time. A welcome event was held at the Hotel Senec, with s...

  15. CAS Accelerator Physics held in Erice, Italy

    CERN Multimedia

    CERN Accelerator School

    2013-01-01

    The CERN Accelerator School (CAS) recently organised a specialised course on Superconductivity for Accelerators, held at the Ettore Majorana Foundation and Centre for Scientific Culture in Erice, Italy from 24 April-4 May, 2013.   Photo courtesy of Alessandro Noto, Ettore Majorana Foundation and Centre for Scientific Culture. Following a handful of summary lectures on accelerator physics and the fundamental processes of superconductivity, the course covered a wide range of topics related to superconductivity and highlighted the latest developments in the field. Realistic case studies and topical seminars completed the programme. The school was very successful with 94 participants representing 23 nationalities, coming from countries as far away as Belorussia, Canada, China, India, Japan and the United States (for the first time a young Ethiopian lady, studying in Germany, attended this course). The programme comprised 35 lectures, 3 seminars and 7 hours of case study. The case studies were p...

  16. Adaptation in CRISPR-Cas Systems.

    Science.gov (United States)

    Sternberg, Samuel H; Richter, Hagen; Charpentier, Emmanuelle; Qimron, Udi

    2016-03-17

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptation. During the past 3 years, significant progress has been made on the genetic requirements and molecular mechanisms of adaptation. Here we review these recent advances, with a focus on the experimental approaches that have been developed, the insights they generated, and a proposed mechanism for self- versus non-self-discrimination during the process of spacer selection. We further describe the regulation of adaptation and the protein players involved in this fascinating process that allows bacteria and archaea to harbor adaptive immunity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. CRISPR/Cas9 advances engineering of microbial cell factories

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Jensen, Michael Krogh; Keasling, Jay D.

    2016-01-01

    interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) have become the method of choice for precision genome engineering in many organisms due to their orthogonality, versatility and efficacy. Here we review the strategies adopted for implementation of RNA-guided CRISPR/Cas9 genome editing......-RNAs will be highlighted. Finally, this review will provide a perspective on the immediate challenges and opportunities foreseen by the use of CRISPR/Cas9 genome engineering and regulation in the context of metabolic engineering....

  18. Grossesse intra murale à propos d'un cas

    OpenAIRE

    de Tové, Kofi-Mensa Savi; Salifou, Kabibou; Imorou, Rachidi Sidi; Biaou, Olivier; Boco, Vicentia

    2015-01-01

    La grossesse intra-murale est la variété la plus rare de grossesse extra-utérine. Il s'agit de la localisation de l’œuf dans l’épaisseur du myomètre. En cas de retard diagnostic, l’évolution peut être catastrophique avec rupture utérine et hémorragie cataclysmique. L’échographie permet dans certains cas un diagnostic pré opératoire. Les auteurs rapportent un cas survenu chez une patiente aux antécédents de curetage.

  19. CAS Leaders Convene to Review Previous Work and Plan Future

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ The 2004 enlarged summer session of the Leading Group of the Communist Party of China (CPC) at CAS was held July 26-31. It came amid a nationwide campaign to study the important thought of the Three Represents and the scientific approach to development advanced by the CPC Central Committee. The meeting coincided with a crucial moment for the development of CAS, as the Academy is about to kick off the third phase of work for the trial implementation of its Knowledge Innovation Program (KIP). A wide range of issues were discussed at this highly efficient and pragmatic meeting, which is expected to significantly influence the development of CAS.

  20. The 13th CAS General Assembly Convenes in Beijing

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The 13th General Assembly of CAS was held from June 5 to 8 in Beijing. Top State leaders were present at the joint opening session of the 13th CAS General Assembly and the Eighth General Assembly of the Chinese Academy of Engineering (CAE)held on the morning of June 5 at the Great Hall of the People. Chinese President HU Jintao delivered an important speech at the ceremony. State Councilor CHEN Zhili made a special report about the Framework for the National Long- and Mid-term Plan for S&T Development in China at the joint plenary session of CAS and CAE assemblies on June 6.

  1. Orbital period determination in an eclipsing dwarf nova HT Cas

    Science.gov (United States)

    Bąkowska, Karolina; Olech, Arkadiusz

    2014-09-01

    HT Cassiopeiae was discovered over seventy years ago (Hoffmeister 1943). Unfortunately, for 35 years this object did not receive any attention, until the eclipses of HT Cas were observed by Bond. After a first analysis, Patterson (1981) called HT Cas "a Rosetta stone among dwarf novae". Since then, the literature on this star is still growing, reaching several dozens of publications. We present an orbital period determination of HT Cas during the November 2010 super-outburst, but also during a longer time span, to check its stability.

  2. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... information on the chemicals present in the body's cells, may also be performed during the MRI exam ... medically necessary. MRI may not always distinguish between cancer tissue and fluid, known as edema . MRI typically ...

  3. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... MRI of the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) is a noninvasive ... of page What are some common uses of the procedure? MR imaging of the head is performed ...

  4. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... information on the chemicals present in the body's cells, may also be performed during the MRI exam ... medically necessary. MRI may not always distinguish between cancer tissue and fluid, known as edema . MRI typically ...

  5. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... MRI of the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) is a noninvasive ... of page What are some common uses of the procedure? MR imaging of the head is performed ...

  6. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  7. A guild of 45 CRISPR-associated (Cas protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

    Directory of Open Access Journals (Sweden)

    Daniel H Haft

    2005-11-01

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

  8. A Guild of 45 CRISPR-Associated (Cas Protein Families and Multiple CRISPR/Cas Subtypes Exist in Prokaryotic Genomes.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

  9. MRI of the Chest

    Medline Plus

    Full Text Available ... contrast material except when absolutely necessary for medical treatment. See the MRI Safety page for more information about pregnancy and MRI. If you have claustrophobia (fear of enclosed spaces) or anxiety, you may want to ask your physician for ...

  10. MRI of the Chest

    Medline Plus

    Full Text Available ... metallic items, which can distort MRI images removable dental work pens, pocket knives and eyeglasses body piercings In most cases, an MRI exam is safe for patients with metal implants, except for a few types. People with the ...

  11. MRI of the Chest

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... Magnetic resonance imaging (MRI) is a noninvasive medical test that physicians use to diagnose medical conditions. MRI ...

  12. MRI of the Chest

    Medline Plus

    Full Text Available ... other internal body structures. MRI does not use ionizing radiation (x-rays). Detailed MR images allow physicians to ... computed tomography (CT) scans, MRI does not utilize ionizing radiation. Instead, radiofrequency pulses re-align hydrogen atoms that ...

  13. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

    Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.

  14. Rewiring Cas9 to Target New PAM Sequences.

    Science.gov (United States)

    Siksnys, Virginijus; Gasiunas, Giedrius

    2016-03-17

    Papers by Anders et al. (2016) and Hirano et al. (2016b), published in this issue of Molecular Cell, show that SpCas9 uses an induced fit mechanism to recognize altered protospacer adjacent motif (PAM) sequences.

  15. CRISPR-Cas : revolutionising genome engineering : in practice - clinical update

    National Research Council Canada - National Science Library

    Pepper, M.S; Nicholson, S.A

    2016-01-01

    ... technologies, genome engineering looks set to become a clinical reality in the near future. This article discusses recent advancements in the technology called 'clustered regularly interspaced palindromic repeat (CRISPR)-associated genes' (CRISPR-Cas...

  16. Application of CRISPR/Cas9 for biomedical discoveries.

    Science.gov (United States)

    Riordan, Sean M; Heruth, Daniel P; Zhang, Li Q; Ye, Shui Qing

    2015-01-01

    The Clustered Regions of Interspersed Palindromic Repeats-Cas9 (CRISPR/Cas9), a viral defense system found in bacteria and archaea, has emerged as a tour de force genome editing tool. The CRISPR/Cas9 system is much easier to customize and optimize because the site selection for DNA cleavage is guided by a short sequence of RNA rather than an engineered protein as in the systems of zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and meganucleases. Although it still suffers from some off-target effects, the CRISPR/Cas9 system has been broadly and successfully applied for biomedical discoveries in a number of areas. In this review, we present a brief history and development of the CRISPR system and focus on the application of this genome editing technology for biomedical discoveries. We then present concise concluding remarks and future directions for this fast moving field.

  17. EU Commissioner Delivers a Speech at CAS Institute

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ European Union (EU) Environment Commissioner Margot Wallstrom gave a talk on cooperation between the EU and China on environmental issues during her trip to the CAS Institute of Geographic Sciences and Natural Resource Research (IGSNRR) on Nov. 13.

  18. CRISPR-Cas9-Guided Genome Engineering in C. elegans.

    Science.gov (United States)

    Kim, Hyun-Min; Colaiácovo, Monica P

    2016-07-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is successfully being used for efficient and targeted genome editing in various organisms, including the nematode C. elegans. Recent studies have developed various CRISPR-Cas9 approaches to enhance genome engineering via two major DNA double-strand break repair pathways: non-homologous end joining and homologous recombination. Here we describe a protocol for Cas9-mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning, as well as injection methods required for delivering Cas9, sgRNAs, and repair template DNA into the C. elegans germline. © 2016 by John Wiley & Sons, Inc.

  19. CAS-EU researchers jointly explore integrated water resources management

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Under the organization of the CAS Institute of Tibetan Plateau Research (ITP),an exploration team composed of researchers from Germany, Austria, Czech, and Nepal carried out studies on the Yarlung Zangbo River Basin from Sept. 12 to 26.

  20. CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A.

    2014-01-01

    Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing, and can be repurposed for numerous DNA targeting applications including transcriptional control. PMID:24766887

  1. Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity.

    Science.gov (United States)

    Tycko, Josh; Myer, Vic E; Hsu, Patrick D

    2016-08-04

    Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing, with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance.

  2. Engineering the Caenorhabditis elegans genome with CRISPR/Cas9.

    Science.gov (United States)

    Waaijers, Selma; Boxem, Mike

    2014-08-01

    The development in early 2013 of CRISPR/Cas9-based genome engineering promises to dramatically advance our ability to alter the genomes of model systems at will. A single, easily produced targeting RNA guides the Cas9 endonuclease to a specific DNA sequence where it creates a double strand break. Imprecise repair of the break can yield mutations, while homologous recombination with a repair template can be used to effect specific changes to the genome. The tremendous potential of this system led several groups to independently adapt it for use in Caenorhabditiselegans, where it was successfully used to generate mutations and to create tailored genome changes through homologous recombination. Here, we review the different approaches taken to adapt CRISPR/Cas9 for C. elegans, and provide practical guidelines for CRISPR/Cas9-based genome engineering.

  3. Editing plant genomes with CRISPR/Cas9.

    Science.gov (United States)

    Belhaj, Khaoula; Chaparro-Garcia, Angela; Kamoun, Sophien; Patron, Nicola J; Nekrasov, Vladimir

    2015-04-01

    CRISPR/Cas9 is a rapidly developing genome editing technology that has been successfully applied in many organisms, including model and crop plants. Cas9, an RNA-guided DNA endonuclease, can be targeted to specific genomic sequences by engineering a separately encoded guide RNA with which it forms a complex. As only a short RNA sequence must be synthesized to confer recognition of a new target, CRISPR/Cas9 is a relatively cheap and easy to implement technology that has proven to be extremely versatile. Remarkably, in some plant species, homozygous knockout mutants can be produced in a single generation. Together with other sequence-specific nucleases, CRISPR/Cas9 is a game-changing technology that is poised to revolutionise basic research and plant breeding.

  4. High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields.

    Science.gov (United States)

    Naumova, Anna V; Akulov, Andrey E; Khodanovich, Marina Yu; Yarnykh, Vasily L

    2017-02-15

    A well-known problem in ultra-high-field MRI is generation of high-resolution three-dimensional images for detailed characterization of white and gray matter anatomical structures. T1-weighted imaging traditionally used for this purpose suffers from the loss of contrast between white and gray matter with an increase of magnetic field strength. Macromolecular proton fraction (MPF) mapping is a new method potentially capable to mitigate this problem due to strong myelin-based contrast and independence of this parameter of field strength. MPF is a key parameter determining the magnetization transfer effect in tissues and defined within the two-pool model as a relative amount of macromolecular protons involved into magnetization exchange with water protons. The objectives of this study were to characterize the two-pool model parameters in brain tissues in ultra-high magnetic fields and introduce fast high-field 3D MPF mapping as both anatomical and quantitative neuroimaging modality for small animal applications. In vivo imaging data were obtained from four adult male rats using an 11.7T animal MRI scanner. Comprehensive comparison of brain tissue contrast was performed for standard R1 and T2 maps and reconstructed from Z-spectroscopic images two-pool model parameter maps including MPF, cross-relaxation rate constant, and T2 of pools. Additionally, high-resolution whole-brain 3D MPF maps were obtained with isotropic 170µm voxel size using the single-point synthetic-reference method. MPF maps showed 3-6-fold increase in contrast between white and gray matter compared to other parameters. MPF measurements by the single-point synthetic reference method were in excellent agreement with the Z-spectroscopic method. MPF values in rat brain structures at 11.7T were similar to those at lower field strengths, thus confirming field independence of MPF. 3D MPF mapping provides a useful tool for neuroimaging in ultra-high magnetic fields enabling both quantitative tissue

  5. Signing Ceremony Between CAS and Schneider Electric Held in Beijing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ On April 9, 2008, a strategic cooperation signing ceremony between the China Association for Stan-dardization (CAS) and Schneider Electric took place at the Diao Yutai Guest Hotel in Beijing. Attending the signing ceremony were Mr Sun Xiaokang, Duty Director of SAC, Mr. Ma Lingcong, Secretary General of CAS, Mr. Noel Girard, Schneider Electric Marketing Director, Mr. Guy Dufrdi sse, Chairman of Schneider Electric (China) and more than twenty high-ranking managers from both companies.

  6. CAS sets up an award to promote international cooperation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Established in 2007, the CAS Award for International Cooperation in Science and Technology is to honor those eminent international experts who have made outstanding contributions to China's global cooperation in science and technology, so as to encourage more efforts in this respect that will lead to the enhancement of CAS innovation capacity and the improvement of its research performance, education and training, management and reputations among the international community.

  7. CAS spearheads R&D program for research facilities

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ China's capacity for indigenous S&T innovation is believed to have been hampered by its lack of home- grown research facilities. To address the problem, a pilot program for the research and development of major S&T facilities has been launched at CAS. The kick-off meeting was held on 28 March in the CAS Technical Institute of Physics and Chemistry in Beijing.

  8. CAS-The Prospect of Work in 2006

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Mission Statement China Association for Standardization (CAS) is to act as a bridge linking nationwide specialists in standardization with social communities. To meet the needs of government,society, market and enterprises, CAS endeavors to disseminate and popularize the standardization knowledge, organize academic forums and seminars, provide technical consultation on standardization, promote domestic and international cooperation and exchanges,and push forward the standardization process in China.

  9. Regulations for CAS Visiting Professorships for Senior International Scientists

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ 1.General Provisions. Article 1 These regulations are made in accordance with the Chinese Academy of Sciences (CAS) "Package Program for Talent Training & Recruitment" and "Guidelines of the Chinese Academy of Sciences for the Implementation of the Program for Attracting Overseas Scientists and Experts and Cultivating Talent through International Exchange",to guide the implementation of the "CAS Visiting Professorships for Senior International Scientists" (hereinafter referred to as the "Visiting Professorships Program").

  10. CAS to deepen scientific cooperation with enterprises and localities

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    On April 10, 2012, an overall strategic partnership agreement between CAS and China Petrochemical Corporation (Sinopec Group) was signed by CAS President BAI Chunli and Chairman of Sinopec Group FU Chengyu, launching collaborations in six key areas including synchrotron radiation technologies, thorium-based molten salt reactor system, and the preparation of basic chemicals via coal-based syngas and high temperature electrolysis.

  11. Winners of 2008 CAS Award for international Scientific Cooperation

    Institute of Scientific and Technical Information of China (English)

    XIN Ling

    2009-01-01

    @@ On 14 January, 2009, CAS honored three foreign scientists for their lasting and fruitful contributions to the collaboration between CAS and the world: Akito Arima, president of the Japan Science Foundation, Yuen-Ron Shen, professor of physics with the University of California at Berkley, and Michel Che, catalyst expert and chair professor at Universite Pierre et Marie Curie. Their association with the Chinese scientific community can be dated back to some three decades ago.

  12. CAS projects winning National Natural Science Awards in 2008

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Editor's Note: At the 2008 National Conference for Science and Technology Awards held earlier this year in Beijing, CAS scientists were honored with 17 second prizes of the National Natural Science Awards, 3 prizes of the Awards for Technical Invention and 14 prizes for National Awards for S&T Progress, respectively. The following is a brief introduction to some CAS projects honored by the National Natural Science Awards.

  13. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

    OpenAIRE

    Raul Torres-Ruiz; Sandra Rodriguez-Perales

    2015-01-01

    The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a ...

  14. Target specificity of the CRISPR-Cas9 system

    OpenAIRE

    Wu, Xuebing; Kriz, Andrea J.; Sharp, Phillip A.

    2014-01-01

    The CRISPR-Cas9 system, naturally a defense mechanism in prokaryotes, has been repurposed as an RNA-guided DNA targeting platform. It has been widely used for genome editing and transcriptome modulation, and has shown great promise in correcting mutations in human genetic diseases. Off-target effects are a critical issue for all of these applications. Here we review the current status on the target specificity of the CRISPR-Cas9 system.

  15. CAS Held the 2nd Yearly Official Business Conference

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ On July 15th 2004, China Association For Standardization (CAS) held official business conference the second time of this year in Beijing, which is its 5th Council Meeting. The conference was moderated by Li Rui, President of CAS's Board of Directors. Vice-presidents Li- Zhonghai, JiaoYunqi and Jing Xiaodong, Secretary-General Ma Lincong and Zhang Wei, and other cadres totally more than 20delegates attended the conference.

  16. Ultrasound- and MRI-Guided Prostate Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound- and MRI-Guided Prostate Biopsy Ultrasound- and MRI- ... Ultrasound-and MRI-guided Prostate Biopsy? What is Ultrasound- and MRI-guided Prostate Biopsy? Ultrasound- and MRI- ...

  17. Rational design of a split-Cas9 enzyme complex

    Science.gov (United States)

    Wright, Addison V.; Sternberg, Samuel H.; Taylor, David W.; Staahl, Brett T.; Bardales, Jorge A.; Kornfeld, Jack E.; Doudna, Jennifer A.

    2015-01-01

    Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding. To investigate the molecular determinants and relevance of the interlobe rearrangement for target recognition and cleavage, we designed a split-Cas9 enzyme in which the nuclease lobe and α-helical lobe are expressed as separate polypeptides. Although the lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. We propose that split-Cas9 can act as a highly regulatable platform for genome-engineering applications. PMID:25713377

  18. Editing plants for virus resistance using CRISPR-Cas.

    Science.gov (United States)

    Green, J C; Hu, J S

    This minireview summarizes recent advancements using the clustered regularly interspaced palindromic repeats-associated nuclease systems (CRISPR-Cas) derived from prokaryotes to breed plants resistant to DNA and RNA viruses. The CRISPR-Cas system represents a powerful tool able to edit and insert novel traits into plants precisely at chosen loci offering enormous advantages to classical breeding. Approaches to engineering plant virus resistance in both transgenic and non-transgenic plants are discussed. Iterations of the CRISPR-Cas system, FnCas9 and C2c2 capable of editing RNA in eukaryotic cells offer a particular advantage for providing resistance to RNA viruses which represent the great majority of known plant viruses. Scientists have obtained conflicting results using gene silencing technology to produce transgenic plants resistant to geminiviruses. CRISPR-Cas systems engineered in plants to target geminiviruses have consistently reduced virus accumulation providing increased resistance to virus infection. CRISPR-Cas may provide novel and reliable approaches to control geminiviruses and other ssDNA viruses such as Banana bunchy top virus (BBTV).

  19. CAS Presents '09 Outstanding S&T Achievement Awards

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ CAS announced winners of its 2009 Science & Technology Achievement Awards on January27,2010 in Beijing. Five research groups were conferred on the awards,namely,the group for the heavy ion research facility in Lanzhou-cooler storage ring(HIRFL-CSR)with the CAS Institute of Modern Physics(IMP),the group for theoretical research into regional space development and practical research into major planning in China with the CAS Institute of Geographic Sciences and Natural Resources Research,the group for the world's first"synthesis glycol from coal"technology with the CAS Fujian Institute of Research on the Structure of Matter,the group for the concomitant satellite for"Shenzhou-Ⅶ"-China's third manned spacecraft-with the CAS Shanghai Engineering Center for Microsatellites,and the group for the visualized casting-forging technology with the CAS Institute of Metal Research.The biennial awards were founded in 2002 to honor individuals and research groups with significant research achievements in the latest five years.Less than 10 individuals or research groups are awarded each time.

  20. CRISPR-Cas9 Based Engineering of Actinomycetal Genomes.

    Science.gov (United States)

    Tong, Yaojun; Charusanti, Pep; Zhang, Lixin; Weber, Tilmann; Lee, Sang Yup

    2015-09-18

    Bacteria of the order Actinomycetales are one of the most important sources of pharmacologically active and industrially relevant secondary metabolites. Unfortunately, many of them are still recalcitrant to genetic manipulation, which is a bottleneck for systematic metabolic engineering. To facilitate the genetic manipulation of actinomycetes, we developed a highly efficient CRISPR-Cas9 system to delete gene(s) or gene cluster(s), implement precise gene replacements, and reversibly control gene expression in actinomycetes. We demonstrate our system by targeting two genes, actIORF1 (SCO5087) and actVB (SCO5092), from the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2). Our CRISPR-Cas9 system successfully inactivated the targeted genes. When no templates for homology-directed repair (HDR) were present, the site-specific DNA double-strand breaks (DSBs) introduced by Cas9 were repaired through the error-prone nonhomologous end joining (NHEJ) pathway, resulting in a library of deletions with variable sizes around the targeted sequence. If templates for HDR were provided at the same time, precise deletions of the targeted gene were observed with near 100% frequency. Moreover, we developed a system to efficiently and reversibly control expression of target genes, deemed CRISPRi, based on a catalytically dead variant of Cas9 (dCas9). The CRISPR-Cas9 based system described here comprises a powerful and broadly applicable set of tools to manipulate actinomycetal genomes.

  1. Advances in electron microscopy: A qualitative view of instrumentation development for macromolecular imaging and tomography.

    Science.gov (United States)

    Schröder, Rasmus R

    2015-09-01

    Macromolecular imaging and tomography of ice embedded samples has developed into a mature imaging technology, in structural biology today widely referred to simply as cryo electron microscopy.(1) While the pioneers of the technique struggled with ill-suited instruments, state-of-the-art cryo microscopes are now readily available and an increasing number of groups are producing excellent high-resolution structural data of macromolecular complexes, of cellular organelles, or the morphology of whole cells. Instrumentation developers, however, are offering yet more novel electron optical devices, such as energy filters and monochromators, aberration correctors or physical phase plates. Here we discuss how current instrumentation has already changed cryo EM, and how newly available instrumentation - often developed in other fields of electron microscopy - may further develop the use and applicability of cryo EM to the imaging of single isolated macromolecules of smaller size or molecules embedded in a crowded cellular environment.

  2. Optimal cytoplasmatic density and flux balance model under macromolecular crowding effects.

    Science.gov (United States)

    Vazquez, Alexei

    2010-05-21

    Macromolecules occupy between 34% and 44% of the cell cytoplasm, about half the maximum packing density of spheres in three dimension. Yet, there is no clear understanding of what is special about this value. To address this fundamental question we investigate the effect of macromolecular crowding on cell metabolism. We develop a cell scale flux balance model capturing the main features of cell metabolism at different nutrient uptakes and macromolecular densities. Using this model we show there are two metabolic regimes at low and high nutrient uptakes. The latter regime is characterized by an optimal cytoplasmatic density where the increase of reaction rates by confinement and the decrease by diffusion slow-down balance. More important, the predicted optimal density is in the range of the experimentally determined density of Escherichia coli.

  3. Macromolecular crowding increases binding of DNA polymerase to DNA: an adaptive effect

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, S.B.; Harrison, B.

    1987-05-01

    Macromolecular crowding extends the range of ionic conditions supporting high DNA polymerase reaction rates. Reactions tested were nick translation and gap-filling by DNA polymerase I of E. coli, nuclease and polymerase activities of the large fragment of that polymerase, and polymerization by the T4 DNA polymerase. For all of these reactions, high concentrations of nonspecific polymers increased enzymatic activity under otherwise inhibitory conditions resulting from relatively high ionic strength. The primary mechanism of the polymer effect seems to be to increase the binding of polymerase to DNA. They suggest that this effect of protein-DNA complexes is only one example of a general metabolic buffering action of crowded solutions on a variety of macromolecular interactions.

  4. The macromolecular crystallography beamline I911-3 at the MAX IV laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Ursby, Thomas, E-mail: thomas.ursby@maxlab.lu.se; Unge, Johan; Appio, Roberto [Lund University, POB 118, Lund SE-221 00 (Sweden); Logan, Derek T. [Lund University, POB 124, Lund SE-221 00 (Sweden); Fredslund, Folmer; Svensson, Christer; Larsson, Krister; Labrador, Ana [Lund University, POB 118, Lund SE-221 00 (Sweden); Thunnissen, Marjolein M. G. M. [Lund University, POB 124, Lund SE-221 00 (Sweden)

    2013-07-01

    The updated macromolecular crystallography beamline I911-3 at the MAX II storage ring is described. The macromolecular crystallography beamline I911-3, part of the Cassiopeia/I911 suite of beamlines, is based on a superconducting wiggler at the MAX II ring of the MAX IV Laboratory in Lund, Sweden. The beamline is energy-tunable within a range between 6 and 18 keV. I911-3 opened for users in 2005. In 2010–2011 the experimental station was completely rebuilt and refurbished such that it has become a state-of-the-art experimental station with better possibilities for rapid throughput, crystal screening and work with smaller samples. This paper describes the complete I911-3 beamline and how it is embedded in the Cassiopeia suite of beamlines.

  5. Romp: The Method of Choice for Precise Macromolecular Engineering and Synthesis of Smart Materials

    Science.gov (United States)

    Khosravi, Ezat; Castle, Thomas C.; Kujawa, Margaret; Leejarkpai, Jan; Hutchings, Lian R.; Hine, Peter J.

    The recent advances in olefin metathesis highlight the impact of Ring Opening Metathesis Polymerisation (ROMP) as a powerful technique for macromolecular engineering and synthesis of smart materials with well-defined structures. ROMP has attracted a considerable research attention recently particularly by industry largely due to the development of well-defined metal complexes as initiators and also because of the award of the Noble Prize for Chemistry in 2005 to three scientists (Chauvin, Grubbs, Schrock) for their contributions in this area. This chapter discusses several interesting examples in order to demonstrate that ROMP is a power tool in macromolecular engineering and that it allows the design and synthesis of polymers with novel topologies.

  6. Long-Wavelength X-Ray Diffraction and Its Applications in Macromolecular Crystallography.

    Science.gov (United States)

    Weiss, Manfred S

    2017-01-01

    For many years, diffraction experiments in macromolecular crystallography at X-ray wavelengths longer than that of Cu-K α (1.54 Å) have been largely underappreciated. Effects caused by increased X-ray absorption result in the fact that these experiments are more difficult than the standard diffraction experiments at short wavelengths. However, due to the also increased anomalous scattering of many biologically relevant atoms, important additional structural information can be obtained. This information, in turn, can be used for phase determination, for substructure identification, in molecular replacement approaches, as well as in structure refinement. This chapter reviews the possibilities and the difficulties associated with such experiments, and it provides a short description of two macromolecular crystallography synchrotron beam lines dedicated to long-wavelength X-ray diffraction experiments.

  7. 3DEM Loupe: Analysis of macromolecular dynamics using structures from electron microscopy.

    Science.gov (United States)

    Nogales-Cadenas, R; Jonic, S; Tama, F; Arteni, A A; Tabas-Madrid, D; Vázquez, M; Pascual-Montano, A; Sorzano, C O S

    2013-07-01

    Electron microscopy (EM) provides access to structural information of macromolecular complexes in the 3-20 Å resolution range. Normal mode analysis has been extensively used with atomic resolution structures and successfully applied to EM structures. The major application of normal modes is the identification of possible conformational changes in proteins. The analysis can throw light on the mechanism following ligand binding, protein-protein interactions, channel opening and other functional macromolecular movements. In this article, we present a new web server, 3DEM Loupe, which allows normal mode analysis of any uploaded EM volume using a user-friendly interface and an intuitive workflow. Results can be fully explored in 3D through animations and movies generated by the server. The application is freely available at http://3demloupe.cnb.csic.es.

  8. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  9. STUDIES ON PAN MACROMOLECULAR SEMICONDUCTING FIBER 1. PREPARATION OF PAN CONDUCTING FIBER TREATED BY STANNIC CHLORIDE AND ITS SEMICONDUCTING BEHAVIOUR

    Institute of Scientific and Technical Information of China (English)

    WANG Dexi; CUI Dayuan; LUO Boliang; WANG Xiugang; WU Renjie

    1984-01-01

    The PAN fiber treated by Lewis acid (e.g. stannic chloride) could be transformed into a macromolecular conducting fiber by further thermal treatment. Depending on thermal treatment condition the resistance of the fiber varied from 103 to 1012 Ω and kept stable after hydrolysis. The fiber has enough strength to be processed by various means. This is a new kind of macromolecular semiconducting fiber having some characteristics similar to those of organic semiconductors.

  10. STUDY ON HYDROLYSIS OF MACROMOLECULAR GELATIN WITH ENZYMES IN COMBINATION MODE

    Institute of Scientific and Technical Information of China (English)

    Ya-qin Huang; Rui Guan; Ming-zhi Huang

    2004-01-01

    The enzymatic hydrolysis of macromolecular gelatin with AS1.398 neutral protease, bromelain and their combinations was studied by estimating the molecular weights of their hydrolytic products. It was discovered that the products hydrolyzed by using combination enzymes had lower molecular weight than those obtained by using single ones,and the kind of enzymes, their combination mode and addition sequence are effective ways to control the molecular weights of gelatin hydrolyzates.

  11. Porphyrin-Cored Polymer Nanoparticles: Macromolecular Models for Heme Iron Coordination.

    Science.gov (United States)

    Rodriguez, Kyle J; Hanlon, Ashley M; Lyon, Christopher K; Cole, Justin P; Tuten, Bryan T; Tooley, Christian A; Berda, Erik B; Pazicni, Samuel

    2016-10-03

    Porphyrin-cored polymer nanoparticles (PCPNs) were synthesized and characterized to investigate their utility as heme protein models. Created using collapsible heme-centered star polymers containing photodimerizable anthracene units, these systems afford model heme cofactors buried within hydrophobic, macromolecular environments. Spectroscopic interrogations demonstrate that PCPNs display redox and ligand-binding reactivity similar to that of native systems and thus are potential candidates for modeling biological heme iron coordination.

  12. CplexA: a Mathematica package to study macromolecular-assembly control of gene expression

    OpenAIRE

    Vilar, J. M. G.; Saiz, L

    2010-01-01

    Summary: Macromolecular assembly vertebrates essential cellular processes, such as gene regulation and signal transduction. A major challenge for conventional computational methods to study these processes is tackling the exponential increase of the number of configurational states with the number of components. CplexA is a Mathematica package that uses functional programming to efficiently compute probabilities and average properties over such exponentially large number of states from the en...

  13. Controlling Macromolecular Topology with Genetically Encoded SpyTag-SpyCatcher Chemistry

    OpenAIRE

    Zhang, Wen-Bin; Sun, Fei; Tirrell, David A.; Arnold, Frances H.

    2013-01-01

    Control of molecular topology constitutes a fundamental challenge in macromolecular chemistry. Here we describe the synthesis and characterization of artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies including circular, tadpole, star, and H-shaped proteins using genetically encoded SpyTag–SpyCatcher chemistry. SpyTag is a short polypeptide that binds its protein partner SpyCatcher and forms isopeptide bonds under physiological conditions. Sequences encoding SpyT...

  14. MRI in perianal fistulae

    Directory of Open Access Journals (Sweden)

    Khera Pushpinder

    2010-01-01

    Full Text Available MRI has become the method of choice for evaluating perianal fistulae due to its ability to display the anatomy of the sphincter muscles orthogonally, with good contrast resolution. In this article we give an outline of the classification of perianal fistulae and present a pictorial assay of sphincter anatomy and the MRI findings in perianal fistulae. This study is based on a retrospective analysis of 43 patients with a clinical diagnosis of perianal fistula. MRI revealed a total of 44 fistulae in 35 patients; eight patients had only perianal sinuses.

  15. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  16. Macromolecular (pro)drugs with concurrent direct activity against the hepatitis C virus and inflammation.

    Science.gov (United States)

    Wohl, Benjamin M; Smith, Anton A A; Jensen, Bettina E B; Zelikin, Alexander N

    2014-12-28

    Macromolecular prodrugs (MPs) are a powerful tool to alleviate side-effects and improve the efficacy of the broad-spectrum antiviral agent ribavirin. In this work, we sought an understanding of what makes an optimal formulation within the macromolecular parameter space--nature of the polymer carrier, average molar mass, drug loading, or a good combination thereof. A panel of MPs based on biocompatible synthetic vinylic and (meth)acrylic polymers was tested in an anti-inflammatory assay with relevance to alleviating inflammation in the liver during hepatitis C infection. Pristine polymer carriers proved to have a pronounced anti-inflammatory activity, a notion which may prove significant in developing MPs for antiviral and anticancer treatments. With conjugated ribavirin, MPs revealed enhanced activity but also higher toxicity. Therapeutic windows and therapeutic indices were determined and discussed to reveal the most potent formulation and those with optimized safety. Polymers were also tested as inhibitors of replication of the hepatitis C viral RNA using a subgenomic viral replicon system. For the first time, negatively charged polymers are revealed to have an intracellular activity against hepatitis C virus replication. Concerted activity of the polymer and ribavirin afforded MPs which significantly increased the therapeutic index of ribavirin-based treatment. Taken together, the systematic investigation of the macromolecular space identified lead candidates with high efficacy and concurrent direct activity against the hepatitis C virus and inflammation.

  17. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics

    Science.gov (United States)

    Moffatt, Ryan; Ma, Buyong; Nussinov, Ruth

    2016-01-01

    Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts. PMID:27124275

  18. Implementation of remote monitoring and diffraction evaluation systems at the Photon Factory macromolecular crystallography beamlines

    Science.gov (United States)

    Yamada, Yusuke; pHonda, Nobuo; Matsugaki, Naohiro; Igarashi, Noriyuki; Hiraki, Masahiko; Wakatsuki, Soichi

    2008-01-01

    Owing to recent advances in high-throughput technology in macromolecular crystallography beamlines, such as high-brilliant X-ray sources, high-speed readout detectors and robotics, the number of samples that can be examined in a single visit to the beamline has increased dramatically. In order to make these experiments more efficient, two functions, remote monitoring and diffraction image evaluation, have been implemented in the macromolecular crystallography beamlines at the Photon Factory (PF). Remote monitoring allows scientists to participate in the experiment by watching from their laboratories, without having to come to the beamline. Diffraction image evaluation makes experiments easier, especially when using the sample exchange robot. To implement these two functions, two independent clients have been developed that work specifically for remote monitoring and diffraction image evaluation. In the macromolecular crystallography beamlines at PF, beamline control is performed using STARS (simple transmission and retrieval system). The system adopts a client–server style in which client programs communicate with each other through a server process using the STARS protocol. This is an advantage of the extension of the system; implementation of these new functions required few modifications of the existing system. PMID:18421163

  19. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics.

    Directory of Open Access Journals (Sweden)

    Tatiana Maximova

    2016-04-01

    Full Text Available Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.

  20. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2013-11-01

    The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.

  1. Brain MRI in Parkinson's disease

    NARCIS (Netherlands)

    Meijer, F.J.A.; Goraj, B.M.

    2014-01-01

    In this review article, conventional brain MRI and advanced MRI techniques in Parkinson`s disease (PD) are discussed, with emphasis on clinical relevance. Conventional brain MRI sequences generally demonstrate limited abnormalities specific for PD and in clinical practice brain MRI is mainly used to

  2. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Head Magnetic resonance imaging (MRI) of the head uses a powerful ... the Head? What is MRI of the Head? Magnetic resonance imaging (MRI) is a noninvasive medical test that ...

  3. A non-inheritable maternal Cas9-based multiple-gene editing system in mice.

    Science.gov (United States)

    Sakurai, Takayuki; Kamiyoshi, Akiko; Kawate, Hisaka; Mori, Chie; Watanabe, Satoshi; Tanaka, Megumu; Uetake, Ryuichi; Sato, Masahiro; Shindo, Takayuki

    2016-01-28

    The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9 overexpression (Cas9 mice). The maCas9 protein in zygotes derived from mating or in vitro fertilization of Tg/+ oocytes and +/+ sperm could successfully edit the target genome. The efficiency of such maCas9-based genome editing was comparable to that of zygote microinjection-based genome editing widely used at present. Furthermore, we demonstrated a novel approach to create "Cas9 transgene-free" gene-modified mice using non-Tg (+/+) zygotes carrying maCas9. The maCas9 protein in mouse zygotes edited nine target loci simultaneously after injection with nine different gRNAs alone. Cas9 mouse-derived zygotes have the potential to facilitate the creation of genetically modified animals carrying the Cas9 transgene, enabling repeatable genome engineering and the production of Cas9 transgene-free mice.

  4. Cas9 in Genetically Modified Food Is Unlikely to Cause Food Allergy.

    Science.gov (United States)

    Nakajima, Osamu; Nishimaki-Mogami, Tomoko; Kondo, Kazunari

    2016-01-01

    Genome editing has undergone rapid development during the last three years. It is anticipated that genetically modified organisms (GMOs) for food purposes will be widely produced using the clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR)/Cas9 system in the near future. However, the Cas9 gene may then enter the genomes of GMOs for food if the breeding process is not strictly managed, which could lead to the Cas9 protein or associated peptides being produced within these organisms. A variety of peptides could theoretically be produced from the Cas9 gene by using open reading frames different from that of Cas9 in the GMOs. In this study, Cas9 and the peptides potentially encoded by Cas9 genes were studied regarding their immunogenicity, in terms of the digestibility of Cas9 and the homology of the peptides to food allergens. First, the digestibility and thermal stability of Cas9 were studied. Digestibility was tested with natural or heat-denatured Cas9 in simulated gastric fluid in vitro. The two types of Cas9 were digested rapidly. Cas9 was also gradually degraded during heat treatment. Second, the peptides potentially encoded by Cas9 genes were examined for their homology to food allergens. Specifically, an 8-mer exact match search and a sliding 80-mer window search were performed using allergen databases. One of the peptides was found to have homology with a food allergen.

  5. MRI of the Chest

    Medline Plus

    Full Text Available ... information on the chemicals present in the body's cells, may also be performed during the MRI exam ... in diagnosing a broad range of conditions, including cancer, heart and vascular disease, heart valve abnormalities, bone ...

  6. MRI of the Chest

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    Full Text Available ... it may cause some medical devices to malfunction. Most orthopedic implants pose no risk, but you should ... or if you have asthma. The contrast material most commonly used for an MRI exam contains a ...

  7. MRI of the Chest

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    Full Text Available ... magnetic field of the MRI unit, metal and electronic items are not allowed in the exam room. ... tell the technologist if you have medical or electronic devices in your body. These objects may interfere ...

  8. MRI of the Chest

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    Full Text Available ... to a CD or uploaded to a digital cloud server. MRI of the chest gives detailed pictures ... artery ( dissection ). See the MRA page for more information. top of page How should I prepare? You ...

  9. MRI of the Chest

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    Full Text Available ... your regular medications as usual. Leave jewelry at home and wear loose, comfortable clothing. You may be ... Jewelry and other accessories should be left at home, if possible, or removed prior to the MRI ...

  10. MRI of the Chest

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    Full Text Available ... imaging (MRI) exam. View full size with caption Pediatric Content Some imaging tests and treatments have special pediatric considerations. The teddy bear denotes child-specific content. ...

  11. Extradural spinal meningioma: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Sato, N. [Department of Diagnostic Radiology, Yale University School of Medicine, P. O. Box 20 8042, New Haven, CT 06520-8042 (United States); Sze, G. [Department of Diagnostic Radiology, Yale University School of Medicine, P. O. Box 20 8042, New Haven, CT 06520-8042 (United States)

    1997-06-01

    We report a case of extradural spinal meningioma with pathologically proven features of malignant transformation. The MRI findings of extradural spinal meningioma and differences in the findings from intradural meningiomas are discussed. (orig.). With 1 fig.

  12. MRI of the Chest

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    Full Text Available ... contrast for an MRI. If you have a history of kidney disease or liver transplant, it will ... Radiology (ACR) and the Radiological Society of North America (RSNA), comprising physicians with expertise in several radiologic ...

  13. MRI of the Chest

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    Full Text Available ... a CD or uploaded to a digital cloud server. MRI of the chest gives detailed pictures of ... suggestion into the following text box: Comment: E-mail: Area code: Phone no: Thank you! Do you ...

  14. MRI of the Chest

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    Full Text Available ... pictures of organs, soft tissues, bone and virtually all other internal body structures. MRI does not use ... include: jewelry, watches, credit cards and hearing aids, all of which can be damaged pins, hairpins, metal ...

  15. MRI of the Chest

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    Full Text Available ... distinguish between cancer tissue and fluid, known as edema . MRI typically costs more and may take more ... with caption Pediatric Content Some imaging tests and treatments have special pediatric considerations. The teddy bear denotes ...

  16. MRI of the Chest

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    Full Text Available ... prior to your scheduled examination. Infants and young children usually require sedation or anesthesia to complete an MRI exam without moving. Whether a child requires sedation depends on the child's age, intellectual ...

  17. MRI of the Chest

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    Full Text Available ... scanner, play the noises that the child might hear during the MRI exam, answer any questions and ... These items include: jewelry, watches, credit cards and hearing aids, all of which can be damaged pins, ...

  18. MRI of the Chest

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    Full Text Available ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... the same effect. A very irregular heartbeat may affect the quality of images obtained using techniques that ...

  19. MRI of the Chest

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    Full Text Available ... Us News Physician Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) - Chest Magnetic resonance imaging ( ... the child can watch a movie while the scan is being performed. Thus, the child remains motionless ...

  20. MRI of the Chest

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    Full Text Available ... may cause some medical devices to malfunction. Most orthopedic implants pose no risk, but you should always ... metal objects. In general, metal objects used in orthopedic surgery pose no risk during MRI. However, a ...

  1. MRI of the Chest

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    Full Text Available ... devices or metal in your body. Guidelines about eating and drinking before your exam vary between facilities. ... fitting and has no metal fasteners. Guidelines about eating and drinking before an MRI exam vary with ...

  2. MRI of the Chest

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    Full Text Available ... scanner. top of page How does the procedure work? Unlike conventional x-ray examinations and computed tomography ( ... clearer and more detailed than with other imaging methods. This detail makes MRI an invaluable tool in ...

  3. MRI of the Chest

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    Full Text Available ... exam time. top of page What will I experience during and after the procedure? Most MRI exams ... uncomfortable to remain still during MR imaging. Others experience a sense of being closed-in (claustrophobia) while ...

  4. MRI of the Chest

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    Full Text Available ... will hear and feel loud tapping or thumping sounds when the coils that generate the radiofrequency pulses ... use headphones to reduce the intensity of the sounds made by the MRI machine. You may be ...

  5. MRI of the Chest

    Science.gov (United States)

    ... surgery pose no risk during MRI. However, a recently placed artificial joint may require the use of ... evaluation with additional views or a special imaging technique. A follow-up examination may also be necessary ...

  6. MRI of the Breast

    Science.gov (United States)

    ... surgery pose no risk during MRI. However, a recently placed artificial joint may require the use of ... evaluation with additional views or a special imaging technique. A follow-up examination may also be necessary ...

  7. MRI of the Chest

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    Full Text Available ... Infants and young children usually require sedation or anesthesia to complete an MRI exam without moving. Whether ... A physician or nurse specializing in sedation or anesthesia for children should be available during the exam ...

  8. MRI of the Chest

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    Full Text Available ... metallic items, which can distort MRI images removable dental work pens, pocket knives and eyeglasses body piercings ... from the contrast material, including nausea, headache and pain at the site of injection. Similarly, patients are ...

  9. MRI of the Chest

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    Full Text Available ... during an MRI scan, but this is rare. Tooth fillings and braces usually are not affected by ... from the contrast material, including nausea, headache and pain at the site of injection. Similarly, patients are ...

  10. MRI of the Chest

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    Full Text Available ... magnetic field is produced by passing an electric current through wire coils in most MRI units. Other ... that are detected by the coils. The electric current does not come in contact with the patient. ...

  11. MRI of the Chest

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    Full Text Available ... any recent surgeries. Some conditions, such as severe kidney disease, may prevent you from being given gadolinium contrast ... an MRI. If you have a history of kidney disease or liver transplant, it will be necessary to ...

  12. MRI of the Chest

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    Full Text Available ... provides movie-like sequential imaging of the cardiovascular system that is important to assess the health and ... the magnet. Some MRI units, called short-bore systems , are designed so that the magnet does not ...

  13. MRI of the Chest

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    Full Text Available ... intercom. Many MRI centers allow a friend or parent to stay in the room as long as they are also screened for safety in the magnetic environment. Children will be given appropriately sized earplugs or headphones ...

  14. MRI of the Chest

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    Full Text Available ... MRI examinations may require you to receive an injection of contrast material into the bloodstream. The radiologist , ... the potential risks. Pregnant women should not receive injections of gadolinium contrast material except when absolutely necessary ...

  15. MRI of the Chest

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    Full Text Available ... allergies and whether there’s a possibility you are pregnant. The magnetic field is not harmful, but it ... if there is any possibility that they are pregnant. MRI has been used for scanning patients since ...

  16. MRI of the Chest

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    Full Text Available ... copied to a CD or uploaded to a digital cloud server. MRI of the chest gives detailed ... the technologist if you have medical or electronic devices in your body. These objects may interfere with ...

  17. MRI of the Chest

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    Full Text Available ... data suggest that it is safe to continue breastfeeding after receiving intravenous contrast. For further information please ... that magnetic resonance imaging harms the fetus, pregnant women usually are advised not to have an MRI ...

  18. MRI of the Chest

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    Full Text Available ... evaluation with additional views or a special imaging technique. A follow-up examination may also be necessary ... vs. risks? Benefits MRI is a noninvasive imaging technique that does not involve exposure to ionizing radiation. ...

  19. MRI of the Chest

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    Full Text Available ... tissue and fluid, known as edema . MRI typically costs more and may take more time to perform ... accredited facilities database . This website does not provide cost information. The costs for specific medical imaging tests, ...

  20. MRI of the Chest

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    Full Text Available ... used in tattoos may contain iron and could heat up during an MRI scan, but this is ... to get a better understanding of the possible charges you will incur. Web page review process: This ...

  1. MRI of the Chest

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    Full Text Available ... may follow your regular daily routine and take food and medications as usual. Some MRI examinations may ... to iodine or x-ray contrast material, drugs, food, or the environment, or if you have asthma. ...

  2. MRI of the Chest

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    Full Text Available ... information on the chemicals present in the body's cells, may also be performed during the MRI exam ... in diagnosing a broad range of conditions, including cancer, heart and vascular disease, heart valve abnormalities, bone ...

  3. MRI of the Chest

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    Full Text Available ... is not harmful, but it may cause some medical devices to malfunction. Most orthopedic implants pose no ... Chest? Magnetic resonance imaging (MRI) is a noninvasive medical test that physicians use to diagnose medical conditions. ...

  4. MRI of the Chest

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    Full Text Available ... to assess the anatomy and function of the heart and its blood flow. Tell your doctor about ... chest cavity, including the mediastinum , chest wall, pleura, heart and vessels, from almost any angle. MRI also ...

  5. MRI of the Chest

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    Full Text Available ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... from the contrast material, including nausea, headache and pain at the site of injection. Similarly, patients are ...

  6. MRI of the Chest

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    Full Text Available ... magnetic field of the MRI unit, metal and electronic items are not allowed in the exam room. ... tell the technologist if you have medical or electronic devices in your body. These objects may interfere ...

  7. MRI of the Chest

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    Full Text Available ... and should not enter the MRI scanning area: cochlear (ear) implant some types of clips used for ... follow-up exam is done because a potential abnormality needs further evaluation with additional views or a ...

  8. MRI of the Chest

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    Full Text Available ... MRI scanners are air-conditioned and well-lit. Music may be played through the headphones to help ... very rare occasions, a few patients experience side effects from the contrast material, including nausea, headache and ...

  9. MRI of the Chest

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    Full Text Available ... of the chest uses a powerful magnetic field, radio waves and a computer to produce detailed pictures ... medical conditions. MRI uses a powerful magnetic field, radio frequency pulses and a computer to produce detailed ...

  10. MRI of the Chest

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    Full Text Available ... it is useful to bring that to the attention of the scheduler before the exam and bring ... does the equipment look like? The traditional MRI unit is a large cylinder-shaped tube surrounded by ...

  11. MRI of the Chest

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    Full Text Available ... may follow your regular daily routine and take food and medications as usual. Some MRI examinations may ... to iodine or x-ray contrast material, drugs, food, or the environment, or if you have asthma. ...

  12. MRI of the Chest

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    Full Text Available ... provides movie-like sequential imaging of the cardiovascular system that is important to assess the health and ... the magnet. Some MRI units, called short-bore systems , are designed so that the magnet does not ...

  13. MRI of the Chest

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    Full Text Available ... x-ray may be taken to detect and identify any metal objects. In general, metal objects used in orthopedic surgery pose no risk during MRI. However, a recently placed artificial joint ...

  14. MRI of the Chest

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    Full Text Available ... metal in your body. Guidelines about eating and drinking before your exam vary between facilities. Unless you ... has no metal fasteners. Guidelines about eating and drinking before an MRI exam vary with the specific ...

  15. MRI of the Chest

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    Full Text Available ... Unless you are told otherwise, take your regular medications as usual. Leave jewelry at home and wear ... your regular daily routine and take food and medications as usual. Some MRI examinations may require you ...

  16. Combined PET/MRI

    DEFF Research Database (Denmark)

    Bailey, D. L.; Pichler, B. J.; Gückel, B.

    2015-01-01

    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...... February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology......, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both...

  17. MRI of the Chest

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    Full Text Available ... be examined on a computer monitor, transmitted electronically, printed or copied to a CD or uploaded to ... magnetic field of the MRI unit, metal and electronic items are not allowed in the exam room. ...

  18. MRI of the Chest

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    Full Text Available ... electronic devices they may have. top of page What does the equipment look like? The traditional MRI ... to the total exam time. top of page What will I experience during and after the procedure? ...

  19. MRI of plantar fasciitis

    Energy Technology Data Exchange (ETDEWEB)

    Roger, B.; Grenier, P. [Service de Radiologie Polyvalente Diagnostique et Interventionelle, Hopital de la Pitie, 83, boulevard de l`Hopital, F-75651 Paris Cedex 13 (France)

    1997-12-01

    At present, MRI is the only imaging method that can precisely visualize lesions of the superficial plantar aponeurosis, whether they be musculoaponeurositides, enthesopathies or tears, and whether they be acute or chronic, with or without complications. By its direct visualization of the lesion, MRI enables an accurate assessment of the injury to be made and thereby better orients the therapeutic strategy. (orig.) With 11 figs., 15 refs.

  20. Posttraumatic pseudolipoma: MRI appearances

    Energy Technology Data Exchange (ETDEWEB)

    Theumann, N.; Abdelmoumene, A.; Wintermark, M.; Schnyder, P.; Gailloud, M.C.; Resnick, D. [CHUV, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland)

    2005-09-01

    The goal of this study was to describe the MRI characteristics of posttraumatic pseudolipomas. Ten patients with previous history of blunt trauma or local surgery were investigated with MRI at the level of their deformity. The etiology was blunt trauma in eight patients and postoperative trauma in two. For all patients medical documentation, in the form of clinical history and physical examination, confirmed that a visible hematoma was present acutely at the same location following the injury and that the contour deformity subsequently appeared. All patients underwent liposuction. Preoperative bilateral MRI examinations were performed on all patients. The mean clinical follow-up was 17.8 months. MRI examinations were interpreted in consensus by two experienced musculoskeletal radiologists with attention to fatty extension (subcutaneous fatty thickness and anatomical extension), asymmetry compared with the asymptomatic side, the presence or absence of fibrous septae or nonfatty components, and patterns of contrast enhancement. Ten posttraumatic pseudolipomas were identified. Clinically, they showed as subcutaneous masses with the consistency of normal adipose tissue. Their locations were the abdomen (n=1), hip (n=1), the upper thigh (n=6), the knee (n=1), and the ankle (n=1). On MRI examinations, using the contralateral side as a control, pseudolipomas appeared as focal fatty masses without a capsule or contrast enhancement. Posttraumatic pseudolipomas may develop at a site of blunt trauma or surgical procedures often antedated by a soft tissue hematoma. Characteristic MRI findings are unencapsulated subcutaneous fatty masses without contrast enhancement. (orig.)

  1. Complementary Information Derived from CRISPR Cas9 Mediated Gene Deletion and Suppression. | Office of Cancer Genomics

    Science.gov (United States)

    CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes.

  2. The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

    Science.gov (United States)

    Rajapaksha Mudalige, Ajith Rathnaweera

    Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40

  3. Spectroscopic studies of three Cepheids with high positive pulsation period increments: SZ Cas, BY Cas, and RU Sct

    Science.gov (United States)

    Usenko, I. A.; Klochkova, V. G.

    2015-07-01

    Three high-resolution spectra have been taken at different times with the 6-m SAO RAS telescope (LYNX and PFES spectrographs) for three Cepheids exhibiting high positive period increments: the small-amplitude (DCEPS) SZ Cas and BY Cas and the classical (DCEP) RU Sct. SZ Cas and RU Sct are members of the Galactic open clusters χ and h Per and Trump 35, respectively. Analysis of the spectra has shown that the interstellar Na I D1 and D2 lines in all objects are considerably stronger than the atmospheric ones and are redshifted in SZ Cas and BY Cas and blushifted in RU Sct. The core of the H α absorption line in BY Cas has an asymmetric knifelike shape, while RU Sct exhibits an intense emission in the blue wing of this line. Such phenomena are observed in long-period Cepheids and bright hypergiants with an extended envelope. In this case, the strong Mg Ib 5183.62 Å and Ba II 5853.67, 6141.713, and 6496.90 Å lines with low χlow in SZ Cas and RU Sct also show characteristic knifelike profiles with an asymmetry in the red region, while the Ba II 4934.095 Å line shows similar profiles in the blue one. The absorption lines of neutral atoms and singly ionized metals with different lowerlevel excitation potentials exhibit different degrees of asymmetry: from a pronounced one with secondary components in BY Cas (similar to those in the small-amplitude Cepheid BG Cru pulsating in the first overtone and having an envelope) to its insignificance or virtual absence in SZ Cas and RU Sct. Analysis of the secular changes in mean T eff determined from photometric color indices and spectra over the last 55 years for these stars has revealed periodic fluctuations of 200 K for SZ Cas and BY Cas and 500 K for RU Sct. For SZ Cas and RU Sct, T eff determined in some years from some color indices show much lower values, which together with the temperature fluctuations can be associated with mass loss and dust formation. Based on these facts, we hypothesize the existence of

  4. Pyo-pneumothorax tuberculeux: à propos de 18 cas

    Science.gov (United States)

    Hicham, Souhi; Hanane, El Ouazzani; Hicham, Janah; Ismaïl, Rhorfi; Ahmed, Abid

    2016-01-01

    Le pyo-pneumothorax tuberculeux est une complication rare mais grave de la tuberculose pulmonaire évolutive. Nous rapportons une série de 18 cas de pyo-pneumothorax tuberculeux colligés au service de Pneumo-Phtisiologie de l'Hôpital Militaire d'Instruction Mohammed V de Rabat entre janvier 2005 et décembre 2009. Il s'agit de 15 hommes et 3 femmes d’âge moyen de 35 ans ±7 ans. 4 patients étaient diabétiques. Le tabagisme était retrouvé chez 9 cas. Le pyo-pneumothorax était du coté droit dans 13 cas. La radiographie thoracique avait montré des lésions cavitaires chez 15 patients et des lésions étendues et bilatérales chez 8 cas. La recherche de BK dans le liquide de tubage gastrique était positive chez 16 cas. Un drainage thoracique associé à un traitement antituberculeux selon le régime 2SRHZ/7RH et une kinésithérapie respiratoire ont été instaurés chez tous les cas. La durée moyenne de drainage pleural était de 4 semaines. Chez 3 cas on avait noté la persistance de la suppuration pleurale ayant nécessité une toilette pleurale sous thoracoscopie avec pleurectomie et exérèse pulmonaire limitée emportant la lésion parenchymateuse tuberculeuse et la persistance d'une volumineuse poche pleurale avec trouble ventilatoire restrictif ayant nécessité une décortication pleurale chirurgicale chez deux cas. L’évolution était favorable avec pachypleurite séquellaire minime chez le reste des cas. Le pyo-pneumothorax tuberculeux est une forme grave, qui est souvent en rapport avec une tuberculose cavitaire active. L’évolution est généralement trainante malgré le traitement antituberculeux et le drainage thoracique, d'où la nécessité d'un diagnostic et un traitement précoce de toute forme de tuberculose. PMID:27583090

  5. SD-CAS: Spin Dynamics by Computer Algebra System.

    Science.gov (United States)

    Filip, Xenia; Filip, Claudiu

    2010-11-01

    A computer algebra tool for describing the Liouville-space quantum evolution of nuclear 1/2-spins is introduced and implemented within a computational framework named Spin Dynamics by Computer Algebra System (SD-CAS). A distinctive feature compared with numerical and previous computer algebra approaches to solving spin dynamics problems results from the fact that no matrix representation for spin operators is used in SD-CAS, which determines a full symbolic character to the performed computations. Spin correlations are stored in SD-CAS as four-entry nested lists of which size increases linearly with the number of spins into the system and are easily mapped into analytical expressions in terms of spin operator products. For the so defined SD-CAS spin correlations a set of specialized functions and procedures is introduced that are essential for implementing basic spin algebra operations, such as the spin operator products, commutators, and scalar products. They provide results in an abstract algebraic form: specific procedures to quantitatively evaluate such symbolic expressions with respect to the involved spin interaction parameters and experimental conditions are also discussed. Although the main focus in the present work is on laying the foundation for spin dynamics symbolic computation in NMR based on a non-matrix formalism, practical aspects are also considered throughout the theoretical development process. In particular, specific SD-CAS routines have been implemented using the YACAS computer algebra package (http://yacas.sourceforge.net), and their functionality was demonstrated on a few illustrative examples.

  6. Targeting Hepatitis B Virus With CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Christoph Seeger

    2014-01-01

    Full Text Available Hepatitis B virus persistence in infected hepatocytes is due to the presence of covalently closed circular DNA (cccDNA, the template for the transcription of viral RNAs. Antiviral therapies with nucleoside analogues inhibit replication of HBV DNA in capsids present in the cytoplasm of infected cells, but do not reduce or destroy nuclear cccDNA. To investigate whether cccDNA derived from infectious HBV could be directly targeted for destruction, we used the CRISPR/Cas9 system in HepG2 cells expressing the HBV receptor sodium taurocholate cotransporting polypeptide (NTCP. We tested different HBV-specific guide RNAs and demonstrated that they could inhibit HBV infections up to eightfold. Inhibition was due to mutations and deletions in cccDNA similar to those observed with chromosomal DNA cleaved by Cas9 and repaired by nonhomologous end joining (NHEJ. Interferon alpha (IFN-α did not have a measurable effect on the antiviral activity of the CRISPR/Cas9 system, suggesting that Cas9 and NHEJ activities are not affected by induction of an innate immune response with the cytokine. Taken together, our results demonstrated that Cas9 can be recruited to cccDNA, opening the possibility for the development of future antiviral strategies aimed at targeting cccDNA for endonucleolytic cleavage with small molecules.

  7. Repurposing CRISPR/Cas9 for in situ functional assays.

    Science.gov (United States)

    Malina, Abba; Mills, John R; Cencic, Regina; Yan, Yifei; Fraser, James; Schippers, Laura M; Paquet, Marilène; Dostie, Josée; Pelletier, Jerry

    2013-12-01

    RNAi combined with next-generation sequencing has proven to be a powerful and cost-effective genetic screening platform in mammalian cells. Still, this technology has its limitations and is incompatible with in situ mutagenesis screens on a genome-wide scale. Using p53 as a proof-of-principle target, we readapted the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR associated 9) genome-editing system to demonstrate the feasibility of this methodology for targeted gene disruption positive selection assays. By using novel "all-in-one" lentiviral and retroviral delivery vectors heterologously expressing both a codon-optimized Cas9 and its synthetic guide RNA (sgRNA), we show robust selection for the CRISPR-modified Trp53 locus following drug treatment. Furthermore, by linking Cas9 expression to GFP fluorescence, we use an "all-in-one" system to track disrupted Trp53 in chemoresistant lymphomas in the Eμ-myc mouse model. Deep sequencing analysis of the tumor-derived endogenous Cas9-modified Trp53 locus revealed a wide spectrum of mutants that were enriched with seemingly limited off-target effects. Taken together, these results establish Cas9 genome editing as a powerful and practical approach for positive in situ genetic screens.

  8. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

    Full Text Available Lin Hou,* Huijuan Zhang,* Yating Wang, Lili Wang, Xiaomin Yang, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: A tumor-targeting carrier, hyaluronic acid (HA-functionalized single-walled carbon nanotubes (SWCNTs, was explored to deliver magnetic resonance imaging (MRI contrast agents (CAs targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.Keywords: gadolinium, magnetic resonance, SWCNTs, hyaluronic acid, contrast agent

  9. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    Science.gov (United States)

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-11-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

  10. Study of Eclipsing Binary and Multiple Systems in OB Associations IV: Cas OB6 Member DN Cas

    CERN Document Server

    Bakis, V; Bilir, S; Eker, Z

    2016-01-01

    An early-type, massive, short-period ($P_{\\rm orb}=2^{\\rm d}.310951$) eclipsing spectroscopic binary DN Cas has been re-visited with new spectral and photometric data. The masses and radii of the components have been obtained as $M_1=19.04\\pm0.07 M_\\odot$, $M_2=13.73\\pm 0.05M_\\odot$ and $R_1=7.22\\pm0.06 R_\\odot$, $R_2=5.79\\pm0.06R_\\odot$, respectively. Both components present synchronous rotation ($V_{\\rm rot1}=160\\,$km s$^{-1}$, $V_{\\rm rot2}=130\\,$km s$^{-1}$) with their orbit. Orbital period analysis yielded a physically bound additional component in the system with a minimum mass of $M_3=0.88 M_\\odot$ orbiting in an eccentric orbit ($e=0.37\\pm0.2$) with an orbital period of $P_{12}=42\\pm9$ yrs. High precision absolute parameters of the system allowed us to derive a distance to DN Cas as 1.7$\\pm$0.2 kpc which locates the system within the borders of the Cas OB6 association (d=1.8 kpc; Mel'nik & Dambis, 2009). The space velocities and the age of DN Cas are in agreement with those of Cas OB6. The age of ...

  11. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

    Directory of Open Access Journals (Sweden)

    Raul Torres-Ruiz

    2015-09-01

    Full Text Available The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers.

  12. Genome engineering using CRISPR-Cas9 system.

    Science.gov (United States)

    Cong, Le; Zhang, Feng

    2015-01-01

    The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is an adaptive immune system that exists in a variety of microbes. It could be engineered to function in eukaryotic cells as a fast, low-cost, efficient, and scalable tool for manipulating genomic sequences. In this chapter, detailed protocols are described for harnessing the CRISPR-Cas9 system from Streptococcus pyogenes to enable RNA-guided genome engineering applications in mammalian cells. We present all relevant methods including the initial site selection, molecular cloning, delivery of guide RNAs (gRNAs) and Cas9 into mammalian cells, verification of target cleavage, and assays for detecting genomic modification including indels and homologous recombination. These tools provide researchers with new instruments that accelerate both forward and reverse genetics efforts.

  13. Harnessing CRISPR-Cas systems for bacterial genome editing.

    Science.gov (United States)

    Selle, Kurt; Barrangou, Rodolphe

    2015-04-01

    Manipulation of genomic sequences facilitates the identification and characterization of key genetic determinants in the investigation of biological processes. Genome editing via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) constitutes a next-generation method for programmable and high-throughput functional genomics. CRISPR-Cas systems are readily reprogrammed to induce sequence-specific DNA breaks at target loci, resulting in fixed mutations via host-dependent DNA repair mechanisms. Although bacterial genome editing is a relatively unexplored and underrepresented application of CRISPR-Cas systems, recent studies provide valuable insights for the widespread future implementation of this technology. This review summarizes recent progress in bacterial genome editing and identifies fundamental genetic and phenotypic outcomes of CRISPR targeting in bacteria, in the context of tool development, genome homeostasis, and DNA repair.

  14. Genome Editing in Human Cells Using CRISPR/Cas Nucleases.

    Science.gov (United States)

    Wyvekens, Nicolas; Tsai, Shengdar Q; Joung, J Keith

    2015-10-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has been broadly adopted for highly efficient genome editing in a variety of model organisms and human cell types. Unlike previous genome editing technologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR/Cas technology does not require complex protein engineering and can be utilized by any researcher proficient in basic molecular biology and cell culture techniques. This unit describes protocols for design and cloning of vectors expressing single or multiplex gRNAs, for transient transfection of human cell lines, and for quantitation of mutation frequencies by T7 endonuclease I assay. These protocols also include guidance for using two improvements that increase the specificity of CRISPR/Cas nucleases: truncated gRNAs and dimeric RNA-guided FokI nucleases.

  15. GENOME EDITING IN HUMAN CELLS USING CRISPR/CAS NUCLEASES

    Science.gov (United States)

    Wyvekens, Nicolas; Tsai, Shengdar; Joung, J. Keith

    2016-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has been broadly adopted for highly efficient genome editing in a variety of model organisms and human cell types. Unlike previous genome editing technologies such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), the CRISPR/Cas technology does not require complex protein engineering and can be utilized by any researcher proficient in basic molecular biology and cell culture techniques. Here we describe protocols for design and cloning of vectors expressing single or multiplex gRNAs, for transient transfection of human cell lines, and for quantitation of mutation frequencies by T7 Endonuclease I assay. These protocols also include guidance for using two improvements that increase the specificity of CRISPR/Cas nucleases: truncated gRNAs and dimeric RNA-guided FokI nucleases. PMID:26423589

  16. CRISPR-Cas adaptation: insights into the mechanism of action.

    Science.gov (United States)

    Amitai, Gil; Sorek, Rotem

    2016-02-01

    Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

  17. Exploiting CRISPR/Cas: Interference Mechanisms and Applications

    Directory of Open Access Journals (Sweden)

    André Plagens

    2013-07-01

    Full Text Available The discovery of biological concepts can often provide a framework for the development of novel molecular tools, which can help us to further understand and manipulate life. One recent example is the elucidation of the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated (Cas that protects bacteria and archaea against viruses or conjugative plasmids. The immunity is based on small RNA molecules that are incorporated into versatile multi-domain proteins or protein complexes and specifically target viral nucleic acids via base complementarity. CRISPR/Cas interference machines are utilized to develop novel genome editing tools for different organisms. Here, we will review the latest progress in the elucidation and application of prokaryotic CRISPR/Cas systems and discuss possible future approaches to exploit the potential of these interference machineries.

  18. Exploiting CRISPR/Cas: Interference Mechanisms and Applications

    Science.gov (United States)

    Richter, Hagen; Randau, Lennart; Plagens, André

    2013-01-01

    The discovery of biological concepts can often provide a framework for the development of novel molecular tools, which can help us to further understand and manipulate life. One recent example is the elucidation of the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) that protects bacteria and archaea against viruses or conjugative plasmids. The immunity is based on small RNA molecules that are incorporated into versatile multi-domain proteins or protein complexes and specifically target viral nucleic acids via base complementarity. CRISPR/Cas interference machines are utilized to develop novel genome editing tools for different organisms. Here, we will review the latest progress in the elucidation and application of prokaryotic CRISPR/Cas systems and discuss possible future approaches to exploit the potential of these interference machineries. PMID:23857052

  19. CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling.

    Science.gov (United States)

    Torres-Ruiz, Raul; Rodriguez-Perales, Sandra

    2015-09-14

    The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers.

  20. Multidimensional diffusion MRI

    Science.gov (United States)

    Topgaard, Daniel

    2017-02-01

    Principles from multidimensional NMR spectroscopy, and in particular solid-state NMR, have recently been transferred to the field of diffusion MRI, offering non-invasive characterization of heterogeneous anisotropic materials, such as the human brain, at an unprecedented level of detail. Here we revisit the basic physics of solid-state NMR and diffusion MRI to pinpoint the origin of the somewhat unexpected analogy between the two fields, and provide an overview of current diffusion MRI acquisition protocols and data analysis methods to quantify the composition of heterogeneous materials in terms of diffusion tensor distributions with size, shape, and orientation dimensions. While the most advanced methods allow estimation of the complete multidimensional distributions, simpler methods focus on various projections onto lower-dimensional spaces as well as determination of means and variances rather than actual distributions. Even the less advanced methods provide simple and intuitive scalar parameters that are directly related to microstructural features that can be observed in optical microscopy images, e.g. average cell eccentricity, variance of cell density, and orientational order - properties that are inextricably entangled in conventional diffusion MRI. Key to disentangling all these microstructural features is MRI signal acquisition combining isotropic and directional dimensions, just as in the field of multidimensional solid-state NMR from which most of the ideas for the new methods are derived.

  1. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kauczor, Hans-Ulrich (ed.) [University Clinic Heidelberg (Germany). Diagnostic and Interventional Radiology

    2009-07-01

    For a long time, only chest X-ray and CT were used to image lung structure, while nuclear medicine was employed to assess lung function. During the past decade significant developments have been achieved in the field of magnetic resonance imaging (MRI), enabling MRI to enter the clinical arena of chest imaging. Standard protocols can now be implemented on up-to-date scanners, allowing MRI to be used as a first-line imaging modality for various lung diseases, including cystic fibrosis, pulmonary hypertension and even lung cancer. The diagnostic benefits stem from the ability of MRI to visualize changes in lung structure while simultaneously imaging different aspects of lung function, such as perfusion, respiratory motion, ventilation and gas exchange. On this basis, novel quantitative surrogates for lung function can be obtained. This book provides a comprehensive overview of how to use MRI for imaging of lung disease. Special emphasis is placed on benign diseases requiring regular monitoring, given that it is patients with these diseases who derive the greatest benefit from the avoidance of ionizing radiation. (orig.)

  2. MRI in Japanese encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Misra, U.K. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Neurology; Kalita, J. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Neurology; Salwani, V. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Gupta, R.K. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology; Gujral, R. [Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India). Dept. of Radiology

    1997-03-01

    We document the MRI features in seven patients with Japanese encephalitis. MRI was carried out on a 1.5 T system within 10-60 days of onset. In all the patients MRI revealed bilateral thalamic lesions, haemorrhagic in five. Signal changes were present in the cerebrum in four patients, the midbrain and cerebellum in three each, the pons in two and the basal ganglia in one. The lesions were haemorrhagic in three of the four patients with lesions in the cortex, two of the three with lesions in the midbrain and cerebellum, but the pontine lesions were haemorrhagic in both patients. Spinal cord involvement was seen in one of the three patients who underwent MRI. In two patients MRI was repeated 3 years after the onset, showing marked reduction in abnormal signal; and all the lesions gave low signal on both T1- and T2-weighted images. Bilateral thalamic involvement, especially haemorrhagic, may be considered characteristic of Japanese encephalitis, especially in endemic areas. (orig.)

  3. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization.

    Science.gov (United States)

    Senturk, Serif; Shirole, Nitin H; Nowak, Dawid G; Corbo, Vincenzo; Pal, Debjani; Vaughan, Alexander; Tuveson, David A; Trotman, Lloyd C; Kinney, Justin B; Sordella, Raffaella

    2017-02-22

    The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter. In particular, when co-expressed with inducible Cre-ER(T2), our system enables parallel, independent manipulation of alleles targeted by Cas9 and traditional recombinase with single-cell specificity. We anticipate this platform will be used for the systematic characterization and identification of essential genes, as well as the investigation of the interactions between functional genes.

  4. CAS – A Journey Has Begun in Aotearoa New Zealand

    Directory of Open Access Journals (Sweden)

    Derek Smith

    2008-08-01

    Full Text Available This paper explores a journey through hand-held technology changes in mathematics teaching and learning and raises questions we as mathematics educators should be considering in the shorter and longer term. New Zealand is embarking on a Computer Algebraic Systems (CAS Pilot Programme in secondary school mathematics. The Ministry of Education and the New Zealand Qualifications Authority have selected secondary schools to be part of a pilot programme in the use of CAS technology in mathematics classes. The aim of the pilot programme is to improve teaching and learning of mathematics through the use of this technology. Six schools in 2005 used CAS technology with Year 9 (13-14 year olds students and, an additional 16 schools joined the programme in 2006. The pilot is planned to continue with an increasing number of schools in subsequent years. By the time students in the pilot schools reach Years 11, 12 and 13, alternative external assessments using the CAS technology will be available. Professional development support and assistance in obtaining and using the technology will be provided to the pilot schools. The project's emphasis in 2005 was on the Geometry and Algebra strands; the Statistics strand was added in 2006. By 2010 the first cohort of project programme students will have been through their secondary mathematics education via a CAS environment. New Zealand teachers have only a finite time to get into CAS technology and integrate it into their teaching practice. This paper discusses a research project based on a mathematics department professional development that is linked to the pilot.

  5. Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation.

    Science.gov (United States)

    Ho, Leon C; Sigal, Ian A; Jan, Ning-Jiun; Yang, Xiaoling; van der Merwe, Yolandi; Yu, Yu; Chau, Ying; Leung, Christopher K; Conner, Ian P; Jin, Tao; Wu, Ed X; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C

    2016-08-26

    The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0-40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

  6. Targeted genome modifications in soybean with CRISPR/Cas9

    OpenAIRE

    Jacobs, Thomas; LaFayette, Peter R.; Schmitz, Robert J.; Parrott, Wayne A.

    2015-01-01

    Background The ability to selectively alter genomic DNA sequences in vivo is a powerful tool for basic and applied research. The CRISPR/Cas9 system precisely mutates DNA sequences in a number of organisms. Here, the CRISPR/Cas9 system is shown to be effective in soybean by knocking-out a green fluorescent protein (GFP) transgene and modifying nine endogenous loci. Results Targeted DNA mutations were detected in 95% of 88 hairy-root transgenic events analyzed. Bi-allelic mutations were detecte...

  7. Applications of CRISPR-Cas9 mediated genome engineering

    Institute of Scientific and Technical Information of China (English)

    Xiao Yang

    2015-01-01

    Targeted mutagenesis based on homologous recombination has been a powerful tool for understanding the mechanisms underlying development, normal physiology, and disease. A recent breakthrough in genome engineering technology based on the class of RNA-guided endonucleases, such as clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9, is further revolutionizing biology and medical studies. The simplicity of the CRISPR-Cas9 system has enabled its widespread applications in generating germline animal models, somatic genome engineering, and functional genomic screening and in treating genetic and infectious diseases. This technology will likely be used in all fields of biomedicine, ranging from basic research to human gene therapy.

  8. Expanding the Biologist's Toolkit with CRISPR-Cas9.

    Science.gov (United States)

    Sternberg, Samuel H; Doudna, Jennifer A

    2015-05-21

    Few discoveries transform a discipline overnight, but biologists today can manipulate cells in ways never possible before, thanks to a peculiar form of prokaryotic adaptive immunity mediated by clustered regularly interspaced short palindromic repeats (CRISPR). From elegant studies that deciphered how these immune systems function in bacteria, researchers quickly uncovered the technological potential of Cas9, an RNA-guided DNA cleaving enzyme, for genome engineering. Here we highlight the recent explosion in visionary applications of CRISPR-Cas9 that promises to usher in a new era of biological understanding and control.

  9. Applications of CRISPR-Cas systems in neuroscience.

    Science.gov (United States)

    Heidenreich, Matthias; Zhang, Feng

    2016-01-01

    Genome-editing tools, and in particular those based on CRISPR-Cas (clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein) systems, are accelerating the pace of biological research and enabling targeted genetic interrogation in almost any organism and cell type. These tools have opened the door to the development of new model systems for studying the complexity of the nervous system, including animal models and stem cell-derived in vitro models. Precise and efficient gene editing using CRISPR-Cas systems has the potential to advance both basic and translational neuroscience research.

  10. Applications of CRISPR-Cas9 mediated genome engineering.

    Science.gov (United States)

    Yang, Xiao

    2015-01-01

    Targeted mutagenesis based on homologous recombination has been a powerful tool for understanding the mechanisms underlying development, normal physiology, and disease. A recent breakthrough in genome engineering technology based on the class of RNA-guided endonucleases, such as clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9, is further revolutionizing biology and medical studies. The simplicity of the CRISPR-Cas9 system has enabled its widespread applications in generating germline animal models, somatic genome engineering, and functional genomic screening and in treating genetic and infectious diseases. This technology will likely be used in all fields of biomedicine, ranging from basic research to human gene therapy.

  11. MRI of oriental cholangiohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Wani, N.A., E-mail: ahmad77chinar@gmail.co [Department of Radiodiagnosis and Imaging, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar (India); Robbani, I.; Kosar, T. [Department of Radiodiagnosis and Imaging, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar (India)

    2011-02-15

    Oriental cholangiohepatitis (OCH) also called recurrent pyogenic cholangitis is characterized by intrahepatic duct calculi, strictures, and recurrent infections. In turn cholangitis can result in multiple hepatic abscesses, further biliary strictures, and in severe cases, progressive hepatic parenchymal destruction, cirrhosis, and portal hypertension. Magnetic resonance cholangiopancreatography (MRCP) and conventional T1-weighted (T1 W) and T2-weighted (T2 W) magnetic resonance imaging (MRI) findings have been described in patients with OCH. MRCP findings include duct dilation, strictures, and calculi. MRCP can help to localize the diseased ducts and determine the severity of involvement. T1 and T2 W sequences reveal the parenchymal changes of atrophy, abscess formation, and portal hypertension in addition to calculi. Post-treatment changes are also well depicted using MRI. Comprehensive, non-invasive assessment is achieved by using conventional MRI and MRCP in OCH providing a roadmap for endoscopic or surgical management.

  12. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Science.gov (United States)

    Ó Conchúir, Shane; Barlow, Kyle A; Pache, Roland A; Ollikainen, Noah; Kundert, Kale; O'Meara, Matthew J; Smith, Colin A; Kortemme, Tanja

    2015-01-01

    The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks) to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  13. Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles.

    Science.gov (United States)

    Blunden, Bianca M; Lu, Hongxu; Stenzel, Martina H

    2013-12-09

    Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

  14. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  15. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Coquel

    2013-04-01

    Full Text Available Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian. Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on

  16. D3, the new diffractometer for the macromolecular crystallography beamlines of the Swiss Light Source

    Energy Technology Data Exchange (ETDEWEB)

    Fuchs, Martin R., E-mail: mfuchs@bnl.gov [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Brookhaven National Laboratory, Mail Stop 745, Upton, NY 11973 (United States); Pradervand, Claude; Thominet, Vincent; Schneider, Roman; Panepucci, Ezequiel; Grunder, Marcel; Gabadinho, Jose; Dworkowski, Florian S. N.; Tomizaki, Takashi; Schneider, Jörg; Mayer, Aline; Curtin, Adrian; Olieric, Vincent; Frommherz, Uli; Kotrle, Goran; Welte, Jörg; Wang, Xinyu; Maag, Stephan [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Schulze-Briese, Clemens [DECTRIS Ltd, Neuenhoferstrasse 107, 5400 Baden (Switzerland); Wang, Meitian [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland)

    2014-02-04

    A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. Building upon and critically extending previous developments realised for the high-resolution endstations of the two undulator beamlines X06SA and X10SA, as well as the super-bend dipole beamline X06DA, the new diffractometer was designed to the following core design goals. (i) Redesign of the goniometer to a sub-micrometer peak-to-peak cylinder of confusion for the horizontal single axis. Crystal sizes down to at least 5 µm and advanced sample-rastering and scanning modes are supported. In addition, it can accommodate the new multi-axis goniometer PRIGo (Parallel Robotics Inspired Goniometer). (ii) A rapid-change beam-shaping element system with aperture sizes down to a minimum of 10 µm for microcrystallography measurements. (iii) Integration of the on-axis microspectrophotometer MS3 for microscopic sample imaging with 1 µm image resolution. Its multi-mode optical spectroscopy module is always online and supports in situ UV/Vis absorption, fluorescence and Raman spectroscopy. (iv) High stability of the sample environment by a mineral cast support construction and by close containment of the cryo-stream. Further features are the support for in situ crystallization plate screening and a minimal achievable detector distance of 120 mm for the Pilatus 6M, 2M and the macromolecular crystallography group’s planned future area detector Eiger 16M.

  17. Optimized beamline design for macromolecular crystallography at the Cornell High Energy Synchrotron Source (CHESS) (abstract)

    Science.gov (United States)

    Schildkamp, Wilfried; Bilderback, Donald; Moffat, Keith

    1989-07-01

    The A1 station on the CHESS wiggler beamline has been the workhorse for most macromolecular crystallographic experiments. This station is equipped with a fixed energy focusing germanium (111) monochromator and a focusing total reflection mirror. Our macromolecular crystallographers made full use of the high flux of more than 1012 photons/s/mm2 and the stable beam conditions, both in position and energy resolution. As a result, the A1 station was heavily oversubscribed. CHESS is presently expanding its capabilities and a new diffraction station for macromolecular crystallography is under construction. This beamline will be powered by a 24-pole hybrid permanent magnet wiggler with a critical energy of 25 keV. A focusing monochromator, which handles a specific heat load of 10 W/mm2, will have a range of tunability which covers all relevant absorption edges from 7 to 15 keV using a Ge(111) crystal. The energy resolution and the focusing properties remain constant within a factor of 2 over the entire tunability range. We expect a brilliance of about 1013 photons/s/mm2/mrad2/0.1% bandpass. The diffraction station will be equipped with an oscillation camera which can be used with x-ray film of 5×5 or 8×10 in. size or alternatively with Kodak storage phosphors. A wide variety of clamp-on accessories, like crystal coolers, fast shutters, helium pathways, polarimeter, etc. are available. The station will contain a beampipe system, which can also be used for small angle scattering experiments with sample-to-detector distances of up to 3000 mm. The entire diffraction station, its control area, a biological preparation area, and a darkroom are to be embedded in a biological safety containment of the level BL3. This will allow diffraction studies of virulent strains of viruses and other biohazards, which could not previously be studied at synchrotron radiation sources before without causing major disruption to the normal laboratory procedure.

  18. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Science.gov (United States)

    Coquel, Anne-Sophie; Jacob, Jean-Pascal; Primet, Mael; Demarez, Alice; Dimiccoli, Mariella; Julou, Thomas; Moisan, Lionel; Lindner, Ariel B; Berry, Hugues

    2013-04-01

    Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular

  19. The "macromolecular tourist": universal temperature dependence of thermal diffusion in aqueous colloidal suspensions.

    Science.gov (United States)

    Iacopini, S; Rusconi, R; Piazza, R

    2006-01-01

    By performing measurements on a large class of macromolecular and colloidal systems, we show that thermophoresis (particle drift induced by thermal gradients) in aqueous solvents displays a distinctive universal dependence on temperature. For systems of particles interacting via temperature-independent forces, this behavior is strictly related to the solvent thermal expansivity, while an additional, T-independent term is needed to account for the behavior of "thermophilic" (migrating to the warmth) particles. The former relation between thermophoresis and thermal expansion may be exploited to envisage other fruitful studies of colloidal diffusion in inhomogeneous fluids.

  20. Simulation of macromolecular liquids with the adaptive resolution molecular dynamics technique

    Science.gov (United States)

    Peters, J. H.; Klein, R.; Delle Site, L.

    2016-08-01

    We extend the application of the adaptive resolution technique (AdResS) to liquid systems composed of alkane chains of different lengths. The aim of the study is to develop and test the modifications of AdResS required in order to handle the change of representation of large molecules. The robustness of the approach is shown by calculating several relevant structural properties and comparing them with the results of full atomistic simulations. The extended scheme represents a robust prototype for the simulation of macromolecular systems of interest in several fields, from material science to biophysics.

  1. INFLUENCE OF THE SOLVENT SWELLING ON MACROMOLECULAR CHOLESTERIC LIQUID CRYSTALLINE STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    Jia Zeng; Yong Huang

    1999-01-01

    Ethyl-cyanoethyl cellulose [(E-CE)C]/cross-linked polyacrylic acid [PAA] molecular composites with cholesteric order were prepared. It was found that the macromolecular cholesteric structure was changed with the swelling of PAA in the composites. The selective reflection of the cholesteric phase shifted to the longer wavelength and the X-ray diffraction angle shifted to the high angle direction during swelling, which suggested that the cholesteric pitch and the number of the layers of ordered (E-CE)C chains in the cholesteric phase were increased.

  2. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution...

  3. Chirality as a physical aspect of structure formation in biological macromolecular systems

    Science.gov (United States)

    Malyshko, E. V.; Tverdislov, V. A.

    2016-08-01

    A novel regularity of hierarchical structures is found in the formation of chiral biological macromolecular systems. The formation of structures with alternating chirality (helical structures) serves as an instrument of stratification. The ability of a carbon atom to form chiral compounds is an important factor that determined the carbon basis of living systems on the Earth as well as their development through a series of chiral bifurcations. In the course of biological evolution, the helical structures became basic elements of the molecular machines in the cell. The discreteness of structural levels allowed the mechanical degrees of freedom formation in the molecular machines in the cell.

  4. MRI of active otosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Ziyeh, S. [Section of Neuroradiology, Universitaetsklinik Freiburg, Breisacherstrasse 64, D-79106 Freiburg (Germany); Berlis, A. [Section of Neuroradiology, Universitaetsklinik Freiburg, Breisacherstrasse 64, D-79106 Freiburg (Germany); Ross, U.H. [Department of Otolaryngology, Universitaetsklinik, Freiburg (Germany); Reinhardt, M.J. [Department of Nuclear Medicine, Universitaetsklinik, Freiburg (Germany); Schumacher, M. [Section of Neuroradiology, Universitaetsklinik Freiburg, Breisacherstrasse 64, D-79106 Freiburg (Germany)

    1997-06-01

    Our aim was to determine whether MRI reliably shows pathology in patients with active otosclerosis (otospongiosis). We studied five patients with clinical and audiometric signs of this disorder and positive findings on high-resolution CT and tympanocochlear scintigraphy. Contrast enhancement of otospongiotic lesions was found in all affected ears, and could be topographically related to demineralised otospongiotic foci on CT. In lesions in the lateral wall of the labyrinth MRI sometimes showed the pathology better than CT, where partial-volume effects could be troublesome. (orig.). With 3 figs., 1 tab.

  5. Introduction to Interventional MRI

    Institute of Scientific and Technical Information of China (English)

    Jarmo Ruohonen; William G.Bradley; Jr.MD

    2002-01-01

    An increasing number of interventional procedures are done under imaging guidance. These include biopsies, drainages and injections. Likewise, imaging guidance and monitoring have enabled the use of sophisticated techniques for minimally invasive therapy of tumors. Since MRI provides the best tissue contrast and lesion sensitivity,the use of MR-guided procedures (MRGP) is quickly gaining momentum. Special hardware and software solutions have been developed that allow more efficient interventional use of the MR scanner.This introduction summarizes the basic concepts of interventional MRI and outlines some of the applications of today and tomorrow.

  6. MRI of osteonecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Saini, A. [Department of Radiology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex (United Kingdom); Saifuddin, A. [Department of Radiology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex (United Kingdom)]. E-mail: asaifuddin@aol.com

    2004-12-01

    Osteonecrosis is a relatively common condition, which may be idiopathic or secondary to a variety of clinical situations. It may involve the subarticular region of a joint, when it is commonly referred to as ischaemic necrosis, or the metaphyseal regions of long bones, when it is referred to as bone infarction. In both situations, early lesions may be radiographically occult. However, magnetic resonance imaging (MRI) is very sensitive in identifying and characterizing osteonecrosis. This review illustrates the varied MRI features of osteonecrosis that enable a confident diagnosis to be made. Complications and differential diagnosis are also considered.

  7. Ultrasound- and MRI-Guided Prostate Biopsy

    Science.gov (United States)

    ... Index A-Z Ultrasound- and MRI-Guided Prostate Biopsy Ultrasound- and MRI-guided prostate biopsy uses imaging ... Biopsy? What is Ultrasound- and MRI-guided Prostate Biopsy? Ultrasound- and MRI-guided prostate biopsies are performed ...

  8. Genome Engineering of Drosophila with the CRISPR RNA-Guided Cas9 Nuclease

    OpenAIRE

    Gratz, Scott J.; Cummings, Alexander M.; Nguyen, Jennifer N.; Hamm, Danielle C.; Donohue, Laura K.; Harrison, Melissa M; Wildonger, Jill; O’Connor-Giles, Kate M.

    2013-01-01

    We have adapted a bacterial CRISPR RNA/Cas9 system to precisely engineer the Drosophila genome and report that Cas9-mediated genomic modifications are efficiently transmitted through the germline. This RNA-guided Cas9 system can be rapidly programmed to generate targeted alleles for probing gene function in Drosophila.

  9. On the Integration of Computer Algebra Systems (CAS) by Canadian Mathematicians: Results of a National Survey

    Science.gov (United States)

    Buteau, Chantal; Jarvis, Daniel H.; Lavicza, Zsolt

    2014-01-01

    In this article, we outline the findings of a Canadian survey study (N = 302) that focused on the extent of computer algebra systems (CAS)-based technology use in postsecondary mathematics instruction. Results suggest that a considerable number of Canadian mathematicians use CAS in research and teaching. CAS use in research was found to be the…

  10. The role of Cas8 in type I CRISPR interference.

    Science.gov (United States)

    Cass, Simon D B; Haas, Karina A; Stoll, Britta; Alkhnbashi, Omer S; Sharma, Kundan; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita; Bolt, Edward L

    2015-05-05

    CRISPR (clustered regularly interspaced short palindromic repeat) systems provide bacteria and archaea with adaptive immunity to repel invasive genetic elements. Type I systems use 'cascade' [CRISPR-associated (Cas) complex for antiviral defence] ribonucleoprotein complexes to target invader DNA, by base pairing CRISPR RNA (crRNA) to protospacers. Cascade identifies PAMs (protospacer adjacent motifs) on invader DNA, triggering R-loop formation and subsequent DNA degradation by Cas3. Cas8 is a candidate PAM recognition factor in some cascades. We analysed Cas8 homologues from type IB CRISPR systems in archaea Haloferax volcanii (Hvo) and Methanothermobacter thermautotrophicus (Mth). Cas8 was essential for CRISPR interference in Hvo and purified Mth Cas8 protein responded to PAM sequence when binding to nucleic acids. Cas8 interacted physically with Cas5-Cas7-crRNA complex, stimulating binding to PAM containing substrates. Mutation of conserved Cas8 amino acid residues abolished interference in vivo and altered catalytic activity of Cas8 protein in vitro. This is experimental evidence that Cas8 is important for targeting Cascade to invader DNA. © 2015 Authors.

  11. Quality assurance in functional MRI

    DEFF Research Database (Denmark)

    Liu, Thomas T; Glover, Gary H; Mueller, Bryon A

    2015-01-01

    Over the past 20 years, functional magnetic resonance imaging (fMRI) has ben- efited greatly from improvements in MRI hardware and software. At the same time, fMRI researchers have pushed the technical limits of MRI systems and greatly in- fluenced the development of state-of-the-art systems....... Minimizing image noise and maximizing system stability is critical in fMRI because the blood oxygenation level- dependent (BOLD) signal changes that are used for most fMRI studies represent only a small fraction of the total MR signal. In addition, multiple imaging volumes must be acquired over time to track...... cognitive processes. As a result, MRI scanners must have excellent time-series stability to accurately measure BOLD signal changes over the course of a long time series (typically on the order of 10 min per scan). fMRI studies are particularly demanding on the scanner hardware because they utilize fast...

  12. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... about pregnancy and MRI. If you have claustrophobia (fear of enclosed spaces) or anxiety, you may want ... projectiles within the MRI scanner room and may cause you and/or others nearby harm. These items ...

  13. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... content. Related Articles and Media MR Angiography (MRA) Magnetic Resonance, Functional (fMRI) - Brain Head and Neck Cancer Treatment Brain Tumor Treatment Magnetic Resonance Imaging (MRI) Safety Alzheimer's Disease Head Injury Brain ...

  14. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... conditions. MRI uses a powerful magnetic field, radio frequency pulses and a computer to produce detailed pictures ... with claustrophobia. Newer open MRI units provide very high quality images for many types of exams. Older ...

  15. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... The teddy bear denotes child-specific content. Related Articles and Media MR Angiography (MRA) Magnetic Resonance, Functional (fMRI) - Brain Head and Neck Cancer Treatment Brain Tumor Treatment Magnetic Resonance Imaging (MRI) ...

  16. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... medically necessary. MRI may not always distinguish between cancer tissue and fluid, known as edema . MRI typically ... Brain Tumors Radiation Therapy for Head and Neck Cancer Others : American Stroke Association National Stroke Association top ...

  17. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... medically necessary. MRI may not always distinguish between cancer tissue and fluid, known as edema . MRI typically ... Brain Tumors Radiation Therapy for Head and Neck Cancer Others : American Stroke Association National Stroke Association top ...

  18. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... or headphones during the exam. MRI scanners are air-conditioned and well-lit. Music may be played ... the limitations of MRI of the Head? High-quality images are assured only if you are able ...

  19. Magnetic Resonance Imaging (MRI) -- Head

    Medline Plus

    Full Text Available ... to remain perfectly still and follow breath-holding instructions while the images are being recorded. If you ... Images related to Magnetic Resonance Imaging (MRI) - Head Videos related to Magnetic Resonance Imaging (MRI) - Head Sponsored ...

  20. Magnetic Resonance Imaging (MRI) Safety

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Magnetic Resonance Imaging (MRI) Safety What is MRI and how does ... the area being scanned include: Metallic spinal rod Plates, pins, screws, or metal mesh used to repair ...