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Sample records for die in-vivo messung

  1. Physik gestern und heute Die Messung elektrostatischer Kräfte

    NASA Astrophysics Data System (ADS)

    Heering, Peter

    2002-11-01

    Im Jahre 1785 veröffentlichte der französische Militäringenieur Charles Augustin Coulomb das Kraft-Abstand-Gesetz für elektrische Ladungen. Bereits zuvor hatte Henry Cavendish auf andere Art und Weise diese Beziehung nachgewiesen, aber nicht publiziert. Entsprechende Experimente wurden auch noch in jüngerer Zeit ausgeführt, da sie eine obere Abschätzung für die Ruhemasse des Photons erlauben.

  2. Messung und Analyse

    NASA Astrophysics Data System (ADS)

    Bathelt, Hartmut; Scheinhardt, Michael; Sell, Hendrik; Sottek, Roland; Guidati, Sandro; Helfer, Martin

    Für die Beurteilung von Akustik und Fahrkomfort eines Fahrzeugs gilt in der Fahrzeugentwicklung immer noch der alte Grundsatz: "Der Kunde fährt nicht am Prüfstand, sondern auf der Straße“. Daher werden Gesamtbeurteilungen des Entwicklungsstandes und Konkurrenzvergleiche (Benchmarking) nach wie vor auf der Straße durchgeführt, meist auf ausgewählten Fahrbahnen am Prüfgelände oder im Rahmen der regelmäßigen Winter- und Sommererprobungen unter extremen Witterungsverhältnissen.

  3. SPHERICAL DIE

    DOEpatents

    Livingston, J.P.

    1959-01-27

    A die is presented for pressing powdered materials into a hemispherical shape of uniforin density and wall thickness comprising a fcmale and male die element held in a stationary spaced relation with the space being equivalent to the wall thickness and defining the hemispherical shape, a pressing ring linearly moveable along the male die element, an inlet to fill the space with powdered materials, a guiding system for moving the pressing ring along the male die element so as to press the powdered material and a heating system for heating the male element so that the powdered material is heated while being pressed.

  4. Physik gestern und heute Suprafluidität - Von den Schwierigkeiten einer Messung

    NASA Astrophysics Data System (ADS)

    Sichau, Christian

    2003-03-01

    Der Vater der Tieftemperaturphysik, Heike Kammerlingh Onnes, benötigte zu Beginn des 20. Jahrhunderts für die Verflüssigung von wenigen Litern Heliums noch mehrere Jahre, eine riesige Apparatur und viel Geld. Heute gelingt dies routinemäßig. Die Untersuchung der Materie bei tiefen Temperaturen, insbesondere zur Suprafluidität, bietet viele Überraschungen.

  5. Sputtered protective coatings for die casting dies

    NASA Technical Reports Server (NTRS)

    Mirtich, M. J.; Nieh, C. Y.; Wallace, J. F.

    1981-01-01

    This investigation determined whether selected ion beam sputtered coatings on H-13 die steel would have the potential of improving the thermal fatigue behavior of the steel used as a die in aluminum die casting. The coatings were selected to test candidate insulators and metals capable of providing protection of the die surface. The studies indicate that 1 micrometer thick W and Pt coatings reduced the thermal fatigue more than any other coating tested and are candidates to be used on a die surface to increase die life.

  6. Wege in die Zukunft

    NASA Astrophysics Data System (ADS)

    Kauermann, Göran; Mosler, Karl

    Die Zukunft stellt große Herausforderungen an die Arbeit der Deutschen Statistischen Gesellschaft. Sie betreffen die gestiegenen Anforderungen der Nutzer von Statistik, die Kommunikationsmöglichkeiten des Internets sowie die Dynamik der statistischen Wissenschaften und ihrer Anwendungsgebiete. Das Kapitel 5 beschreibt, wie sich die Gesellschaft diesen Herausforderungen stellt und welche Ziele sie sich in der wissenschaftlichen Zusammenarbeit und im Kampf gegen das Innumeratentum gesetzt hat.

  7. Periodisches Hitzdrahtverfahren zur Messung von Wärme- und Temperaturleitfähigkeit von geringen Stoffmengen

    NASA Astrophysics Data System (ADS)

    Griesinger, A.; Spindler, K.; Hahne, E.

    Zusammenfassung Es wird ein Meßverfahren zur gleichzeitigen Bestimmung der Wärme- und der Temperaturleitfähigkeit von geringen Stoffmengen beschrieben. Neben Messungen an hochviskosen Flüssigkeiten eignet sich das Verfahren besonders für Messungen an Pulver-Schüttungen. Das Meßverfahren basiert auf dem transienten Hitzdraht-Verfahren. In einem dünnen Platindraht fließt ein sinusförmiger Wechselstrom, der den Draht periodisch erwärmt. Es entstehen thermische Wellen, die in die umgebende Probe eindringen. Die Amplitude und die Phasenlage der thermischen Wellen in der Probe hängen von der Temperaturleitfähigkeit a und der Wärmeleitfähigkeit λ der Probe ab. Die Temperaturschwingung in der Probe wird mit Hilfe des Platindrahtes gemessen, der gleichzeitig als Widerstandsthermometer eingesetzt wird. Meßwerte von Wasser und Glycerin zeigen eine gute Übereinstimmung mit Literaturwerten. Das Meßverfahren zeichnet sich dadurch aus, daß zur Bestimmung der Wärme- und Temperaturleitfähigkeit nur 13 ml einer Probe benötigt werden. Es werden Meßwerte einer Zeolith-Schüttung unter Wasserstoffbeladung dargestellt. A measuring procedure for the simultaneous determination of the thermal conductivity and thermal diffusivity of small quantities is described. The procedure is suited for high-viscous fluids and for powdery material. The measuring principle is based on the transient hot-wire method. A sinusoidal alternating current flows through a thin platinum wire and heats up the wire periodically. This results in thermal waves, which penetrate into the surrounding sample. The amplitude and the phase shift of the thermal waves depend on the thermal diffusivity ``a'' and the thermal conductivity ``λ'' of the sample. The temperature oscillation in the sample is measured by means of the platinum wire, which is simultaneously applied as a resistance thermometer. The values measured for water and glycerine correspond well to those given in literature. Results of the

  8. EDITORIAL: Nanotechnology in vivo Nanotechnology in vivo

    NASA Astrophysics Data System (ADS)

    Demming, Anna

    2010-04-01

    -imaging labels [4]. A surface hydroxyl group renders silicon quantum dots soluble in water and the photoluminescence can be made stable with oxygen-passivation. In addition, researchers in Japan have demonstrated how the initially modest yield in the preparation of silicon quantum dots can be improved to tens of milligrams per batch, thus further promoting their application in bio-imaging [5]. In the search for non-toxic quantum dots, researchers at the Amrita Centre for Nanoscience in India have prepared heavy metal-free quantum dot bio-probes based on single phase ZnS [6]. The quantum dots are selectively doped with metals, transition metals and halides to provide tuneable luminescence properties, and they are surface conjugated with folic acid for cancer targeting. The quantum dots were demonstrated to be water-soluble, non-toxic in normal and cancer cell lines, and have bright, tuneable luminescence. So far most of the quantum dots developed for bio-imaging have had excitation and emission wavelengths in the visible spectrum, which is highly absorbed by tissue. This limits imaging with these quantum dots to superficial tissues. This week, researchers in China and the US reported work developing functionalized dots for in vivo tumour vasculature in the infrared part of the spectrum [7]. In addition the quantum dots were functionalised with glycine-aspartic acid (RGD) peptides, which target the vasculature of almost all types of growing tumours, unlike antibody- or aptamer-mediated targeting strategies that are specific to a particular cancer type. In this issue, researchers in China and the US demonstrate a novel type of contrast agent for ultrasonic tumour imaging [8]. Contrast-enhanced ultrasonic tumour imaging extends the diagnostic and imaging capabilities of traditional techniques. The use of nanoparticles as ultrasound contrast agents exploits the presence of open pores in the range of 380 to 780 nm in tumour blood vessels, which enhance the permeability and retention

  9. Displaced capillary dies

    DOEpatents

    Kalejs, Juris P.; Chalmers, Bruce; Surek, Thomas

    1984-01-01

    An asymmetrical shaped capillary die made exclusively of graphite is used to grow silicon ribbon which is capable of being made into solar cells that are more efficient than cells produced from ribbon made using a symmetrically shaped die.

  10. Displaced capillary dies

    DOEpatents

    Kalejs, Juris P.; Chalmers, Bruce; Surek, Thomas

    1982-01-01

    An asymmetrical shaped capillary die made exclusively of graphite is used to grow silicon ribbon which is capable of being made into solar cells that are more efficient than cells produced from ribbon made using a symmetrically shaped die.

  11. The Ambiguous Dying Syndrome

    ERIC Educational Resources Information Center

    Bern-Klug, Mercedes

    2004-01-01

    More than one-half of the 2.4 million deaths that will occur in the United States in 2004 will be immediately preceded by a time in which the likelihood of dying can best be described as "ambiguous." Many people die without ever being considered "dying" or "at the end of life." These people may miss out on the…

  12. In vivo dosimetry for IMRT

    SciTech Connect

    Vial, Philip

    2011-05-05

    In vivo dosimetry has a well established role in the quality assurance of 2D radiotherapy and 3D conformal radiotherapy. The role of in vivo dosimetry for IMRT is not as well established. IMRT introduces a range of technical issues that complicate in vivo dosimetry. The first decade or so of IMRT implementation has largely relied upon pre-treatment phantom based dose verification. During that time, several new devices and techniques for in vivo dosimetry have emerged with the promise of providing the ultimate form of IMRT dose verification. Solid state dosimeters continue to dominate the field of in vivo dosimetry in the IMRT era. In this report we review the literature on in vivo dosimetry for IMRT, with an emphasis on clinical evidence for different detector types. We describe the pros and cons of different detectors and techniques in the IMRT setting and the roles that they are likely to play in the future.

  13. HIGH PRESSURE DIES

    DOEpatents

    Wilson, W.B.

    1960-05-31

    A press was invented for subjecting specimens of bismuth, urania, yttria, or thoria to high pressures and temperatures. The press comprises die parts enclosing a space in which is placed an electric heater thermally insulated from the die parts so as not to damage them by heat. The die parts comprise two opposed inner frustoconical parts and an outer part having a double frustoconical recess receiving the inner parts. The die space decreases in size as the inner die parts move toward one another against the outer part and the inner parts, though very hard, do not fracture because of the mode of support provided by the outer part.

  14. Tacrine: In vivo veritas.

    PubMed

    Jarrott, Bevyn

    2017-02-01

    Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.

  15. In vivo microscopy✩

    PubMed Central

    Peti-Peterdi, János

    2016-01-01

    This article summarizes the past, present, and future promise of multiphoton excitation fluorescence microscopy for intravital kidney imaging. During the past 15 years, several high-power visual research approaches have been developed using multiphoton imaging to study the normal functions of the healthy, intact, living kidney, and the various molecular and cellular mechanisms of the development of kidney diseases. In this review, the main focus will be on intravital multiphoton imaging of the glomerulus, the structure and function of the glomerular filtration barrier, especially the podocyte. Examples will be given for the combination of two powerful research tools, in vivo multiphoton imaging and mouse genetics using commercially available whole animal models for the detailed characterization of glomerular cell types, their function and fate, and for the better understanding of the molecular mechanisms of glomerular pathologies. One of the new modalities of multiphoton imaging, serial imaging of the same glomerulus in the same animal over several days will be emphasized for its potential for further advancing the field of nephrology research. PMID:26968479

  16. In vivo microscopy.

    PubMed

    Peti-Peterdi, János

    2016-04-01

    This article summarizes the past, present, and future promise of multiphoton excitation fluorescence microscopy for intravital kidney imaging. During the past 15years, several high-power visual research approaches have been developed using multiphoton imaging to study the normal functions of the healthy, intact, living kidney, and the various molecular and cellular mechanisms of the development of kidney diseases. In this review, the main focus will be on intravital multiphoton imaging of the glomerulus, the structure and function of the glomerular filtration barrier, especially the podocyte. Examples will be given for the combination of two powerful research tools, in vivo multiphoton imaging and mouse genetics using commercially available whole animal models for the detailed characterization of glomerular cell types, their function and fate, and for the better understanding of the molecular mechanisms of glomerular pathologies. One of the new modalities of multiphoton imaging, serial imaging of the same glomerulus in the same animal over several days will be emphasized for its potential for further advancing the field of nephrology research.

  17. Die singulation method

    DOEpatents

    Swiler, Thomas P.; Garcia, Ernest J.; Francis, Kathryn M.

    2013-06-11

    A method is disclosed for singulating die from a semiconductor substrate (e.g. a semiconductor-on-insulator substrate or a bulk silicon substrate) containing an oxide layer (e.g. silicon dioxide or a silicate glass) and one or more semiconductor layers (e.g. monocrystalline or polycrystalline silicon) located above the oxide layer. The method etches trenches through the substrate and through each semiconductor layer about the die being singulated, with the trenches being offset from each other around at least a part of the die so that the oxide layer between the trenches holds the substrate and die together. The trenches can be anisotropically etched using a Deep Reactive Ion Etching (DRIE) process. After the trenches are etched, the oxide layer between the trenches can be etched away with an HF etchant to singulate the die. A release fixture can be located near one side of the substrate to receive the singulated die.

  18. Die singulation method

    DOEpatents

    Swiler, Thomas P [Albuquerque, NM; Garcia, Ernest J [Albuquerque, NM; Francis, Kathryn M [Rio Rancho, NM

    2014-01-07

    A method is disclosed for singulating die from a semiconductor substrate (e.g. a semiconductor-on-insulator substrate or a bulk silicon substrate) containing an oxide layer (e.g. silicon dioxide or a silicate glass) and one or more semiconductor layers (e.g. monocrystalline or polycrystalline silicon) located above the oxide layer. The method etches trenches through the substrate and through each semiconductor layer about the die being singulated, with the trenches being offset from each other around at least a part of the die so that the oxide layer between the trenches holds the substrate and die together. The trenches can be anisotropically etched using a Deep Reactive Ion Etching (DRIE) process. After the trenches are etched, the oxide layer between the trenches can be etched away with a HF etchant to singulate the die. A release fixture can be located near one side of the substrate to receive the singulated die.

  19. Sputtered protective coatings for die casting dies

    NASA Technical Reports Server (NTRS)

    Mirtich, M. J.; Nieh, C.-Y.; Wallace, J. F.

    1981-01-01

    Three experimental research designs investigating candidate materials and processes involved in protective die surface coating procedures by sputter deposition, using ion beam technologies, are discussed. Various pre-test results show that none of the coatings remained completely intact for 15,000 test cycles. The longest lifetime was observed for coatings such as tungsten, platinum, and molybdenum which reduced thermal fatigue, but exhibited oxidation and suppressed crack initiation only as long as the coating did not fracture. Final test results confirmed earlier findings and coatings with Pt and W proved to be the candidate materials to be used on a die surface to increase die life. In the W-coated specimens, which remained intact on the surface after thermal fatigue testing, no oxidation was found under the coating, although a few cracks formed on the surface where the coating broke down. Further research is planned.

  20. Extrusion die and method

    DOEpatents

    Lipp, G. Daniel

    1994-04-26

    A method and die apparatus for manufacturing a honeycomb body of rhombic cell cross-section by extrusion through an extrusion die of triangular cell discharge slot configuration, the die incorporating feedholes at selected slot intersections only, such that slot segments communicating directly with the feedholes discharge web material and slot segments not so connected do not discharge web material, whereby a rhombic cell cross-section in the extruded body is provided.

  1. The Angry Dying Patient.

    PubMed

    Houston, Robert E.

    1999-02-01

    Over 25 years ago, Kubler-Ross identified anger as a predictable part of the dying process. When the dying patient becomes angry in the clinical setting, all types of communication become strained. Physicians can help the angry dying patient through this difficult time by using 10 rules of engagement. When physicians engage and empathize with these patients, they improve the patient's response to pain and they reduce patient suffering. When physicians educate patients on their normal responses to dying and enlist them in the process of family reconciliation, they can impact the end-of-life experience in a positive way.

  2. Die Soldering in Aluminium Die Casting

    SciTech Connect

    Han, Q.; Kenik, E.A.; Viswanathan, S.

    2000-03-15

    Two types of tests, dipping tests and dip-coating tests were carried out on small steel cylinders using pure aluminum and 380 alloy to investigate the mechanism of die soldering during aluminum die casting. Optical and scanning electron microscopy were used to study the morphology and composition of the phases formed during soldering. A soldering mechanism is postulated based on experimental observations. A soldering critical temperature is postulated at which iron begins to react with aluminum to form an aluminum-rich liquid phase and solid intermetallic compounds. When the temperature at the die surface is higher than this critical temperature, the aluminum-rich phase is liquid and joins the die with the casting during the subsequent solidification. The paper discusses the mechanism of soldering for the case of pure aluminum and 380 alloy casting in a steel mold, the factors that promote soldering, and the strength of the bond formed when soldering occurs. conditions, an aluminum-rich soldering layer may also form over the intermetallic layer. Although a significant amount of research has been conducted on the nature of these intermetallics, little is known about the conditions under which soldering occurs.

  3. Is Dying Young Worse than Dying Old?

    ERIC Educational Resources Information Center

    Jecker, Nancy S.; Schneiderman, Lawrence J.

    1994-01-01

    Notes that, in contemporary Western society, people feel death of small child is greater injustice than death of older adult and experience correspondingly greater sorrow, anger, regret, or bitterness when very young person dies. Contrasts these attitudes with those of ancient Greece and shows relevance that different attitudes toward death have…

  4. Micromechanical die attachment surcharge

    DOEpatents

    Filter, William F.; Hohimer, John P.

    2002-01-01

    An attachment structure is disclosed for attaching a die to a supporting substrate without the use of adhesives or solder. The attachment structure, which can be formed by micromachining, functions purely mechanically in utilizing a plurality of shaped pillars (e.g. round, square or polygonal and solid, hollow or slotted) that are formed on one of the die or supporting substrate and which can be urged into contact with various types of mating structures including other pillars, a deformable layer or a plurality of receptacles that are formed on the other of the die or supporting substrate, thereby forming a friction bond that holds the die to the supporting substrate. The attachment structure can further include an alignment structure for precise positioning of the die and supporting substrate to facilitate mounting the die to the supporting substrate. The attachment structure has applications for mounting semiconductor die containing a microelectromechanical (MEM) device, a microsensor or an integrated circuit (IC), and can be used to form a multichip module. The attachment structure is particularly useful for mounting die containing released MEM devices since these devices are fragile and can otherwise be damaged or degraded by adhesive or solder mounting.

  5. Extrusion die and method

    DOEpatents

    Lipp, G. Daniel

    1994-05-03

    A method and die apparatus for manufacturing a honeycomb body of triangular cell cross-section and high cell density, the die having a combination of (i) feedholes feeding slot intersections and (ii) feedholes feeding slot segments not supplied from slot intersections, whereby a reduction in feedhole count is achieved while still retaining good extrusion efficiency and extrudate uniformity.

  6. Die Kometenmission Rosetta

    NASA Astrophysics Data System (ADS)

    Krüger, Harald

    2016-11-01

    Die Rosetta-Mission ist ein Meilenstein in der Erforschung der Kometen und ihrer Entstehung. Eine der größten üerraschungen war die unregelmäßge hantelförmige Gestalt des Zielkometen 67P/Tschurjumow-Gerassimenko. Er besteht wahrscheinlich aus zwei Einzelkörpern, die durch ihre Schwerkraft aneinander gehalten werden. Seine Oberfläche ist sehr rau und zeigt eine sehr vielf ältige Morphologie, die auf eine Vielzahl von ablaufenden Prozessen hindeutet. Der Kometenkern ist vermutlich auf Gr ößnskalen von mehr als etwa 10 bis 100 Metern homogen, Inhomogenitäten auf kleineren Skalen k nnten f r seine Aktivä t verantwortlich sein. Diese ist auf kleine Gebiete konzentriert, und auch Oberflächenveränderungen, die sich innerhalb von einigen Tagen bis wenigen Wochen abspielen, sind lokal. Im Kometenmaterial wurde eine Vielzahl an organischen Substanzen gemessen, die zum Teil als Schlüsselmoleküle für die Synthese der Grundbausteine des Lebens gelten, wie wir es kennen.

  7. Death, dying, and domination.

    PubMed

    Spindelman, Marc

    2008-06-01

    This Article critiques conventional liberal arguments for the right to die on liberal grounds. It contends that these arguments do not go far enough to recognize and address private, and in particular structural, forms of domination. It presents an alternative that does, which is thus more respectful of true freedom in the context of death and dying, and also more consistent with liberalism. After discussing obstacles to the achievement of a right to die that encompasses freedom from both public and private domination, the Article closes with a significant reform project within bioethics that might help bring it about.

  8. Monitoring protein stability in vivo.

    PubMed

    Ignatova, Zoya

    2005-08-24

    Reduced protein stability in vivo is a prerequisite to aggregation. While this is merely a nuisance factor in recombinant protein production, it holds a serious impact for man. This review focuses on specific approaches to selectively determine the solubility and/or stability of a target protein within the complex cellular environment using different detection techniques. Noninvasive techniques mapping folding/misfolding events on a fast time scale can be used to unravel the complexity and dynamics of the protein aggregation process and factors altering protein solubility in vivo. The development of approaches to screen for folding and solubility in vivo should facilitate the identification of potential components that improve protein solubility and/or modulate misfolding and aggregation and may provide a therapeutic benefit.

  9. Experimental Cryosurgery Investigations In Vivo

    PubMed Central

    Gage, A.A.; Baust, J.M.; Baust, J.G.

    2009-01-01

    Cryosurgery is the use of freezing temperatures to elicit an ablative response in a targeted tissue. This review provides a global overview of experimentation in vivo which has been the basis of advancement of this widely applied therapeutic option. The cellular and tissue-related events that underlie the mechanisms of destruction, including direct cell injury (cryolysis), vascular stasis, apoptosis and necrosis, are described and are related to the optimal methods of technique of freezing to achieve efficacious therapy. In vivo experiments with major organs, including wound healing, the putative immunological response following thawing, and the use of cryoadjunctive strategies to enhance cancer cell sensitivity to freezing, are described. PMID:19833119

  10. When a Baby Dies.

    ERIC Educational Resources Information Center

    Church, Martha Jo; And Others

    Written especially for grieving mothers whose babies have died, this booklet offers an overview of stages and experiences through which bereaved parents commonly pass. Specifically, the text is intended to give comfort to bereaved parents, offer insight into the grieving process, and provide thoughts on leave-taking ceremonies. The first section…

  11. When Somebody Dies

    MedlinePlus

    ... to have fun with. That absence leaves a big hole in our lives. Maybe you had a pet that died . Remember the first few times you walked into the house after your dog or cat was gone? It was strange not to have ...

  12. Die Kosmologie der Griechen.

    NASA Astrophysics Data System (ADS)

    Mittelstraß, J.

    Contents: 1. Mythische Eier. 2. Thales-Welten. 3. "Alles ist voller Götter". 4. Griechische Astronomie. 5. "Rettung der Phänomene". 6. Aristotelische Kosmololgie. 7. Aristoteles-Welt und Platon-Welt. 8. Noch einmal: die Göttlichkeit der Welt. 9. Griechischer Idealismus.

  13. When Somebody Dies

    MedlinePlus

    ... A A What's in this article? When — and How — Does It Happen? Where Do Dead People Go? What Does Grieving Mean? What About Me? If I'm Going to Die Someday, What Should I Do Now? en español ...

  14. Terahertz pulsed imaging in vivo

    NASA Astrophysics Data System (ADS)

    Pickwell-MacPherson, E.

    2011-03-01

    Terahertz (1012 Hz) pulsed imaging is a totally non-destructive and non-ionising imaging modality and thus potential applications in medicine are being investigated. In this paper we present results using our hand-held terahertz probe that has been designed for in vivo use. In particular, we use the terahertz probe to perform reflection geometry in vivo measurements of human skin. The hand-held terahertz probe gives more flexibility than a typical flat-bed imaging system, but it also results in noisier data and requires existing processing methods to be improved. We describe the requirements and limitations of system geometry, data acquisition rate, image resolution and penetration depth and explain how various factors are dependent on each other. We show how some of the physical limitations can be overcome using novel data processing methods.

  15. In vivo imaging of sulfotransferases

    DOEpatents

    Barrio, Jorge R; Kepe, Vladimir; Small, Gary W; Satyamurthy, Nagichettiar

    2013-02-12

    Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with .sup.18F, .sup.123I, .sup.124I, .sup.125I, or .sup.11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

  16. Aeromonas salmonicida grown in vivo.

    PubMed Central

    Garduño, R A; Thornton, J C; Kay, W W

    1993-01-01

    The virulent fish pathogen Aeromonas salmonicida was rapidly killed in vivo when restricted inside a diffusion chamber implanted intraperitoneally in rainbow trout. After a period of regrowth, the survivors had acquired resistance to host-mediated bacteriolysis, phagocytosis, and oxidative killing, properties which were subsequently lost by growth in vitro. Resistance to bacteriolysis and phagocytosis was associated with a newly acquired capsular layer revealed by acidic polysaccharide staining and electron microscopy. This capsular layer shielded the underlying, regular surface array (S-layer) from immunogold labeling with a primary antibody to the S-layer protein. Resistance to oxidative killing was mediated by a mechanism not associated with the presence of the capsular layer. An attenuated vaccine strain of A. salmonicida grown in vivo failed to express the capsular layer. Consequently, the in vivo-grown cells of this attenuated strain remained as sensitive to bacteriolysis, and as avidly adherent to macrophages, as the in vitro-grown cells. The importance of these new virulence determinants and their relation to the known virulence factors of A. salmonicida are discussed. Images PMID:8359906

  17. Herausforderungen durch die deutsche Wiedervereinigung

    NASA Astrophysics Data System (ADS)

    Stäglin, Reiner

    Die Wiedervereinigung stellte auch die Statistik vor große Aufgaben. Die als Organ der staatlichen Planung staatsnah orientierte Statistik der DDR musste auf das zur Neutralität und wissenschaftlichen Unabhängigkeit verpflichtete System der Bundesrepublik umgestellt werden. Ebenso verlangten die Universitäten eine Neuorientierung. Die Deutsche Statistische Gesellschaft hat sich vor allem dreier Aufgaben mit großem Engagement, aber auch mit Bedachtsamkeit angenommen: Aufnahme und Integration der Statistiker aus den neuen Bundesländern in die Gesellschaft, Begleitung der Neuausrichtung des Faches Statistik an deren Hochschulen und Sicherung sowie Nutzung von Datenbeständen der ehemaligen DDR.

  18. Modeling the Mechanical Performance of Die Casting Dies

    SciTech Connect

    R. Allen Miller

    2004-02-27

    The following report covers work performed at Ohio State on modeling the mechanical performance of dies. The focus of the project was development and particularly verification of finite element techniques used to model and predict displacements and stresses in die casting dies. The work entails a major case study performed with and industrial partner on a production die and laboratory experiments performed at Ohio State.

  19. Die kalte Zunge

    NASA Astrophysics Data System (ADS)

    Bartels, Sören; Müller, Rüdiger

    Gefühlte Temperaturen. Ist ein Null Grad Celsius kalter Metallstab eigentlich kälter als ein Holzstab mit der selben Temperatur? Rein physikalisch gesehen natürlich nicht, aber wenn wir beide Stäbe anfassen, kommt uns der Metallstab deutlich kälter vor. Und wer kennt nicht die Szene aus dem Film Dumm und Dümmer in der Harry mit seiner Zunge am Metallrahmen des Skilifts hängen bleibt.Würde das auch passieren, wenn man an einem eiskalten Stück Holz lecken würde? Wohl kaum, doch woran liegt das eigentlich? Unterschiedliche Materialien haben verschiedene Fähigkeiten, Wärme zu übertragen und zu leiten. So transportiert Metall die von der Zunge ausgehende Wärme sehr schnell weiter und verändert seine Temperatur kaum, während die Zunge abkühlt. Holz hingegen leitet Wärme fast gar nicht und daher wird der Teil, der von der Zunge berührt wird, aufgewärmt.

  20. Heated die facilitates tungsten forming

    NASA Technical Reports Server (NTRS)

    Chattin, J. H.; Haystrick, J. E.; Laughlin, J. C.; Leidy, R. A.

    1966-01-01

    Tungsten forming in a press brake employs a bottom die assembly with a heating manifold between two water-cooled die sections. The manifold has hydrogen-oxygen burners spaced along its length for even heat during forming.

  1. Designing a Die for Hydroforming

    NASA Astrophysics Data System (ADS)

    Vasile, Radu

    2016-12-01

    Designing a die is in every application field an intensive process of bringing together know how from design, testing and every-day use from previous dies with the new application requirements. Contribution deals with a knowledge oriented, modular and feature integrated computer aided design system for die development. This paper describes the concepts behind designing a hydroforming die for sheet metal forming, with easy application-use in small workshops for testing hydroforming capabilities of different materials.

  2. Towards a disposable in vivo miniature implantable fluorescence detector

    NASA Astrophysics Data System (ADS)

    Bellis, Stephen; Jackson, J. Carlton; Mathewson, Alan

    2006-02-01

    In the field of fluorescent microscopy, neuronal activity, diabetes and drug treatment are a few of the wide ranging biomedical applications that can be monitored with the use of dye markers. Historically, in-vivo fluorescent detectors consist of implantable probes coupled by optical fibre to sophisticated bench-top instrumentation. These systems typically use laser light to excite the fluorescent marker dies and using sensors, such as the photo-multiplier tube (PMT) or charge coupled devices (CCD), detect the fluorescent light that is filtered from the total excitation. Such systems are large and expensive. In this paper we highlight the first steps toward a fully implantable in-vivo fluorescence detection system. The aim is to make the detector system small, low cost and disposable. The current prototype is a hybrid platform consisting of a vertical cavity surface emitting laser (VCSEL) to provide the excitation and a filtered solid state Geiger mode avalanche photo-diode (APD) to detect the emitted fluorescence. Fluorescence detection requires measurement of extremely low levels of light so the proposed APD detectors combine the ability to count individual photons with the added advantage of being small in size. At present the exciter and sensor are mounted on a hybrid PCB inside a 3mm diameter glass tube.This is wired to external electronics, which provide quenching, photon counting and a PC interface. In this configuration, the set-up can be used for in-vitro experimentation and in-vivo analysis conducted on animals such as mice.

  3. Improving in vivo calibration phantoms

    SciTech Connect

    Lynch, T.P.; Olsen, P.C.

    1991-10-01

    Anthropomorphic phantoms have been the basis for quantification of radioactive material in the body using in vivo measurements. The types of phantoms used and the degree of anthropomorphic detail vary depending on the counting application, the radioactive material to be measured, phantom availability and cost. Consequently, measurement results for the same types of radioactive material from different facilities are not always comparable. At a February 1990 meeting at the National Institute of Standards and Technology (NIST) the need to develop the gold standards'' or primary reference standards for in vivo phantoms was discussed in detail. The consensus of the attendees at the meeting was that the state of the art in phantoms was adequate as a starting point and that there was no need to start phantom development from scratch. In particular, the torso phantom developed at the Lawrence Livermore National Laboratory (LLNL) and its commercial progeny, the bottle manikin absorption (BOMAB) phantom and the American National Standards Institute (ANSI) Standard N44.3 thyroid phantom, were identified as the starting points for the development of the primary reference standards. Working groups at the meeting subsequently recommended design improvements for the existing phantom designs. The implementation of these recommendations is the subject of this paper.

  4. Dying with dignity.

    PubMed

    Madan, T N

    1992-08-01

    Death is a theme of central importance in all cultures, but the manner in which it is interpreted varies from society to society. Even so, traditional cultures, including Christian, Hindu and Jain religious traditions, exhibited a positive attitude to death and did not look upon it in a dualistic framework of good vs bad, or desirable vs undesirable. Nor was pessimism the dominant mood in their thinking about death itself. A fundamental paradigm shift occurred in the West in the eighteenth century when death was desacralized and transformed into a secular event amenable to human manipulation. From those early beginnings, dying and death have been thoroughly medicalized and brought under the purview of high technology in the twentieth century. Once death is seen as a problem for professional management, the hospital displaces the home, and specialists with different kinds and degrees of expertise take over from the family. Everyday speech and the religious idiom yield place to medical jargon. The subject (an ageing, sick or dying person) becomes the object of this make-believe yet real world. As the object of others' professional control, he or she loses the freedom of self-assessment, expression and choice. Or, he or she may be expected to choose when no longer able to do so. Thus, not only freedom but dignity also is lost, and lawyers join doctors in crisis manipulation and perpetuation. Although the modern medical culture has originated in the West, it has gradually spread to all parts of the world, subjugating other kinds of medical knowledge and other attitudes to dying and death.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. In vivo dosimetry in brachytherapy

    SciTech Connect

    Tanderup, Kari; Beddar, Sam; Andersen, Claus E.; Kertzscher, Gustavo; Cygler, Joanna E.

    2013-07-15

    In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.

  6. Nonionizing photoacoustic cystography in vivo.

    PubMed

    Kim, Chulhong; Jeon, Mansik; Wang, Lihong V

    2011-09-15

    We demonstrate the feasibility of a novel and nonionizing process for bladder imaging in vivo, called photoacoustic cystography (PAC). Using a photoacoustic imaging system, we have successfully imaged a rat bladder filled with clinically used Methylene Blue (MB) dye. An image contrast of ~8 was achieved. Further, spectroscopic PAC confirmed the accumulation of MB in the bladder. Using a laser pulse energy of less than 1 mJ/cm² (1/20 of the ANSI safety limit), a deeply (1.2 cm) positioned bladder in biological tissues was clearly visible in the PA image. Our results suggest that PAC can potentially provide a nonionizing, relatively cheap, and portable tool for bladder mapping. Among our clinical interests, nonionizing PAC with an injection of MB can potentially monitor vesicoureteral reflux in children.

  7. In Vivo EPR For Dosimetry

    PubMed Central

    Swartz, Harold M.; Burke, Greg; Coey, M.; Demidenko, Eugene; Dong, Ruhong; Grinberg, Oleg; Hilton, James; Iwasaki, Akinori; Lesniewski, Piotr; Kmiec, Maciej; Lo, Kai-Ming; Nicolalde, R. Javier; Ruuge, Andres; Sakata, Yasuko; Sucheta, Artur; Walczak, Tadeusz; Williams, Benjamin B.; Mitchell, Chad; Romanyukha, Alex; Schauer, David A.

    2007-01-01

    As a result of terrorism, accident, or war, populations potentially can be exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. In many of the plausible scenarios there is an urgent need to make the determination very soon after the event and while the subject is still present. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently for classifying individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose with an error approximately ± 50 cGy over the range of interest for acute biological effects of radiation, assuming repeated measurements of the tooth in the mouth of the subject. The time required for acquisition, the lower limit, and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. The magnet system that is currently used, while potentially deployable, is somewhat large and heavy, requiring that it be mounted on a small truck or trailer. Several smaller magnets, including an intraoral magnet are under development, which would extend the ease of use of this technique. PMID:18591988

  8. Accurate defect die placement and nuisance defect reduction for reticle die-to-die inspections

    NASA Astrophysics Data System (ADS)

    Wen, Vincent; Huang, L. R.; Lin, C. J.; Tseng, Y. N.; Huang, W. H.; Tuo, Laurent C.; Wylie, Mark; Chen, Ellison; Wang, Elvik; Glasser, Joshua; Kelkar, Amrish; Wu, David

    2015-10-01

    Die-to-die reticle inspections are among the simplest and most sensitive reticle inspections because of the use of an identical-design neighboring-die for the reference image. However, this inspection mode can have two key disadvantages: (1) The location of the defect is indeterminate because it is unclear to the inspector whether the test or reference image is defective; and (2) nuisance and false defects from mask manufacturing noise and tool optical variation can limit the usable sensitivity. The use of a new sequencing approach for a die-to-die inspection can resolve these issues without any additional scan time, without sacrifice in sensitivity requirement, and with a manageable increase in computation load. In this paper we explore another approach for die-to-die inspections using a new method of defect processing and sequencing. Utilizing die-to-die double arbitration during defect detection has been proven through extensive testing to generate accurate placement of the defect in the correct die to ensure efficient defect disposition at the AIMS step. The use of this method maintained the required inspection sensitivity for mask quality as verified with programmed-defectmask qualification and then further validated with production masks comparing the current inspection approach to the new method. Furthermore, this approach can significantly reduce the total number of defects that need to be reviewed by essentially eliminating the nuisance and false defects that can result from a die-to-die inspection. This "double-win" will significantly reduce the effort in classifying a die-to-die inspection result and will lead to improved cycle times.

  9. Where people die.

    PubMed Central

    Katz, B P; Zdeb, M S; Therriault, G D

    1979-01-01

    Death certificates for 1977 filed with the New York State Department of Health were studied to determine where people died. Data were examined by the location and cause of death and by the age, sex, race, and marital status of the decedent. Comparisons were made with a similar study in which U.S. data were used for 1958 events. Approximately 60 percent of all the 1977 deaths in upstate New York occurred in hospitals; only 27 percent occurred outside an institution. The location of death varied by all the factors studied. Within all age categories, males had a higher percentage of hospital deaths. In those age categories in which nursing home deaths comprised a significant proportion of total deaths, females had a higher percentage of such deaths than males. Differences in the location of death according to its cause reflect the nature of the cause of death, for example, whether it was of sudden onset or the result of chronic disease. Most people do not consider in advance where they might die. The idea that age, sex, and marital status, as well as the more obvious cause, all play a part in the location may seem surprising. Yet all these factors were found to be associated withe location of deaths in upstate New York, and there is no reason to believe that this association does not hold true for the entire nation. More research, however, needs to be done based on more years and other geographic artal stutus may be instructive as to the present state of health resources. PMID:515338

  10. Maintaining Low Voiding Solder Die Attach for Power Die While Minimizing Die Tilt

    SciTech Connect

    Hamm, Randy; Peterson, Kenneth A.

    2015-10-01

    This paper addresses work to minimize voiding and die tilt in solder attachment of a large power die, measuring 9.0 mm X 6.5 mm X 0.1 mm (0.354” x 0.256” x 0.004”), to a heat spreader. As demands for larger high power die continue, minimizing voiding and die tilt is of interest for improved die functionality, yield, manufacturability, and reliability. High-power die generate considerable heat, which is important to dissipate effectively through control of voiding under high thermal load areas of the die while maintaining a consistent bondline (minimizing die tilt). Voiding was measured using acoustic imaging and die tilt was measured using two different optical measurement systems. 80Au-20Sn solder reflow was achieved using a batch vacuum solder system with optimized fixturing. Minimizing die tilt proved to be the more difficult of the two product requirements to meet. Process development variables included tooling, weight and solder preform thickness.

  11. Graphite/Thermoplastic-Pultrusion Die

    NASA Technical Reports Server (NTRS)

    Wilson, Maywood L.; Frye, Mark W.; Johnson, Gary S.; Stanfield, Clarence E.

    1990-01-01

    Attachment to extruder produces thermoplastic-impregnated graphite tape. Consists of profile die, fiber/resin collimator, and crosshead die body. Die designed to be attached to commercially available extrusion machine capable of extruding high-performance thermoplastics. Simple attachment to commercial extruder enables developers of composites to begin experimenting with large numbers of proprietary resins, fibers, and hybrid composite structures. With device, almost any possible fiber/resin combination fabricated.

  12. Die Milchstraße.

    NASA Astrophysics Data System (ADS)

    Henbest, N.; Couper, H.

    This book is a German translation, by M. Röser, from the English original "The guide to the Galaxy", published in 1994 (see Abstr. 61.003.065). Contents: 1. Die Entdeckung unserer Galaxis. 2. Die Lokale Gruppe. 3. Die Geographie der Galaxis. 4. Der Perseus-Arm. 5. Der Orion-Arm. 6. Unsere lokale Nachbarschaft: ein typischer Winkel der Galaxis. 7. Der Sagittarius-Arm: innerhalb der Sonnenumlaufbahn. 8. Das Zentrum der Galaxis.

  13. Bioluminescent bacterial imaging in vivo.

    PubMed

    Baban, Chwanrow K; Cronin, Michelle; Akin, Ali R; O'Brien, Anne; Gao, Xuefeng; Tabirca, Sabin; Francis, Kevin P; Tangney, Mark

    2012-11-04

    This video describes the use of whole body bioluminesce imaging (BLI) for the study of bacterial trafficking in live mice, with an emphasis on the use of bacteria in gene and cell therapy for cancer. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumors following systemic administration. Bacteria engineered to express the lux gene cassette permit BLI detection of the bacteria and concurrently tumor sites. The location and levels of bacteria within tumors over time can be readily examined, visualized in two or three dimensions. The method is applicable to a wide range of bacterial species and tumor xenograft types. This article describes the protocol for analysis of bioluminescent bacteria within subcutaneous tumor bearing mice. Visualization of commensal bacteria in the Gastrointestinal tract (GIT) by BLI is also described. This powerful, and cheap, real-time imaging strategy represents an ideal method for the study of bacteria in vivo in the context of cancer research, in particular gene therapy, and infectious disease. This video outlines the procedure for studying lux-tagged E. coli in live mice, demonstrating the spatial and temporal readout achievable utilizing BLI with the IVIS system.

  14. In vivo generator for radioimmunotherapy

    DOEpatents

    Mausner, Leonard F.; Srivastava, Suresh G.; Straub, Rita F.

    1988-01-01

    The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

  15. In vivo generator for radioimmunotherapy

    DOEpatents

    Mausner, Leonard F.; Srivastava, Suresh G.; Straub, Rita F.

    1988-11-01

    The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

  16. I Could Have Died Laughing.

    ERIC Educational Resources Information Center

    Maher, Michael Forrest; Smith, Douglas

    1993-01-01

    Notes that caregivers of the dying would do well to consider the prescriptive power of humor when confronting the challenges of healthy care for the terminally ill. Addresses laughter as the best medicine not only for the dying person but also for family and principal caregivers. Includes examples of therapeutic use of humor with the terminally…

  17. A Comparison of General Case In Vivo and General Case Simulation Plus In Vivo Training.

    ERIC Educational Resources Information Center

    McDonnell, John J.; Ferguson, Brad

    1988-01-01

    The study examined the relative effectiveness and efficiency of general case in vivo and general case simulation plus in vivo training in teaching six students with moderate and severe disabilities to purchase items in fast-food restaurants. Although both strategies led to reliable performance in nontrained settings, the in vivo instruction…

  18. Adapt or die?

    PubMed

    Visser, S S; Nel, A H

    1996-12-01

    The worldwide economic recession and the concomitant limited stock of finances have had an influence on the available money of every household and have also inhibited the improvement of socio-economic conditions and medicine. The Reconstruction and Development Programme (RDP) has the objective of improving the living conditions of the people with regard to housing, education, training and health care. The latter seems to be a major problem which has to be addressed with the emphasis on the preventive and promotional aspects of health care. A comprehensive health care system did not come into being property in the past because of the maldistribution of health care services, personnel and differences in culture and health care beliefs and values. The question that now arises, is how to render a quality health care service within the constraints of inadequate financing and resources. A comprehensive literature study has been done with reference to quality health care and financing followed by a survey of existing health services and finances. Recommendations are made about minimum requirements to be accepted if one were to adapt rather than die in terms of the provision of healthcare: the decentralization and rationalization of the administration of health care, the stress on and realization of effective and efficient primary health care, the acceptance of participative management in health providing organizations, the provision of financial management training for health care managers and the application of management accounting principles for the improvement of the efficiency and effectiveness of management.

  19. Two Piece Compaction Die Design

    SciTech Connect

    Coffey, Ethan N

    2010-03-01

    Compaction dies used to create europium oxide and tantalum control plates were modeled using ANSYS 11.0. Two-piece designs were considered in order to make the dies easier to assemble than the five-piece dies that were previously used. The two areas of concern were the stresses at the interior corner of the die cavity and the distortion of the cavity wall due to the interference fit between the two pieces and the pressure exerted on the die during the compaction process. A successful die design would have stresses less than the yield stress of the material and a maximum wall distortion on the order of 0.0001 in. Design factors that were investigated include the inner corner radius, the value of the interference fit, the compaction force, the size of the cavity, and the outer radius and geometry of the outer ring. The results show that for the europium oxide die, a 0.01 in. diameter wire can be used to create the cavity, leading to a 0.0055 in. radius corner, if the radial interference fit is 0.003 in. For the tantalum die, the same wire can be used with a radial interference fit of 0.001 in. Also, for the europium oxide die with a 0.003 in. interference fit, it is possible to use a wire with a diameter of 0.006 in. for the wire burning process. Adding a 10% safety factor to the compaction force tends to lead to conservative estimates of the stresses but not for the wall distortion. However, when the 10% safety factor is removed, the wall distortion is not affected enough to discard the design. Finally, regarding the europium oxide die, when the cavity walls are increased by 0.002 in. per side or the outer ring is made to the same geometry as the tantalum die, all the stresses and wall distortions are within the desired range. Thus, the recommendation is to use a 0.006 in. diameter wire and a 0.003 in. interference fit for the europium oxide die and a 0.01 in. diameter wire and a 0.001 in. interference fit for the tantalum die. The dies can also be made to have the

  20. Tailoring vessel morphology in vivo

    NASA Astrophysics Data System (ADS)

    Gould, Daniel Joseph

    Tissue engineering is a rapidly growing field which seeks to provide alternatives to organ transplantation in order to address the increasing need for transplantable tissues. One huge hurdle in this effort is the provision of thick tissues; this hurdle exists because currently there is no way to provide prevascularized or rapidly vascularizable scaffolds. To design thick, vascularized tissues, scaffolds are needed that can induce vessels which are similar to the microvasculature found in normal tissues. Angiogenic biomaterials are being developed to provide useful scaffolds to address this problem. In this thesis angiogenic and cell signaling and adhesion factors were incorporated into a biomimetic poly(ethylene glycol) (PEG) hydrogel system. The composition of these hydrogels was precisely tuned to induce the formation of differing vessel morphology. To sensitively measure induced microvascular morphology and to compare it to native microvessels in several tissues, this thesis developed an image-based tool for quantification of scale invariant and classical measures of vessel morphology. The tool displayed great utility in the comparison of native vessels and remodeling vessels in normal tissues. To utilize this tool to tune the vessel response in vivo, Flk1::myr-mCherry fluorescently labeled mice were implanted with Platelet Derived Growth Factor-BB (PDGF-BB) and basic Fibroblast Growth Factor (FGF-2) containing PEG-based hydrogels in a modified mouse corneal angiogenesis assay. Resulting vessels were imaged with confocal microscopy, analyzed with the image based tool created in this thesis to compare morphological differences between treatment groups, and used to create a linear relationship between space filling parameters and dose of growth factor release. Morphological parameters of native mouse tissue vessels were then compared to the linear fit to calculate the dose of growth factors needed to induce vessels similar in morphology to native vessels

  1. How dying cells alert the immune system to danger

    PubMed Central

    Kono, Hajime; Rock, Kenneth L.

    2009-01-01

    When a cell dies in vivo the event does not go unnoticed. The host has evolved mechanisms to detect the death of cells and rapidly investigate the nature of their demise. If cell death is a result of natural causes, that is, it is part of normal physiological processes, then there is little threat to the organism. In this situation, little else is done other than removing the corpse. However, if cells have died as the consequence of some violence or disease, then both defence and repair mechanisms are mobilized. The importance of this process to host defence and disease pathogenesis has only been appreciated relatively recently. This article will review our current knowledge of these processes. PMID:18340345

  2. Dying: A universal human experience?

    PubMed

    Bregman, L

    1989-03-01

    This paper explores the question, "Is there a universal psychological experience suffered by all dying persons?" a question to which the popular theory of Kübler-Ross presupposes an affirmative answer. Our answer takes three steps: first, a comparison between the Kübler-Ross model of dying and that of the late medievalBook of the Craft of Dying centered upon the five Kübler-Ross "stages"; second, a philosophical critique of the terms of this comparison; and third, a revised look at the alleged similarities between the two models, providing a deeper look at the moral and spiritual assumptions behind each.

  3. Die Sonne, Stern unserer Erde

    NASA Astrophysics Data System (ADS)

    Lang, Kenneth R.; Ehlers, A.

    Dieses reich bebilderte Buch gibt eine Einführung in die Physik der Sonne und ihre Bedeutung für die Erde. Gestützt auf neueste Forschungsergebnisse aus Radioteleskop- und Satellitenbeobachtungen beschreibt der Autor die gewaltigen atomenergetischen Prozesse der Sonne, ihren geheimnisvollen Neutrinofluß, ihre seismischen Aktivitäten, Magnetfelder und Sonnenflecke, Korona, Sonnenausbrüche und Protuberanzen, den Sonnenwind, und die außerordentlich wichtige und vielfältige Bedeutung des Sonnenlichts, das Leben auf der Erde entstehen läßt und es auch gefährdet. Gut verständlich und in ansprechender Sprache geschrieben ist es ein wunderbares Buch für den Leser populärwissenschaftlicher Literatur, ein wertvolles Geschenk für Studenten der Astronomie und verwandter Disziplinen sowie Amateurastronomen.

  4. Noninvasive photoacoustic microscopy of methemoglobin in vivo

    PubMed Central

    Tang, Min; Zhou, Yong; Zhang, Ruiying; Wang, Lihong V.

    2015-01-01

    Abstract. Due to the various causes of methemoglobinemia and its potential to be confused with other diseases, in vivo measurements of methemoglobin have significant applications in the clinic. Using photoacoustic microscopy (PAM), we quantified the average and the distributed percentage of methemoglobin both in vitro and in vivo. Based on the absorption spectra of methemoglobin, oxyhemoglobin, and deoxyhemoglobin, three wavelengths were chosen to differentiate methemoglobin from the others. The methemoglobin concentrations calculated from the photoacoustic signals agreed well with the preset concentrations. Then we imaged the methemoglobin percentage in microtubes that mimicked blood vessels. Average percentages calculated for five samples with different methemoglobin concentrations also agreed well with the preset values. Finally, we demonstrated the ability of PAM to detect methemoglobin in vivo in a mouse ear. Our results show that PAM can quantitatively image methemoglobin distribution in vivo. PMID:25760655

  5. REFRACTORY DIE FOR EXTRUDING URANIUM

    DOEpatents

    Creutz, E.C.

    1959-08-11

    A die is presented for the extrusion of metals, said die being formed of a refractory complex oxide having the composition M/sub n/O/sub m/R/sub x/O/sub y/ where M is magnesium, zinc, manganese, or iron, R is aluminum, chromic chromium, ferric iron, or manganic manganese, and m, n, x, and y are whole numbers. Specific examples are spinel, magnesium aluminate, magnetite, magnesioferrite, chromite, and franklinite.

  6. Tumor detection in vivo NIRF images

    NASA Astrophysics Data System (ADS)

    Celenk, Mehmet; Yang, Lin; Kamalakar, Ganti; Bleyle, Derek J.; Sunkara, Sudhir K.; Wang, Yufei; Prudich, Philip; Huang, Yuangcui; Zhou, Qiang

    2004-05-01

    Recent developments in the field of biotechnology and imaging systems have enabled real-time in vivo imaging at both the cellular and molecular level. This paper focuses on a technique that has been designed to detect tumor cells in vivo when using NIRF (near-infrared 705-715 nm range fluorescence) images. Experimental results indicate that the algorithm offers reasonably accurate estimates of the tumor parameters in the presence of white noise and varying background.

  7. In vivo studies of opiate receptors

    SciTech Connect

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  8. Clinical management of dying patients.

    PubMed Central

    Gavrin, J; Chapman, C R

    1995-01-01

    Dying is universal, and death should be a peaceful time. Myriad comfort measures are available in the last weeks before life ends. Discussions about end-of-life issues often suffer from lack of informed opinion. Palliative care experts have identified specific somatic and psychological sources of distress for dying patients and their loved ones. Pain, shortness of breath, nausea and vomiting, and fear of abandonment contribute substantially to both physical and psychological discomfort toward the end of life. Simple, effective methods exist for relieving those symptoms. Knowledge about the natural events associated with dying and an informed approach to medical and psychological interventions contribute to systematic and successful comfort care. We describe the origin of physical and psychological distress at the end of life and provide strategies for alleviating many of the discomforts. PMID:7571591

  9. Noninvasive photoacoustic microscopy of methemoglobin in vivo

    NASA Astrophysics Data System (ADS)

    Tang, Min; Zhou, Yong; Zhang, Ruiying; Wang, Lihong V.

    2015-03-01

    Various causes can lead to methemoglobinemia, and it has the potential to be confused with other diseases. In vivo measurements of methemoglobin have significant applications in the clinics. We quantified the average and the distributed percentage of methemoglobin both in vitro and in vivo using photoacoustic microscopy (PAM). Based on the absorption spectra of methemoglobin, oxyhemoglobin, and deoxyhemoglobin, three wavelengths were chosen to differentiate methemoglobin from the others. We imaged the methemoglobin percentage in microtubes that mimicked blood vessels as a phantom experiment. The methemoglobin concentrations calculated from the photoacoustic signals were in accordance with the preset concentrations. We also demonstrated the ability of PAM to quantitatively image methemoglobin distribution in vivo in a mouse ear.

  10. Bioluminescence imaging of myeloperoxidase activity in vivo

    PubMed Central

    Gross, Shimon; Gammon, Seth T; Moss, Britney L; Rauch, Daniel; Harding, John; Heinecke, Jay W; Ratner, Lee; Piwnica-Worms, David

    2010-01-01

    The myeloperoxidase (MPO) system of activated phagocytes is central to normal host defense mechanisms, and dysregulated MPO contributes to the pathogenesis of inflammatory disease states ranging from atherosclerosis to cancer. Here we show that upon systemic administration, the small molecule luminol enables noninvasive bioluminescence imaging (BLI) of MPO activity in vivo. Luminol-BLI allowed quantitative longitudinal monitoring of MPO activity in animal models of acute dermatitis, mixed allergic contact hypersensitivity, focal arthritis and spontaneous large granular lymphocytic tumors. Bioluminescence colocalized with histological sites of inflammation and was totally abolished in gene-deleted Mpo−/− mice, despite massive tissue infiltration of neutrophils and activated eosinophils, indicating that eosinophil peroxidase did not contribute to luminol-BLI in vivo. Thus, luminol-BLI provides a noninvasive, specific and highly sensitive optical readout of phagocyte-mediated MPO activity in vivo and may enable new diagnostic applications in a wide range of acute and chronic inflammatory conditions. PMID:19305414

  11. In vivo absorption spectroscopy for absolute measurement.

    PubMed

    Furukawa, Hiromitsu; Fukuda, Takashi

    2012-10-01

    In in vivo spectroscopy, there are differences between individual subjects in parameters such as tissue scattering and sample concentration. We propose a method that can provide the absolute value of a particular substance concentration, independent of these individual differences. Thus, it is not necessary to use the typical statistical calibration curve, which assumes an average level of scattering and an averaged concentration over individual subjects. This method is expected to greatly reduce the difficulties encountered during in vivo measurements. As an example, for in vivo absorption spectroscopy, the method was applied to the reflectance measurement in retinal vessels to monitor their oxygen saturation levels. This method was then validated by applying it to the tissue phantom under a variety of absorbance values and scattering efficiencies.

  12. In vivo cell tracking with bioluminescence imaging.

    PubMed

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong-Cheol

    2015-03-01

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  13. Outer Hair Cell Electromotility in vivo

    NASA Astrophysics Data System (ADS)

    Ramamoorthy, Sripriya; Nuttall, Alfred L.

    2011-11-01

    The effectiveness of outer hair cell (OHC) electro-motility in vivo has been challenged by the expected low-pass filtering of the transmembrane potential due to the cell's own capacitance. The OHC electromotility is characterized here by an electromechanical ratio defined as the ratio of the OHC contraction to the transmembrane potential. This ratio has been measured in isolated cells to be approximately 26 nm/mV. We estimate the OHC electromechanical ratio in vivo from the recently measured displacements of the reticular lamina and the basilar membrane near the 19 kHz characteristic frequency in the basal region of guinea pig cochlea. Our analysis strongly suggests OHC electromotility process is effective for cochlear amplification in vivo at least around the characteristic frequency of the basal location in spite of the low-pass filtering.

  14. The low synaptic release probability in vivo.

    PubMed

    Borst, J Gerard G

    2010-06-01

    The release probability, the average probability that an active zone of a presynaptic terminal releases one or more vesicles following an action potential, is tightly regulated. Measurements in cultured neurons or in slices indicate that this probability can vary greatly between synapses, but on average it is estimated to be as high as 0.5. In vivo, however, the size of synaptic potentials is relatively independent of recent history, suggesting that release probability is much lower. Possible causes for this discrepancy include maturational differences, a higher spontaneous activity, a lower extracellular calcium concentration and more prominent tonic inhibition by ambient neurotransmitters during in vivo recordings. Existing evidence thus suggests that under physiological conditions in vivo, presynaptic action potentials trigger the release of neurotransmitter much less frequently than what is observed in in vitro preparations.

  15. Bioluminescence imaging of myeloperoxidase activity in vivo.

    PubMed

    Gross, Shimon; Gammon, Seth T; Moss, Britney L; Rauch, Daniel; Harding, John; Heinecke, Jay W; Ratner, Lee; Piwnica-Worms, David

    2009-04-01

    The myeloperoxidase (MPO) system of activated phagocytes is central to normal host defense mechanisms, and dysregulated MPO contributes to the pathogenesis of inflammatory disease states ranging from atherosclerosis to cancer. Here we show that upon systemic administration, the small molecule luminol enables noninvasive bioluminescence imaging (BLI) of MPO activity in vivo. Luminol-BLI allowed quantitative longitudinal monitoring of MPO activity in animal models of acute dermatitis, mixed allergic contact hypersensitivity, focal arthritis and spontaneous large granular lymphocytic tumors. Bioluminescence colocalized with histological sites of inflammation and was totally abolished in gene-deleted Mpo(-/-) mice, despite massive tissue infiltration of neutrophils and activated eosinophils, indicating that eosinophil peroxidase did not contribute to luminol-BLI in vivo. Thus, luminol-BLI provides a noninvasive, specific and highly sensitive optical readout of phagocyte-mediated MPO activity in vivo and may enable new diagnostic applications in a wide range of acute and chronic inflammatory conditions.

  16. [Dying with cancer: Hollywood lessons].

    PubMed

    Niemeyer, Fernanda; Kruse, Maria Henriqueta Luce

    2013-12-01

    The study attempts to understand how dying from cancer is portrayed by five movies produced in Hollywood between 1993 and 2006. Based on the cultural studies and their post-structuralism version and supported by the notions of discourse and subjectivity, as proposed by philosopher Michel Foucault, we suggest one of the possible readings of the movie picture corpus. We assess how the movie picture discourse acts as a cultural pedagogy that produces ways of seeing dying with cancer: immortalizing the healthy body image, silencing death, taking care of the dead body and, finally, accepting death. Our proposal is intended to stimulate reflections that may contribute to care and education in nursing.

  17. Portable punch and die jig

    DOEpatents

    Lewandowski, Edward F.; Anderson, Petrus A.

    1978-01-01

    A portable punch and die jig includes a U-shaped jig of predetermined width having a slot of predetermined width in the base thereof extending completely across the width of the jig adapted to fit over the walls of rectangular tubes and a punch and die assembly disposed in a hole extending through the base of the jig communicating with the slot in the base of the jig for punching a hole in the walls of the rectangular tubes at precisely determined locations.

  18. Die Herz-Lungen-Maschine

    NASA Astrophysics Data System (ADS)

    Krane, Markus; Bauernschmitt, Robert; Lange, Rüdiger

    Das Kapitel der modernen Herzchirurgie mit Einsatz der Herz-Lungen-Maschine am Menschen beginnt am 6. Mai 1953, als J. Gibbon bei einer 18-jährigen Patientin einen angeborenen Defekt in der Vorhofscheidewand verschließt [1]. Mit ersten experimentellen Versuchen zur extrakorporalen Zirkulation begann Gibbon bereits in den 30er Jahren des 20. Jahrhunderts. Die Grundlage für die heute gebräuchliche Rollerpumpe schufen Porter und Bradley mit ihrer "rotary pump“, welche sie 1855 zum Patent anmeldeten. Diese Pumpe wurde von DeBakey und Schmidt modifiziert und entspricht im Wesentlichen noch der heute sich im Routinebetrieb befindlichen Rollerpumpe [2].

  19. In vitro and in vivo corrosion of the novel magnesium alloy Mg-La-Nd-Zr: influence of the measurement technique and in vivo implant location.

    PubMed

    Reifenrath, J; Marten, A-K; Angrisani, N; Eifler, R; Weizbauer, A

    2015-08-12

    For the evaluation of new magnesium-based alloys, many different in vitro and in vivo methods are used. It was the aim of the current study to perform in vitro and in vivo corrosion studies of the new alloy Mg-La-Nd-Zr for its evaluation as a promising new degradable material and to compare commonly used evaluation methods. Die casted and subsequent extruded cylindrical pins (Ø1.5 mm; length 7 mm, [Formula: see text]) were implanted subcutaneously ([Formula: see text]), intramuscular ([Formula: see text]) and intramedullary ([Formula: see text]) in female Lewis rats with a postoperative follow up of 8 weeks; subsequent μ-computed tomographical analyses (XTremeCT and μCT80) were performed as well as weight analysis prior to and after implantation. Cubes (5 mm  ×  4 mm  ×  4 mm; surface area, 1.12 cm(2); [Formula: see text]) were used for in vitro corrosion (HBSS and RPMI 1640 + 10% FBS medium) and cytocompatibility studies (L929 cells). First of all it could be stated that implant location strongly influences the in vivo corrosion rate. In particular, intramedullary implanted pins corroded faster than pins in a subcutaneous or intramuscular environment. Considering the different evaluation methods, the calculated ex vivo μCT-based corrosion rates resulted in comparable values to the corrosion rates calculated by the weight loss method, especially after chromatic acid treatment of the explanted pins. The in vitro methods used tend to show similar corrosion rates compared to in vivo corrosion, especially when a RPMI medium was used, and therefore are suitable to predict corrosion trends prior to in vivo studies. Regarding cytocompatibility, the novel magnesium alloy Mg-La-Nd-Zr showed sufficient cell viability and therefore can be considered as a promising alloy for further applications.

  20. Optical stimulation of neural tissue in vivo

    NASA Astrophysics Data System (ADS)

    Wells, Jonathon; Kao, Chris; Mariappan, Karthik; Albea, Jeffrey; Jansen, E. Duco; Konrad, Peter; Mahadevan-Jansen, Anita

    2005-03-01

    For more than a century, the traditional method of stimulating neural activity has been based on electrical methods, and it remains the gold standard to date. We report a technological breakthrough in neural activation in which low-level, pulsed infrared laser light is used to elicit compound nerve and muscle potentials in mammalian peripheral nerve in vivo. Optically induced neural action potentials are spatially precise, artifact free, and damage free and are generated by use of energies well below tissue ablation threshold. Thus optical stimulation presents a simple yet novel approach to contact-free in vivo neural activation that has major implications for clinical neurosurgery, basic neurophysiology, and neuroscience.

  1. Cubosomes for in vivo fluorescence lifetime imaging

    NASA Astrophysics Data System (ADS)

    Biffi, Stefania; Andolfi, Laura; Caltagirone, Claudia; Garrovo, Chiara; Falchi, Angela M.; Lippolis, Vito; Lorenzon, Andrea; Macor, Paolo; Meli, Valeria; Monduzzi, Maura; Obiols-Rabasa, Marc; Petrizza, Luca; Prodi, Luca; Rosa, Antonella; Schmidt, Judith; Talmon, Yeshayahu; Murgia, Sergio

    2017-02-01

    Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.

  2. Cubosomes for in vivo fluorescence lifetime imaging.

    PubMed

    Biffi, Stefania; Andolfi, Laura; Caltagirone, Claudia; Garrovo, Chiara; Falchi, Angela M; Lippolis, Vito; Lorenzon, Andrea; Macor, Paolo; Meli, Valeria; Monduzzi, Maura; Obiols-Rabasa, Marc; Petrizza, Luca; Prodi, Luca; Rosa, Antonella; Schmidt, Judith; Talmon, Yeshayahu; Murgia, Sergio

    2017-02-03

    Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.

  3. Attitudes on Death and Dying.

    ERIC Educational Resources Information Center

    Andrus, Charles E.

    This paper explored attitudes toward death and dying revealed through interviews with members of the clergy, the medical profession, funeral directors, nursing home residents, and selected others. The sampling was small and results are not intended to be representative of the groups to which these people belong. Rather, the study may be used as a…

  4. Robert Merton Dies at 92

    ERIC Educational Resources Information Center

    Snell, Joel C.

    2006-01-01

    This article features Robert Merton, who died recently at age 92. Merton came into this world as a Jewish baby named Meyer Schkolnick. He lived in South Philly where his parents wrenched a living as blue-collar workers. Merton chose an Anglicized name to move into the Yankee dominated America of the 20's and 30's. At Harvard, he studied under…

  5. In vivo functions of natural killer cells

    SciTech Connect

    Pollack, S.B.

    1983-01-01

    This review focuses on recent experiments in which the natural killed (NK) compartment has been directly manipulated in vivo either by passive transfer of NK-enriched cell populations or by selection depletion of NK cells. These data have provided direct evidence for the role of NK cells in vivo. It is evident that even these experiments have inherent limitations due to the complexity of in vivo interactions. In the aggregate, however, these data build a compelling case for the in vivo activity of NK cells and for their biologic importance. Most of the experiments were carried out in mice. Although there is heterogeneity among NK cells, these studies deal mainly with classical NK cells defined as bone marrow-derived, non-B (Ig/sup -/), non-T (Lyt 1/sup -/2/sup -/) lymphocytes that are nonadherent and bear the NK-associated antigens NK-1 and asialo-GMl. A natural model which has been exploited to study NK cells in the intact host is also discussed.

  6. In-vivo optical investigation of psoriasis

    NASA Astrophysics Data System (ADS)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-03-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  7. In vivo dosimetry in external beam radiotherapy

    SciTech Connect

    Mijnheer, Ben; Beddar, Sam; Izewska, Joanna; Reft, Chester

    2013-07-15

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks.

  8. The thermal fatigue resistance of H-13 Die Steel for aluminum die casting dies

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The effects of welding, five selected surface coatings, and stress relieving on the thermal fatigue resistance of H-13 Die Steel for aluminum die casting dies were studied using eleven thermal fatigue specimens. Stress relieving was conducted after each 5,000 cycle interval at 1050 F for three hours. Four thermal fatigue specimens were welded with H-13 or maraging steel welding rods at ambient and elevated temperatures and subsequently, subjected to different post-weld heat treatments. Crack patterns were examined at 5,000, 10,000, and 15,000 cycles. The thermal fatigue resistance is expressed by two crack parameters which are the average maximum crack and the average cracked area. The results indicate that a significant improvement in thermal fatigue resistance over the control was obtained from the stress-relieving treatment. Small improvements were obtained from the H-13 welded specimens and from a salt bath nitrogen and carbon-surface treatment. The other surface treatments and welded specimens either did not affect or had a detrimental influence on the thermal fatigue properties of the H-13 die steel.

  9. Should assisted dying be legalised?

    PubMed

    Frost, Thomas D G; Sinha, Devan; Gilbert, Barnabas J

    2014-01-15

    When an individual facing intractable pain is given an estimate of a few months to live, does hastening death become a viable and legitimate alternative for willing patients? Has the time come for physicians to do away with the traditional notion of healthcare as maintaining or improving physical and mental health, and instead accept their own limitations by facilitating death when requested? The Universities of Oxford and Cambridge held the 2013 Varsity Medical Debate on the motion "This House Would Legalise Assisted Dying". This article summarises the key arguments developed over the course of the debate. We will explore how assisted dying can affect both the patient and doctor; the nature of consent and limits of autonomy; the effects on society; the viability of a proposed model; and, perhaps most importantly, the potential need for the practice within our current medico-legal framework.

  10. Guide for extrusion dies eliminates straightening operation

    NASA Technical Reports Server (NTRS)

    Gyorgak, C. A.; Hoover, R. J.

    1964-01-01

    To prevent distortion of extruded metal, a guidance assembly is aligned with the die. As the metal emerges from the extrusion dies, it passes directly into the receiver and straightening tube system, and the completed extrusion is withdrawn.

  11. In vivo bioreactors for mandibular reconstruction.

    PubMed

    Tatara, A M; Wong, M E; Mikos, A G

    2014-12-01

    Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current gold standard is free tissue flap transfer, this treatment is limited in fidelity by the shape of the harvested tissue and can result in significant donor site morbidity. To address these problems, in vivo bioreactors have been explored as an approach to generate autologous prefabricated tissue flaps. These bioreactors are implanted in an ectopic site in the body, where ossified tissue grows into the bioreactor in predefined geometries and local vessels are recruited to vascularize the developing construct. The prefabricated flap can then be harvested with vessels and transferred to a mandibular defect for optimal reconstruction. The objective of this review article is to introduce the concept of the in vivo bioreactor, describe important preclinical models in the field, summarize the human cases that have been reported through this strategy, and offer future directions for this exciting approach.

  12. Invadopodia and basement membrane invasion in vivo

    PubMed Central

    Lohmer, Lauren L; Kelley, Laura C; Hagedorn, Elliott J; Sherwood, David R

    2014-01-01

    Over 20 years ago, protrusive, F-actin-based membrane structures, termed invadopodia, were identified in highly metastatic cancer cell lines. Invadopodia penetrate artificial or explanted extracellular matrices in 2D culture conditions and have been hypothesized to facilitate the migration of cancer cells through basement membrane, a thin, dense, barrier-like matrix surrounding most tissues. Despite intensive study, the identification of invadopodia in vivo has remained elusive and until now their possible roles during invasion or even existence have remained unclear. Studies in remarkably different cellular contexts—mouse tumor models, zebrafish intestinal epithelia, and C. elegans organogenesis—have recently identified invadopodia structures associated with basement membrane invasion. These studies are providing the first in vivo insight into the regulation, function, and role of these fascinating subcellular devices with critical importance to both development and human disease. PMID:24717190

  13. A system to study aneuploidy in vivo

    PubMed Central

    Pfau, Sarah J.; Amon, Angelika

    2016-01-01

    Aneuploidy, an imbalanced chromosome number, is associated with both cancer and developmental disorders such as Down syndrome (DS). To determine how aneuploidy affects cellular and organismal physiology, we have developed a system to evaluate aneuploid cell fitness in vivo. By transplanting hematopoietic stem cells (HSCs) into recipient mice after ablation of recipient hematopoiesis by lethal irradiation, we can directly compare the fitness of HSCs derived from a range of aneuploid mouse models with that of euploid HSCs. This experimental system can also be adapted to assess the interplay between aneuploidy and tumorigenesis. We hope that further characterization of aneuploid cells in vivo will provide insight both into the origins of hematopoietic phenotypes observed in DS individuals as well as the role of different types of aneuploid cells in the genesis of cancers of the blood. PMID:26936868

  14. In vivo tissue engineering of musculoskeletal tissues.

    PubMed

    McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

    2011-10-01

    Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues.

  15. In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids.

    PubMed

    Nair, Jerald J; Bastida, Jaume; van Staden, Johannes

    2016-01-01

    The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects.

  16. Multiphoton spectroscopy of human skin in vivo

    NASA Astrophysics Data System (ADS)

    Breunig, Hans G.; Weinigel, Martin; König, Karsten

    2012-03-01

    In vivo multiphoton-intensity images and emission spectra of human skin are reported. Optical sections from different depths of the epidermis and dermis have been measured with near-infrared laser-pulse excitation. While the intensity images reveal information on the morphology, the spectra show emission characteristics of main endogenous skin fluorophores like keratin, NAD(P)H, melanin, elastin and collagen as well as of second harmonic generation induced by the excitation-light interaction with the dermal collagen network.

  17. High-throughput in vivo vertebrate screening

    PubMed Central

    Pardo-Martin, Carlos; Chang, Tsung-Yao; Koo, Bryan Kyo; Gilleland, Cody L.; Wasserman, Steven C.; Yanik, Mehmet Fatih

    2010-01-01

    We demonstrate a high-throughput platform for cellular-resolution in vivo pharmaceutical and genetic screens on zebrafish larvae. The system automatically loads animals from reservoirs or multiwell plates, and positions and orients them for high-speed confocal imaging and laser manipulation of both superficial and deep organs within 19 seconds without damage. We show small-scale test screening of retinal axon guidance mutants and neuronal regeneration assays in combination with femtosecond laser microsurgery. PMID:20639868

  18. In vivo protein cross-linking.

    PubMed

    Agou, Fabrice; Ye, Fei; Véron, Michel

    2004-01-01

    In the cell, homo- and heteroassociations of polypeptide chains evolve and take place within subcellular compartments that are crowded with many other cellular macromolecules. In vivo chemical cross-linking of proteins is a powerful method to examine changes in protein oligomerization and protein-protein interactions upon cellular events such as signal transduction. This chapter is intended to provide a guide to the selection of the cell-membrane-permeable cross-linkers, the optimization of in vivo cross-linking conditions, and the identification of specific cross-links in a cellular context where the frequency of random collisions is high. By combining the chemoselectivity of the homo-bifunctional cross-linker and the length of its spacer arm with knowledge on the protein structure, we show that selective cross-links can be introduced specifically on either the dimer or the hexamer form of the same polypeptide in vitro as well as in vivo, using the human type B nucleoside diphosphate kinase as a protein model.

  19. In vivo confocal microscopy of toxic keratopathy

    PubMed Central

    Chen, Y; Le, Q; Hong, J; Gong, L; Xu, J

    2017-01-01

    Purpose To explore the morphological characteristics of toxic keratopathy (TK), which clinically presented as superficial punctate keratopathy (SPK), with the application of in vivo laser-scanning confocal microscopy (LSCM), and evaluate its potential in the early diagnosis of TK. Patients and methods This was a cross-sectional study involving 16 patients with TK and 16 patients with dry eye (DE), demonstrating SPK under slit-lamp observation, and 10 normal eyes were enrolled in the study. All participants underwent history interviews, fluorescein staining, tear film break-up time (BUT) tests, Schirmer tests, and in vivo LSCM. Results The area grading of corneal fluorescein punctate staining was higher in the TK group than the DE group. Measured by in vivo LSCM, superficial epithelial cell density was lower in the TK group than that of DE group. The sub-basal nerve presented lower density and tortuosity in the TK group than the DE group. Most notably, deposits with a snow-like appearance were observed in the epithelium in 12/16 (75.0%) of the TK cases, but none in the DE group (P<0.05). Conclusion The SPK in TK patients was characterized by more widespread punctate staining, a lower density of superficial epithelial cells and sub-basal nerves, and a typical snow-like pattern of deposits in the epithelium by LSCM. These features might facilitate early diagnosis of TK from other disorders manifested as SPK. PMID:27740620

  20. Luminescent probes for optical in vivo imaging

    NASA Astrophysics Data System (ADS)

    Texier, Isabelle; Josserand, Veronique; Garanger, Elisabeth; Razkin, Jesus; Jin, Zhaohui; Dumy, Pascal; Favrot, Marie; Boturyn, Didier; Coll, Jean-Luc

    2005-04-01

    Going along with instrumental development for small animal fluorescence in vivo imaging, we are developing molecular fluorescent probes, especially for tumor targeting. Several criteria have to be taken into account for the optimization of the luminescent label. It should be adapted to the in vivo imaging optical conditions : red-shifted absorption and emission, limited overlap between absorption and emission for a good signal filtering, optimized luminescence quantum yield, limited photo-bleaching. Moreover, the whole probe should fulfill the biological requirements for in vivo labeling : adapted blood-time circulation, biological conditions compatibility, low toxicity. We here demonstrate the ability of the imaging fluorescence set-up developed in LETI to image the bio-distribution of molecular probes on short times after injection. Targeting with Cy5 labeled holo-transferrin of subcutaneous TS/Apc (angiogenic murine breast carcinoma model) or IGROV1 (human ovarian cancer) tumors was achieved. Differences in the kinetics of the protein uptake by the tumors were evidenced. IGROV1 internal metastatic nodes implanted in the peritoneal cavity could be detected in nude mice. However, targeted metastatic nodes in lung cancer could only be imaged after dissection of the mouse. These results validate our fluorescence imaging set-up and the use of Cy5 as a luminescent label. New fluorescent probes based on this dye and a molecular delivery template (the RAFT molecule) can thus be envisioned.

  1. Contoured Orifice for Silicon-Ribbon Die

    NASA Technical Reports Server (NTRS)

    Mackintosh, B. H.

    1985-01-01

    Die configuration encourages purity and stable growth. Contour of die orifice changes near ribbon edges. As result, silicon ribbon has nearly constant width and little carbon contamination. Die part of furnace being developed to produce high-quality, low-cost material for solar cells.

  2. Die Welt des Herrn Kuhn

    NASA Astrophysics Data System (ADS)

    Kern, Daniela

    Eines Morgens erwachte Herr Kuhn fröstelnd und staunte darüber, dass es in seinerWohnung eiskalt war. Dennoch quälte er sich aus seiner kuscheligen Bettdecke heraus und schlurfte ins Bad. "Hoffentlich wird wenigstens das Wasser warm", dachte er sich, als er den Wasserhahn betätigte - aber es kam nicht nur kein warmesWasser, außer einem unheilvollen Gluckser kam gar nichts aus der Leitung. "Dann werde ich wohl mal den Klempner anrufen", sprach er sich leise in den Bart und griff zu seinem Handy - doch das Netz war tot! Herr Kuhn begann nun, sich ernsthaft Sorgen zu machen, "Oje, was ist denn heute nur los? Ist irgendetwas Schlimmes passiert?" Um einen besseren Überblick über die Lage zu bekommen und sich austauschen zu können, brannte er nun förmlich darauf, rauszugehen und zur Arbeit zu fahren. An anderen Tagen, die er frisch geduscht und mit Kaffee und Marmeladen-Brot begann, war er selten so motiviert. So ging er also nun mit leerem Magen aus dem Haus. Hätte er den Versuch unternommen, sein tägliches Marmeladenbrot zuzubereiten, und dafür den Kühlschrank geöffnet, um das Marmeladenglas herauszunehmen, wäre ihm aufgefallen, dass auch die Stromversorgung Störungen unterworfen war, unschön zu erkennen an den ersten grünen, felligen Inseln auf seinem Lieblingskäse.

  3. Human tendon behaviour and adaptation, in vivo

    PubMed Central

    Magnusson, S Peter; Narici, Marco V; Maganaris, Constantinos N; Kjaer, Michael

    2008-01-01

    Tendon properties contribute to the complex interaction of the central nervous system, muscle–tendon unit and bony structures to produce joint movement. Until recently limited information on human tendon behaviour in vivo was available; however, novel methodological advancements have enabled new insights to be gained in this area. The present review summarizes the progress made with respect to human tendon and aponeurosis function in vivo, and how tendons adapt to ageing, loading and unloading conditions. During low tensile loading or with passive lengthening not only the muscle is elongated, but also the tendon undergoes significant length changes, which may have implications for reflex responses. During active loading, the length change of the tendon far exceeds that of the aponeurosis, indicating that the aponeurosis may more effectively transfer force onto the tendon, which lengthens and stores elastic energy subsequently released during unloading, in a spring-like manner. In fact, data recently obtained in vivo confirm that, during walking, the human Achilles tendon provides elastic strain energy that can decrease the energy cost of locomotion. Also, new experimental evidence shows that, contrary to earlier beliefs, the metabolic activity in human tendon is remarkably high and this affords the tendon the ability to adapt to changing demands. With ageing and disuse there is a reduction in tendon stiffness, which can be mitigated with resistance exercises. Such adaptations seem advantageous for maintaining movement rapidity, reducing tendon stress and risk of injury, and possibly, for enabling muscles to operate closer to the optimum region of the length–tension relationship. PMID:17855761

  4. Could magnetic resonance provide in vivo histology?

    PubMed

    Dominietto, Marco; Rudin, Markus

    2014-01-13

    THE DIAGNOSIS OF A SUSPECTED TUMOR LESION FACES TWO BASIC PROBLEMS: detection and identification of the specific type of tumor. Radiological techniques are commonly used for the detection and localization of solid tumors. Prerequisite is a high intrinsic or enhanced contrast between normal and neoplastic tissue. Identification of the tumor type is still based on histological analysis. The result depends critically on the sampling sites, which given the inherent heterogeneity of tumors, constitutes a major limitation. Non-invasive in vivo imaging might overcome this limitation providing comprehensive three-dimensional morphological, physiological, and metabolic information as well as the possibility for longitudinal studies. In this context, magnetic resonance based techniques are quite attractive since offer at the same time high spatial resolution, unique soft tissue contrast, good temporal resolution to study dynamic processes and high chemical specificity. The goal of this paper is to review the role of magnetic resonance techniques in characterizing tumor tissue in vivo both at morphological and physiological levels. The first part of this review covers methods, which provide information on specific aspects of tumor phenotypes, considered as indicators of malignancy. These comprise measurements of the inflammatory status, neo-vascular physiology, acidosis, tumor oxygenation, and metabolism together with tissue morphology. Even if the spatial resolution is not sufficient to characterize the tumor phenotype at a cellular level, this multiparametric information might potentially be used for classification of tumors. The second part discusses mathematical tools, which allow characterizing tissue based on the acquired three-dimensional data set. In particular, methods addressing tumor heterogeneity will be highlighted. Finally, we address the potential and limitation of using MRI as a tool to provide in vivo tissue characterization.

  5. Monitoring in vivo function of cortical microglia.

    PubMed

    Brawek, Bianca; Garaschuk, Olga

    2017-03-14

    Microglia, the innate immune cells of the brain, are becoming increasingly recognized as an important player both in the context of physiological brain function and brain pathology. To fulfill their executive functions microglia can modify their morphology, migrate or move their processes in a directed fashion, and modify the intracellular Ca(2+) dynamics leading to modifications in gene expression, phagocytosis, release of cytokines and other inflammation markers, etc. Here we describe the recently developed tools enabling in vivo monitoring of morphology and Ca(2+) signaling of microglia and show how these techniques may be used for examining microglial function in healthy and diseased brain.

  6. In vivo virtual intraoperative surgical photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Han, Seunghoon; Lee, Changho; Kim, Sehui; Jeon, Mansik; Kim, Jeehyun; Kim, Chulhong

    2013-11-01

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  7. In vivo Noninvasive Small Animal Molecular Imaging

    PubMed Central

    Youn, Hyewon; Hong, Kee-Jong

    2012-01-01

    The remarkable efforts that are made on molecular imaging technologies demonstrate its potential importance and range of applications. The generation of disease-specific animal models, and the developments of target-specific probes and genetically encoded reporters are another important component. Continued improvements in the instrumentation, the identification of novel targets and genes, and the availability of improved imaging probes should be made. Multimodal imaging probes should provide easier transitions between laboratory studies, including small animal studies and clinical applications. Here, we reviewed basic strategies of noninvasive in vivo imaging methods in small animals to introducing the concept of molecular imaging. PMID:24159487

  8. In Vivo Nanodetoxication for Acute Uranium Exposure.

    PubMed

    Guzmán, Luis; Durán-Lara, Esteban F; Donoso, Wendy; Nachtigall, Fabiane M; Santos, Leonardo S

    2015-06-15

    Accidental exposure to uranium is a matter of concern, as U(VI) is nephrotoxic in both human and animal models, and its toxicity is associated to chemical toxicity instead of radioactivity. We synthesized different PAMAM G4 and G5 derivatives in order to prove their interaction with uranium and their effect on the viability of red blood cells in vitro. Furthermore, we prove the effectiveness of the selected dendrimers in an animal model of acute uranium intoxication. The dendrimer PAMAM G4-Lys-Fmoc-Cbz demonstrated the ability to chelate the uranyl ion in vivo, improving the biochemical and histopathologic features caused by acute intoxication with uranium.

  9. In vivo NMR imaging of deuterium

    NASA Astrophysics Data System (ADS)

    Müller, S.; Seelig, J.

    D 2O is used as a contrast agent for studying anatomical images and flow in vivo by deuterium NMR. A deuterium image of the head of a living rat after administration of D 2O (5% v/v) in the drinking water is shown. It was obtained in 14 min with a surface coil and has a spatial resolution of about one millimeter. The application of D 2O as a tracer is discussed and the inflow of heavy water into the brain of a rat is recorded in a time series of deuterium images. Spatially resolved inflow time constants have been determined.

  10. Characteristics of in vivo radiotherapy dosimetry.

    PubMed

    Edwards, C R; Mountford, P J

    2009-11-01

    The recent discussion and debate about the use of in vivo dosimetry as a routine component of the radiotherapy treatment process has not included the limitations introduced by the physical characteristics of the detectors. Although a robust calibration procedure will ensure acceptable uncertainties in the measurements of tumour dose, further work is required to confirm the accuracy of critical organ measurements with a diode or a thermoluminescent dosemeter outside the main field owing to limitations caused by a non-uniform X-ray energy response of the detector, differences between the X-ray energy spectrum inside and outside the main field, and contaminating electrons.

  11. In vivo virtual intraoperative surgical photoacoustic microscopy

    SciTech Connect

    Han, Seunghoon Kim, Sehui Kim, Jeehyun E-mail: chulhong@postech.edu; Lee, Changho Jeon, Mansik; Kim, Chulhong E-mail: chulhong@postech.edu

    2013-11-11

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  12. Laser microspectrofluorometry of photopigments in vivo

    NASA Astrophysics Data System (ADS)

    Colombetti, G.; Ghetti, F.; Lenci, F.; Polacco, E.; Posudin, Yu I.; Campani, E.

    1981-12-01

    A study of the spectral properties of photopigments of microorganisms is of major importance for the understanding of molecular mechanisms whereby these can respond to changes in external illumination conditions. Microspectroscopy in vivo using a tunable dye laser as an excitation source was employed to solve this problem for the case of the unicellular algae Euglena gracilis. This experimental approach made it possible to study fluorescence excitation spectra of photopigments, their average lifetime, and any photochemical reactions which may accompany the absorption of light.

  13. Methods of in vivo radiation measurement

    DOEpatents

    Huffman, Dennis D.; Hughes, Robert C.; Kelsey, Charles A.; Lane, Richard; Ricco, Antonio J.; Snelling, Jay B.; Zipperian, Thomas E.

    1990-01-01

    Methods of and apparatus for in vivo radiation measurements relay on a MOSFET dosimeter of high radiation sensitivity with operates in both the passive mode to provide an integrated dose detector and active mode to provide an irradiation rate detector. A compensating circuit with a matched unirradiated MOSFET is provided to operate at a current designed to eliminate temperature dependence of the device. Preferably, the MOSFET is rigidly mounted in the end of a miniature catheter and the catheter is implanted in the patient proximate the radiation source.

  14. Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

    PubMed Central

    da Silva, Cristiane França; Batista, Denise da Gama Jaen; De Araújo, Julianna Siciliano; Batista, Marcos Meuser; Lionel, Jessica; de Souza, Elen Mello; Hammer, Erica Ripoll; da Silva, Patricia Bernardino; De Mieri, Maria; Adams, Michael; Zimmermann, Stefanie; Hamburger, Matthias; Brun, Reto; Schühly, Wolfgang

    2013-01-01

    In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection. PMID:23939901

  15. Methods of assessment of thrombosis in vivo

    SciTech Connect

    Dewanjee, M.K.

    1987-01-01

    The contributions of platelets and clotting factors in thrombosis on injured vessel and cardiovascular prostheses have been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and humans with /sup 111/In-labeled platelets, /sup 123/I- and /sup 131/I-labeled fibrinogen, /sup 111/In-labeled antibody to the fibrinogen receptor on the platelet membrane and to fibrin. Thrombus localization by imaging was possible for large thrombus in vessel with deep injury of thrombogenic surface in the acute phase. A single layer of adherent platelets could not be imaged, due to the high background radioactivity present in blood. Thrombogenicity of grafts was compared with that of contralateral vessel. The dynamic process of platelet deposition could be followed accurately using the in vivo imaging technique. In addition, in vitro quantification permits determination of platelet and fibrin density and of the number of fibrin monomers per platelet in thrombus. The roles of prostacyclin, thromboxane inhibitors, and nonsteroidal antiinflammatory drugs have also been evaluated in animals models and humans. The tracer techniques thus provide invaluable information about platelet-fibrin deposition, its organization and dissolution, and for development of less thrombogenic surfaces for use in cardiovascular prostheses. 53 references.

  16. Multidimensional In Vivo Hazard Assessment Using Zebrafish

    PubMed Central

    Tanguay, Robert L.

    2014-01-01

    There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies. PMID:24136191

  17. In vivo laser axotomy in C. elegans.

    PubMed

    Byrne, Alexandra B; Edwards, Tyson J; Hammarlund, Marc

    2011-05-19

    Neurons communicate with other cells via axons and dendrites, slender membrane extensions that contain pre- or post-synaptic specializations. If a neuron is damaged by injury or disease, it may regenerate. Cell-intrinsic and extrinsic factors influence the ability of a neuron to regenerate and restore function. Recently, the nematode C. elegans has emerged as an excellent model organism to identify genes and signaling pathways that influence the regeneration of neurons(1-6). The main way to initiate neuronal regeneration in C. elegans is laser-mediated cutting, or axotomy. During axotomy, a fluorescently-labeled neuronal process is severed using high-energy pulses. Initially, neuronal regeneration in C. elegans was examined using an amplified femtosecond laser(5). However, subsequent regeneration studies have shown that a conventional pulsed laser can be used to accurately sever neurons in vivo and elicit a similar regenerative response(1,3,7). We present a protocol for performing in vivo laser axotomy in the worm using a MicroPoint pulsed laser, a turnkey system that is readily available and that has been widely used for targeted cell ablation. We describe aligning the laser, mounting the worms, cutting specific neurons, and assessing subsequent regeneration. The system provides the ability to cut large numbers of neurons in multiple worms during one experiment. Thus, laser axotomy as described herein is an efficient system for initiating and analyzing the process of regeneration.

  18. Activity ratios of thorium daughters in vivo

    SciTech Connect

    Toohey, R.E.; Rundo, J.; Sha, J.Y.; Essling, M.A.; Pedersen, J.C.; Slane, J.M.

    1984-01-01

    A computerized method of least squares has been used to analyze the /sup 228/Ac and /sup 212/Pb-/sup 212/Bi and daughter ..gamma..-ray spectra obtained in vivo from 133 former workers at a thorium refinery. In addition, the exhalation rate of /sup 220/Rn was determined for each subject and expressed as pCi of emanating /sup 224/Ra. This value was added to the /sup 212/Pb value determined from the ..gamma..-ray measurements to obtain the total /sup 224/Ra present, and the ratio of /sup 224/Ra to /sup 228/Ac was calculated. Values of the ratio ranged from 0.52 +- 0.32 to 2.1 +- 1.7, with a weighted mean of 0.92 +- 0.17. However, it appears that the ratio observed in a given case is characteristic for that case alone; the computed mean value may not be meaningful. The least squares fitting procedure and the overall calibration of the counting system were validated by measurements of /sup 224/Ra in the lungs of one subject postmortem, compared with results obtained from the same subject in vivo. 6 references, 5 figures.

  19. Biomedical Applications of Sodium MRI In Vivo

    PubMed Central

    Madelin, Guillaume; Regatte, Ravinder R.

    2013-01-01

    In this article, we present an up-to-date overview of the potential biomedical applications of sodium MRI in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most of human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: (1) the role of sodium in biological tissues, (2) a short review on sodium magnetic resonance, and (3) a review of some studies on sodium MRI on different organs/diseases to date. PMID:23722972

  20. Aneuploidy in mammalian somatic cells in vivo.

    PubMed

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed.

  1. Long-term in vivo pineal microdialysis.

    PubMed

    Sun, Xing; Liu, Tiecheng; Deng, Jie; Borjigin, Jimo

    2003-09-01

    This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

  2. Phosphatase activities analyzed by in vivo expressions.

    PubMed

    Schweighofer, Alois; Ayatollahi, Zahra; Meskiene, Irute

    2009-01-01

    Protein phosphatases act to reverse phosphorylation-related modifications induced by protein kinases. Type 2C protein phosphatases (PP2C) are monomeric Ser/Thr phosphatases that require a metal for their activity and are abundant in prokaryotes and eukaryotes. In plants, such as Medicago and Arabidopsis PP2Cs control several essential processes, including ABA signaling, development, and wound-induced mitogen-activated protein kinase (MAPK) pathways. In vitro assays with recombinant proteins and yeast two-hybrid systems usually provide initial information about putative PP2C substrates; however, these observations have to be verified in vivo. Therefore, a method for transient expression in isolated Arabidopsis suspension cell protoplasts was developed to assay PP2C action in living cells. This system has proven to be very useful in producing active enzymes and their substrates and in performing enzymatic reactions in vivo. Transient gene expression in isolated cells enabled assembly of functional protein kinase cascades and the creation of phosphorylated targets for PP2Cs. The method is based on the co-transformation and transient co-expression of different PP2C proteins with MAPK. It shows that epitope-tagged PP2C and MAPK proteins exhibit high enzymatic activities and produce substantial protein amounts easily monitored by Western blot analysis. Additionally, PP2C phosphatase activities can be directly tested in protein extracts from protoplasts, suggesting a possibility for analysis of activities of new PP2C family members.

  3. In vivo proton range verification: a review

    NASA Astrophysics Data System (ADS)

    Knopf, Antje-Christin; Lomax, Antony

    2013-08-01

    Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

  4. In Vivo Bioluminescence Imaging of Intratumoral Bacteria.

    PubMed

    Cronin, Michelle; Akin, Ali R; Francis, Kevin P; Tangney, Mark

    2016-01-01

    This chapter describes the use of whole-body bioluminescent imaging (BLI) for the study of bacterial trafficking in live mice, with an emphasis on the use of bacteria in therapy of cancer. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumors following systemic administration. Bacteria engineered to express the lux gene cassette permit BLI detection of the bacteria and tumor sites concurrently. The location and levels of bacteria within tumors over time can be readily examined, visualized in two or three dimensions. The method is applicable to a wide range of bacterial species and tumor xenograft types. This article describes the protocol for analysis of bioluminescent bacteria within subcutaneous tumor-bearing mice. This powerful, and inexpensive, real-time imaging strategy represents an ideal method for the study of bacteria in vivo in the context of cancer research. This protocol outlines the procedure for studying lux-tagged Escherichia coli and Bifidobacterium breve in mice, demonstrating the spatial and temporal readout from 2D and 3D BLI achievable with whole-body in vivo luminescence imaging.

  5. In vivo iron–sulfur cluster formation

    PubMed Central

    Raulfs, Estella C.; O'Carroll, Ina P.; Dos Santos, Patricia C.; Unciuleac, Mihaela-Carmen; Dean, Dennis R.

    2008-01-01

    It has been proposed that iron–sulfur [Fe-S] clusters destined for the maturation of [Fe-S] proteins can be preassembled on a molecular scaffold designated IscU. In the present article, it is shown that production of the intact Azotobacter vinelandii [Fe-S] cluster biosynthetic machinery at levels exceeding the amount required for cellular maturation of [Fe-S] proteins results in the accumulation of: (i) apo-IscU, (ii) an oxygen-labile [2Fe-2S] cluster-loaded form of IscU, and (iii) IscU complexed with the S-delivery protein, IscS. It is suggested that these species represent different stages of the [Fe-S] cluster assembly process. Substitution of the IscU Asp39 residue by Ala results in the in vivo trapping of a stoichiometric, noncovalent, nondissociating IscU–IscS complex that contains an oxygen-resistant [Fe-S] species. In aggregate, these results validate the scaffold hypothesis for [Fe-S] cluster assembly and indicate that in vivo [Fe-S] cluster formation is a dynamic process that involves the reversible interaction of IscU and IscS. PMID:18562278

  6. In Vivo Ischemia Detection by Luminescent Nanothermometers.

    PubMed

    Ximendes, Erving Clayton; Rocha, Uéslen; Del Rosal, Blanca; Vaquero, Alberto; Sanz-Rodríguez, Francisco; Monge, Luis; Ren, Fuqiang; Vetrone, Fiorenzo; Ma, Dongling; García-Solé, José; Jacinto, Carlos; Jaque, Daniel; Fernández, Nuria

    2017-02-01

    There is an urgent need to develop new diagnosis tools for real in vivo detection of first stages of ischemia for the early treatment of cardiovascular diseases and accidents. However, traditional approaches show low sensitivity and a limited penetration into tissues, so they are only applicable for the detection of surface lesions. Here, it is shown how the superior thermal sensing capabilities of near infrared-emitting quantum dots (NIR-QDs) can be efficiently used for in vivo detection of subcutaneous ischemic tissues. In particular, NIR-QDs make possible ischemia detection by high penetration transient thermometry studies in a murine ischemic hindlimb model. NIR-QDs nanothermometers are able to identify ischemic tissues by means of their faster thermal dynamics. In addition, they have shown to be capable of monitoring both the revascularization and damage recovery processes of ischemic tissues. This work demonstrates the applicability of fluorescence nanothermometry for ischemia detection and treatment, as well as a tool for early diagnosis of cardiovascular disease.

  7. In Vivo Tractography of Fetal Association Fibers

    PubMed Central

    Mitter, Christian; Prayer, Daniela; Brugger, Peter C.; Weber, Michael; Kasprian, Gregor

    2015-01-01

    Association fibers connect different cortical areas within the same hemisphere and constitute an essential anatomical substrate for a diverse range of higher cognitive functions. So far a comprehensive description of the prenatal in vivo morphology of these functionally important pathways is lacking. In the present study, diffusion tensor imaging (DTI) and tractography were used to visualize major association fiber tracts and the fornix in utero in preselected non-motion degraded DTI datasets of 24 living unsedated fetuses between 20 and 34 gestational weeks (GW). The uncinate fasciculus and inferior fronto-occipital fasciculus were depicted as early as 20 GW, while in vivo 3D visualization of the inferior longitudinal fasciculus, cingulum and fornix was successful in older fetuses during the third trimester. Provided optimal scanning conditions, in utero DTI and tractography have the potential to provide a more accurate anatomical definition of developing neuronal networks in the human fetal brain. Knowledge about the normal prenatal 3D association tract morphology may serve as reference for their assessment in common developmental diseases. PMID:25742520

  8. In vivo effects of cardiotrophin-1.

    PubMed

    Jin, H; Yang, R; Keller, G A; Ryan, A; Ko, A; Finkle, D; Swanson, T A; Li, W; Pennica, D; Wood, W I; Paoni, N F

    1996-12-01

    Cardiotrophin-1 (CT-1) is a recently discovered cytokine that was isolated based on its ability to induce cardiac myocyte hypertrophy in vitro. In this study, the effects of chronic administration of CT-1 to mice (0.5 or 2 microg by intraperitoneal injection, twice a day for 14 days) were determined. A dose-dependent increase in both the heart weight and ventricular weight to body ratios was observed in the treated groups. The body weights of the animals were unaffected. These results indicate that CT-1 can induce cardiac hypertrophy in vivo. CT-1 was not specific for the heart, however. It stimulated the growth of the liver, kidney, and spleen, and caused atrophy of the thymus. CT-1 administration also increased the platelet counts by 70%, with no change in mean platelet volume. Red blood cell counts were increased in the treated animals, and there was a concomitant increase in haemoglobin concentration. Thus, CT-1 has a broad spectrum of biological activities in vivo. This observation is consistent with previous in-vitro findings showing that the mRNA for CT-1 is expressed in several tissues, and that CT-1 can function through binding to the leukaemia inhibitory factor (LIF) receptor and signalling through the gp130 pathway.

  9. Aggregation states of phosphoribulokinase (PRK) in vivo

    SciTech Connect

    Porter, M.A.; Hartman, F.C. )

    1989-04-01

    Spinach PRK, extracted from either light- or dark-harvested tissue (LHT or DHT) in the presence of DTT, has a M{sub r} of 90 kDa and is fully active. Consistent with an earlier study extraction of LHT in the absence of DTT results in two forms of inactive PRK, M{sub r} 90 kDa (LMW) and M{sub r}> 550 kDa (HMW). If 400 mM (NH{sub 4}){sub 2}SO{sub 4} without DTT is included during extraction, the active LMW predominates implicating it as the major, functional form in vivo during periods of illumination. Either high- or low-sale extraction of DHT reveals mostly HMW; prolonged incubation of the high-salt extract causes disaggregation of LMW without activation. These data suggest that the dark form of PRK in vivo is an aggregate, formed by either self-association or by interactions with other proteins. Salt-induced disaggregation of HMW is inconsistent with intermolecular disulfides crosslinking the aggregated PRK; therefore, oxidation-induced conformational changes must promote aggregation.

  10. Quantitative profiling of initiating ribosomes in vivo.

    PubMed

    Gao, Xiangwei; Wan, Ji; Liu, Botao; Ma, Ming; Shen, Ben; Qian, Shu-Bing

    2015-02-01

    Cells have evolved exquisite mechanisms to fine-tune the rate of protein synthesis in response to stress. Systemic mapping of start-codon positions and precise measurement of the corresponding initiation rate would transform our understanding of translational control. Here we present quantitative translation initiation sequencing (QTI-seq), with which the initiating ribosomes can be profiled in real time at single-nucleotide resolution. Resultant initiation maps not only delineated variations of start-codon selection but also highlighted a dynamic range of initiation rates in response to nutrient starvation. The integrated data set provided unique insights into principles of alternative translation and mechanisms controlling different aspects of translation initiation. With RiboTag mice, QTI-seq permitted tissue-specific profiling of initiating ribosomes in vivo. Liver cell-specific ribosome profiling uncovered a robust translational reprogramming of the proteasome system in fasted mice. Our findings illuminated the prevalence and dynamic nature of translational regulation pivotal to physiological adaptation in vivo.

  11. Evaluation of permanent die coatings to improve the wear resistance of die casting dies. Final project report, January 1, 1995--April 30, 1997

    SciTech Connect

    Shivpuri, R.

    1997-09-18

    Die Casting dies are subject to severe service conditions during the die casting operation. While these severe conditions are necessary to achieve high production rates, they cause the dies which are commonly made of H13 die steel, to suffer frequent failures. The major die failure mechanisms are erosion or washout, Heat checking, soldering and corrosion. Due to their geometrical complexity, die casting dies are very expensive (some dies cost over a million dollars), and thus a large number of parts have to be produced by a die, to justify this cost and leverage the advantages of the die casting process (high production rates, low manpower costs). A potential increase in the die service life, thus has a significant impact on the economics of the die; casting operation. There are many ways to extend die life: developing new wear resistant die materials, developing new surface treatments including coatings, improving heat treatment of existing H13 dies, using better lubricants that can protect the die material, or modifying the die geometry and process parameters to reduce the intensity of wear. Of these the use of coatings to improve the wear resistance of the die surface has shown a lot of promise. Consequently, use of coatings in the die casting industry and their wide use to decrease die wear can improve significantly the productivity of shop operations resulting in large savings in material and energy usage.

  12. Die singulation method and package formed thereby

    DOEpatents

    Anderson, Robert C [Tucson, AZ; Shul, Randy J [Albuquerque, NM; Clews, Peggy J [Tijeras, NM; Baker, Michael S [Albuquerque, NM; De Boer, Maarten P [Albuquerque, NM

    2012-08-07

    A method is disclosed for singulating die from a substrate having a sacrificial layer and one or more device layers, with a retainer being formed in the device layer(s) and anchored to the substrate. Deep Reactive Ion Etching (DRIE) etching of a trench through the substrate from the bottom side defines a shape for each die. A handle wafer is then attached to the bottom side of the substrate, and the sacrificial layer is etched to singulate the die and to form a frame from the retainer and the substrate. The frame and handle wafer, which retain the singulated die in place, can be attached together with a clamp or a clip and to form a package for the singulated die. One or more stops can be formed from the device layer(s) to limit a sliding motion of the singulated die.

  13. Vacuum die attach for integrated circuits

    DOEpatents

    Schmitt, E.H.; Tuckerman, D.B.

    1991-09-10

    A thin film eutectic bond for attaching an integrated circuit die to a circuit substrate is formed by coating at least one bonding surface on the die and substrate with an alloying metal, assembling the die and substrate under compression loading, and heating the assembly to an alloying temperature in a vacuum. A very thin bond, 10 microns or less, which is substantially void free, is produced. These bonds have high reliability, good heat and electrical conduction, and high temperature tolerance. The bonds are formed in a vacuum chamber, using a positioning and loading fixture to compression load the die, and an IR lamp or other heat source. For bonding a silicon die to a silicon substrate, a gold silicon alloy bond is used. Multiple dies can be bonded simultaneously. No scrubbing is required. 1 figure.

  14. Reinraumtechnik für die Medizintechnik

    NASA Astrophysics Data System (ADS)

    Petek, Max; Jungbluth, Martin; Krampe, Erhard

    Die Reinraumtechnik ist heute ein unverzichtbarer Bestandteil bei der Fertigung von Produkten der Life Sciences, den Bereichen Pharma, Lebensmittel, Kosmetik und Medizintechnik. In Anbetracht der langen Historie der Medizintechnik ist sie jedoch eine sehr junge Disziplin. Die Bedeutung von Keimen und die richtige Einschätzung ihrer Größe wurden zwar sehr früh bereits durch Paracelsus erkannt, jedoch wurden daraus noch keine speziellen oder kontinuierlich umgesetzten Hygienevorschriften abgeleitet. Die erste bekannte technische Umsetzung von Hygieneempfehlungen geht auf den Franzosen François Nicolas Appert zurück, der eine aseptische Abfüllmethode für Lebensmittel entwickelte und diese 1810 veröffentlichte [1]. Die erste dokumentierte medizinische Umsetzung stellten Hygienevorschriften für Ärzte dar, die Ignaz Philipp Semmelweis nach 1847 in der Wiener Klinik für Geburtshilfe einführte [2].

  15. Vacuum die attach for integrated circuits

    DOEpatents

    Schmitt, Edward H.; Tuckerman, David B.

    1991-01-01

    A thin film eutectic bond for attaching an integrated circuit die to a circuit substrate is formed by coating at least one bonding surface on the die and substrate with an alloying metal, assembling the die and substrate under compression loading, and heating the assembly to an alloying temperature in a vacuum. A very thin bond, 10 microns or less, which is substantially void free, is produced. These bonds have high reliability, good heat and electrical conduction, and high temperature tolerance. The bonds are formed in a vacuum chamber, using a positioning and loading fixture to compression load the die, and an IR lamp or other heat source. For bonding a silicon die to a silicon substrate, a gold silicon alloy bond is used. Multiple dies can be bonded simultaneously. No scrubbing is required.

  16. THz Medical Imaging: in vivo Hydration Sensing

    PubMed Central

    Taylor, Zachary D.; Singh, Rahul S.; Bennett, David B.; Tewari, Priyamvada; Kealey, Colin P.; Bajwa, Neha; Culjat, Martin O.; Stojadinovic, Alexander; Lee, Hua; Hubschman, Jean-Pierre; Brown, Elliott R.; Grundfest, Warren S.

    2015-01-01

    The application of THz to medical imaging is experiencing a surge in both interest and federal funding. A brief overview of the field is provided along with promising and emerging applications and ongoing research. THz imaging phenomenology is discussed and tradeoffs are identified. A THz medical imaging system, operating at ~525 GHz center frequency with ~125 GHz of response normalized bandwidth is introduced and details regarding principles of operation are provided. Two promising medical applications of THz imaging are presented: skin burns and cornea. For burns, images of second degree, partial thickness burns were obtained in rat models in vivo over an 8 hour period. These images clearly show the formation and progression of edema in and around the burn wound area. For cornea, experimental data measuring the hydration of ex vivo porcine cornea under drying is presented demonstrating utility in ophthalmologic applications. PMID:26085958

  17. Nucleosome dynamics during chromatin remodeling in vivo.

    PubMed

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation.

  18. Trafficking of Aminoglycosides Into Endolymph in Vivo

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Steyger, Peter S.

    2009-02-01

    In vitro, aminoglycosides increase the stiffness of cochlear hair cell stereocilia, altering bundle motion and transduction kinetics. Aminoglycosides also permeate the mechanosensitive transduction channel and rapidly initiate cytotoxicity in hair cells. If these effects occur in vivo, aminoglycosides would need to enter endolymph. The most direct route for systemically-administered aminoglycosides to enter endolymph is by trafficking from strial capillaries across the stria vascularis. An as-yet-unidentified active transporter is required to translocate aminoglycosides from the intra-strial space into the cytoplasm of marginal cells. Once in marginal cells, aminoglycosides would passively flow down the electrochemical gradient into endolymph. We present data that support a trans-strial trafficking route of aminoglycosides into endolymph, where they can then interfere with the mechanosensitive hair bundles.

  19. In Vivo Biomarkers for Targeting Colorectal Neoplasms

    PubMed Central

    Hsiung, Pei-Lin; Wang, Thomas

    2011-01-01

    Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

  20. Implantable optoelectronic probes for in vivo optogenetics.

    PubMed

    Iseri, Ege; Kuzum, Duygu

    2017-02-15

    More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

  1. Implantable optoelectronic probes for in vivo optogenetics

    NASA Astrophysics Data System (ADS)

    Iseri, Ege; Kuzum, Duygu

    2017-06-01

    More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

  2. In vivo OCT microangiography of rodent iris.

    PubMed

    Choi, Woo June; Zhi, Zhongwei; Wang, Ruikang K

    2014-04-15

    We report on the functional optical coherence tomography (OCT) imaging of iris tissue morphology and microcirculation in living small animals. Anterior segments of healthy mouse and rat eyes are imaged with high-speed spectral domain OCT (SD-OCT) utilizing ultrahigh sensitive optical microangiography (UHS-OMAG) imaging protocol. 3D iris microvasculature is produced by the use of an algorithm that calculates absolute differences between the amplitudes of the OCT interframes. We demonstrate that the UHS-OMAG is capable of delineating iris microvascular beds in the mouse and rat with capillary-level resolution. Furthermore, the fast imaging speed enables dynamic imaging of iris micro-vascular response during drug-induced pupil dilation. We believe that this OCT angiographic approach has a great potential for in situ and in vivo monitoring of the microcirculation within iris tissue beds in rodent disease models that have microvascular involvement.

  3. An excitatory GABA loop operating in vivo

    PubMed Central

    Astorga, Guadalupe; Bao, Jin; Marty, Alain; Augustine, George J.; Franconville, Romain; Jalil, Abdelali; Bradley, Jonathan; Llano, Isabel

    2015-01-01

    While it has been proposed that the conventional inhibitory neurotransmitter GABA can be excitatory in the mammalian brain, much remains to be learned concerning the circumstances and the cellular mechanisms governing potential excitatory GABA action. Using a combination of optogenetics and two-photon calcium imaging in vivo, we find that activation of chloride-permeable GABAA receptors in parallel fibers (PFs) of the cerebellar molecular layer of adult mice causes parallel fiber excitation. Stimulation of PFs at submaximal stimulus intensities leads to GABA release from molecular layer interneurons (MLIs), thus creating a positive feedback loop that enhances excitation near the center of an activated PF bundle. Our results imply that elevated chloride concentration can occur in specific intracellular compartments of mature mammalian neurons and suggest an excitatory role for GABAA receptors in the cerebellar cortex of adult mice. PMID:26236197

  4. Quantifying drug-protein binding in vivo.

    SciTech Connect

    Buchholz, B; Bench, G; Keating III, G; Palmblad, M; Vogel, J; Grant, P G; Hillegonds, D

    2004-02-17

    Accelerator mass spectrometry (AMS) provides precise quantitation of isotope labeled compounds that are bound to biological macromolecules such as DNA or proteins. The sensitivity is high enough to allow for sub-pharmacological (''micro-'') dosing to determine macromolecular targets without inducing toxicities or altering the system under study, whether it is healthy or diseased. We demonstrated an application of AMS in quantifying the physiologic effects of one dosed chemical compound upon the binding level of another compound in vivo at sub-toxic doses [4].We are using tissues left from this study to develop protocols for quantifying specific binding to isolated and identified proteins. We also developed a new technique to quantify nanogram to milligram amounts of isolated protein at precisions that are comparable to those for quantifying the bound compound by AMS.

  5. 3D Ultrafast Ultrasound Imaging In Vivo

    PubMed Central

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-01-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative real-time imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in three dimensions based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32×32 matrix-array probe. Its capability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3-D Shear-Wave Imaging, 3-D Ultrafast Doppler Imaging and finally 3D Ultrafast combined Tissue and Flow Doppler. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3-D Ultrafast Doppler was used to obtain 3-D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, for the first time, the complex 3-D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, and the 3-D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3-D Ultrafast Ultrasound Imaging for the 3-D real-time mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra- and inter-observer variability. PMID:25207828

  6. In Vivo Dedifferentiation of Adult Adipose Cells

    PubMed Central

    Lu, Feng; Dong, Ziqing; Chang, Qiang; Gao, Jianhua

    2015-01-01

    Introduction Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown. Methods A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining. Results The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells. Conclusions Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a

  7. 3D ultrafast ultrasound imaging in vivo.

    PubMed

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-07

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability.

  8. Mesenchymal stem cells show radioresistance in vivo.

    PubMed

    Singh, Sarvpreet; Kloss, Frank R; Brunauer, Regina; Schimke, Magdalena; Jamnig, Angelika; Greiderer-Kleinlercher, Brigitte; Klima, Günter; Rentenberger, Julia; Auberger, Thomas; Hächl, Oliver; Rasse, Michael; Gassner, Robert; Lepperdinger, Günter

    2012-04-01

    Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells' self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.

  9. 3D ultrafast ultrasound imaging in vivo

    NASA Astrophysics Data System (ADS)

    Provost, Jean; Papadacci, Clement; Esteban Arango, Juan; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability.

  10. Dimerization of visual pigments in vivo

    PubMed Central

    Zhang, Tao; Cao, Li-Hui; Kumar, Sandeep; Enemchukwu, Nduka O.; Zhang, Ning; Lambert, Alyssia; Zhao, Xuchen; Jones, Alex; Wang, Shixian; Dennis, Emily M.; Fnu, Amrita; Ham, Sam; Rainier, Jon; Yau, King-Wai; Fu, Yingbin

    2016-01-01

    It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin+Lrat−/−) expressing, transgenically, short-wavelength–sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor’s outer segment. In R-opsin’s absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin’s presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptide-competition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling. PMID:27462111

  11. In vivo light dosimetry for pleural PDT

    NASA Astrophysics Data System (ADS)

    Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Culligan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

    2009-02-01

    In-vivo light Dosimetry for patients undergoing photodynamic therapy (PDT) is one of the important dosimetry quantities critical for predicting PDT outcome. This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area, and its accuracy as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here were enrolled in Phase II clinical trial of Photofrin-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. The ages of the patients studied varied from 34 to 69 year old. All patients were administered 2mg per kg body weight Photoprin 24 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with laser light with a light fluence of 60 J/cm^2 at 630nm. Fluence rate (mW/cm^2) and cumulative fluence (J/cm^2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 30%. The mean fluence rate delivery varied from 37.84 to 94.05 mW/cm^2 and treatment time varied from 1762 to 5232s. We have established a correlation between the treatment time and the treatment volume. The results are discussed using an integrating sphere theory and the measured tissue optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

  12. In vivo Raman spectroscopy of cervix cancers

    NASA Astrophysics Data System (ADS)

    Rubina, S.; Sathe, Priyanka; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Krishna, C. Murali

    2014-03-01

    Cervix-cancer is the third most common female cancer worldwide. It is the leading cancer among Indian females with more than million new diagnosed cases and 50% mortality, annually. The high mortality rates can be attributed to late diagnosis. Efficacy of Raman spectroscopy in classification of normal and pathological conditions in cervix cancers on diverse populations has already been demonstrated. Our earlier ex vivo studies have shown the feasibility of classifying normal and cancer cervix tissues as well as responders/non-responders to Concurrent chemoradiotherapy (CCRT). The present study was carried out to explore feasibility of in vivo Raman spectroscopic methods in classifying normal and cancerous conditions in Indian population. A total of 182 normal and 132 tumor in vivo Raman spectra, from 63 subjects, were recorded using a fiberoptic probe coupled HE-785 spectrometer, under clinical supervision. Spectra were acquired for 5 s and averaged over 3 times at 80 mW laser power. Spectra of normal conditions suggest strong collagenous features and abundance of non-collagenous proteins and DNA in case of tumors. Preprocessed spectra were subjected to Principal Component-Linear Discrimination Analysis (PCLDA) followed by leave-one-out-cross-validation. Classification efficiency of ~96.7% and 100% for normal and cancerous conditions respectively, were observed. Findings of the study corroborates earlier studies and suggest applicability of Raman spectroscopic methods in combination with appropriate multivariate tool for objective, noninvasive and rapid diagnosis of cervical cancers in Indian population. In view of encouraging results, extensive validation studies will be undertaken to confirm the findings.

  13. The Right To Die. Public Talk Series.

    ERIC Educational Resources Information Center

    Pasquerella, Lynn

    This program guide on the right to die provides policy issue information where ethical concerns have a prominent place. Three positions about the right to die are presented: (1) mercy killing and assisted suicide should be legally permitted in certain cases; (2) legal status should be given to living wills and other advance directives that would…

  14. Energy Consumption of Die Casting Operations

    SciTech Connect

    Jerald Brevick; clark Mount-Campbell; Carroll Mobley

    2004-03-15

    Molten metal processing is inherently energy intensive and roughly 25% of the cost of die-cast products can be traced to some form of energy consumption [1]. The obvious major energy requirements are for melting and holding molten alloy in preparation for casting. The proper selection and maintenance of melting and holding equipment are clearly important factors in minimizing energy consumption in die-casting operations [2]. In addition to energy consumption, furnace selection also influences metal loss due to oxidation, metal quality, and maintenance requirements. Other important factors influencing energy consumption in a die-casting facility include geographic location, alloy(s) cast, starting form of alloy (solid or liquid), overall process flow, casting yield, scrap rate, cycle times, number of shifts per day, days of operation per month, type and size of die-casting form of alloy (solid or liquid), overall process flow, casting yield, scrap rate, cycle times, number of shifts per day, days of operation per month, type and size of die-casting machine, related equipment (robots, trim presses), and downstream processing (machining, plating, assembly, etc.). Each of these factors also may influence the casting quality and productivity of a die-casting enterprise. In a die-casting enterprise, decisions regarding these issues are made frequently and are based on a large number of factors. Therefore, it is not surprising that energy consumption can vary significantly from one die-casting enterprise to the next, and within a single enterprise as function of time.

  15. Prediction of Part Distortion in Die Casting

    SciTech Connect

    R. Allen Miller

    2005-03-30

    The die casting process is one of the net shape manufacturing techniques and is widely used to produce high production castings with tight tolerances for many industries. An understanding of the stress distribution and the deformation pattern of parts produced by die casting will result in less deviation from the part design specification, a better die design and eventually more productivity and cost savings. This report presents methods that can be used to simulate the die casting process in order to predict the deformation and stresses in the produced part and assesses the degree to which distortion modeling is practical for die casting at the current time. A coupled thermal-mechanical finite elements model was used to simulate the die casting process. The simulation models the effect of thermal and mechanical interaction between the casting and the die. It also includes the temperature dependant material properties of the casting. Based on a designed experiment, a sensitivity analysis was conducted on the model to investigate the effect of key factors. These factors include the casting material model, material properties and thermal interaction between casting and dies. To verify the casting distortion predictions, it was compared against the measured dimensions of produced parts. The comparison included dimensions along and across the parting plane and the flatness of one surface.

  16. Die Evolution der Religiosität

    NASA Astrophysics Data System (ADS)

    Voland, Eckart

    Ein konsequent darwinischer Blick auf den Menschen bedeutet, auch im Denken, Fühlen und Handeln biologische Anpassungsgeschichte zu suchen, denn auch die psychischen und mentalen Eigenheiten des Homo sapiens unterliegen der natürlichen Selektion. Lässt sich die religiöse Lebenspraxis von Menschen daher auch aus einer Fitnessperspektive betrachten?

  17. Death and Dying: Issues for Educational Gerontologists.

    ERIC Educational Resources Information Center

    Wass, Hannelore, Myers, Jane E.

    1984-01-01

    Reviews research on death orientations, the dying process, and bereavement, with a major focus on the elderly. Suggests that relevant knowledge about death and dying are important for gerontological practitioners and proposes that death-related content be systematically integrated into academic curricula at the preservice and inservice levels.…

  18. Apparatus for restraining and transporting dies

    DOEpatents

    Allison, James W.; LaBarre, Timothy L.

    1994-01-01

    Apparatus for restraining and transporting dies in punch press operations is provided. A floatation platen for supporting a die on the platen's upper surface has a plurality of recessed gas exhaust ports on the platen's lower surface. A source of pressurized gas delivers gas to a platen manifold, for delivery to orifices located in the gas exhaust ports. The flow of gas is controlled by a first valve adjacent the gas source and a second valve adjacent the manifold, with the second valve being used to control the gas flow during movement of the die. In this fashion, a die may be moved on a cushion of air from one workstation to a selected second workstation. A moveable hydraulically operated restraining fixture is also provided, for clamping the die in position during the compacting phase, and for releasing the die after completion of the compacting phase by releasing the hydraulic pressure on the restraining fixture. When pressure in the hydraulic cylinders on the restraining fixture is reversed, the restraining fixture will retract so that there is no contact between the die and the restraining fixture, thereby allowing the die to be removed from a first workstation and moved to a second selected workstation.

  19. Student Nurses' Perception of Death and Dying

    ERIC Educational Resources Information Center

    Niederriter, Joan E.

    2009-01-01

    Student nurses are involved in caring for patients who are actively dying or who have been told they have a terminal illness and are faced with the process of dying. Students encounter these patients in hospitals, nursing homes, at home or in hospice care settings. According to Robinson (2004), "nurses are the healthcare providers that are most…

  20. In Vivo Monitoring Program Manual, PNL-MA-574

    SciTech Connect

    Lynch, Timothy P.

    2010-07-01

    An overview of the administration for the In Vivo Monitoring Program (IVMP) for Hanford. This includes organizational structure and program responsibilities; coordination of in vivo measurements; scheduling measurements; performing measurements; reporting results; and quality assurance. Overall responsibility for the management of the IVMP rests with the Program Manager (PM). The PM is responsible for providing the required in vivo counting services for Hanford Site contractor employees in accordance with Department of Energy (DOE) requirements and the specific statements of work.

  1. Passive in vivo elastography from skeletal muscle noise

    SciTech Connect

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-05-07

    Measuring the in vivo elastic properties of muscles (e.g., stiffness) provides a means for diagnosing and monitoring muscular activity. The authors demonstrated a passive in vivo elastography technique without an active external radiation source. This technique instead uses cross correlations of contracting skeletal muscle noise recorded with skin-mounted sensors. Each passive sensor becomes a virtual in vivo shear wave source. The results point to a low-cost, noninvasive technique for monitoring biomechanical in vivo muscle properties. The efficacy of the passive elastography technique originates from the high density of cross paths between all sensor pairs, potentially achieving the same sensitivity obtained from active elastography methods.

  2. Passive in vivo elastography from skeletal muscle noise

    NASA Astrophysics Data System (ADS)

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-05-01

    Measuring the in vivo elastic properties of muscles (e.g., stiffness) provides a means for diagnosing and monitoring muscular activity. The authors demonstrated a passive in vivo elastography technique without an active external radiation source. This technique instead uses cross correlations of contracting skeletal muscle noise recorded with skin-mounted sensors. Each passive sensor becomes a virtual in vivo shear wave source. The results point to a low-cost, noninvasive technique for monitoring biomechanical in vivo muscle properties. The efficacy of the passive elastography technique originates from the high density of cross paths between all sensor pairs, potentially achieving the same sensitivity obtained from active elastography methods.

  3. In-vivo multispectral video endoscopy towards in-vivo hyperspectral video endoscopy.

    PubMed

    Hohmann, Martin; Kanawade, R; Klämpfl, F; Douplik, A; Mudter, J; Neurath, M F; Albrecht, H

    2016-07-12

    For in-vivo diagnostics of cancer and pre-cancer in the stomach, there is no endoscopic procedure offering both high sensitivity and high specificity. Our data suggest that multispectral or hyperspectral imaging may be helpful to solve this problem. It is successfully applied to the detection and analysis of easily reachable carcinomas, ex-vivo samples of hollow organ mucosal carcinomas and also histological samples. An endoscopy system which allows flexible multispectral videoendoscopy for in-vivo diagnostics has so far been unavailable. To overcome this problem, we modified a standard Olympus endoscopy system to conduct in-vivo multispectral imaging of the upper GI tract. The pilot study is performed on 14 patients with adeno carcinomas in the stomach. For analysis, Support Vector Machine with linear and Gaussian Kernel, AdaBoost, RobustBoost and Random-Forest-walk are used and compared for the data classification with a leave-one-out strategy. The margin of the carcinoma for the training of the classifier is drawn by expert-labeling. The cancer findings are cross-checked by biopsies. We expect that the present study will help to improve the further development of hyperspectral endoscopy and to overcome some of the problems to be faced in this process.

  4. Influence of die geometry and material selection on the behavior of protective die covers in closed-die forging

    NASA Astrophysics Data System (ADS)

    Yu, Yingyan; Rosenstock, Dirk; Wolfgarten, Martin; Hirt, Gerhard

    2016-10-01

    Due to the fact that tooling costs make up to 30% of total costs of the final forged part, the tool life is always one main research topic in closed-die forging [1]. To improve the wear resistance of forging dies, many methods like nitriding and deposition of ceramic layers have been used. However, all these methods will lose its effect after a certain time, then tool repair or exchange is needed, which requires additional time and costs. A new method, which applies an inexpensive and changeable sheet metal on the forging die to protect it from abrasive wear, was firstly proposed in [2]. According to the first investigation, the die cover is effective for decreasing thermal and mechanical loads, but there are still several challenges to overcome in this concept, like wrinkling and thinning of the die cover. Therefore, an experimental study using different geometries and die cover materials is presented within this work. The results indicate the existence of feasible application cases of this concept, since conditions are found under which a die cover made of 22MnB5 still keeps its original shape even after 7 forging cycles.

  5. Viral Vectors for in Vivo Gene Transfer

    NASA Astrophysics Data System (ADS)

    Thévenot, E.; Dufour, N.; Déglon, N.

    The transfer of DNA into the nucleus of a eukaryotic cell (gene transfer) is a central theme of modern biology. The transfer is said to be somatic when it refers to non-germline organs of a developed individual, and germline when it concerns gametes or the fertilised egg of an animal, with the aim of transmitting the relevant genetic modification to its descendents [1]. The efficient introduction of genetic material into a somatic or germline cell and the control of its expression over time have led to major advances in understanding how genes work in vivo, i.e., in living organisms (functional genomics), but also to the development of innovative therapeutic methods (gene therapy). The efficiency of gene transfer is conditioned by the vehicle used, called the vector. Desirable features for a vector are as follows: Easy to produce high titer stocks of the vector in a reproducible way. Absence of toxicity related to transduction (transfer of genetic material into the target cell, and its expression there) and no immune reaction of the organism against the vector and/or therapeutic protein. Stability in the expression of the relevant gene over time, and the possibility of regulation, e.g., to control expression of the therapeutic protein on the physiological level, or to end expression at the end of treatment. Transduction of quiescent cells should be as efficient as transduction of dividing cells. Vectors currently used fall into two categories: non-viral and viral vectors. In non-viral vectors, the DNA is complexed with polymers, lipids, or cationic detergents (described in Chap. 3). These vectors have a low risk of toxicity and immune reaction. However, they are less efficient in vivo than viral vectors when it comes to the number of cells transduced and long-term transgene expression. (Naked DNA transfer or electroporation is rather inefficient in the organism. This type of gene transfer will not be discussed here, and the interested reader is referred to the

  6. Translational In Vivo Models for Cardiovascular Diseases.

    PubMed

    Fliegner, Daniela; Gerdes, Christoph; Meding, Jörg; Stasch, Johannes-Peter

    2016-01-01

    Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases.

  7. Sustained TRPA1 activation in vivo.

    PubMed

    Koivisto, A

    2012-02-01

    Transient receptor potential A1 (TRPA1) is a calcium permeable non-selective cation channel that is selectively localized to peptidergic C-fibres in the pain pathway. TRPA1 is highly conserved across the animal kingdom and it is able to detect a wide range of potentially toxic environmental chemicals. An unusual mechanism of TRPA1 activation was recently elucidated in which reactive agonists bind covalently to cysteines and lysine in the intracellular N-terminus. Despite a covalent activation mechanism, only transient TRPA1 activation is seen in the maintained presence of reactive agonists in whole-cell patch clamp experiments. I suggest that previous patch clamp studies are performed under conditions that do not fully mimic all aspects of TRPA1 activation. Here, I argue that compelling evidence exists for sustained TRPA1 activation in several chronic (neuropathic) pain-related pathophysiological conditions in vivo. I discuss briefly putative mechanisms that are likely to contribute to and maintain sustained TRPA1 agonist levels through increased production and/or decreased metabolism and inactivation. Chronic pain can be understood as a false alarm evoked by sustained and increased levels of endogenous TRPA1 agonists in various pathophysiological conditions.

  8. Optical stimulation of peripheral nerves in vivo

    NASA Astrophysics Data System (ADS)

    Wells, Jonathon D.

    This dissertation documents the emergence and validation of a new clinical tool that bridges the fields of biomedical optics and neuroscience. The research herein describes an innovative method for direct neurostimulation with pulsed infrared laser light. Safety and effectiveness of this technique are first demonstrated through functional stimulation of the rat sciatic nerve in vivo. The Holmium:YAG laser (lambda = 2.12 mum) is shown to operate at an optimal wavelength for peripheral nerve stimulation with advantages over standard electrical neural stimulation; including contact-free stimulation, high spatial selectivity, and lack of a stimulation artifact. The underlying biophysical mechanism responsible for transient optical nerve stimulation appears to be a small, absorption driven thermal gradient sustained at the axonal layer of nerve. Results explicitly prove that low frequency optical stimulation can reliably stimulate without resulting in tissue thermal damage. Based on the positive results from animal studies, these optimal laser parameters were utilized to move this research into the clinic with a combined safety and efficacy study in human subjects undergoing selective dorsal rhizotomy. The clinical Holmium:YAG laser was used to effectively stimulate human dorsal spinal roots and elicit functional muscle responses recorded during surgery without evidence of nerve damage. Overall these results predict that this technology can be a valuable clinical tool in various neurosurgical applications.

  9. Novel thermosensitive chitosan hydrogels: in vivo evaluation.

    PubMed

    Patois, Emilie; Osorio-da Cruz, Suzanne; Tille, Jean-Christophe; Walpoth, Beat; Gurny, Robert; Jordan, Olivier

    2009-11-01

    Chitosan is an attractive biopolymer for the preparation of hydrogels. Its unique combination of biocompatibility, biodegradability, bioadhesivity, and tissue-promoting abilities allows pharmaceutical applications. We investigated novel thermosensitive hydrogels based on chitosan homogeneously reacetylated to a deacetylation degree of about 50%, combined with selected polyols or polyoses such as trehalose, a nontoxic polysaccharide. The latter, a gel-inducing and lyoprotective agent enabled the formulation to be lyophilized and rehydrated without affecting the thermosensitive behavior. This made possible long-term storage and promoted its use in a clinical setup. The thermally induced sol-gel transition allowed injectability and in situ setting. Rheological characterization revealed that storage moduli could be increased by one decade by increasing the chitosan concentration from 1.4 to 2.2% (w/w). Evaluation in vivo provided evidence of in situ implant formation in subcutaneous tissue of Sprague-Dawley rats and permanence for up to 3 months. Histopathological analysis demonstrated a mild, chronic, inflammatory reaction that disappeared with the complete absorption of the gel implant over a few months period. Such in situ forming hydrogels could be advantageous for specific applications in drug delivery and tissue engineering.

  10. Astrocytes regulate cortical state switching in vivo

    PubMed Central

    Poskanzer, Kira E.; Yuste, Rafael

    2016-01-01

    The role of astrocytes in neuronal function has received increasing recognition, but disagreement remains about their function at the circuit level. Here we use in vivo two-photon calcium imaging of neocortical astrocytes while monitoring the activity state of the local neuronal circuit electrophysiologically and optically. We find that astrocytic calcium activity precedes spontaneous circuit shifts to the slow-oscillation–dominated state, a neocortical rhythm characterized by synchronized neuronal firing and important for sleep and memory. Further, we show that optogenetic activation of astrocytes switches the local neuronal circuit to this slow-oscillation state. Finally, using two-photon imaging of extracellular glutamate, we find that astrocytic transients in glutamate co-occur with shifts to the synchronized state and that optogenetically activated astrocytes can generate these glutamate transients. We conclude that astrocytes can indeed trigger the low-frequency state of a cortical circuit by altering extracellular glutamate, and therefore play a causal role in the control of cortical synchronizations. PMID:27122314

  11. Uncoupling Caveolae from Intracellular Signaling In Vivo

    PubMed Central

    Kraehling, Jan R.; Hao, Zhengrong; Lee, Monica Y.; Vinyard, David J.; Velazquez, Heino; Liu, X.; Stan, Radu V.; Brudvig, Gary W.; Sessa, William C.

    2015-01-01

    Rationale Caveolin-1 negatively regulates eNOS derived NO production and this has been mapped to several residues on Cav-1 including F92. Herein, we reasoned that endothelial expression of an F92ACav-1 transgene would let us decipher the mechanisms and relationships between caveolae structure and intracellular signaling. Objective This study was designed to separate caveolae formation from its downstream signaling effects. Methods and Results An endothelial-specific doxycycline-regulated mouse model for the expression of Cav-1-F92A was developed. Blood pressure by telemetry and nitric oxide bioavailability by electron paramagnetic resonance and phosphorylation of VASP were determined. Caveolae integrity in the presence of Cav-1-F92A was measured by stabilization of Cav-2, sucrose gradient and electron microscopy. Histological analysis of heart and lung, echocardiography and signaling were performed. Conclusions This study shows that mutant Cav-1-F92A forms caveolae structures similar to WT but leads to increases in NO bioavailability in vivo thereby demonstrating that caveolae formation and downstream signaling events occur through independent mechanisms. PMID:26602865

  12. Wireless Monitoring of Liver Hemodynamics In Vivo

    SciTech Connect

    Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance; Farquhar, Ethan; Cote, Gerard L.

    2014-01-01

    Liver transplants have their highest technical failure rate in the first two weeks following surgery. Currently, there are limited devices for continuous, real-time monitoring of the graft. In this work, a three wavelengths system is presented that combines near-infrared spectroscopy and photoplethysmography with a processing method that can uniquely measure and separate the venous and arterial oxygen contributions. This strategy allows for the quantification of tissue oxygen consumption used to study hepatic metabolic activity and to relate it to tissue stress. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two in vivo porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.135 mL/min/g of tissue. We show the possibility of using the pulsatile wave to measure the arterial oxygen saturation similar to pulse oximetry. The signal is also used to extract the venous oxygen saturation from the direct current (DC) levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19% and 1.39% respectively when no vascular occlusions were induced. This error increased to 2.82% and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of a commercial oximetry catheter used as a reference. This work is the first realization of a wireless optical sensor for continuous monitoring of hepatic hemodynamics.

  13. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

    Uhoda, E; Goffin, V; Pierard, G E

    2003-12-01

    Skin is subjected to many environmental threats, some of which altering the structure and function of the stratum corneum. Among them, surfactants are recognized factors that may influence irritant contact dermatitis. The present study was conducted to compare the variations in skin capacitance and corneosurfametry (CSM) reactivity before and after skin exposure to repeated subclinical injuries by 2 hand dishwashing liquids. A forearm immersion test was performed on 30 healthy volunteers. 2 daily soak sessions were performed for 5 days. At inclusion and the day following the last soak session, skin capacitance was measured and cyanoacrylate skin-surface strippings were harvested. The latter specimens were used for the ex vivo microwave CSM. Both types of assessments clearly differentiated the 2 hand dishwashing liquids. The forearm immersion test allowed the discriminant sensitivity of CSM to increase. Intact skin capacitance did not predict CSM data. By contrast, a significant correlation was found between the post-test conductance and the corresponding CSM data. In conclusion, a forearm immersion test under realistic conditions can discriminate the irritation potential between surfactant-based products by measuring skin conductance and performing CSM. In vivo skin preconditioning by surfactants increases CSM sensitivity to the same surfactants.

  14. Difficulty in dislodging in vivo fixed radiostrontium.

    PubMed

    Sonawane, V R; Jagtap, V S; Pahuja, D N; Rajan, M G R; Samuel, A M

    2004-07-01

    Many trials based on the basic phenomena of isotopic dilution, adsorption, ion exchange, chelation, etc., have been attempted for the decorporation of radiostrontium, particularly Sr, after its entry in the in vivo system. We have recently demonstrated a non-isotopic carrier effect of some common calcium salts (calcium = 9 mg mL) to reduce the whole body retention of radiostrontium, if administered within 2 h after radiostrontium exposure and furthermore once daily, in rats, supplemented with calcium fortified diet. However, 25-30% of radiostrontium (compared to 50-60% in untreated animals) was still found to be retained in the animal even after 2 wk of treatment. Trial of some simple interventional measures, which would not adversely affect the animal metabolism, like pyrophosphate and magnesium sulfate, sodium citrate, chitin (a bio-absorbent), crown ether (a metal-chelator), and ammonium chloride, was therefore attempted to dislodge this remaining radiostrontium by switching over these animals to normal diet and subjecting them to different lines of treatment with these simple interventions through diet and drinking water separately for a further 4 wk. However, this remaining portion of radiostrontium is fixed in the bone and is difficult to dislodge.

  15. Interproximal enamel reduction: an in vivo study.

    PubMed

    Paganelli, Corrado; Zanarini, Matteo; Pazzi, Elisabetta; Marchionni, Silvia; Visconti, Luca; Alessandri Bonetti, Giulio

    2015-01-01

    The study aimed to investigate the morphology and composition of the interproximal reduced enamel after exposition to saliva and casein phosphopeptide amorphous calcium phosphate with sodium fluoride (CPP-ACPF). Fourteen patients undergoing an orthodontic treatment with 4 premolars extractions participated to the study. Interproximal enamel reduction (IER) was performed on mesial surfaces of 3 extractive premolars for each patient while 1 served as untreated control. Premolars were assigned to 4 groups: No-S group, sound enamel as control; S-Ex group, stripped and immediately extracted enamel; S-Sal group, stripped and exposed to saliva enamel; S-CPP group, stripped enamel treated with CPP-ACPF. Teeth were extracted at different times, depending on the group they were assigned to and sliced into mesial and distal halves. Mesial surfaces were subjected to environmental scanning electron microscopy with energy dispersive X-ray spectrometry (ESEM/EDX) and to scanning electron microscopy (SEM) analysis. ESEM/EDX investigations showed no statistically significant differences in the content of calcium and phosphate between the 4 groups. SEM observations showed no difference in the morphological appearance of stripped enamel after 30 days of exposure to saliva and CPP-ACPF. Saliva and CPP-ACPF effects on stripped enamel in vivo showed no difference after 30 days.

  16. In vivo photoacoustic imaging of mouse embryos

    NASA Astrophysics Data System (ADS)

    Laufer, Jan; Norris, Francesca; Cleary, Jon; Zhang, Edward; Treeby, Bradley; Cox, Ben; Johnson, Peter; Scambler, Pete; Lythgoe, Mark; Beard, Paul

    2012-06-01

    The ability to noninvasively image embryonic vascular anatomy in mouse models is an important requirement for characterizing the development of the normal cardiovascular system and malformations in the heart and vascular supply. Photoacoustic imaging, which can provide high resolution non invasive images of the vasculature based upon optical absorption by endogenous hemoglobin, is well suited to this application. In this study, photoacoustic images of mouse embryos were obtained ex vivo and in vivo. The images show intricate details of the embryonic vascular system to depths of up to 10 mm, which allowed whole embryos to be imaged in situ. To achieve this, an all-optical photoacoustic scanner and a novel time reversal image reconstruction algorithm, which provide deep tissue imaging capability while maintaining high spatial resolution and contrast were employed. This technology may find application as an imaging tool for preclinical embryo studies in developmental biology as well as more generally in preclinical and clinical medicine for studying pathologies characterized by changes in the vasculature.

  17. In vivo experimental models of epilepsy.

    PubMed

    Rubio, Carmen; Rubio-Osornio, Moises; Retana-Márquez, Socorro; Verónica Custodio, Marisol López; Paz, Carlos

    2010-12-01

    This study reviews the different in vivo experimental models that have been used for the study of epileptogenesis. In this review we will focus on how to replicate the different models that have led to the study of partial seizures, as well as generalized seizures and the status epilepticus. The main characteristics that participate in the processes that generate and modulate the manifestations of different models of epileptogenesis are described. The development of several models of experimental epilepsy in animals has clearly helped the study of specific brain areas capable of causing convulsions. The experimental models of epilepsy also have helped in the study the mechanisms and actions of epilepsy drugs. In order to develop experimental animal models of epilepsy, animals are generally chosen according to the kind of epilepsy that can be developed and studied. It is currently known that animal species can have epileptic seizures similar to those in humans. However, it is important to keep in mind that it has not been possible to entirely evaluate all manifestations of human epilepsy. Notwithstanding, these experimental models of epilepsy have allowed a partial understanding of most of the underlying mechanisms of this disease.

  18. Approaches to localized NMR spectroscopy in vivo

    SciTech Connect

    Garwood, M.G.

    1985-01-01

    Nuclear magnetic resonance (NMR) techniques are developed which allow spatially localized spectra to be obtained from living tissue. The localization methods are noninvasive and exploit the enhanced sensitivity afforded by surface coil probes. Techniques are investigated by computer simulation and experimentally verified by the use of phantom samples. The feasibility and utility of the techniques developed in this research are demonstrated by /sup 31/P spatial localization experiments involving various in vivo organs. In the first part of the thesis, two feasible approaches to localized spectroscopy, which were developed by other laboratories are theoretically analyzed by computer simulation. An alternative approach is provided by the rotating frame zeugmatography experiment which affords chemical-shift spectra displayed as a function of penetration distance into the sample. The further modification of the rotating frame experiment is developed, the Fourier series window (FSW) approach, which utilizes various types of window functions to afford localization in one or a few tissue regions of interest with high sensitivity. Theoretical comparisons with depth pulse methods are also included, along with methods to refine adverse off-resonance behavior.

  19. Neuronal avalanches in spontaneous activity in vivo.

    PubMed

    Hahn, Gerald; Petermann, Thomas; Havenith, Martha N; Yu, Shan; Singer, Wolf; Plenz, Dietmar; Nikolic, Danko

    2010-12-01

    Many complex systems give rise to events that are clustered in space and time, thereby establishing a correlation structure that is governed by power law statistics. In the cortex, such clusters of activity, called "neuronal avalanches," were recently found in local field potentials (LFPs) of spontaneous activity in acute cortex slices, slice cultures, the developing cortex of the anesthetized rat, and premotor and motor cortex of awake monkeys. At present, it is unclear whether neuronal avalanches also exist in the spontaneous LFPs and spike activity in vivo in sensory areas of the mature brain. To address this question, we recorded spontaneous LFPs and extracellular spiking activity with multiple 4 × 4 microelectrode arrays (Michigan Probes) in area 17 of adult cats under anesthesia. A cluster of events was defined as a consecutive sequence of time bins Δt (1-32 ms), each containing at least one LFP event or spike anywhere on the array. LFP cluster sizes consistently distributed according to a power law with a slope largely above -1.5. In two thirds of the corresponding experiments, spike clusters also displayed a power law that displayed a slightly steeper slope of -1.8 and was destroyed by subsampling operations. The power law in spike clusters was accompanied with stronger temporal correlations between spiking activities of neurons that spanned longer time periods compared with spike clusters lacking power law statistics. The results suggest that spontaneous activity of the visual cortex under anesthesia has the properties of neuronal avalanches.

  20. Thermal Assisted In Vivo Gene Electrotransfer

    PubMed Central

    Donate, Amy; Bulysheva, Anna; Edelblute, Chelsea; Jung, Derrick; Malik, Mohammad A.; Guo, Siqi; Burcus, Niculina; Schoenbach, Karl; Heller, Richard

    2016-01-01

    Gene electrotransfer is an effective approach for delivering plasmid DNA to a variety of tissues. Delivery of molecules with electric pulses requires control of the electrical parameters to achieve effective delivery. Since discomfort or tissue damage may occur with high applied voltage, the reduction of the applied voltage while achieving the desired expression may be an important improvement. One possible approach is to combine electrotransfer with exogenously applied heat. Previous work performed in vitro demonstrated that increasing temperature before pulsing can enhance gene expres sion and made it possible to reduce electric fields while maintaining expression levels. In the study reported here, this combination was evaluated in vivo using a novel electrode device designed with an inserted laser for application of heat. The results obtained in this study demonstrated that increased temperature during electrotransfer increased expression or maintained expression with a reduction in applied voltage. With further optimization this approach may provide the basis for both a novel method and a novel instrument that may greatly enhance translation of gene electrotransfer. PMID:27029944

  1. Engineering Endochondral Bone: In Vivo Studies

    PubMed Central

    Oliveira, Serafim M.; Mijares, Dindo Q.; Turner, Gloria; Amaral, Isabel F.; Barbosa, Mário A.

    2009-01-01

    The use of biomaterials to replace lost bone has been a common practice for decades. More recently, the demands for bone repair and regeneration have pushed research into the use of cultured cells and growth factors in association with these materials. Here we report a novel approach to engineer new bone using a transient cartilage scaffold to induce endochondral ossification. Chondrocyte/chitosan scaffolds (both a transient cartilage scaffold—experimental—and a permanent cartilage scaffold—control) were prepared and implanted subcutaneously in nude mice. Bone formation was evaluated over a period of 5 months. Mineralization was assessed by Faxitron, micro computed tomography, backscatter electrons, and Fourier transform infrared spectroscopy analyses. Histological analysis provided further information on tissue changes in and around the implanted scaffolds. The deposition of ectopic bone was detected in the surface of the experimental implants as early as 1 month after implantation. After 3 months, bone trabeculae and bone marrow cavities were formed inside the scaffolds. The bone deposited was similar to the bone of the mice vertebra. Interestingly, no bone formation was observed in control implants. In conclusion, an engineered transient cartilage template carries all the signals necessary to induce endochondral bone formation in vivo. PMID:18759673

  2. In vivo multiphoton nanosurgery on cortical neurons.

    PubMed

    Sacconi, Leonardo; O'Connor, Rodney P; Jasaitis, Audrius; Masi, Alessio; Buffelli, Mario; Pavone, Francesco S

    2007-01-01

    Two-photon microscopy has been used to perform high spatial resolution imaging of spine plasticity in the intact neocortex of living mice. Multiphoton absorption has also been used as a tool for the selective disruption of cellular structures in living cells and simple organisms. In this work, we exploit the spatial localization of multiphoton excitation to perform selective lesions on the neuronal processes of cortical neurons in living mice expressing fluorescent proteins. Neurons are irradiated with a focused, controlled dose of femtosecond laser energy delivered through cranial optical windows. The morphological consequences are then characterized with time lapse 3-D two-photon imaging over a period of minutes to days after the procedure. This methodology is applied to dissect single dendrites with submicrometric precision without causing any visible collateral damage to the surrounding neuronal structures. The spatial precision of this method is demonstrated by ablating individual dendritic spines, while sparing the adjacent spines and the structural integrity of the dendrite. The combination of multiphoton nanosurgery and in vivo imaging in mammals represents a promising tool for neurobiology and neuropharmacology research.

  3. Tracking Mouse Bone Marrow Monocytes In Vivo

    PubMed Central

    Hamon, Pauline; Rodero, Mathieu Paul; Combadière, Christophe; Boissonnas, Alexandre

    2015-01-01

    Real time multiphoton imaging provides a great opportunity to study cell trafficking and cell-to-cell interactions in their physiological 3-dimensionnal environment. Biological activities of immune cells mainly rely on their motility capacities. Blood monocytes have short half-life in the bloodstream; they originate in the bone marrow and are constitutively released from it. In inflammatory condition, this process is enhanced, leading to blood monocytosis and subsequent infiltration of the peripheral inflammatory tissues. Identifying the biomechanical events controlling monocyte trafficking from the bone marrow towards the vascular network is an important step to understand monocyte physiopathological relevance. We performed in vivo time-lapse imaging by two-photon microscopy of the skull bone marrow of the Csf1r-Gal4VP16/UAS-ECFP (MacBlue) mouse. The MacBlue mouse expresses the fluorescent reporters enhanced cyan fluorescent protein (ECFP) under the control of a myeloid specific promoter 1, in combination with vascular network labelling. We describe how this approach enables the tracking of individual medullar monocytes in real time to further quantify the migratory behaviour within the bone marrow parenchyma and the vasculature, as well as cell-to-cell interactions. This approach provides novel insights into the biology of the bone marrow monocyte subsets and allows to further address how these cells can be influenced in specific pathological conditions. PMID:25867540

  4. Measuring apoptosis in mammals in vivo.

    PubMed

    Newbold, Andrea; Martin, Ben P; Cullinane, Carleen; Bots, Michael

    2014-11-03

    Apoptosis is a mode of cell death that is essential in multicellular organisms for the removal of superfluous, damaged, or potentially dangerous cells during development, infection, or normal tissue homeostasis. To prevent inflammation, cells undergoing apoptosis produce "find-me" signals that trigger the recruitment of phagocytes, which clear the apoptotic cells on recognition of "eat-me" signals. Despite the loss of billions of cells per day by apoptosis in the human body, the number of apoptotic cells found in healthy tissue is surprisingly low and reflects the efficiency of this process. However, in certain conditions (e.g., in cancer cells responding to chemotherapy), the number of apoptotic cells is too high to be efficiently cleared by phagocytes, and apoptotic cells can be observed. In these situations, the detection of apoptosis may be helpful in monitoring disease progression as well as in predicting the responses of tumors to anticancer therapies. Here we introduce various methods for monitoring apoptotic cells in vivo using a murine model of B-cell lymphoma and a solid tumor xenograft.

  5. Die chemische Fixierung von Kryptonisotopen in Zeolith 5 A — Voraussetzung für die Messung von 25 keV Neutroneneinfang- querschnitten mit der Aktivierungstechnik/ The Chemical Fixation of Kr Isotopes in Zeolite 5 A.- Prerequisite for the Determination of 25 keV Neutron Capture Cross Sections with the Activation Method

    NASA Astrophysics Data System (ADS)

    Penzhorn, R.-D.; Walter, G.; Beer, H.

    1983-07-01

    By chemical fixation of Kr in zeolite 5 A adequate samples can be obtained to determine the capture cross section of reactions such as 84 Kr (n, γ) 85Krm and 86Kr (n, γ) 87Kr. The employed zeolite loading was of the order 52-66 [cm3 STP Kr/g zeolite]. The capture cross section of the reaction 84Kr(n, γ) 85Krm was determined at thermal and 25 keV neutron energy. The value obtained at 25 keV is of relevance to the stellar nucleosynthesis of heavy elements.

  6. An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

    PubMed Central

    2011-01-01

    In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD) in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation. PMID:22165954

  7. In vivo and in vitro mixture modeling of endocrine disruptors

    EPA Science Inventory

    Humans, fish and wildlife are exposed to more than one chemical at a time. There is concern over the potential effects of exposure to mixtures of EDs. We have conducted invitro and in vivo studies to determine how EDs in mixtures interact. Our in vivo studies have examined the ef...

  8. In vivo analysis of Pim-1 deficiency.

    PubMed Central

    Laird, P W; van der Lugt, N M; Clarke, A; Domen, J; Linders, K; McWhir, J; Berns, A; Hooper, M

    1993-01-01

    The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase which is predominantly expressed in hematopoietic organs and gonads in mammals. Overexpression of Pim-1 predisposes to lymphomagenesis in mice. To develop a further understanding of Pim-1 in molecular terms, as well as in terms of its potential role in hematopoietic development, we have generated mice deficient in Pim-1 function. Pim-1-deficient mice are ostensibly normal, healthy and fertile. Detailed comparative analyses of the hematopoietic systems of the mutant mice and their wild-type littermates showed that they are indistinguishable for most of the parameters studied. Our analyses revealed one unexpected phenotype that correlated with the level of Pim-1 expression: Pim-1 deficiency correlated with a erythrocyte microcytosis, whereas overexpression of Pim-1 in E mu-Pim-1-transgenic mice resulted in erythrocyte macrocytosis. In order to confirm that the observed decrease in erythrocyte Mean Cell Volume (MCV) was attributable to the Pim-1 deficiency, we developed mice transgenic for a Pim-1 gene construct with its own promoter and showed that this transgene could restore the low erythrocyte Mean Cell Volume observed in the Pim-1-deficient mice to near wild-type levels. These results might be relevant to the observed involvement of the Pim-1 gene in mouse erythroleukemogenesis. The surprising lack of a readily observed phenotype in the lymphoid compartment of the Pim-1-deficient mice, suggests a heretofore unrecognized degree of in vivo functional redundancy of this highly conserved proto-oncogene. Images PMID:8233823

  9. Is there a moral duty to die?

    PubMed

    Corlett, J A

    2001-01-01

    In recent years, there has been a great deal of philosophical discussion about the alleged moral right to die. If there is such a moral right, then it would seem to imply a moral duty of others to not interfere with the exercise of the right. And this might have important implications for public policy insofar as public policy ought to track what is morally right. But is there a moral duty to die? If so, under what conditions, if any, ought one to have such a duty, and why? In this paper, I distinguish between different moral grounds for the putative moral duty to die: deontological, intuitionist, and contractarian. Subsequently, I argue in support of Paul Menzel's theory of health care distribution. More precisely, I concur with his claim that there is a moral duty to die inexpensively in health care contexts. Then I provide and defend a philosophical analysis of the conditions in which such a duty could exist.

  10. House of Lords debates assisted dying (again).

    PubMed

    2003-07-01

    Lord Joffe's Patient (Assisted Dying) Bill (see Bulletin 187) had its Second Reading on 6 June. The debate was lively, informed and inevitably somewhat polarised. However, some common themes emerged and are outlined below.

  11. Casting Characteristics of Aluminum Die Casting Alloys

    SciTech Connect

    Makhlouf M. Makhlouf; Diran Apelian

    2002-02-05

    The research program investigates the casting characteristics of selected aluminum die casting alloys. Specifically, the alloys' tendencies towards die soldering and sludge formation, and the alloys' fluidity and machinability are evaluated. It was found that: When the Fe and Mn contents of the alloy are low; caution has to be taken against possible die soldering. When the alloy has a high sludge factor, particularly a high level of Fe, measures must be taken to prevent the formation of large hardspots. For this kind of alloy, the Fe content should be kept at its lowest allowable level and the Mn content should be at its highest possible level. If there are problems in die filling, measures other than changing the alloy chemistry need to be considered first. In terms of alloy chemistry, the elements that form high temperature compounds must be kept at their lowest allowable levels. The alloys should not have machining problems when appropriate machining techniques and machining parameters are used.

  12. Percutaneous Valve Replacement: Significance of Different Delivery Systems In Vitro and In Vivo

    SciTech Connect

    Attmann, Tim; Lutter, Georg Quaden, Rene; Jahnke, Thomas; Rumberg, Kristin; Cremer, Jochen; Muller-Hulsbeck, Stefan

    2006-06-15

    Background and purpose. Percutaneous heart valve replacement is an exciting growing field in cardiovascular medicine yet still with some major problems. Only sophisticated improvement of the instruments could make it a real alternative to conventional surgery. Therefore, the aim of this study was to evaluate different delivery devices for percutaneous heart valve replacement in vitro and in vivo. Methods. A catheter prototype designed by our group, and two commercially available devices for the delivery of esophageal stents and aortic endoprostheses, were tested. After in vitro experiments, an ovine animal model of transfemoral pulmonary valve implantation was established using biological valved self-expanding stents. Only the delivery device for aortic endografts (Medtronic, Talent, Santa Rosa, CA, USA) allowed fast in vitro procedures without material fatigue. This device was chosen for the in vivo tests. Results. Technical success was achieved in 9 of 10 animals (90%). One animal died after perforation of the ventricular wall. Orthotopic pulmonary placement was performed in 6 animals and intentional supravalvular valved stent placement in 3 animals. Conclusions. An adequate in vitro model for this evolving field of interventional heart valve replacement is presented. Furthermore, the present study pinpoints the key characteristics that are mandatory for a delivery system in percutaneous pulmonary valve implantation. With regard to the delivery device's ductility observed during this 'venous' study, an approach to transfemoral aortic valve implantation seems feasible.

  13. Thick film silicon growth techniques. [die materials

    NASA Technical Reports Server (NTRS)

    Bates, H. E.; Mlavsky, A. I.; Jewett, D. N.; White, V. E.

    1973-01-01

    The research which was directed toward finding an improved die material is reported. Wetting experiments were conducted with various materials to determine their compatibility with silicon. Work has also continued toward the development of quartz as a die material as new techniques have provided more optimistic results than observed in the past. As a result of the thermal modification previously described, improvements in growth stability have contributed to an increase in ribbon quality.

  14. Machining of Silicon-Ribbon-Forming Dies

    NASA Technical Reports Server (NTRS)

    Menna, A. A.

    1985-01-01

    Carbon extension for dies used in forming silicon ribbon crystals machined precisely with help of special tool. Die extension has edges beveled toward narrow flats at top, with slot precisely oriented and centered between flats and bevels. Cutting tool assembled from standard angle cutter and circular saw or saws. Angle cutters cuts bevels while slot saw cuts slot between them. In alternative version, custom-ground edges or additional circular saws also cut flats simultaneously.

  15. In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

    PubMed Central

    Tang, Ho Lam; Tang, Ho Man; Fung, Ming Chiu; Hardwick, J. Marie

    2017-01-01

    Caspases are the key mediators of apoptotic cell death via their proteolytic activity. When caspases are activated in cells to levels detectable by available technologies, apoptosis is generally assumed to occur shortly thereafter. Caspases can cleave many functional and structural components to cause rapid and complete cell destruction within a few minutes. However, accumulating evidence indicates that in normal healthy cells the same caspases have other functions, presumably at lower enzymatic levels. Studies of non-apoptotic caspase activity have been hampered by difficulties with detecting low levels of caspase activity and with tracking ultimate cell fate in vivo. Here, we illustrate the use of an ultrasensitive caspase reporter, CaspaseTracker, which permanently labels cells that have experienced caspase activity in whole animals. This in vivo dual color CaspaseTracker biosensor for Drosophila melanogaster transiently expresses red fluorescent protein (RFP) to indicate recent or on-going caspase activity, and permanently expresses green fluorescent protein (GFP) in cells that have experienced caspase activity at any time in the past yet did not die. Importantly, this caspase-dependent in vivo biosensor readily reveals the presence of non-apoptotic caspase activity in the tissues of organ systems throughout the adult fly. This is demonstrated using whole mount dissections of individual flies to detect biosensor activity in healthy cells throughout the brain, gut, malpighian tubules, cardia, ovary ducts and other tissues. CaspaseTracker detects non-apoptotic caspase activity in long-lived cells, as biosensor activity is detected in adult neurons and in other tissues at least 10 days after caspase activation. This biosensor serves as an important tool to uncover the roles and molecular mechanisms of non-apoptotic caspase activity in live animals. PMID:27929458

  16. FK506 augments activation-induced programmed cell death of T lymphocytes in vivo.

    PubMed Central

    Migita, K; Eguchi, K; Kawabe, Y; Tsukada, T; Mizokami, A; Nagataki, S

    1995-01-01

    FK506 is an immunosuppressive drug that inhibits T cell receptor-mediated signal transduction. This drug can induce immunological tolerance in allograft recipients. In this study, we investigated the in vivo effects of FK506 on T cell receptor-mediated apoptosis induction. Injection of anti-CD3 antibody (Ab) in mice resulted in the elimination of CD4+ CD8+ thymocytes by DNA fragmentation. FK506 treatment significantly augmented thymic apoptosis induced by in vivo anti-CD3 Ab administration. Increased thymic apoptosis resulted in the disappearance of CD4+ CD8+ thymocytes after anti-CD3 Ab/FK506 treatment. DNA fragmentation triggered by FK506 was induced exclusively in antigen-stimulated T cells, since enhanced DNA fragmentation induced by in vivo staphylococcal enterotoxin B (SEB) injection was confirmed in SEB-reactive V beta 8+ thymocytes but not in SEB-nonreactive V beta 6+ thymocytes. In addition to thymocytes, mature peripheral T cells also die by activation-induced programmed cell death. A similar effect of FK506 on activation-induced programmed cell death was observed in SEB-activated peripheral spleen T cells. In contrast, cyclosporin A treatment did not enhance activation-induced programmed cell death of thymocytes and peripheral T cells. Apoptosis is required for the generation and maintenance of self-tolerance in the immune system. Our findings suggest that FK506-triggered apoptosis after elimination of antigen-activated T cells may represent a potential mechanism of the immunological tolerance achieved by FK506 treatment. Images PMID:7543492

  17. Celestial Fireworks from Dying Stars

    NASA Astrophysics Data System (ADS)

    2011-04-01

    This image of the nebula NGC 3582, which was captured by the Wide Field Imager on the MPG/ESO 2.2-metre telescope at ESO's La Silla Observatory in Chile, shows giant loops of gas bearing a striking resemblance to solar prominences. These loops are thought to have been ejected by dying stars, but new stars are also being born within this stellar nursery. These energetic youngsters emit intense ultraviolet radiation that makes the gas in the nebula glow, producing the fiery display shown here. NGC 3582 is part of a large star-forming region in the Milky Way, called RCW 57. It lies close to the central plane of the Milky Way in the southern constellation of Carina (The Keel of Jason's ship, the Argo). John Herschel first saw this complex region of glowing gas and dark dust clouds in 1834, during his stay in South Africa. Some of the stars forming in regions like NGC 3582 are much heavier than the Sun. These monster stars emit energy at prodigious rates and have very short lives that end in explosions as supernovae. The material ejected from these dramatic events creates bubbles in the surrounding gas and dust. This is the probable cause of the loops visible in this picture. This image was taken through multiple filters. From the Wide Field Imager, data taken through a red filter are shown in green and red, and data taken through a filter that isolates the red glow characteristic of hydrogen are also shown in red. Additional infrared data from the Digitized Sky Survey are shown in blue. The image was processed by ESO using the observational data identified by Joe DePasquale, from the United States [1], who participated in ESO's Hidden Treasures 2010 astrophotography competition [2]. The competition was organised by ESO in October-November 2010, for everyone who enjoys making beautiful images of the night sky using astronomical data obtained using professional telescopes. Notes [1] Joe searched through ESO's archive and identified datasets that he used to compose his

  18. Viral Nanoparticles for In vivo Tumor Imaging

    PubMed Central

    Wen, Amy M.; Lee, Karin L.; Yildiz, Ibrahim; Bruckman, Michael A.; Shukla, Sourabh; Steinmetz, Nicole F.

    2012-01-01

    proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect12. The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease. PMID:23183850

  19. Living until we die: reflections on the dying person's spiritual agenda.

    PubMed

    Anderson, Herbert

    2006-03-01

    The spiritual agenda for the dying presumes a willingness to face the reality of imminent death. It also depends on support from caregivers who will encourage whatever agency is possible for the one who is dying. The spiritual practices that will enhance agency for the dying include remembering, thanking, relinquishing, waiting, and trusting. The absence of abandonment and the dependable presence of caregivers are essential to create communities and relationships in which hope can be found and sustained.

  20. Elevated in vivo strontium-90 from nuclear weapons test fallout among cancer decedents: a case-control study of deciduous teeth.

    PubMed

    Mangano, Joseph J; Sherman, Janette D

    2011-01-01

    Risks to health from large-scale atmospheric nuclear weapons testing are still relatively unknown. A sample of 85,000 deciduous teeth collected from Americans born during the bomb-testing years assessed risk by in vivo measurement of residual strontium-90 (Sr-90) concentrations, using liquid scintillation spectrometry. The authors' analysis included 97 deciduous teeth from persons born between 1959 and 1961 who were diagrosed with cancer, and 194 teeth of matched controls. Average Sr-90 in teeth of persons who died of cancer was significantly greater than for controls (OR = 2.22; p < 0.04). This discovery suggests that many thousands have died or will die of cancer due to exposure to fallout, far more than previously believed.

  1. Thermal Modelling In Pressure Die Casting

    NASA Astrophysics Data System (ADS)

    Rasgado, M. T. Alonso; Davey, K.; Watari, H.

    2004-06-01

    The pressure die casting process is cyclic and the temperature levels in the die are principally dictated by the total energy received from the casting. It is thus extremely important that any solidification model for the casting is able to predict energy extraction rates to a high degree of accuracy. In this paper an efficient three dimensional hybrid thermal model for the pressure die casting process is described. The finite element method (FEM) is used for modelling heat transfer in the casting, coupled to a boundary element (BE) model for the die. The FEM can efficiently account for the non-linearity introduced by the release of latent heat on solidification, whereas the BEM is ideally suited for modelling linear heat conduction in the die, as surface temperatures are of principal importance. The FE formulation for the casting is based on a control volume capacitance method, which is shown to provide high accuracy and stability. This method is similar to the apparent and effective heat capacitance methods, which are popular approaches used where conduction predominates over other heat transfer mechanisms. These methods involve the specification of element or nodal capacitances to accommodate for the release of latent heat. Unfortunately they suffer from a major drawback in that energy is not correctly transported through elements and so providing a source of inaccuracy. The control volume capacitance method allows for the transport of mass arising from volumetric shrinkage and ensures that energy is correctly transported. The BE model caters for surface phenomena such as boiling in the cooling channels, which is important, as this effectively controls the manner in which energy is extracted. The die temperature is decomposed into two components, one a steady-state part and the other a time-dependent perturbation. This approach enables the transient die temperatures to be calculated in an efficient way, since only die surfaces close to the die cavity are

  2. Label-free optical activation of astrocyte in vivo

    NASA Astrophysics Data System (ADS)

    Choi, Myunghwan; Yoon, Jonghee; Ku, Taeyun; Choi, Kyungsun; Choi, Chulhee

    2011-07-01

    As the most abundant cell type in the central nervous system, astrocyte has been one of main research topics in neuroscience. Although various tools have been developed, at present, there is no tool that allows noninvasive activation of astrocyte in vivo without genetic or pharmacological perturbation. Here we report a noninvasive label-free optical method for physiological astrocyte activation in vivo using a femtosecond pulsed laser. We showed the laser stimulation robustly induced astrocytic calcium activation in vivo and further verified physiological relevance of the calcium increase by demonstrating astrocyte mediated vasodilation in the brain. This novel optical method will facilitate noninvasive physiological study on astrocyte function.

  3. Plasma and Cavitation Dynamics during Pulsed Laser Microsurgery in vivo

    SciTech Connect

    Hutson, M. Shane; Ma Xiaoyan

    2007-10-12

    We compare the plasma and cavitation dynamics underlying pulsed laser microsurgery in water and in fruit fly embryos (in vivo)--specifically for nanosecond pulses at 355 and 532 nm. We find two key differences. First, the plasma-formation thresholds are lower in vivo --especially at 355 nm--due to the presence of endogenous chromophores that serve as additional sources for plasma seed electrons. Second, the biological matrix constrains the growth of laser-induced cavitation bubbles. Both effects reduce the disrupted region in vivo when compared to extrapolations from measurements in water.

  4. Compassionate community networks: supporting home dying.

    PubMed

    Abel, Julian; Bowra, Jon; Walter, Tony; Howarth, Glennys

    2011-09-01

    How may communities be mobilised to help someone dying at home? This conceptual article outlines the thinking behind an innovative compassionate community project being developed at Weston-super-Mare, UK. In this project, a health professional mentors the dying person and their carer to identify and match: (a) the tasks that need to be done and (b) the members of their social network who might help with these tasks. Network members may subsequently join a local volunteer force to assist others who are network poor. Performing practical tasks may be more acceptable to some family, friends and neighbours than having to engage in a conversation about dying, and provides a familiarity with dying that is often lacking in modern societies, so in this model, behavioural change precedes attitudinal change. The scheme rejects a service delivery model of care in favour of a community development model, but differs from community development schemes in which the mentor is a volunteer rather than a health professional, and also from those approaches that strive to build community capacity before any one individual dying person is helped. The pros and cons of each approach are discussed. There is a need for evaluation of this and similar schemes, and for basic research into naturally occurring resource mobilisation at the end of life.

  5. In vivo spectral micro-imaging of tissue

    DOEpatents

    Demos, Stavros G; Urayama, Shiro; Lin, Bevin; Saroufeem, Ramez; Ghobrial, Moussa

    2012-11-27

    In vivo endoscopic methods an apparatuses for implementation of fluorescence and autofluorescence microscopy, with and without the use of exogenous agents, effectively (with resolution sufficient to image nuclei) visualize and categorize various abnormal tissue forms.

  6. Current problems and potential techniques in in vivo glucose monitoring.

    PubMed

    Wickramasinghe, Y; Yang, Y; Spencer, S A

    2004-09-01

    Accurate in vivo monitoring of glucose concentration would be a valuable asset, particularly for management of diabetes and preterm infants during critical care. In vivo glucose monitoring devices can be divided into two categories: implanted and non-invasive. Extensive research into in vivo glucose monitoring over recent decades has not resulted in the widespread use of clinically reliable monitoring systems. For implanted devices, poor biocompatibility of the materials used for fabrication remains a major challenge, whilst progress in the commercial development of non-invasive devices is hampered by the problem of multiple interference between the detected signals and the biological components. In this review, the methods available for in in-vivo glucose monitoring are described and the associated problems are discussed.

  7. A method to study in vivo stability of DNA nanostructures.

    PubMed

    Surana, Sunaina; Bhatia, Dhiraj; Krishnan, Yamuna

    2013-11-01

    DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more DNA sequences by their self-assembly. Due to the molecularly programmable as well as modular nature of DNA, such designer DNA architectures have great potential for in cellulo and in vivo applications. However, demonstrations of functionality in living systems necessitates a method to assess the in vivo stability of the relevant nanostructures. Here, we outline a method to quantitatively assay the stability and lifetime of various DNA nanostructures in vivo. This exploits the property of intact DNA nanostructures being uptaken by the coelomocytes of the multicellular model organism Caenorhabditis elegans. These studies reveal that the present fluorescence based assay in coelomocytes of C. elegans is an useful in vivo test bed for measuring DNA nanostructure stability.

  8. Quantifying and imaging engineered nanomaterials in vivo: challenges and techniques.

    PubMed

    He, Xiao; Ma, Yuhui; Li, Meng; Zhang, Peng; Li, Yuanyuan; Zhang, Zhiyong

    2013-05-27

    Quantifying and imaging the engineered nanomaterials (ENMs) in vivo can provide information on the bio-distribution and fate of ENMs in living systems. A necessary amount of in vivo quantitative data is indispensable to verify the extrapolation from in vitro tests, to modify the predictive models of ENM exposure, and to underpin the risk management strategy for ENMs. However, it remains a challenge to quantitatively assess the bio-distribution of ENMs under realistic exposure, their long-term deposition (especially in non-targeted tissues), their passage across the natural barriers, and the impacts of nano-bio interactions on their in vivo behaviors. Some commonly used techniques for in vivo ENM quantification, such as electron microscopy, fluorescence-based detection, atomic spectroscopy, radiotracing, and techniques basing on synchrotron radiation are reviewed, and their technical characteristics, the state of the art, limitations, and future prospects are addressed.

  9. In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles.

    PubMed

    Lee, Dongwon; Khaja, Sirajud; Velasquez-Castano, Juan C; Dasari, Madhuri; Sun, Carrie; Petros, John; Taylor, W Robert; Murthy, Niren

    2007-10-01

    The overproduction of hydrogen peroxide is implicated in the development of numerous diseases and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo. In this report, we demonstrate that nanoparticles formulated from peroxalate esters and fluorescent dyes can image hydrogen peroxide in vivo with high specificity and sensitivity. The peroxalate nanoparticles image hydrogen peroxide by undergoing a three-component chemiluminescent reaction between hydrogen peroxide, peroxalate esters and fluorescent dyes. The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460-630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species. The peroxalate nanoparticles were capable of imaging hydrogen peroxide in the peritoneal cavity of mice during a lipopolysaccharide-induced inflammatory response. We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability.

  10. Imaging agents for in vivo magnetic resonance and scintigraphic imaging

    DOEpatents

    Engelstad, Barry L.; Raymond, Kenneth N.; Huberty, John P.; White, David L.

    1991-01-01

    Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided.

  11. Imaging agents for in vivo magnetic resonance and scintigraphic imaging

    DOEpatents

    Engelstad, B.L.; Raymond, K.N.; Huberty, J.P.; White, D.L.

    1991-04-23

    Methods are provided for in vivo magnetic resonance imaging and/or scintigraphic imaging of a subject using chelated transition metal and lanthanide metal complexes. Novel ligands for these complexes are provided. No Drawings

  12. Strategies for In Vivo Imaging Using Fluorescent Proteins.

    PubMed

    Hoffman, Robert M

    2016-08-26

    Fluorescent proteins have enabled the color-coding of cells growing in vivo. Noninvasive imaging of cells expressing fluorescent proteins has allowed the real-time determination of the behavior on cancer cells, the progression of infection, the differentiation of stem cells, and interaction of stromal and cancer cells. Cancer cells in the nucleus and cytoplasm can visualize in vivo nuclear-cytoplasmic dynamics in vivo including: mitosis, apoptosis, cell-cycle phase, and differential behavior of nucleus and cytoplasm that occurs during cancer-cell deformation. Linking spectrally-distinct fluorescent proteins with cell-cycle-specific proteins results in color-coding the phases of the cell cycle. With the use of fluorescent proteins, literally any cellular or molecular function can be imaged in vivo. This article is protected by copyright. All rights reserved.

  13. Two-base DNA hairpin-loop structures in vivo.

    PubMed Central

    Davison, A; Leach, D R

    1994-01-01

    In vitro studies have revealed that DNA hairpin-loops usually contain four unpaired bases. However, a small subset of sequences can form two-base loops. We have previously described an in vivo assay that is sensitive to tight loop formation and have set out to test whether DNA sequences known to form two-base loops in vitro also form tight loops in vivo. It is shown that the sequences 5'dCNNG and 5'dTNNA behave as predicted if they favour two-base loop formation in vivo, a result that is consistent with previously described in vitro studies. The ability of specific DNA sequences to form tight loops in vivo has implications for their potential to form transient structures involved in gene regulation, recombination and mutagenesis. PMID:7971265

  14. An evaluation of preference for video and in vivo modeling.

    PubMed

    Geiger, Kaneen B; Leblanc, Linda A; Dillon, Courtney M; Bates, Stephanie L

    2010-01-01

    We assessed preference for video or in vivo modeling using a concurrent-chains arrangement with 3 children with autism. The two modeling conditions produced similar acquisition rates and no differential selection (i.e., preference) for all 3 participants.

  15. The Expanding Toolbox of In Vivo Bioluminescent Imaging

    PubMed Central

    Xu, Tingting; Close, Dan; Handagama, Winode; Marr, Enolia; Sayler, Gary; Ripp, Steven

    2016-01-01

    In vivo bioluminescent imaging (BLI) permits the visualization of engineered bioluminescence from living cells and tissues to provide a unique perspective toward the understanding of biological processes as they occur within the framework of an authentic in vivo environment. The toolbox of in vivo BLI includes an inventory of luciferase compounds capable of generating bioluminescent light signals along with sophisticated and powerful instrumentation designed to detect and quantify these light signals non-invasively as they emit from the living subject. The information acquired reveals the dynamics of a wide range of biological functions that play key roles in the physiological and pathological control of disease and its therapeutic management. This mini review provides an overview of the tools and applications central to the evolution of in vivo BLI as a core technology in the preclinical imaging disciplines. PMID:27446798

  16. Probing Tumor Microenvironment with In Vivo Phage Display

    DTIC Science & Technology

    2013-07-01

    peptides may result in an efficient probe for breast tumor imaging and therapy . 15. SUBJECT TERMS Carcinoma-associated fibroblast; phage display...In Vivo Phage Display PRINCIPAL INVESTIGATOR: Dr. Erkki Ruoslahti CONTRACTING ORGANIZATION: Sanford Burnham Medical Research Institute...COVERED 01 July 2012 – 30 June 2013 4. TITLE AND SUBTITLE Probing Tumor Microenvironment with In Vivo Phage Display 5a. CONTRACT NUMBER W81XWH

  17. Monitoring Retroviral RNA Dimerization In Vivo via Hammerhead Ribozyme Cleavage

    PubMed Central

    Pal, Bijay K.; Scherer, Lisa; Zelby, Laurie; Bertrand, Edouard; Rossi, John J.

    1998-01-01

    We have used a strategy for colocalization of Psi (Ψ)-tethered ribozymes and targets to demonstrate that Ψ sequences are capable of specific interaction in the cytoplasm of both packaging and nonpackaging cells. These results indicate that current in vitro dimerization models may have in vivo counterparts. The methodology used may be applied to further genetic analyses on Ψ domain interactions in vivo. PMID:9733882

  18. Portable optical fiber probe for in vivo brain temperature measurements.

    PubMed

    Musolino, Stefan; Schartner, Erik P; Tsiminis, Georgios; Salem, Abdallah; Monro, Tanya M; Hutchinson, Mark R

    2016-08-01

    This work reports on the development of an optical fiber based probe for in vivo measurements of brain temperature. By utilizing a thin layer of rare-earth doped tellurite glass on the tip of a conventional silica optical fiber a robust probe, suitable for long-term in vivo measurements of temperature can be fabricated. This probe can be interrogated using a portable optical measurement setup, allowing for measurements to be performed outside of standard optical laboratories.

  19. In vivo localized proton spectroscopic studies of human gastrocnemius muscle

    SciTech Connect

    Narayana, P.A.; Jackson, E.F.; Hazle, J.D.; Fotedar, L.K.; Kulkarni, M.V.; Flamig, D.P.

    1988-10-01

    In vivo proton magnetic resonance spectroscopy studies of gastrocnemius muscle were performed in six normal volunteers. Both spatially resolved spectroscopy (SPARS) and stimulated echo acquisition mode (STEAM) sequences were used for volume localization. A number of water suppression sequences have been combined with these localization schemes. Among the various techniques investigated in these studies, STEAM with an inversion pulse (T1-discriminated spectrum) seems to have the best potential for in vivo localized high-resolution proton spectroscopy studies of human muscle.

  20. Semiconductor quantum dot toxicity in a mouse in vivo model

    NASA Astrophysics Data System (ADS)

    Bozrova, Svetlana V.; Baryshnikova, Maria A.; Nabiev, Igor; Sukhanova, Alyona

    2017-01-01

    Quantum dots (QDs) are increasingly widely used in clinical medicine. Their most promising potential applications are cancer diagnosis, including in vivo tumour imaging and targeted drug delivery. In this connection, the main questions are whether or not QDs are toxic for humans and, if they are, what concentration is relatively harmless. We have carried out in vivo experiments with CdSe/ZnS fluorescent semiconductor core/shell QDs, which are currently the most widely used in research.

  1. Portable optical fiber probe for in vivo brain temperature measurements

    PubMed Central

    Musolino, Stefan; Schartner, Erik P.; Tsiminis, Georgios; Salem, Abdallah; Monro, Tanya M.; Hutchinson, Mark R.

    2016-01-01

    This work reports on the development of an optical fiber based probe for in vivo measurements of brain temperature. By utilizing a thin layer of rare-earth doped tellurite glass on the tip of a conventional silica optical fiber a robust probe, suitable for long-term in vivo measurements of temperature can be fabricated. This probe can be interrogated using a portable optical measurement setup, allowing for measurements to be performed outside of standard optical laboratories. PMID:27570698

  2. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  3. Killing, letting die and moral perception.

    PubMed

    Gillett, Grant

    1994-10-01

    There are a number of arguments that purport to show, in general terms, that there is no difference between killing and letting die. These are used to justify active euthanasia on the basis of the reasons given for allowing patients to die. I argue that the general and abstract arguments fail to take account of the complex and particular situations which are found in the care of those with terminal illness. When in such situations, there are perceptions and intuitions available that do not easily find propositional form but lead most of those whose practice is in the care of the dying to resist active euthanasia. I make a plea for their intuitions to be heeded above the sterile voice of abstract premises and arguments by examining the completeness of the outline form of the pro-euthanasia argument. In doing so, I make use of Nussbaum's discussion of moral perception and general claims to be found in the literature of moral particularism.

  4. CAE Based Die Face Engineering Development to Contribute to the Revitalization of the Tool & Die Industry

    NASA Astrophysics Data System (ADS)

    Tang, Arthur; Lee, Wing C.; St. Pierre, Shawn; He, Jeanne; Liu, Kesu; Chen, Chin C.

    2005-08-01

    Over the past two decades, the Computer Aided Engineering (CAE) tools have emerged as one of the most important engineering tools in various industries, due to its flexibility and accuracy in prediction. Nowadays, CAE tools are widely used in the sheet metal forming industry to predict the forming feasibility of a wide variety of complex components, ranging from aerospace and automotive components to household products. As the demand of CAE based formability accelerates, the need for a robust and streamlined die face engineering tool becomes more crucial, especially in the early stage when the tooling layout is not available, but a product design decision must be made. Ability to generate blank, binder and addendum surfaces with an appropriate layout of Drawbead, Punch Opening Line, Trim Line are the primary features and functions of a CAE based die face engineering tool. Once the die face layout is ready, a formability study should be followed to verify the die face layout is adequate to produce a formable part. If successful, the established die face surface should be exported back to the CAD/CAM environment to speed up the tooling and manufacturing design process with confidence that this particular part is formable with this given die face. With a CAE tool as described above, the tool & die industry will be greatly impacted as the processes will enable the bypass of hardware try-out and shorten the overall vehicle production timing. The trend has shown that OEMs and first tiers will source to low cost producers in the world which will have a negative impact to the traditional tool & die makers in the developed countries. CAE based tool as described should be adopted, along with many other solutions, in order to maintain efficiency of producing high quality product and meeting time-to-market requirements. This paper will describe how a CAE based die face engineering (DFE) tool could be further developed to enable the traditional tool & die makers to meet the

  5. Die Arbeitsunfähigkeit in der Statistik der GKV

    NASA Astrophysics Data System (ADS)

    Busch, Klaus

    Der vorliegende Beitrag gibt anhand der Statistiken des Bundesministeriums für Gesundheit (BMG) einen Überblick über die Arbeitsunfähigkeitsdaten der Gesetzlichen Krankenkassen (GKV). Zunächst werden die Arbeitsunfähigkeitsstatistiken der Krankenkassen und die Erfassung der Arbeitsunfähigkeit erläutert. Hiernach wird auf die Entwicklung der Fehlzeiten auf GKV-Ebene eingegangen. Ebenfalls wird Bezug auf die Unterschiede der Fehlzeiten zwischen den verschiedenen Kassen genommen.

  6. In-vivo Stretch of Term Human Fetal Membranes

    PubMed Central

    Joyce, EM; Diaz, P; Tamarkin, S; Moore, R; Strohl, A; Stetzer, B; Kumar, D; Sacks, MS; Moore, JJ

    2015-01-01

    Introduction Fetal membranes (FM) usually fail prior to delivery during term labor, but occasionally fail at preterm gestation, precipitating preterm birth. To understand the FM biomechanical properties underlying these events, study of the baseline in-vivo stretch experienced by the FM is required. This study's objective was to utilize high resolution MRI imaging to determine in-vivo FM stretch. Methods Eight pregnant women (38.4±0.4wks) underwent abdominal-pelvic MRI prior to (2.88±0.83d) caesarean delivery. Software was utilized to determine the total FM in-vivo surface area (SA) and that of its components: placental disc and reflected FM. At delivery, the SA of the disc and FM in the relaxed state were measured. In-vivo (stretched) to delivered SA ratios were calculated. FM fragments were then biaxially stretched to determine the force required to re-stretch the FM back to in-vivo SA. Results Total FM SA, in-vivo vs delivered, was 2135.51±108.47 cm2 vs 842.59±35.86 cm2; reflected FM was 1778.42±107.39 cm2 vs 545.41±22.90 cm2, and disc was 357.10±28.08 cm2 vs 297.18±22.14 cm2. The ratio (in-vivo to in-vitro SA) of reflected FM was 3.26±0.11 and disc was 1.22±0.10. Reflected FM re-stretched to in-vivo SA generated a tension of 72.26N/m, corresponding to approximate pressure of 15.4mmHg. FM rupture occurred at 295.08 ± 31.73N/m corresponding to approximate pressure of 34mmHg. Physiological SA was 70% of that at rupture. Discussion FM are significantly distended in-vivo. FM collagen fibers were rapidly recruited once loaded and functioned near the failure state during in-vitro testing, suggesting that, in-vivo, minimal additional (beyond physiological) stretch may facilitate rapid, catastrophic failure. PMID:26907383

  7. Effect of Die Strength and Work Piece Strength on the Wear of Hot Forging Dies

    NASA Astrophysics Data System (ADS)

    Levy, B. S.; Van Tyne, C. J.

    2015-01-01

    The effect of the strength ratio extracted from an Archard model for wear is used to describe the wear rates expected in hot forging dies. In the current study, the strength ratio is the strength of the hot forging die to the strength of the work piece. Three hot forging die steels are evaluated. The three die steels are FX, 2714, and WF. To determine the strength of the forging die, a continuous function has been developed that describes the yield strength of three die steels for temperatures from 600 to 700 °C and for times up to 20 h (i.e., tempering times of up to 20 h). The work piece material is assumed to be AISI 1045. Based on the analysis, the wear resistance of WF should be superior and FX should be slightly better than 2714. Decreasing the forging temperature increases the strength ratio, because the strength of the die surface increases faster than the flow strength of AISI 1045. The increase in the strength ratio indicates a decrease in the expected wear rate.

  8. Wissenschaft, die unsere Kultur verändert. Tiefenschichten des Streits um die Evolutionstheorie

    NASA Astrophysics Data System (ADS)

    Patzelt, Werner J.

    Die Evolutionstheorie ist eine der erfolgreichsten wissenschaftlichen Theorien. Sie erlaubt es, unsere Herkunft zu verstehen und riskante Merkmale gerade der menschlichen Spezies zu begreifen. Zugleich ist die Evolutionstheorie eine der umstrittensten Theorien. Das liegt nicht an ihrer empirischen Tragfähigkeit, sondern an ihrem Gegenstand. Sie handelt nämlich nicht nur - wie Hunderte andere wissenschaftliche Theorien - von der "Welt da draußen“, sondern vor allem auch von uns selbst und von unserem Platz in dieser Welt. Den einen gilt sie obendrein als Überwinderin religiösen Aberglaubens, den anderen als neuer Zugang zu Gott und seinem Wirken in der Welt. Ferner sehen die einen in der Evolution eine unbezweifelbare Tatsache gleich der Schwerkraft oder dem Holocaust, die anderen aber eine - noch oder dauerhaft - unbewiesene Hypothese oder gar eine falsche Schöpfungslehre. Und während die meisten Streitfragen solcher Art nach wechselseitig akzeptierten Regeln ‚normaler Wissenschaft‘ geklärt werden, wird bei der Frage nach dem Woher unserer Spezies und Kultur die intellektuelle Zuständigkeit von Wissenschaft mitunter überhaupt bezweifelt. Anscheinend geht es schon um recht tiefe Schichten unserer Kultur und nicht nur der wissenschaftlichen, wenn - wie seit 150 Jahren - um die Evolutionstheorie gestritten wird. Wie sehen diese Schichten aus?

  9. Investigation of Die Stress Profiles during Powder Compaction using Instrumented Die

    SciTech Connect

    Hong, Sung-tae; Hovanski, Yuri; Lavender, Curt A.; Weil, K. Scott

    2008-06-01

    The radial stress profile in a cylindrical die during compaction of titanium (Ti) powder was investigated by experiments. The concept of an instrumented die was extended to design an enhanced instrumented die. Custom-made strain gage pins were used to measure the radial stress during powder compaction. The test fixture was designed to simulate double-action pressing. The measured die stress profile for Ti powder was compared with that for a commercially available iron (Fe) powder. The stress history shows that an appreciable residual stress remains in the die in the radial direction after the axial compaction stress is removed from the powder. Furthermore, the radial stress profile in the die, while under maximum axial compaction stress, is more uniform across the height of the Fe compact than that of the Ti compact. In addition, the residual stress profile in the die in the radial direction reduces symmetrically in both directions beyond the height of the compact for both powders. Finally, the Ti powder shows a significantly higher frictional coefficient at the maximum axial compaction stress, and consequently a higher maximum axial ejection stress than the Fe powder.

  10. Disposable Fluidic Actuators for Miniature In-Vivo Surgical Robotics.

    PubMed

    Pourghodrat, Abolfazl; Nelson, Carl A

    2017-03-01

    Fusion of robotics and minimally invasive surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems to miniature in-vivo robotics. However, with miniaturization of electric-motor-driven surgical robots, there comes a trade-off between the size of the robot and its capability. Slow actuation, low load capacity, sterilization difficulties, leaking electricity and transferring produced heat to tissues, and high cost are among the key limitations of the use of electric motors in in-vivo applications. Fluid power in the form of hydraulics or pneumatics has a long history in driving many industrial devices and could be exploited to circumvent these limitations. High power density and good compatibility with the in-vivo environment are the key advantages of fluid power over electric motors when it comes to in-vivo applications. However, fabrication of hydraulic/pneumatic actuators within the desired size and pressure range required for in-vivo surgical robotic applications poses new challenges. Sealing these types of miniature actuators at operating pressures requires obtaining very fine surface finishes which is difficult and costly. The research described here presents design, fabrication, and testing of a hydraulic/pneumatic double-acting cylinder, a limited-motion vane motor, and a balloon-actuated laparoscopic grasper. These actuators are small, seal-less, easy to fabricate, disposable, and inexpensive, thus ideal for single-use in-vivo applications. To demonstrate the ability of these actuators to drive robotic joints, they were modified and integrated in a robotic arm. The design and testing of this surgical robotic arm are presented to validate the concept of fluid-power actuators for in-vivo applications.

  11. A profile of silicosis cases who died.

    PubMed

    Phoon, W H

    1982-01-01

    Silicosis cases which had been notified by doctors and confirmed after investigations were followed up by the Industrial Health Division. Up to August 1981, a total of 313 persons were confirmed as having the disease. Of these, 59 had died. The majority of these 59 persons had had their silica exposure in the granite quarries. 13 had been exposed to "rubber powder" which contained a high percentage of free silica. 52 of those who died were male, and their average age at death was 60.87 years. This did not appear to be significantly shorter than their life expectancy of 65.1 years. But the average age of death for the 7 women was 58.86 years, which was much shorter than their life expectancy of 70 years. Many of the men died from causes unrelated to silicosis. But 6 of the 7 women had progressive massive fibrosis (PMF) and they apparently died of the disease or complications arising from it.

  12. Expectation and Variation with a Virtual Die

    ERIC Educational Resources Information Center

    Watson, Jane; English, Lyn

    2015-01-01

    By the time students reach the middle years they have experienced many chance activities based on dice. Common among these are rolling one die to explore the relationship of frequency and theoretical probability, and rolling two dice and summing the outcomes to consider their probabilities. Although dice may be considered overused by some, the…

  13. Stamping Die Making. 439-318/320.

    ERIC Educational Resources Information Center

    Yunke, P.; And Others

    Each unit in this curriculum guide on stamping die making contains an introduction, objectives, materials required, lessons, space for notes, figures, and diagrams. There are 29 units in this guide, dealing with the following topics: EZ-MILL programming; EZ-MILL BATT; print of punch and EZ-MILL part programming; download to Computer Numerical…

  14. Care of the Dying: A Swedish Perspective

    ERIC Educational Resources Information Center

    Feigenberg, Loma; Fulton, Robert

    1977-01-01

    This article illustrates various aspects of terminal care, and shows that rules and norms for such care do not exist today. The authors advocate the formulation of an aim for humane treatment of dying patients, and its application in a manner appropriate to Swedish medical concepts and Swedish conditions. (Author)

  15. Asymmetric Die Grows Purer Silicon Ribbon

    NASA Technical Reports Server (NTRS)

    Kalejs, J. P.; Chalmers, B.; Surek, T.

    1983-01-01

    Concentration of carbide impurities in silicon ribbon is reduced by growing crystalline ribbon with die one wall higher than other. Height difference controls shape of meniscus at liquid/crystal interface and concentrates silicon carbide impurity near one of broad faces. Opposite face is left with above-average purity. Significantly improves efficiency of solar cells made from ribbon.

  16. Ceramic for Silicon-Shaping Dies

    NASA Technical Reports Server (NTRS)

    Sekercioglu, I.; Wills, R. R.

    1982-01-01

    Silicon beryllium oxynitride (SiBON) is a promising candidate material for manufacture of shaping dies used in fabricating ribbons or sheets of silicon. It is extremely stable, resists thermal shock, and has excellent resistance to molten silicon. SiBON is a solid solution of beryllium silicate in beta-silicon nitride.

  17. The Onion and "When Legends Die."

    ERIC Educational Resources Information Center

    Bell, Loren C.

    1984-01-01

    Describes the eight layers in Thomas Black Bull's ("When the Legends Die") journey to spiritual rebirth and stresses that students can easily identify these layers and can thereby achieve a clearer understanding of the relationship between structure and meaning in fiction. (CRH)

  18. Counseling Older Persons: Careers, Retirement, Dying.

    ERIC Educational Resources Information Center

    Sinick, Daniel

    The focus of this monograph is on three areas of counseling with older clients: career counseling, retirement counseling, and counseling regarding death and dying. The portion on career counseling includes reasons older persons change careers, obstacles they are likely to face when seeking employment, myths surrounding the employability of older…

  19. Mold Die Making. 439-322/324.

    ERIC Educational Resources Information Center

    Yunke, P.; And Others

    Each unit in this curriculum guide on mold die making contains an introduction, objectives, materials required, lessons, space for notes, figures, and diagrams. There are 10 units in this guide: (1) introduction to Electrical Discharge Machining (EDM); (2) EDM principles; (3) the single pulse; (4) EDM safety; (5) electrode material; (6) electrode…

  20. [Companionship for women dying of AIDS].

    PubMed

    Gerlach, E

    1999-01-01

    This report reflects the experience of accompanying HIV-infected women during the process of dying using their curriculi vitae as examples of different modes of dealing with fatal illness. The text contains paintings of past and contemporary art concerning death and eros and poetry as a form of therapy.

  1. The Academic Study of Death and Dying.

    ERIC Educational Resources Information Center

    Amend, Edward W.

    The current study of death and dying is an example of constant change and development in academic disciplines. While the discussion of death in time of crisis is hard, if not impossible, youthful undergraduates find this topic to be of considerable interest. For them, a course can be organized effectively as a small and intimate seminar, which…

  2. Systemic inflammation regulates microglial responses to tissue damage in vivo

    PubMed Central

    Gyoneva, Stefka; Davalos, Dimitrios; Biswas, Dipankar; Swanger, Sharon A.; Garnier-Amblard, Ethel; Loth, Francis; Akassoglou, Katerina; Traynelis, Stephen F.

    2015-01-01

    Microglia, the resident immune cells of the central nervous system, exist in either a “resting” state associated with physiological tissue surveillance or an “activated” state in neuroinflammation. We recently showed that ATP is the primary chemoattractor to tissue damage in vivo and elicits opposite effects on the motility of activated microglia in vitro through activation of adenosine A2A receptors. However, whether systemic inflammation affects microglial responses to tissue damage in vivo remains largely unknown. Using in vivo two-photon imaging of mice, we show that injection of lipopolysaccharide (LPS) at levels that can produce both clear neuroinflammation and some features of sepsis significantly reduced the rate of microglial response to laser-induced ablation injury in vivo. Under pro-inflammatory conditions, microglial processes initially retracted from the ablation site, but subsequently moved toward and engulfed the damaged area. Analyzing the process dynamics in 3D cultures of primary microglia indicated that only A2A, but not A1 or A3 receptors, mediate process retraction in LPS-activated microglia. The A2A receptor antagonists caffeine and preladenant reduced adenosine-mediated process retraction in activated microglia in vitro. Finally, administration of preladenant before induction of laser ablation in vivo accelerated the microglial response to injury following systemic inflammation. The regulation of rapid microglial responses to sites of injury by A2A receptors could have implications for their ability to respond to the neuronal death occurring under conditions of neuroinflammation in neurodegenerative disorders. PMID:24807189

  3. Biowaiver: an alternative to in vivo pharmacokinetic bioequivalence studies.

    PubMed

    Mishra, V; Gupta, U; Jain, N K

    2010-03-01

    Bioequivalence is a vital concern in drug development even more significant in the case of Narrow Therapeutic Index (NTI) drugs. In clinical development of New Chemical Entities (NCE), bioequivalence studies necessitate to be performed when the formulation of the pharmaceutical dosage form has been changed. In vivo pharmacokinetic data can be used as surrogate parameters for in vivo solubility and permeability data. The Biopharmaceutics Classification System (BCS) has emerged as a helpful tool in product development by alluding to the in vivo performance of the active substance. The bio-relevance of the BCS properties and the in vitro release are best expressed through a correlation between in vitro and in vivo data. Recently BCS has been implemented for waiving bioequivalence studies on the basis of the solubility and gastrointestinal permeability of drug substance and can be strategically deployed to save time and resources during generic drug development. The BCS has been adopted as a very useful tool for in vivo drug design and development worldwide, particularly in terms of regulatory standards. A BCS-based biowaiver has become an important and cost-saving tool in approval of generic drugs.

  4. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    PubMed

    Szymanska, Barbara; Wilczynska-Kalak, Urszula; Kang, Min H; Liem, Natalia L M; Carol, Hernan; Boehm, Ingrid; Groepper, Daniel; Reynolds, C Patrick; Stewart, Clinton F; Lock, Richard B

    2012-01-01

    Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL), or for re-induction post relapse, use a combination of vincristine (VCR), a glucocorticoid, and L-asparaginase (ASP) with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX) and ASP (VXL) against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  5. Visually Relating Gene Expression and in vivo DNA Binding Data

    SciTech Connect

    Huang, Min-Yu; Mackey, Lester; Ker?,; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  6. mito-QC illuminates mitophagy and mitochondrial architecture in vivo.

    PubMed

    McWilliams, Thomas G; Prescott, Alan R; Allen, George F G; Tamjar, Jevgenia; Munson, Michael J; Thomson, Calum; Muqit, Miratul M K; Ganley, Ian G

    2016-08-01

    Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed "mito-QC," a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities.

  7. A biomagnetic system for in vivo cancer imaging

    PubMed Central

    Flynn, E R; Bryant, H C

    2007-01-01

    An array of highly sensitive biomagnetic sensors of the superconducting quantum interference detector (SQUID) type can identify disease in vivo by detecting and imaging microscopic amounts of nanoparticles. We describe in detail procedures and parameters necessary for implementation of in vivo detection through the use of antibody-labelled magnetic nanoparticles as well as methods of determining magnetic nanoparticle properties. We discuss the weak field magnetic sensor SQUID system, the method of generating the magnetic polarization pulse to align the magnetic moments of the nanoparticles, and the measurement techniques to measure their magnetic remanence fields following this pulsed field. We compare these results to theoretical calculations and predict optimal properties of nanoparticles for in vivo detection. PMID:15798322

  8. A biomagnetic system for in vivo cancer imaging

    NASA Astrophysics Data System (ADS)

    Flynn, E. R.; Bryant, H. C.

    2005-03-01

    An array of highly sensitive biomagnetic sensors of the superconducting quantum interference detector (SQUID) type can identify disease in vivo by detecting and imaging microscopic amounts of nanoparticles. We describe in detail procedures and parameters necessary for implementation of in vivo detection through the use of antibody-labelled magnetic nanoparticles as well as methods of determining magnetic nanoparticle properties. We discuss the weak field magnetic sensor SQUID system, the method of generating the magnetic polarization pulse to align the magnetic moments of the nanoparticles, and the measurement techniques to measure their magnetic remanence fields following this pulsed field. We compare these results to theoretical calculations and predict optimal properties of nanoparticles for in vivo detection.

  9. Delivery of Therapeutic RNAs Into Target Cells IN VIVO

    NASA Astrophysics Data System (ADS)

    Ng, Mei Ying; Hagen, Thilo

    2014-02-01

    RNA-based therapy is one of the most promising approaches to treat human diseases. Specifically, the use of short interfering RNA (siRNA) siRNA and microRNA (miRNA) mimics for in vivo RNA interference has immense potential as it directly lowers the expression of the therapeutic target protein. However, there are a number of major roadblocks to the successful implementation of siRNA and other RNA based therapies in the clinic. These include the instability of RNAs in vivo and the difficulty to efficiently deliver the RNA into the target cells. Hence, various innovative approaches have been taken over the years to develop effective RNA delivery methods. These methods include liposome-, polymeric nanoparticle- and peptide-mediated cellular delivery. In a recent innovative study, bioengineered bacterial outer membrane vesicles were used as vehicles for effective delivery of siRNA into cells in vivo.

  10. Estrogenicity of phytosterols evaluated in vitro and in vivo.

    PubMed

    Nakari, Tarja

    2005-01-01

    The estrogenic activity of two phytosterol preparations was evaluated in vitro and in vivo. For the in vitro evaluation, freshly separated hepatocytes of rainbow trout were used. By contrast, the in vivo evaluation was performed by injecting the phytosterols intraperitoneally into juvenile rainbow trout. Both assays confirmed the estrogenic activity of the phytosterols. The in vitro screening technique, based on the synthesis and secretion of vitellogenin from the isolated liver cells, produced a clear, significant curve in response to the presence of both phytosterol mixtures. In the in vivo tests, the phytosterol preparations caused significant increases in plasma vitellogenin concentrations of juvenile fish. These shortterm assays proved to be suitable for assessing the estrogenic activity of phytosterols.

  11. Tracking immune cells in vivo using magnetic resonance imaging.

    PubMed

    Ahrens, Eric T; Bulte, Jeff W M

    2013-10-01

    The increasing complexity of in vivo imaging technologies, coupled with the development of cell therapies, has fuelled a revolution in immune cell tracking in vivo. Powerful magnetic resonance imaging (MRI) methods are now being developed that use iron oxide- and ¹⁹F-based probes. These MRI technologies can be used for image-guided immune cell delivery and for the visualization of immune cell homing and engraftment, inflammation, cell physiology and gene expression. MRI-based cell tracking is now also being applied to evaluate therapeutics that modulate endogenous immune cell recruitment and to monitor emerging cellular immunotherapies. These recent uses show that MRI has the potential to be developed in many applications to follow the fate of immune cells in vivo.

  12. Quantitating intracellular oxygen tension in vivo by phosphorescence lifetime measurement

    PubMed Central

    Hirakawa, Yosuke; Yoshihara, Toshitada; Kamiya, Mako; Mimura, Imari; Fujikura, Daichi; Masuda, Tsuyoshi; Kikuchi, Ryohei; Takahashi, Ippei; Urano, Yasuteru; Tobita, Seiji; Nangaku, Masaomi

    2015-01-01

    Hypoxia appears to have an important role in pathological conditions in many organs such as kidney; however, a method to quantify intracellular oxygen tension in vivo has not been well established. In this study, we established an optical method to quantify oxygen tension in mice kidneys using a cationic lipophilic phosphorescence probe, BTPDM1, which has an intracellular oxygen concentration-sensitive phosphorescence lifetime. Since this probe is distributed inside the tubular cells of the mice kidney, we succeeded in detecting acute renal hypoxic conditions and chronic kidney disease. This technique enabled us to estimate intracellular partial pressures of oxygen in vivo by extrapolating the calibration curve generated from cultured tubular cells. Since intracellular oxygen tension is directly related to cellular hypoxic reactions, such as the activation of hypoxia-inducible factors, our method will shed new light on hypoxia research in vivo. PMID:26644023

  13. In vivo genomic footprint of a yeast centromere.

    PubMed Central

    Densmore, L; Payne, W E; Fitzgerald-Hayes, M

    1991-01-01

    We have used in vivo genomic footprinting to investigate the protein-DNA interactions within the conserved DNA elements (CDEI, CDEII, and CDEIII) in the centromere from chromosome III of the yeast Saccharomyces cerevisiae. The in vivo footprint pattern obtained from wild-type cells shows that some guanines within the centromere DNA are protected from methylation by dimethyl sulfate. These results are consistent with studies demonstrating that yeast cells contain sequence-specific centromere DNA-binding proteins. Our in vivo experiments on chromosomes with mutant centromeres show that some mutations which affect chromosome segregation also alter the footprint pattern caused by proteins bound to the centromere DNA. The results of this study provide the first fine-structure map of proteins bound to centromere DNA in living yeast cells and suggest a direct correlation between these protein-DNA interactions and centromere function. Images PMID:1986217

  14. Transgenic Mouse Models Enabling Photolabeling of Individual Neurons In Vivo

    PubMed Central

    Peter, Manuel; Bathellier, Brice; Fontinha, Bruno; Pliota, Pinelopi; Haubensak, Wulf; Rumpel, Simon

    2013-01-01

    One of the biggest tasks in neuroscience is to explain activity patterns of individual neurons during behavior by their cellular characteristics and their connectivity within the neuronal network. To greatly facilitate linking in vivo experiments with a more detailed molecular or physiological analysis in vitro, we have generated and characterized genetically modified mice expressing photoactivatable GFP (PA-GFP) that allow conditional photolabeling of individual neurons. Repeated photolabeling at the soma reveals basic morphological features due to diffusion of activated PA-GFP into the dendrites. Neurons photolabeled in vivo can be re-identified in acute brain slices and targeted for electrophysiological recordings. We demonstrate the advantages of PA-GFP expressing mice by the correlation of in vivo firing rates of individual neurons with their expression levels of the immediate early gene c-fos. Generally, the mouse models described in this study enable the combination of various analytical approaches to characterize living cells, also beyond the neurosciences. PMID:23626779

  15. In Vivo Radionuclide Generators for Diagnostics and Therapy

    PubMed Central

    Edem, Patricia E.; Fonslet, Jesper; Kjær, Andreas; Herth, Matthias

    2016-01-01

    In vivo radionuclide generators make complex combinations of physical and chemical properties available for medical diagnostics and therapy. Perhaps the best-known in vivo generator is 212Pb/212Bi, which takes advantage of the extended half-life of 212Pb to execute a targeted delivery of the therapeutic short-lived α-emitter 212Bi. Often, as in the case of 81Rb/81Kr, chemical changes resulting from the transmutation of the parent are relied upon for diagnostic value. In other instances such as with extended alpha decay chains, chemical changes may lead to unwanted consequences. This article reviews some common and not-so-common in vivo generators with the purpose of understanding their value in medicine and medical research. This is currently relevant in light of a recent push for alpha emitters in targeted therapies, which often come with extended decay chains. PMID:28058040

  16. In vivo demonstration of surgical task assistance using miniature robots.

    PubMed

    Hawks, Jeff A; Kunowski, Jacob; Platt, Stephen R

    2012-10-01

    Laparoscopy is beneficial to patients as measured by less painful recovery and an earlier return to functional health compared to conventional open surgery. However, laparoscopy requires the manipulation of long, slender tools from outside the patient's body. As a result, laparoscopy generally benefits only patients undergoing relatively simple procedures. An innovative approach to laparoscopy uses miniature in vivo robots that fit entirely inside the abdominal cavity. Our previous work demonstrated that a mobile, wireless robot platform can be successfully operated inside the abdominal cavity with different payloads (biopsy, camera, and physiological sensors). We hope that these robots are a step toward reducing the invasiveness of laparoscopy. The current study presents design details and results of laboratory and in vivo demonstrations of several new payload designs (clamping, cautery, and liquid delivery). Laboratory and in vivo cooperation demonstrations between multiple robots are also presented.

  17. Formation of active bacterial luciferase between interspecific subunits in vivo.

    PubMed

    Almashanu, S; Tuby, A; Hadar, R; Einy, R; Kuhn, J

    1995-01-01

    Interspecific complementation between luxAs and luxBs from Vibrio harveyi, Vibrio fischeri, Photobacterium leiognathi and Xenorhabdus luminescens was examined in vivo. The individual genes from these species were cloned on different compatible plasmids or amplified by PCR and brought together to yield cis combinations without extraneous DNA. The beta subunits from V. harveyi and X. luminescens form active enzyme only with alpha subunits from one of these species. All other combinations yield active enzymes. The lack of activity of the V. harveyi and X. luminescens beta subunits with the alpha subunits from V. fischeri and P. leiognathi results from a lack of association. This was shown by in vivo competition in which these beta subunits were overproduced in comparison with the beta and alpha of V. fischeri. No reduction in light was found. Overall, the in vivo results parallel those found in vitro using isolated denatured subunits and renaturation by removal of the denaturant.

  18. Favipiravir elicits antiviral mutagenesis during virus replication in vivo.

    PubMed

    Arias, Armando; Thorne, Lucy; Goodfellow, Ian

    2014-10-21

    Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

  19. In vivo acoustic and photoacoustic focusing of circulating cells

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2016-03-01

    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

  20. Imaging tumor microscopic viscosity in vivo using molecular rotors

    PubMed Central

    Shimolina, Lyubov’ E.; Izquierdo, Maria Angeles; López-Duarte, Ismael; Bull, James A.; Shirmanova, Marina V.; Klapshina, Larisa G.; Zagaynova, Elena V.; Kuimova, Marina K.

    2017-01-01

    The microscopic viscosity plays an essential role in cellular biophysics by controlling the rates of diffusion and bimolecular reactions within the cell interior. While several approaches have emerged that have allowed the measurement of viscosity and diffusion on a single cell level in vitro, the in vivo viscosity monitoring has not yet been realized. Here we report the use of fluorescent molecular rotors in combination with Fluorescence Lifetime Imaging Microscopy (FLIM) to image microscopic viscosity in vivo, both on a single cell level and in connecting tissues of subcutaneous tumors in mice. We find that viscosities recorded from single tumor cells in vivo correlate well with the in vitro values from the same cancer cell line. Importantly, our new method allows both imaging and dynamic monitoring of viscosity changes in real time in live animals and thus it is particularly suitable for diagnostics and monitoring of the progress of treatments that might be accompanied by changes in microscopic viscosity. PMID:28134273

  1. Bioorthogonal Oxime Ligation Mediated In Vivo Cancer Targeting.

    PubMed

    Tang, Li; Yin, Qian; Xu, Yunxiang; Zhou, Qin; Cai, Kaimin; Yen, Jonathan; Dobrucki, Lawrence W; Cheng, Jianjun

    2015-04-01

    Current cancer targeting relying on specific biological interaction between cell surface antigen and respective antibody or its analogue has proven to be effective in the treatment of different cancers; however, this strategy has its own limitations, such as heterogeneity of cancer cells and immunogenicity of the biomacromolecule binding ligands. Bioorthogonal chemical conjugation has emerged as an attractive alternative to biological interaction for in vivo cancer targeting. Here, we report an in vivo cancer targeting strategy mediated by bioorthogonal oxime ligation. Oxyamine group, the artificial target, is introduced onto 4T1 murine breast cancer cells through liposome delivery and fusion. Poly(ethylene glycol) -polylactide (PEG-PLA) nanoparticle (NP) is surface-functionalized with aldehyde groups as targeting ligands. The improved in vivo cancer targeting of PEG-PLA NPs is achieved through specific and efficient chemical reaction between the oxyamine and aldehyde groups.

  2. Evaluation of novel radiation sensitizers in vitro and in vivo

    SciTech Connect

    Adams, G.E.; Sheldon, P.W.; Stratford, I.J.

    1982-03-01

    In principle, radiation sensitizers with therapeutic ratios greater than that of misonidazole can be obtained either by increasing sensitizing efficiency, decreasing toxicity or preferably both. This paper illustrates, firstly that a 5-nitroimidazole (S73-0662) with an electron affinity close to that of metronidazole shows sensitizing efficiency similar to misonidazole both in vitro and in vivo. The suggestion is made that the compound should receive a detailed toxicological study to acertain if its toxicity is lower than misonidazole. Secondly, Imuran, a 5-substituted 4-nitroimidazole and one of a series of compounds which show sensitizing efficiencies in vitro much greater then would be predicted from electron affinity considerations, also shows good sensitization in vivo. Compounds in this series are generally metabolically unstable and the positive results with Imuran in vivo provide a direction for future synthesis of novel sensitizers.

  3. In vivo specificity of EcoRI DNA methyltransferase.

    PubMed Central

    Smith, D W; Crowder, S W; Reich, N O

    1992-01-01

    The EcoRI adenine DNA methyltransferase forms part of a bacterial restriction/modification system; the methyltransferase modifies the second adenine within the canonical site GAATTC, thereby preventing the EcoRI endonuclease from cleaving this site. We show that five noncanonical EcoRI sites (TAATTC, CAATTC, GTATTC, GGATTC and GAGTTC) are not methylated in vivo under conditions when the canonical site is methylated. Only when the methyltransferase is overexpressed is partial in vivo methylation of the five sites detected. Our results suggest that the methyltransferase does not protect host DNA against potential endonuclease-mediated cleavage at noncanonical sites. Our related in vitro analysis of the methyltransferase reveals a low level of sequence-discrimination. We propose that the high in vivo specificity may be due to the active removal of methylated sequences by DNA repair enzymes (J. Bacteriology (1987), 169 3243-3250). Images PMID:1461739

  4. In vivo acoustic and photoacoustic focusing of circulating cells

    PubMed Central

    Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2016-01-01

    In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models. PMID:26979811

  5. Photoacoustic molecular imaging for in vivo liver iron quantitation

    NASA Astrophysics Data System (ADS)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  6. Progress Toward In Vivo Use of siRNAs-II

    PubMed Central

    Rettig, Garrett R; Behlke, Mark A

    2012-01-01

    RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006. PMID:22186795

  7. Rational design of fluorophores for in vivo applications.

    PubMed

    Ptaszek, Marcin

    2013-01-01

    Several classes of small organic molecules exhibit properties that make them suitable for fluorescence in vivo imaging. The most promising candidates are cyanines, squaraines, boron dipyrromethenes, porphyrin derivatives, hydroporphyrins, and phthalocyanines. The recent designing and synthetic efforts have been dedicated to improving their optical properties (shift the absorption and emission maxima toward longer wavelengths and increase the brightness) as well as increasing their stability and water solubility. The most notable advances include development of encapsulated cyanine dyes with increased stability and water solubility, squaraine rotaxanes with increased stability, long-wavelength-absorbing boron dipyrromethenes, long-wavelength-absorbing porphyrin and hydroporphyrin derivatives, and water-soluble phthalocyanines. Recent advances in luminescence and bioluminescence have made self-illuminating fluorophores available for in vivo applications. Development of new types of hydroporphyrin energy-transfer dyads gives the promise for further advances in in vivo multicolor imaging.

  8. Microsensors for in vivo Measurement of Glutamate in Brain Tissue

    PubMed Central

    Qin, Si; van der Zeyden, Miranda; Oldenziel, Weite H.; Cremers, Thomas I.F.H.; Westerink, Ben H.C.

    2008-01-01

    Several immobilized enzyme-based electrochemical biosensors for glutamate detection have been developed over the last decade. In this review, we compare first and second generation sensors. Structures, working mechanisms, interference prevention, in vitro detection characteristics and in vivo performance are summarized here for those sensors that have successfully detected brain glutamate in vivo. In brief, first generation sensors have a simpler structure and are faster in glutamate detection. They also show a better sensitivity to glutamate during calibration in vitro. For second generation sensors, besides their less precise detection, their fabrication is difficult to reproduce, even with a semi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo, but the reported basal levels are different. In general, second generation sensors detect higher basal levels of glutamate compared with the results obtained from first generation sensors. However, whether the detected glutamate is indeed from synaptic sources is an issue that needs further attention. PMID:27873904

  9. Bioorthogonal Oxime Ligation Mediated In Vivo Cancer Targeting

    PubMed Central

    Tang, Li; Yin, Qian; Xu, Yunxiang; Zhou, Qin; Cai, Kaimin; Yen, Jonathan; Dobrucki, Lawrence W.

    2015-01-01

    Current cancer targeting relying on specific biological interaction between cell surface antigen and respective antibody or its analogue has proven to be effective in the treatment of different cancers; however, this strategy has its own limitations, such as heterogeneity of cancer cells and immunogenicity of the biomacromolecule binding ligands. Bioorthogonal chemical conjugation has emerged as an attractive alternative to biological interaction for in vivo cancer targeting. Here, we report an in vivo cancer targeting strategy mediated by bioorthogonal oxime ligation. Oxyamine group, the artificial target, is introduced onto 4T1 murine breast cancer cells through liposome delivery and fusion. Poly(ethylene glycol) -polylactide (PEG-PLA) nanoparticle (NP) is surface-functionalized with aldehyde groups as targeting ligands. The improved in vivo cancer targeting of PEG-PLA NPs is achieved through specific and efficient chemical reaction between the oxyamine and aldehyde groups. PMID:26146536

  10. Estimation of In Vivo Bone Strength Using Ultrasound Signals

    NASA Astrophysics Data System (ADS)

    Nogata, Fumio; Shimamoto, Akira; Habu, Toshihiko

    A new method for estimating in vivo bone strength using ultrasound inspection is described, which can allow diagnose of osteoporosis from the viewpoint of mechanical integrity. The method was based on the two-dimensional area fraction of bone calculated from the difference in the speed of ultrasound propagation through cancellous bone. Then bulk Young's modulus was calculated for various architectures of the cancellous bone with the bone area fraction (S) using finite element method. Since there was a good relationship between the BMD (bone mineral density) by DXA (dual energy x-ray absorptiometry) method and the bone area fraction by ultrasound inspection, the technique also allows the estimation of in vivo BMD of the spine, which has been traditionally used at medical area to diagnose osteoporosis. Note that the periodic estimation of the bulk Young's modulus and strength applying the technique is effective to predict the fracture risk for in vivo bone.

  11. Glucocorticoids enhance the in vivo migratory response of human monocytes.

    PubMed

    Yeager, Mark P; Pioli, Patricia A; Collins, Jane; Barr, Fiona; Metzler, Sara; Sites, Brian D; Guyre, Paul M

    2016-05-01

    Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6h to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24h after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation.

  12. Adenosine produced from adenine nucleotides through an interaction between apoptotic cells and engulfing macrophages contributes to the appearance of transglutaminase 2 in dying thymocytes.

    PubMed

    Sándor, Katalin; Pallai, Anna; Duró, Edina; Legendre, Pascal; Couillin, Isabelle; Sághy, Tibor; Szondy, Zsuzsa

    2017-03-01

    Transglutaminase 2 (TG2) has been known for a long time to be associated with the in vivo apoptosis program of various cell types, including T cells. Though the expression of the enzyme is strongly induced in mouse thymocytes following apoptosis induction in vivo, no significant induction of TG2 can be detected, when thymocytes are induced to die by the same stimuli in vitro indicating that signals arriving from the tissue environment are required for the proper in vivo induction of the enzyme. Previous studies from our laboratory have demonstrated that two of these signals, transforming growth factor-β (TGF-β) and retinoids, are produced by macrophages engulfing apoptotic cells. However, in addition to TGF-β and retinoids, engulfing macrophages produce adenosine as well. Here, we show that in vitro adenosine, adenosine, and retinoic acid or adenosine, TGF-β and retinoic acids together can significantly enhance the TG2 mRNA expression in dying thymocytes. The effect of adenosine is mediated via adenosine A2A receptors (A2ARs) and the A2AR-triggered adenylate cyclase signaling pathway. In accordance, loss of A2ARs in A2AR null mice significantly attenuates the in vivo induction of TG2 following apoptosis induction in the thymus indicating that adenosine indeed contributes in vivo to the apoptosis-related appearance of the enzyme. We also demonstrate that adenosine is produced extracellularly during engulfment of apoptotic thymocytes, partly from adenine nucleotides released via thymocyte pannexin-1 channels. Our data reveal a novel crosstalk between macrophages and apoptotic cells, in which apoptotic cell uptake-related adenosine production contributes to the appearance of TG2 in the dying thymocytes.

  13. Quantification of Lung Metastases from In Vivo Mouse Models.

    PubMed

    Chang, Joan; Erler, Janine T

    2016-01-01

    Cancer research has made significant progress in terms of understanding and targeting primary tumors; however, the challenge remains for the successful treatment of metastatic cancers. This highlights the importance to use in vivo models to study the metastatic process, as well as for preclinical testing of compounds that could inhibit metastasis. As a result, proper quantification of metastases from in vivo models is of the utmost significance. Here, we provide a detailed protocol for collecting and handling lung tissues from mice, and guidance for subsequent analysis of metastases, as well as interpretation of data.

  14. Modeling disease in vivo with CRISPR/Cas9

    PubMed Central

    Dow, Lukas E.

    2015-01-01

    The recent advent of CRISPR/Cas9-mediated genome editing has created a wave of excitement across the scientific research community, carrying the promise of simple and effective genomic manipulation of nearly any cell type. CRISPR has quickly become the preferred tool for genetic manipulation, and shows incredible promise as a platform for studying gene function in vivo. Here, I discuss the current application of CRISPR technology to create new in vivo disease models, with a particular focus on how these tools, derived from an adaptive bacterial immune system, are helping us better model the complexity of human cancer. PMID:26432018

  15. Translating cell biology in vitro to immunity in vivo

    NASA Astrophysics Data System (ADS)

    Boes, Marianne; Ploegh, Hidde L.

    2004-07-01

    The elimination of pathogens and pathogen-infected cells initially rests on the rapid deployment of innate immune defences. Should these defences fail, it is the lymphocytes - T cells and B cells - with their antigen-specific receptors that must rise to the task of providing adaptive immunity. Technological advances are now allowing immunologists to correlate data obtained in vitro with in vivo functions. A better understanding of T-cell activation in vivo could lead to more effective strategies for the treatment and prevention of infectious and autoimmmune diseases.

  16. Ultrafast imaging of in vivo muscle contraction using ultrasound

    NASA Astrophysics Data System (ADS)

    Deffieux, Thomas; Gennisson, Jean-Luc; Tanter, Mickaël; Fink, Mathias; Nordez, Antoine

    2006-10-01

    In this letter, an innovative way of imaging transient and local shear vibrations of an in vivo contracting muscle is proposed. The principle is to use an ultrafast ultrasound scanner (up to 5000framess-1) able to follow with a submillimeter resolution the motion of the muscle tissue in a two dimensional plane. This ultrafast echographic imaging technique leads to both local and transient in vivo studies of the contraction of a muscle as reported by these first experiments done on the biceps brachii.

  17. Opto-ultrasound imaging in vivo in deep tissue

    NASA Astrophysics Data System (ADS)

    Si, Ke; YanXu; Zheng, Yao; Zhu, Xinpei; Gong, Wei

    2016-02-01

    It is of keen importance of deep tissue imaging with high resolution in vivo. Here we present an opto-ultrasound imaging method which utilizes an ultrasound to confine the laser pulse in a very tiny spot as a guide star. The results show that the imaging depth is 2mm with a resolution of 10um. Meanwhile, the excitation power we used is less than 2mW, which indicates that our methods can be applied in vivo without optical toxicity and optical bleaching due to the excitation power.

  18. In vivo heating of magnetic nanoparticles in alternating magnetic field.

    PubMed

    Babincová, M; Altanerová, V; Altaner, C; Cicmanec, P; Babinec, P

    2004-08-01

    We have evaluated heating capabilities of new magnetic nanoparticles. In in vitro experiments they were exposed to an alternating magnetic field with frequency 3.5 MHz and induction 1.5 mT produced in three turn pancake coil. In in vivo experiments rats with injected magnetic nanoparticles were also exposed to an ac field. An optimal increase of temperature of the tumor to 44 degrees C was achieved after 10 minutes of exposure. Obtained results showed that magnetic nanoparticles may be easily heated in vitro as well as in vivo, and may be therefore useful for hyperthermic therapy of cancer.

  19. Modeling Disease In Vivo With CRISPR/Cas9.

    PubMed

    Dow, Lukas E

    2015-10-01

    The recent advent of CRISPR/Cas9-mediated genome editing has created a wave of excitement across the scientific research community, carrying the promise of simple and effective genomic manipulation of nearly any cell type. CRISPR has quickly become the preferred tool for genetic manipulation, and shows incredible promise as a platform for studying gene function in vivo. I discuss the current application of CRISPR technology to create new in vivo disease models, with a particular focus on how these tools, derived from an adaptive bacterial immune system, are helping us to better model the complexity of human cancer.

  20. Manipulating the in vivo immune response by targeted gene knockdown.

    PubMed

    Lieberman, Judy

    2015-08-01

    Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer-siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic.

  1. Lifetime-based photoacoustic oxygen sensing in vivo

    NASA Astrophysics Data System (ADS)

    Ray, Aniruddha; Rajian, Justin Rajesh; Lee, Yong-Eun Koo; Wang, Xueding; Kopelman, Raoul

    2012-05-01

    The determination of oxygen levels in blood and other tissues in vivo is critical for ensuring proper body functioning, for monitoring the status of many diseases, such as cancer, and for predicting the efficacy of therapy. Here we demonstrate, for the first time, a lifetime-based photoacoustic technique for the measurement of oxygen in vivo, using an oxygen sensitive dye, enabling real time quantification of blood oxygenation. The results from the main artery in the rat tail indicated that the lifetime of the dye, quantified by the photoacoustic technique, showed a linear relationship with the blood oxygenation levels in the targeted artery.

  2. Application of in vivo laser scanning microscope in dermatology

    NASA Astrophysics Data System (ADS)

    Lademann, Juergen; Richter, H.; Otberg, N.; Lawrenz, F.; Blume-Peytavi, U.; Sterry, W.

    2003-10-01

    The state of the art of in-vivo and in-vitro penetration measurements of topically applied substances is described. Only optical techniques represent online measuring methods based on the absorption or scattering properties of the topically applied substances. Laser scanning microscopy (LSM) has become a promising method for investigations in dermatology and skin physiology, after it was possible to analyze the skin surface on any body side in-vivo. In the present paper the application of a dermatological laser scanning microscope for penetration and distribution measurements of topically applied substances is described. The intercellular and follicular penetration pathways were studied.

  3. OCT-based in vivo tissue injury mapping

    NASA Astrophysics Data System (ADS)

    Baran, Utku; Li, Yuandong; Wang, Ruikang K.

    2016-03-01

    Tissue injury mapping (TIM) is developed by using a non-invasive in vivo optical coherence tomography to generate optical attenuation coefficient and microvascular map of the injured tissue. Using TIM, the infarct region development in mouse cerebral cortex during stroke is visualized. Moreover, we demonstrate the in vivo human facial skin structure and microvasculature during an acne lesion development. The results indicate that TIM may help in the study and the treatment of various diseases by providing high resolution images of tissue structural and microvascular changes.

  4. In vivo melanoma depth detection by a handheld photoacoustic microscope

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Xing, Wenxin; Maslov, Konstantin I.; Cornelius, Lynn A.; Wang, Lihong V.

    2015-03-01

    We developed a handheld photoacoustic microscope (PAM) to detect melanoma and determine tumor depth in nude mice in vivo. Compared to our previous PAM system for melanoma imaging, a new light delivery mechanism is introduced to improve light penetration. We show that melanomas with 4.1 mm and 3.3 mm thicknesses can be successfully detected in phantom and in vivo experiments, respectively. With its deep melanoma imaging ability and novel handheld design, this system is promising for clinical melanoma diagnosis, prognosis, and surgical planning for patients at the bedside.

  5. Corticothalamic Feedback Controls Sleep Spindle Duration In Vivo

    PubMed Central

    Bonjean, Maxime; Baker, Tanya; Lemieux, Maxime; Timofeev, Igor; Sejnowski, Terrence; Bazhenov, Maxim

    2011-01-01

    Spindle oscillations are commonly observed during stage two of non-REM sleep. During sleep spindles, the cerebral cortex and thalamus interact through feedback connections. Both initiation and termination of spindle oscillations are thought to originate in the thalamus, based on thalamic recordings and computational models, although some in vivo results suggest otherwise. Here, we have used computer modeling and in vivo multisite recordings from the cortex and the thalamus in cats to examine the involvement of the cortex in spindle oscillations. We found that although the propagation of spindles depended on synaptic interaction within the thalamus, the initiation and termination of spindle sequences critically involved corticothalamic influences. PMID:21697364

  6. Spiritual aspects of death and dying.

    PubMed Central

    Mermann, A. C.

    1992-01-01

    Dying is an event beyond our comprehension, an experience that can only be imagined. Patients with cancer have a gift denied many others: some time to prepare for the approaching end of life. This time can be used to bring old conflicts to a close, to say goodbye and seek forgiveness from others, to express love and gratitude for the gifts of a life. Physicians can help patients by being aware of the spiritual dimensions to life that many patients have. In major religious traditions, death is accepted as the natural end of the gift of life and as a point of transition to another, yet unknown, existence. For many patients, it is not death that is feared, but abandonment. The physician's awareness of the spiritual needs of patients can make care of the dying more rewarding and fulfilling for all concerned. PMID:1519377

  7. Architecture for on-die interconnect

    SciTech Connect

    Khare, Surhud; More, Ankit; Somasekhar, Dinesh; Dunning, David S.

    2016-03-15

    In an embodiment, an apparatus includes: a plurality of islands configured on a semiconductor die, each of the plurality of islands having a plurality of cores; and a plurality of network switches configured on the semiconductor die and each associated with one of the plurality of islands, where each network switch includes a plurality of output ports, a first set of the output ports are each to couple to the associated network switch of an island via a point-to-point interconnect and a second set of the output ports are each to couple to the associated network switches of a plurality of islands via a point-to-multipoint interconnect. Other embodiments are described and claimed.

  8. Clayton's compromises and the assisted dying debate.

    PubMed

    Parker, Malcolm

    2015-03-01

    Richard Huxtable has recently argued that while assisted dying has been both repeatedly condemned and commended, a compromise resolution is possible. Following critique of other purported solutions, he argues for a new legal offence of "compassionate killing" as a plausible compromise between supporters and opponents of legalised assisted dying, because it offers something of significance to both sides. However, it turns out that "compassionate killing" would leave both sides with insufficient net benefit for the proposal to qualify as a compromise between them. By analogy with another apparently intractable bioethical debate, concerning destructive embryo research, this column rejects Huxtable's solution as another "Clayton's compromise". True compromise is not possible in bioethical debates involving divisions over deeply held values and world views. Resolving such debates inevitably involves the substitution of one dominant world view with another.

  9. Questions about the behaviour of bacterial pathogens in vivo.

    PubMed Central

    Smith, H

    2000-01-01

    Bacterial pathogens cause disease in man and animals. They have unique biological properties, which enable them to colonize mucous surfaces, penetrate them, grow in the environment of the host, inhibit or avoid host defences and damage the host. The bacterial products responsible for these five biological requirements are the determinants of pathogenicity (virulence determinants). Current knowledge comes from studies in vitro, but now interest is increasing in how bacteria behave and produce virulence determinants within the infected host. There are three aspects to elucidate: bacterial activities, the host factors that affect them and the metabolic interactions between the two. The first is relatively easy to accomplish and, recently, new methods for doing this have been devised. The second is not easy because of the complexity of the environment in vivo and its ever-changing face. Nevertheless, some information can be gained from the literature and by new methodology. The third aspect is very difficult to study effectively unless some events in vivo can be simulated in vitro. The objectives of the Discussion Meeting were to describe the new methods and to show how they, and conventional studies, are revealing the activities of bacterial pathogens in vivo. This paper sets the scene by raising some questions and suggesting, with examples, how they might be answered. Bacterial growth in vivo is the primary requirement for pathogenicity. Without growth, determinants of the other four requirements are not formed. Results from the new methods are underlining this point. The important questions are as follows. What is the pattern of a developing infection and the growth rates and population sizes of the bacteria at different stages? What nutrients are present in vivo and how do they change as infection progresses and relate to growth rates and population sizes? How are these nutrients metabolized and by what bacterial mechanisms? Which bacterial processes handle

  10. Fewer Patients Die During Hospital Inspection Weeks: Study

    MedlinePlus

    ... 164254.html Fewer Patients Die During Hospital Inspection Weeks: Study Slight differences in death rates were possibly ... likely to die if they are treated during weeks that inspectors are checking on the staff, a ...

  11. Historical review of die drool phenomenon during plastics extrusion

    NASA Astrophysics Data System (ADS)

    Musil, Jan; Zatloukal, Martin

    2013-04-01

    Die drool phenomenon is defined as unwanted spontaneous accumulation of extruded polymer melt on open faces of extrusion die during extrusion process. Such accumulated material builds up on the die exit and frequently or continually sticks onto the extruded product and thus damages it. Since die drool appears, extrusion process must be shut down and die exit must be manually cleaned which is time and money consuming. Although die drool is complex phenomenon and its formation mechanism is not fully understood yet, variety of proposed explanations of its formation mechanism and also many ways to its elimination can be found in open literature. Our review presents in historical order breakthrough works in the field of die drool research, shows many ways to suppress it, introduces methods for its quantitative evaluation and composition analysis and summarizes theories of die drool formation mechanism which can be helpful for extrusion experts.

  12. Educating and training India's next generation of in vivo pharmacologists

    PubMed Central

    Lewis, David I.

    2016-01-01

    The Indian Pharmaceutical Industry is undergoing rapid development and expansion. Critical to this process, and the future of drug discovery in India is the continued education and training of integrative or in vivo pharmacologists, equipped with the knowledge, skills and expertise to undertake studies using laboratory animals. Modern in vivo pharmacologists not only require manual or technical skills, but a much broader education including in animal welfare, ethics, the principles of the replacement, refinement and reduction of animals in research, and nonanimal alternative techniques. This education, training, and continued professional development throughout their careers can be provided, in part, through the use of online e-learning resources. While many excellent resources exist, they are hard to locate and not widely known to the community. To address this issue, Education and Training Resources in In vivo Sciences, a free website which provides access to free open access e-learning resources in in vivo pharmacology was developed. Use of this resource by researchers and educators will result in better-trained researchers and members of ethical review committees, which in turn will raise animal welfare standards, minimize the pain, suffering and distress of laboratory animals, and enhance scientific research. PMID:27298489

  13. In vivo continuous evolution of genes and pathways in yeast

    PubMed Central

    Crook, Nathan; Abatemarco, Joseph; Sun, Jie; Wagner, James M.; Schmitz, Alexander; Alper, Hal S.

    2016-01-01

    Directed evolution remains a powerful, highly generalizable approach for improving the performance of biological systems. However, implementations in eukaryotes rely either on in vitro diversity generation or limited mutational capacities. Here we synthetically optimize the retrotransposon Ty1 to enable in vivo generation of mutant libraries up to 1.6 × 107 l−1 per round, which is the highest of any in vivo mutational generation approach in yeast. We demonstrate this approach by using in vivo-generated libraries to evolve single enzymes, global transcriptional regulators and multi-gene pathways. When coupled to growth selection, this approach enables in vivo continuous evolution (ICE) of genes and pathways. Through a head-to-head comparison, we find that ICE libraries yield higher-performing variants faster than error-prone PCR-derived libraries. Finally, we demonstrate transferability of ICE to divergent yeasts, including Kluyveromyces lactis and alternative S. cerevisiae strains. Collectively, this work establishes a generic platform for rapid eukaryotic-directed evolution across an array of target cargo. PMID:27748457

  14. Introduction: feature issue on In Vivo Microcirculation Imaging.

    PubMed

    Dunn, Andrew K; Leitgeb, Rainer; Wang, Ruikang K; Zhang, Hao F

    2011-07-01

    The editors introduce the Biomedical Optics Express feature issue, "In Vivo Microcirculation Imaging," which includes 14 contributions from the biomedical optics community, covering such imaging techniques as optical coherence tomography, photoacoustic microscopy, laser Doppler /speckle imaging, and near infrared spectroscopy and fluorescence imaging.

  15. Recent advances in microscopic techniques for visualizing leukocytes in vivo

    PubMed Central

    Jain, Rohit; Tikoo, Shweta; Weninger, Wolfgang

    2016-01-01

    Leukocytes are inherently motile and interactive cells. Recent advances in intravital microscopy approaches have enabled a new vista of their behavior within intact tissues in real time. This brief review summarizes the developments enabling the tracking of immune responses in vivo. PMID:27239292

  16. HIM-herbal ingredients in-vivo metabolism database

    PubMed Central

    2013-01-01

    Background Herbal medicine has long been viewed as a valuable asset for potential new drug discovery and herbal ingredients’ metabolites, especially the in vivo metabolites were often found to gain better pharmacological, pharmacokinetic and even better safety profiles compared to their parent compounds. However, these herbal metabolite information is still scattered and waiting to be collected. Description HIM database manually collected so far the most comprehensive available in-vivo metabolism information for herbal active ingredients, as well as their corresponding bioactivity, organs and/or tissues distribution, toxicity, ADME and the clinical research profile. Currently HIM contains 361 ingredients and 1104 corresponding in-vivo metabolites from 673 reputable herbs. Tools of structural similarity, substructure search and Lipinski’s Rule of Five are also provided. Various links were made to PubChem, PubMed, TCM-ID (Traditional Chinese Medicine Information database) and HIT (Herbal ingredients’ targets databases). Conclusions A curated database HIM is set up for the in vivo metabolites information of the active ingredients for Chinese herbs, together with their corresponding bioactivity, toxicity and ADME profile. HIM is freely accessible to academic researchers at http://www.bioinformatics.org.cn/. PMID:23721660

  17. Carbon Nanomaterials Interfacing with Neurons: An In vivo Perspective

    PubMed Central

    Baldrighi, Michele; Trusel, Massimo; Tonini, Raffaella; Giordani, Silvia

    2016-01-01

    Developing new tools that outperform current state of the art technologies for imaging, drug delivery or electrical sensing in neuronal tissues is one of the great challenges in neurosciences. Investigations into the potential use of carbon nanomaterials for such applications started about two decades ago. Since then, numerous in vitro studies have examined interactions between these nanomaterials and neurons, either by evaluating their compatibility, as vectors for drug delivery, or for their potential use in electric activity sensing and manipulation. The results obtained indicate that carbon nanomaterials may be suitable for medical therapies. However, a relatively small number of in vivo studies have been carried out to date. In order to facilitate the transformation of carbon nanomaterial into practical neurobiomedical applications, it is essential to identify and highlight in the existing literature the strengths and weakness that different carbon nanomaterials have displayed when probed in vivo. Unfortunately the current literature is sometimes sparse and confusing. To offer a clearer picture of the in vivo studies on carbon nanomaterials in the central nervous system, we provide a systematic and critical review. Hereby we identify properties and behavior of carbon nanomaterials in vivo inside the neural tissues, and we examine key achievements and potentially problematic toxicological issues. PMID:27375413

  18. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming.

    PubMed

    Mitani, Yasuyuki; Vagnozzi, Ronald J; Millay, Douglas P

    2017-01-01

    Knowledge regarding cellular fusion and nuclear reprogramming may aid in cell therapy strategies for skeletal muscle diseases. An issue with cell therapy approaches to restore dystrophin expression in muscular dystrophy is obtaining a sufficient quantity of cells that normally fuse with muscle. Here we conferred fusogenic activity without transdifferentiation to multiple non-muscle cell types and tested dystrophin restoration in mouse models of muscular dystrophy. We previously demonstrated that myomaker, a skeletal muscle-specific transmembrane protein necessary for myoblast fusion, is sufficient to fuse 10T 1/2 fibroblasts to myoblasts in vitro. Whether myomaker-mediated heterologous fusion is functional in vivo and whether the newly introduced nonmuscle nuclei undergoes nuclear reprogramming has not been investigated. We showed that mesenchymal stromal cells, cortical bone stem cells, and tail-tip fibroblasts fuse to skeletal muscle when they express myomaker. These cells restored dystrophin expression in a fraction of dystrophin-deficient myotubes after fusion in vitro. However, dystrophin restoration was not detected in vivo although nuclear reprogramming of the muscle-specific myosin light chain promoter did occur. Despite the lack of detectable dystrophin reprogramming by immunostaining, this study indicated that myomaker could be used in nonmuscle cells to induce fusion with muscle in vivo, thereby providing a platform to deliver therapeutic material.-Mitani, Y., Vagnozzi, R. J., Millay, D. P. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming.

  19. In vivo static field perturbations in magnetic resonance

    NASA Astrophysics Data System (ADS)

    Koch, Kevin Matthew

    2007-12-01

    Fundamental magnetic resonance (MR) theory assumes the spatial homogeneity of a dominating static magnetic field B = B 0ẑ. When this assumption is violated, a myriad of artifacts and compromising factors are introduced to MR spectra and images. Though in vivo nuclear magnetic resonance (NMR) is one of the most widely used scientific and diagnostic tools in medicine and biology, it remains haunted by the continual and persistant ghost of B0 inhomogeneity. An inclusive list of in vivo NMR applications severely impacted by B0 inhomogeneity could go on ad infinitum. Examples of such applications include neurosurgical utility in functional magnetic resonance imaging (fMRI), cerebral metabolic flux mapping, cerebral diffusion tractography, and abdominal diagnostic imaging. Given this wide impact on in vivo NMR, significant effort has been exerted in developing methods of compensating B0 inhomogeneity. Complicating this task is the sample-specific nature of in vivo B 0 inhomogeneity and its exacerbation with ever increasing B 0 field strengths. State of the art B 0 inhomogeneity compensation is currently at a critical juncture where homogenization demands are overwhelming the outer capabilities of existing technology and methods. This thesis addresses the B 0 inhomogeneity problem in the mammalian brain and presents novel solutions to the homogenization technology stalemate.

  20. In vivo axial loading of the mouse tibia.

    PubMed

    Melville, Katherine M; Robling, Alexander G; van der Meulen, Marjolein C H

    2015-01-01

    Noninvasive methods to apply controlled, cyclic loads to the living skeleton are used as anabolic procedures to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days.

  1. ASSESSING TCDD WASTING SYNDROME IN AN IN VIVO OBESITY MODEL

    EPA Science Inventory

    TCDD is a by-product of incineration commonly found as a microcontaminant in the food supply. The TCDD wasting syndrome, characterized by prolonged weight loss, has been examined for decades. Much of this work has focused on high dose in vivo and in vitro studies....

  2. In vivo liver electroporation: optimization and demonstration of therapeutic efficacy.

    PubMed

    Jaichandran, S; Yap, Steven T B; Khoo, Adrian B M; Ho, Liam Pock; Tien, Sim Leng; Kon, Oi Lian

    2006-03-01

    Adverse effects (death and leukemogenesis) from viral vector-mediated gene therapy have renewed interest in plasmids as safer, more scalable, simple, and cost-effective vectors. Electroporation and hydrodynamic delivery are two techniques that improve the efficiency of plasmid-mediated gene transfer. The liver is a good tissue platform for targeted transfer of therapeutically relevant genes for correction of metabolic disorders, for example, hemophilia A. However, in vivo electroporation of liver has not yet been shown to achieve therapeutic efficacy of systemically active, secreted transgenic proteins. We have investigated the effect of field strength, pulse duration, pulse number, electrical waveforms, electrode contact area, plasmid administration routes, and injection technique on the efficiency of in vivo electrotransfer of naked plasmid to liver. Plasmid injection into a systemic vein was superior to intrahepatic injection. Unlike in vivo muscle electroporation, high-voltage pulses and microsecond pulses offered no advantage. Optimal electroporation conditions were 8-10 uni- or bipolar pulses of 20 msec, each at 250 V/cm. Using a nonhydrodynamic technique that greatly enhanced electrotransfer efficiency with minimal tissue injury, we demonstrate for the first time that liverdirected in vivo electroporation of factor VIII cDNA achieved significant phenotypic correction in hemophilic mice.

  3. IN VIVO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN THE RAT

    EPA Science Inventory

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased agricultural and residential use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and cis-permethrin in the rat. Hair on...

  4. Performance testing of radiobioassay laboratories: In vivo measurements, Final Report

    SciTech Connect

    MacLellan, J.A.; Traub, R.J.; Olsen, P.C.

    1990-04-01

    A study of two rounds of in vivo laboratory performance testing was undertaken by Pacific Northwest Laboratory (PNL) to determine the appropriateness of the in vivo performance criteria of draft American National Standards Institute (ANSI) standard ANSI N13.3, Performance Criteria for Bioassay.'' The draft standard provides guidance to in vivo counting facilities regarding the sensitivity, precision, and accuracy of measurements for certain categories of commonly assayed radionuclides and critical regions of the body. This report concludes the testing program by presenting the results of the Round Two testing. Testing involved two types of measurements: chest counting for radionuclide detection in the lung, and whole body counting for detection of uniformly distributed material. Each type of measurement was further divided into radionuclide categories as defined in the draft standard. The appropriateness of the draft standard criteria by measuring a laboratory's ability to attain them were judged by the results of both round One and Round Two testing. The testing determined that performance criteria are set at attainable levels, and the majority of in vivo monitoring facilities passed the criteria when complete results were submitted. 18 refs., 18 figs., 15 tabs.

  5. Analysis of the mutations inducedd by conazole fungicides in vivo

    EPA Science Inventory

    The mouse liver tumorigenic conazo1e fungicides triadimefon and propiconazo1e have previously been shown to be in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazo1e myc1obutani1 ...

  6. A Comparison of In Vitro and In Vivo Asexual Embryogenesis.

    PubMed

    Hand, Melanie L; de Vries, Sacco; Koltunow, Anna M G

    2016-01-01

    In plants, embryogenesis generally occurs through the sexual process of double fertilization, which involves a haploid sperm cell fusing with a haploid egg cell to ultimately give rise to a diploid embryo. Embryogenesis can also occur asexually in the absence of fertilization, both in vitro and in vivo. Somatic or gametic cells are able to differentiate into embryos in vitro following the application of plant growth regulators or stress treatments. Asexual embryogenesis also occurs naturally in some plant species in vivo, from either ovule cells as part of a process defined as apomixis, or from somatic leaf tissue in other species. In both in vitro and in vivo asexual embryogenesis, the embryo precursor cells must attain an embryogenic fate without the act of fertilization. This review compares the processes of in vitro and in vivo asexual embryogenesis including what is known regarding the genetic and epigenetic regulation of each process, and considers how the precursor cells are able to change fate and adopt an embryogenic pathway.

  7. On-chip immobilization of planarians for in vivo imaging.

    PubMed

    Dexter, Joseph P; Tamme, Mary B; Lind, Christine H; Collins, Eva-Maria S

    2014-09-17

    Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra.

  8. In vivo dermal absorption of pyrethroid pesticides in the rat.

    EPA Science Inventory

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and permethrin in the rat. Hair on the dorsal side of anesthetized adult m...

  9. In vivo neuronal calcium imaging in C. elegans.

    PubMed

    Chung, Samuel H; Sun, Lin; Gabel, Christopher V

    2013-04-10

    The nematode worm C. elegans is an ideal model organism for relatively simple, low cost neuronal imaging in vivo. Its small transparent body and simple, well-characterized nervous system allows identification and fluorescence imaging of any neuron within the intact animal. Simple immobilization techniques with minimal impact on the animal's physiology allow extended time-lapse imaging. The development of genetically-encoded calcium sensitive fluorophores such as cameleon and GCaMP allow in vivo imaging of neuronal calcium relating both cell physiology and neuronal activity. Numerous transgenic strains expressing these fluorophores in specific neurons are readily available or can be constructed using well-established techniques. Here, we describe detailed procedures for measuring calcium dynamics within a single neuron in vivo using both GCaMP and cameleon. We discuss advantages and disadvantages of both as well as various methods of sample preparation (animal immobilization) and image analysis. Finally, we present results from two experiments: 1) Using GCaMP to measure the sensory response of a specific neuron to an external electrical field and 2) Using cameleon to measure the physiological calcium response of a neuron to traumatic laser damage. Calcium imaging techniques such as these are used extensively in C. elegans and have been extended to measurements in freely moving animals, multiple neurons simultaneously and comparison across genetic backgrounds. C. elegans presents a robust and flexible system for in vivo neuronal imaging with advantages over other model systems in technical simplicity and cost.

  10. In vivo imaging of immune cell trafficking in cancer.

    PubMed

    Ottobrini, Luisa; Martelli, Cristina; Trabattoni, Daria Lucia; Clerici, Mario; Lucignani, Giovanni

    2011-05-01

    Tumour establishment, progression and regression can be studied in vivo using an array of imaging techniques ranging from MRI to nuclear-based and optical techniques that highlight the intrinsic behaviour of different cell populations in the physiological context. Clinical in vivo imaging techniques and preclinical specific approaches have been used to study, both at the macroscopic and microscopic level, tumour cells, their proliferation, metastasisation, death and interaction with the environment and with the immune system. Fluorescent, radioactive or paramagnetic markers were used in direct protocols to label the specific cell population and reporter genes were used for genetic, indirect labelling protocols to track the fate of a given cell subpopulation in vivo. Different protocols have been proposed to in vivo study the interaction between immune cells and tumours by different imaging techniques (intravital and whole-body imaging). In particular in this review we report several examples dealing with dendritic cells, T lymphocytes and macrophages specifically labelled for different imaging procedures both for the study of their physiological function and in the context of anti-neoplastic immunotherapies in the attempt to exploit imaging-derived information to improve and optimise anti-neoplastic immune-based treatments.

  11. In-vivo morphologic and spectroscopic investigation of Psoriasis

    NASA Astrophysics Data System (ADS)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-07-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  12. Monitoring tumor metastasis by in vivo imaging and flow cytometer

    NASA Astrophysics Data System (ADS)

    Gu, Zhenqin; Guo, Jin; Liu, Guangda; Li, Yan; Chen, Yun; Chen, Tong; Wang, Chen; Wei, Xunbin

    2009-08-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  13. Mitochondrial energetics is impaired in vivo in aged skeletal muscle.

    PubMed

    Gouspillou, Gilles; Bourdel-Marchasson, Isabelle; Rouland, Richard; Calmettes, Guillaume; Biran, Marc; Deschodt-Arsac, Véronique; Miraux, Sylvain; Thiaudiere, Eric; Pasdois, Philippe; Detaille, Dominique; Franconi, Jean-Michel; Babot, Marion; Trézéguet, Véronique; Arsac, Laurent; Diolez, Philippe

    2014-02-01

    With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with (31) P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness ('elasticity') of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.

  14. In Vitro and In Vivo Gene Delivery by Recombinant Baculoviruses

    PubMed Central

    Tani, Hideki; Limn, Chang Kwang; Yap, Chan Choo; Onishi, Masayoshi; Nozaki, Masami; Nishimune, Yoshitake; Okahashi, Nobuo; Kitagawa, Yoshinori; Watanabe, Rie; Mochizuki, Rika; Moriishi, Kohji; Matsuura, Yoshiharu

    2003-01-01

    Although recombinant baculovirus vectors can be an efficient tool for gene transfer into mammalian cells in vitro, gene transduction in vivo has been hampered by the inactivation of baculoviruses by serum complement. Recombinant baculoviruses possessing excess envelope protein gp64 or other viral envelope proteins on the virion surface deliver foreign genes into a variety of mammalian cell lines more efficiently than the unmodified baculovirus. In this study, we examined the efficiency of gene transfer both in vitro and in vivo by recombinant baculoviruses possessing envelope proteins derived from either vesicular stomatitis virus (VSVG) or rabies virus. These recombinant viruses efficiently transferred reporter genes into neural cell lines, primary rat neural cells, and primary mouse osteal cells in vitro. The VSVG-modified baculovirus exhibited greater resistance to inactivation by animal sera than the unmodified baculovirus. A synthetic inhibitor of the complement activation pathway circumvented the serum inactivation of the unmodified baculovirus. Furthermore, the VSVG-modified baculovirus could transduce a reporter gene into the cerebral cortex and testis of mice by direct inoculation in vivo. These results suggest the possible use of the recombinant baculovirus vectors in combination with the administration of complement inhibitors for in vivo gene therapy. PMID:12941888

  15. On-chip immobilization of planarians for in vivo imaging

    PubMed Central

    Dexter, Joseph P.; Tamme, Mary B.; Lind, Christine H.; Collins, Eva-Maria S.

    2014-01-01

    Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra. PMID:25227263

  16. Efficient in vivo Vascularization of Tissue Engineering Scaffolds

    PubMed Central

    Hegen, Anja; Blois, Anna; Tiron, Crina E.; Hellesøy, Monica; Micklem, David R.; Nör, Jacques E.; Akslen, Lars A.; Lorens, James B.

    2010-01-01

    The success of tissue engineering depends on the rapid and efficient formation of a functional blood vasculature. Adult blood vessels comprise endothelial cells and peri-vascular mural cells that assemble into patent tubules ensheathed by a basement membrane during angiogenesis. Using individual vessel components, we characterized intra-scaffold microvessel self-assembly efficiency in a physiological in vivo tissue engineering implant context. Primary human microvascular endothelial- and vascular smooth muscle cells were seeded at different ratios in poly-L lactic acid (PLLA) scaffolds enriched with basement membrane proteins (Matrigel) and implanted subcutaneously into immunocompromised mice. Temporal intra-scaffold microvessel formation, anastomosis and perfusion were monitored by immunohistochemical, flow cytometric and in vivo multiphoton fluorescence microscopy analysis. Vascularization in the tissue engineering context was strongly enhanced in the implants seeded with a complete complement of blood vessel components: Human microvascular endothelial and vascular smooth muscle cells in vivo assembled a patent microvasculature within Matrigel-enriched PLLA scaffolds that anastomosed with the host circulation during the first week of implantation. Multiphoton fluorescence angiographic analysis of the intra-scaffold microcirculation showed a uniform, branched microvascular network. 3-D image reconstruction analysis of hPASMC distribution within vascularized implants was non-random and displayed a preferential peri-vascular localization. Hence, efficient microvessel self-assembly, anastomosis and establishment of a functional microvasculture in the native hypoxic in vivo tissue engineering context is promoted by providing a complete set of vascular components. PMID:20865694

  17. Optical and imaging techniques for in-vivo sunscreens investigation

    NASA Astrophysics Data System (ADS)

    Utz, Sergei R.; Knuschke, Peter; Sinichkin, Yuri P.

    1996-01-01

    The methods available for testing the efficacy of topical sunscreens have improved considerably in recent years. Nevertheless, so far no simple and rapid test has been proposed to measure in vivo transmission spectra of sunscreens in the UVA region. Spectral changes that occur after sunscreen application were measured with a fluorescence spectrometer (LS 50B, Perkin Elmer, UK) equipped with a Y-shape quartz guide for in vivo measurements. Three sunscreens with different protection factors in the UVA range were tested. The excitation-emission maps of human collagen, skin, and sunscreens were analyzed. Visual demonstrations of the protective effects of sunscreens were also performed with photo- and video imaging techniques. As a consequence of the human skin and sunscreen's fluorescence map analysis, the optimal spectral regions (both for direct and indirect fluorescence measurements) were detected. In vivo fluorescence and remittance spectroscopy were used to investigate the time dependence in transmission spectra of epidermis with applied sunscreens. We also evaluate the feasibility of in vivo fluorescence measurements for the investigation of the sunscreen's water-resistance. The procedure is simple, and values obtained can be used to predict UVA protection on the basis of the mathematical algorithms.

  18. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    EPA Science Inventory

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC.

    Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  19. In vitro/in vivo correlations in transdermal product development.

    PubMed

    Ghosh, Priyanka; Milewski, Mikolaj; Paudel, Kalpana

    2015-01-01

    As per the US FDA's guidance for industry entitled 'Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations', in vitro-in vivo correlations (IVIVC) can be used to establish a dissolution test as a surrogate for human bioequivalence studies and certain scale-up and postapproval changes. However, at the present time, establishment of a transdermal IVIVC is not used to support biowaiver claims in late phases of clinical development or postapproval changes (major formulation changes, i.e., >10% changes in inactive ingredients) to the best of the authors' knowledge. The value of developing an IVIVC for percutaneous drugs lies mainly in facilitating permeation testing of transdermal drug candidates and formulation performance optimization at much lower cost as compared with carrying out multiple in vivo studies. The present article will introduce the concept of transdermal IVIVC, outlining certain limitations to its applicability, in vitro and in vivo methods, regulatory product development requirements and the most common approaches to establish an IVIVC for a transdermal drug. Additionally, this article will also summarize some challenges and recent advancements in this field, along with selected academic examples of transdermal IVIVCs.

  20. Use of GFP for in vivo imaging: concepts and misconceptions

    NASA Astrophysics Data System (ADS)

    Hoffman, Robert M.

    2008-02-01

    Although GFP and fluorescent proteins are used extensively for in vivo imaging, there are many misconceptions about GFP imaging especially compared to luciferase. GFP is not toxic, indeed, transgenic animals with GFP expressed in every cell (1) live as long as non-transgenic animals. Cancer cells with GFP are as aggressive and malignant as the cells without GFP (2-4). Cell lines can be made very bright with fluorescent proteins with no toxicity. The in vivo signal from fluorescent proteins is at least 1,000 times greater than luciferase (5). GFP is so bright that a single molecule of GFP can be seen in a bacterium (6). GFP can be observed through the skin on deep organs (7). Skin autofluorescence presents no problem for in vivo GFP imaging with proper filters (8). Fur can be rapidly clipped removing this autofluorescence (9). GFP is readily quantified by the image area which correlates to tumor volume (10). There are now numerous clones of GFP, RFP, YFP and proteins that change color (11) that can be used in vivo.

  1. In vivo brain viscoelastic properties measured by magnetic resonance elastography.

    PubMed

    Green, Michael A; Bilston, Lynne E; Sinkus, Ralph

    2008-08-01

    Magnetic resonance elastography (MRE) is a non-invasive imaging technique used to visualise and quantify mechanical properties of tissue, providing information beyond what can be currently achieved with standard MR sequences and could, for instance, provide new insight into pathological processes in the brain. This study uses the MRE technique at 3 T to extract the complex shear modulus for in vivo brain tissue utilizing a full three-dimensional approach to reconstruction, removing contributions of the dilatational wave by application of the curl operator. A calibrated phantom is used to benchmark the MRE measurements, and in vivo results are presented for healthy volunteers. The results provide data for in vivo brain storage modulus (G'), finding grey matter (3.1 kPa) to be significantly stiffer than white matter (2.7 kPa). The first in vivo loss modulus (G'') measurements show no significant difference between grey matter (2.5 kPa) and white matter (2.5 kPa).

  2. Non-invasive in vivo measurement of macular carotenoids

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2009-01-01

    A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

  3. Anatomical Region-Specific In Vivo Wireless Communication Channel Characterization.

    PubMed

    Demir, Ali Fatih; Abbasi, Qammer; Ankarali, Zekeriyya Esat; Alomainy, Akram; Qaraqe, Khalid; Serpedin, Erchin; Arslan, Huseyin

    2016-10-19

    In vivo wireless body area networks (WBANs) and their associated technologies are shaping the future of healthcare by providing continuous health monitoring and noninvasive surgical capabilities, in addition to remote diagnostic and treatment of diseases. To fully exploit the potential of such devices, it is necessary to characterize the communication channel which will help to build reliable and high-performance communication systems. This paper presents an in vivo wireless communication channel characterization for male torso both numerically and experimentally (on a human cadaver) considering various organs at 915 MHz and 2.4 GHz. A statistical path loss (PL) model is introduced, and the anatomical region-specific parameters are provided. It is found that the mean PL in dB scale exhibits a linear decaying characteristic rather than an exponential decaying profile inside the body, and the power decay rate is approximately twice at 2.4 GHz as compared to 915 MHz. Moreover, the variance of shadowing increases significantly as the in vivo antenna is placed deeper inside the body since the main scatterers are present in the vicinity of the antenna. Multipath propagation characteristics are also investigated to facilitate proper waveform designs in the future wireless healthcare systems, and a rootmean- square (RMS) delay spread of 2.76 ns is observed at 5 cm depth. Results show that the in vivo channel exhibit different characteristics than the classical communication channels, and location dependency is very critical for accurate, reliable, and energy-efficient link budget calculations.

  4. Apoptosis-inducing effect of a palladium(II) saccharinate complex of terpyridine on human breast cancer cells in vitro and in vivo.

    PubMed

    Ari, Ferda; Cevatemre, Buse; Armutak, Elif Ilkay Ikitimur; Aztopal, Nazlihan; Yilmaz, Veysel T; Ulukaya, Engin

    2014-09-01

    The anti-growth effect of a palladium(II) complex-[PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2″-terpyridine)-was tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in vivo. The mode of cell death was determined by both histological and biochemical methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the palladium(II) saccharinate complex of terpyridine represents a potentially active novel complex for the breast cancer treatment, thus warrants further studies.

  5. In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae.

    PubMed

    Harada, Y; Morinaga, Y; Kaku, N; Nakamura, S; Uno, N; Hasegawa, H; Izumikawa, K; Kohno, S; Yanagihara, K

    2014-11-01

    The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.

  6. Clinical applications of in vivo fluorescence confocal laser scanning microscopy

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  7. Methods of in-vivo mouse lung micro-CT

    NASA Astrophysics Data System (ADS)

    Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

    2005-04-01

    Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

  8. A Contextualist Thanatology: A Pragmatic Approach to Death and Dying

    ERIC Educational Resources Information Center

    Reck, Andrew J.

    1977-01-01

    Denying the value of death but accepting its reality, the author points to dying, not death, as the problematic phenomenon with which a pragmatist thanatology must deal. It is suggested that dying contains opportunities for growth--for the dying as well as for their surviving friends and relatives. (Author)

  9. Darwin als Sehhilfe für die Psychologie - Evolutionspsychologie

    NASA Astrophysics Data System (ADS)

    Schwab, Frank

    Im Folgenden geht es um Einäugige, stereoskopisches Sehen, weite und enge Horizonte, Monokel und Sonnenbrillen. Der Beitrag versucht die Metapher des Sehens und der Sehhilfen anzuwenden, um so zu verdeutlichen, welchen Gewinn die herkömmliche Psychologie durch die Verwendung einer Darwin'schen Brille erlangen kann.

  10. A Contingency Framework for Listening to the Dying

    ERIC Educational Resources Information Center

    Vora, Erika; Vora, Ariana

    2008-01-01

    Listening to the dying poses special challenges. This paper proposes a contingency framework for describing and assessing various circumstances when listening to the dying. It identifies current approaches to listening, applies the contingency framework toward effectively listening to the dying, and proposes a new type of listening called…

  11. Die and telescoping punch form convolutions in thin diaphragm

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Die and punch set forms convolutions in thin dished metal diaphragm without stretching the metal too thin at sharp curvatures. The die corresponds to the metal shape to be formed, and the punch consists of elements that progressively slide against one another under the restraint of a compressed-air cushion to mate with the die.

  12. 5 Ways to Cope When a Loved One Dies

    MedlinePlus

    ... Week of Healthy Breakfasts Shyness 5 Ways to Cope When a Loved One Dies KidsHealth > For Teens > 5 Ways to Cope When a Loved One Dies Print A A ... Here are 5 ideas that might help you cope when someone you love has died: Join in ...

  13. 25 CFR 304.2 - Marking and ownership of dies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Marking and ownership of dies. 304.2 Section 304.2 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.2 Marking and ownership of dies. All dies used to mark silver will be provided by...

  14. 25 CFR 304.2 - Marking and ownership of dies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Marking and ownership of dies. 304.2 Section 304.2 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.2 Marking and ownership of dies. All dies used to mark silver will be provided by...

  15. 25 CFR 304.5 - Dies to identify tribe.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Dies to identify tribe. 304.5 Section 304.5 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.5 Dies to identify tribe. Dies are marked with name of tribe. A Navajo stamp will...

  16. 25 CFR 304.2 - Marking and ownership of dies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Marking and ownership of dies. 304.2 Section 304.2 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.2 Marking and ownership of dies. All dies used to mark silver will be provided by...

  17. 25 CFR 304.2 - Marking and ownership of dies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Marking and ownership of dies. 304.2 Section 304.2 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.2 Marking and ownership of dies. All dies used to mark silver will be provided by...

  18. 25 CFR 304.5 - Dies to identify tribe.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Dies to identify tribe. 304.5 Section 304.5 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.5 Dies to identify tribe. Dies are marked with name of tribe. A Navajo stamp will...

  19. 25 CFR 304.5 - Dies to identify tribe.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Dies to identify tribe. 304.5 Section 304.5 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.5 Dies to identify tribe. Dies are marked with name of tribe. A Navajo stamp will...

  20. 25 CFR 304.5 - Dies to identify tribe.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Dies to identify tribe. 304.5 Section 304.5 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.5 Dies to identify tribe. Dies are marked with name of tribe. A Navajo stamp will...

  1. 25 CFR 301.3 - Specifications of dies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Specifications of dies. 301.3 Section 301.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.3 Specifications of dies. Dies used are to be entirely hand-made, with no...

  2. 25 CFR 304.5 - Dies to identify tribe.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Dies to identify tribe. 304.5 Section 304.5 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.5 Dies to identify tribe. Dies are marked with name of tribe. A Navajo stamp will...

  3. 25 CFR 301.4 - Application of dies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Application of dies. 301.4 Section 301.4 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.4 Application of dies. Dies are to be applied to the object with the aid...

  4. 25 CFR 301.4 - Application of dies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Application of dies. 301.4 Section 301.4 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.4 Application of dies. Dies are to be applied to the object with the aid...

  5. 25 CFR 301.4 - Application of dies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Application of dies. 301.4 Section 301.4 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.4 Application of dies. Dies are to be applied to the object with the aid...

  6. 25 CFR 301.3 - Specifications of dies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Specifications of dies. 301.3 Section 301.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.3 Specifications of dies. Dies used are to be entirely hand-made, with no...

  7. 25 CFR 301.4 - Application of dies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Application of dies. 301.4 Section 301.4 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.4 Application of dies. Dies are to be applied to the object with the aid...

  8. 25 CFR 301.3 - Specifications of dies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Specifications of dies. 301.3 Section 301.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.3 Specifications of dies. Dies used are to be entirely hand-made, with no...

  9. 25 CFR 301.4 - Application of dies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Application of dies. 301.4 Section 301.4 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.4 Application of dies. Dies are to be applied to the object with the aid...

  10. 25 CFR 301.3 - Specifications of dies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Specifications of dies. 301.3 Section 301.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.3 Specifications of dies. Dies used are to be entirely hand-made, with no...

  11. 25 CFR 301.3 - Specifications of dies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Specifications of dies. 301.3 Section 301.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER AND TURQUOISE PRODUCTS; STANDARDS § 301.3 Specifications of dies. Dies used are to be entirely hand-made, with no...

  12. Imaging cellular dynamics in vivo with multicolor fluorescent proteins

    NASA Astrophysics Data System (ADS)

    Hoffman, Robert M.

    2005-04-01

    The new field of in vivo cell biology is being developed with multi-colored fluorescent proteins. With the use of fluorescent proteins, the behavior of individual cells can be visualized in the living animal. An example of the new cell biology is dual-color fluorescence imaging using red fluorescent protein (RFP)-expressing tumors transplanted in green fluorescent protein (GFP)-expressing transgenic mice. These models show with great clarity the details of the tumor-stroma cell-cell interaction especially tumor-induced angiogenesis, tumor-infiltrating lymphocytes, stromal fibroblasts and macrophages. Another example is the color-coding of cells with RFP or GFP such that both cell types and their interaction can be simultaneously visualized in vivo. Stem cells can also be visualized and tracked in vivo with fluorescent proteins. Mice, in which the regulatory elements of the stem-cell marker nestin drive GFP expression, can be used to visualize hair follicle stem cells including their ability to form hair follicles as well as blood vessels. Dual-color cells expressing GFP in the nucleus and RFP in the cytoplasm enable real-time visualization of nuclear-cytoplasm dynamics including cell cycle events and apoptosis. Dual-color cells also enable the in vivo imaging of cell and nuclear deformation as well as trafficking in capillaries in living animals. Multiple-color labeling of cells will enable multiple events to be simultaneously visualized in vivo including cell-cell interaction, gene expression, ion fluxes, protein and organelle trafficking, chromosome dynamics and numerous other processes currently still studied in vitro.

  13. In Vivo Multiphoton Microscopy of Basal Cell Carcinoma

    PubMed Central

    Balu, Mihaela; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.; Kelly, Kristen M.

    2015-01-01

    Importance Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment. Objectives To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images. Design, Setting, and Participants Imaging in patients with BCC was performed at the University of California–Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings. Main Outcomes and Measures MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis. Results The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors. Conclusions and Relevance This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination. PMID:25909650

  14. Dynamic conformal arc therapy: Transmitted signal in vivo dosimetry

    SciTech Connect

    Piermattei, Angelo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; D'Angelillo, Rolando Maria; Cellini, Francesco; Trodella, Lucio; D'Onofrio, Guido; Grimaldi, Luca; Cilla, Savino; Fidanzio, Andrea; Placidi, Elisa; Azario, Luigi

    2008-05-15

    A method for the determination of the in vivo isocenter dose, D{sub iso}, has been applied to the dynamic conformal arc therapy (DCAT) for thoracic tumors. The method makes use of the transmitted signal, S{sub t,{alpha}}, measured at different gantry angles, {alpha}, by a small ion chamber positioned on the electronic portal imaging device. The in vivo method is implemented by a set of correlation functions obtained by the ratios between the transmitted signal and the midplane dose in a solid phantom, irradiated by static fields. The in vivo dosimetry at the isocenter for the DCAT requires the convolution between the signals , S{sub t,{alpha}}, and the dose reconstruction factors, C{sub {alpha}}, that depend on the patient's anatomy and on its tissue inhomogeneities along the beam central axis in the {alpha} direction. The C{sub {alpha}} factors are obtained by processing the patient's computed tomography scan. The method was tested by taking measurements in a cylindrical phantom and in a Rando Alderson phantom. The results show that the difference between the convolution calculations and the phantom measurements is within {+-}2%. The in vivo dosimetry of the stereotactic DCAT for six lung tumors, irradiated with three or four arcs, is reported. The isocenter dose up to 17 Gy per therapy fraction was delivered on alternating days for three fractions. The agreement obtained in this pilot study between the total in vivo dose D{sub iso} and the planned dose D{sub iso,TPS} at the isocenter is {+-}4%. The method has been applied on the DCAT obtaining a more extensive monitoring of possible systematic errors, the effect of which can invalidate the current therapy which uses a few high-dose fractions.

  15. Grand Challenge Competition to Predict In Vivo Knee Loads

    PubMed Central

    Fregly, Benjamin J.; Besier, Thor F.; Lloyd, David G.; Delp, Scott L.; Banks, Scott A.; Pandy, Marcus G.; D’Lima, Darryl D.

    2013-01-01

    Impairment of the human neuromusculoskeletal system can lead to significant mobility limitations and decreased quality of life. Computational models that accurately represent the musculoskeletal systems of individual patients could be used to explore different treatment options and ultimately to optimize clinical outcome. The most significant barrier to model-based treatment design is validation of model-based estimates of in vivo contact and muscle forces. This paper introduces an annual “Grand Challenge Competition to Predict In Vivo Knee Loads” based on a series of comprehensive publicly available in vivo data sets for evaluating musculoskeletal model predictions of contact and muscle forces in the knee. The data sets come from patients implanted with force-measuring tibial prostheses. Following a historical review of musculoskeletal modeling methods used for estimating knee muscle and contact forces, we describe the first two data sets used for the first two competitions and summarize four subsequent data sets to be used for future competitions. These data sets include tibial contact force, video motion, ground reaction, muscle EMG, muscle strength, static and dynamic imaging, and implant geometry data. Competition participants create musculoskeletal models to predict tibial contact forces without having access to the corresponding in vivo measurements, which are not released until after each year’s competition submissions. These blinded predictions provide an unbiased evaluation of the capabilities and limitations of musculoskeletal modeling methods. The paper concludes with a discussion of how these unique data sets can be used by the musculoskeletal modeling research community to improve the estimation of in vivo muscle and contact forces and ultimately to help make musculoskeletal models clinically useful. PMID:22161745

  16. Differentiating suicide decedents who died using firearms from those who died using other methods.

    PubMed

    Anestis, Michael D; Khazem, Lauren R; Anestis, Joye C

    2017-02-22

    Studies have documented a link between gun ownership and suicide, but little is known about characteristics of those most likely to use a gun in a suicide attempt rather than alternative methods. We examined which factors differentiate suicide decedents who died using a gun from those who died by other methods. We further examined whether such findings are consistent within the subcomponent of our larger sample comprised entirely of gun owning suicide decedents. Data reflect 267 suicide decedents, with data provided by individuals who identified as having lost someone to suicide (loss survivors). Within the full sample, a higher proportion of gun-owning and male suicide decedents died by firearm. Further, individuals who had previously discussed suicide or engaged in one or more non-lethal suicide attempts were less likely to die by suicide using a gun. Within the subsample of gun owning suicide decedents, a greater proportion of decedents who stored guns at home and in unsecure locations died from self-inflected gunshot wounds. These findings add clarity to the relationship between firearm ownership and death by suicide at the individual level. Furthermore, these findings are consistent with the notion that means safety implementation may represent a vital suicide prevention tool.

  17. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    PubMed Central

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

  18. In vivo cardiomyocyte response to YTX- and AZA-1-induced damage: autophagy versus apoptosis.

    PubMed

    Ferreiro, Sara F; Vilariño, Natalia; Carrera, Cristina; Louzao, M Carmen; Santamarina, Germán; Cantalapiedra, Antonio G; Cifuentes, J Manuel; Crespo, Andrés; Botana, Luis M

    2017-04-01

    Yessotoxins (YTX) and azaspiracids (AZAs) are marine toxins produced by phytoplanktonic dinoflagellates that get accumulated in filter feeding shellfish and finally reach human consumers through the food web. Both toxin classes are worldwide distributed, and food safety authorities have regulated their content in shellfish in many countries. Recently, YTXs and AZAs have been described as compounds with subacute cardiotoxic potential in rats owed to alterations of the cardiovascular function and ultrastructural heart damage. These molecules are also well known in vitro inducers of cell death. The aim of this study was to explore the presence of cardiomyocyte death after repeated subacute exposure of rats to AZA-1 and YTX for 15 days. Because autophagy and apoptosis are often found in dying cardiomyocytes, several autophagic and apoptotic markers were determined by western blot in heart tissues of these rats. The results showed that hearts from YTX-treated rats presented increased levels of the autophagic markers microtubule-associated protein light chain 3-II (LC3-II) and beclin-1, nevertheless AZA-1-treated hearts evidenced increased levels of the apoptosis markers cleaved caspase-3 and -8, cleaved PARP and Fas ligand. Therefore, while YTX-induced damage to the heart triggers autophagic processes, apoptosis activation occurs in the case of AZA-1. For the first time, activation of cell death signals in cardiomyocytes is demonstrated for these toxins with in vivo experiments, which may be related to alterations of the cardiovascular function.

  19. Antigen Presented by Tumors in Vivo Determines the Nature of CD8+ T Cell Cytotoxicity

    PubMed Central

    Shanker, Anil; Brooks, Alan D.; Jacobsen, Kristen M.; Wine, John W.; Wiltrout, Robert H.; Yagita, Hideo; Sayers, Thomas J.

    2009-01-01

    The biological relevance of the perforin and Fas ligand (FasL) cytolytic pathways of CD8+ T lymphocytes (CTL) for cancer immunotherapy is controversial. We investigated the importance of these pathways in a murine renal cell carcinoma expressing influenza viral hemagglutinin as a defined surrogate antigen (Renca-HA). Following Renca-HA injection, all FasL-dysfunctional FasLgld/gld mice (n = 54) died from Renca-HA tumors by day 62. By contrast, perforin−/− (51%, n = 45) and Faslpr/lpr (55%, n = 51) mice remained tumor-free at day 360. Blocking FasL in vivo inhibited tumor rejection in these mice. Moreover, established Renca-HA tumors were cleared more efficiently by adoptively transferred HA518–526-specific T cell receptor-transgenic CTL utilizing FasL rather than perforin. Strikingly, a range of mouse tumor cells presenting low concentrations of immunogenic peptide were all preferentially lysed by the FasL but not the Pfp-mediated effector pathway of CTL, whereas at higher peptide concentrations the preference in effector pathway usage by CTL was lost. Interestingly, a number of human renal cancer lines were also susceptible to FasL-mediated cytotoxicity. Therefore, the FasL cytolytic pathway may be particularly important for eradicating Fas-sensitive tumors presenting low levels of MHC class-I-associated antigens following adoptive T cell therapy. PMID:19654302

  20. In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against chlamydia.

    PubMed Central

    Niki, Y; Kimura, M; Miyashita, N; Soejima, R

    1994-01-01

    The in vitro and in vivo activities of azithromycin against chlamydia were investigated. The MIC of azithromycin for five standard strains of different species of chlamydia and six wild-type strains of Chlamydia pneumoniae was 0.125 microgram/ml, which was superior to that of erythromycin but inferior to those of clarithromycin and minocycline. However, the therapeutic effect of a 7-day course of azithromycin at a dose of 10 mg/kg of body weight administered orally once daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 14 days after infection, which was the same as that for treatment with minocycline administered at 10 mg/kg twice daily; all erythromycin treated animals died within 10 days. When treatment was discontinued 3 days after the infection, the survival rate for mice treated with azithromycin was 90% and that for mice administered minocycline was 30%. These results suggest that azithromycin may be useful in the treatment of respiratory infections caused by intracellular pathogens, including chlamydia because of its excellent accumulation within host cells. PMID:7840560

  1. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets.

    PubMed

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone.

  2. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling

    PubMed Central

    Ko, A; Kanehisa, A; Martins, I; Senovilla, L; Chargari, C; Dugue, D; Mariño, G; Kepp, O; Michaud, M; Perfettini, J-L; Kroemer, G; Deutsch, E

    2014-01-01

    Clinical oncology heavily relies on the use of radiotherapy, which often leads to merely transient responses that are followed by local or distant relapse. The molecular mechanisms explaining radioresistance are largely elusive. Here, we identified a dual role of autophagy in the response of cancer cells to ionizing radiation. On one hand, we observed that the depletion of essential autophagy-relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of human or mouse cancer cell lines to irradiation, both in vitro (where autophagy inhibition increased radiation-induced cell death and decreased clonogenic survival) and in vivo, after transplantation of the cell lines into immunodeficient mice (where autophagy inhibition potentiated the tumour growth-inhibitory effect of radiotherapy). On the other hand, when tumour proficient or deficient for autophagy were implanted in immunocompetent mice, it turned out that defective autophagy reduced the efficacy of radiotherapy. Indeed, radiotherapy elicited an anti-cancer immune response that was dependent on autophagy-induced ATP release from stressed or dying tumour cells and was characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural injection of an ecto-ATPase inhibitor restored the immune infiltration of autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory effect of ionizing irradiation. Altogether, our results reveal that beyond its cytoprotective function, autophagy confers immunogenic properties to tumours, hence amplifying the efficacy of radiotherapy in an immunocompetent context. This has far-reaching implications for the development of pharmacological radiosensitizers. PMID:24037090

  3. In Vivo Analysis of Hypertension: Induction of Hypertension, In Vivo Kinase Manipulation, and Assessment of Physiologic Outputs.

    PubMed

    Eguchi, Satoru; Elliott, Katherine

    2017-01-01

    Using an in vivo model system to study signal transduction will include several steps: (1) induce hypertension in the animal, (2) manipulate kinase activation and signal transduction pathways as desired, and (3) observe physiologic outputs. This chapter provides the reader with overviews of the techniques our lab uses to manipulate signal transduction pathways and determine the effects on hypertension.

  4. Energy Saving Melting and Revert Reduction Technology (E-SMARRT): Development of Surface Engineered Coating Systems for Aluminum Pressure Die Casting Dies: Towards a 'Smart' Die Coating

    SciTech Connect

    Dr. John J. Moore; Dr. Jianliang Lin,

    2012-07-31

    The main objective of this research program was to design and develop an optimal coating system that extends die life by minimizing premature die failure. In high-pressure aluminum die-casting, the die, core pins and inserts must withstand severe processing conditions. Many of the dies and tools in the industry are being coated to improve wear-resistance and decrease down-time for maintenance. However, thermal fatigue in metal itself can still be a major problem, especially since it often leads to catastrophic failure (i.e. die breakage) as opposed to a wear-based failure (parts begin to go out of tolerance). Tooling costs remain the largest portion of production costs for many of these parts, so the ability prevent catastrophic failures would be transformative for the manufacturing industry.The technology offers energy savings through reduced energy use in the die casting process from several factors, including increased life of the tools and dies, reuse of the dies and die components, reduction/elimination of lubricants, and reduced machine down time, and reduction of Al solder sticking on the die. The use of the optimized die coating system will also reduce environmental wastes and scrap parts. Current (2012) annual energy saving estimates, based on initial dissemination to the casting industry in 2010 and market penetration of 80% by 2020, is 3.1 trillion BTU's/year. The average annual estimate of CO2 reduction per year through 2020 is 0.63 Million Metric Tons of Carbon Equivalent (MM TCE).

  5. Accurate Die Design for Automotive Panel Stamping Considering the Compensation Related with Die Deflection and Blank Thinning

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Xu, Dongkai; Xia, Guodong; Li, Xifeng; Chen, Jieshi; Zhang, Jian; Yan, Wei; Li, Yue

    2011-08-01

    In order to improve assembly accuracy, automotive body panels have to be fabricated with higher dimensional and surface quality requirements, therefore the die faces should be designed more accurately to consider more relevant factors. In the presented study, we proposed algorithms to realize the following functions: through forming process simulation, the thinning distribution on the deformed blank was extracted as first kind of compensation; through die structural CAE analysis which automatically mapped the boundary contact forces onto the die surfaces from process simulation results, the die deflection was calculated as second kind of compensation. These two quantitative contributions were added together to compensate the die face. The proposed methodologies were programmed and integrated with LS-Dyna and HyperWorks, and also integrated with Autoform and CATIA linear CAE functionalities separately. In addition, a software toolkit to calculate the contacting ratio was also developed to evaluate the effectiveness of die face compensation. The second toolkit developed was verified by an automotive structural part forming die design, through die compensation and geometric optimization, the predicted contact ratio between the die face and formed blank was improved a lot, and the first toolkit was testified by a fender drawing die design. It shows that the die face compensation can be realized and integrated seamlessly between CAD model, process simulation model and die structural CAE model with the help of data I/O tools developed by the authors.

  6. Method and apparatus for die forming metal sheets and extrusions

    NASA Astrophysics Data System (ADS)

    Darter, John L.

    1986-06-01

    The invention comprises an apparatus for die forming metal sheets and extrusions which utilizes die blocks of low melting temperature metallic material. The die blocks are formed in an adjustable mold which comprises a mold box, a pivotable dam within the mold box and blocking means for locking the pivotable dam member in a desired angular position. Once a desired die block angle is ascertained for a particular joggle, the pivotable member of the mold box is adjusted to produce the desired angle in the die casting made in the mold box.

  7. Sheet metal stamping die design for warm forming

    DOEpatents

    Ghosh, Amit K.

    2003-04-22

    In metal stamping dies, by taking advantage of improved material flow by selectively warming the die, flat sections of the die can contribute to the flow of material throughout the workpiece. Local surface heating can be accomplished by placing a heating block in the die. Distribution of heating at the flat lower train central regions outside of the bend region allows a softer flow at a lower stress to enable material flow into the thinner, higher strain areas at the bend/s. The heating block is inserted into the die and is powered by a power supply.

  8. Euthanasia, assisted dying and the right to die in Ghana: a socio-legal analysis.

    PubMed

    Owusu-Dapaa, Ernest

    2013-12-01

    There is unanimity among states to protect the continuation of life of the individual as a safeguard against their collective extinction. The right to life is accordingly guaranteed but its antithesis, the right to die is the subject of an unending debate. The controversy over the right to die is deepened by rapid advances in medicine, creating the capability for prolongation of life beyond the span which one's natural strength can endure. Ghana's supreme law explicitly guarantees the right to life but remains ambiguous on right to die, particularly euthanasia and assisted dying. Thus, some of the other rights, such as the right to dignity and not to be tortured, can creatively be exploited to justify some instances of euthanasia. Ghana's criminal code largely proscribes euthanasia. Notwithstanding, proscription of euthanasia and assisted dying by the law, in Ghana's empirical work undertaken in some of the communities in Ghana, suggests that euthanasia is quietly practisedin health facilities and private homes, especially in the rural areas. Contrary to the popular reasons assigned in the literature of the Western world, with respect to the practice or quest for legalization of euthanasia as being a necessity for providing relief from pain or hopeless quality of life, empirical data from social and anthropological studies conducted in Ghana reveal that poverty is the motivation for informal euthanasia practice in Ghana rather than genuine desire on part of patients to die or their relatives to see to their accelerated death. Apart from poverty, traditional cultural values of African societies consider non-natural death as a taboo and ignominy to the victim and his family. Thus, any move by the government to legalize euthanasia will need to be informed by widely held consultations and a possible referendum; otherwise the law may be just a mere transplant of Western models of legislation on euthanasia without reflecting the ethos of the African people.

  9. Dying cancer patients talk about euthanasia.

    PubMed

    Eliott, Jaklin A; Olver, Ian N

    2008-08-01

    Within developed nations, there is increasing public debate about and apparent endorsement of the appropriateness of euthanasia as an autonomous choice to die in the face of intolerable suffering. Surveys report socio-demographic differences in rates of acceptance of euthanasia, but there is little in-depth analysis of how euthanasia is understood and positioned within the social and moral lives of individuals, particularly those who might be considered suitable candidates-for example, terminally-ill cancer patients. During discussions with 28 such patients in Australia regarding medical decisions at the end of life, euthanasia was raised by 13 patients, with the others specifically asked about it. Twenty-four patients spoke positively of euthanasia, 19 of these voicing some concerns. None identified euthanasia as a currently favoured option. Four were completely against it. Endorsement for euthanasia was in the context of a hypothetical future or for a hypothetical other person, or temporally associated with acute pain. Arguments supporting euthanasia framed the issue as a matter of freedom of choice, as preserving dignity in death, and as curbing intolerable pain and suffering, both of the patient and of those around them. A common analogy featured was that of euthanising a dog. These arguments were typically presented as self-evident justification for euthanasia, construed as an appropriate choice to die, with opposers positioned as morally inferior or ignorant. The difficulties of ensuring 'choice' and the moral connotations of 'choosing to die,' however, worked to problematise the appropriateness of euthanising specific individuals. We recommend further empirical investigation of the moral and social meanings associated with euthanasia.

  10. In vitro - in vivo correlation: from theory to applications.

    PubMed

    Emami, Jaber

    2006-01-01

    A key goal in pharmaceutical development of dosage forms is a good understanding of the in vitro and in vivo performance of the dosage forms. One of the challenges of biopharmaceutics research is correlating in vitro drug release information of various drug formulations to the in vivo drug profiles (IVIVC). Thus the need for a tool to reliably correlate in vitro and in vivo drug release data has exceedingly increased. Such a tool shortens the drug development period, economizes the resources and leads to improved product quality. Increased activity in developing IVIVCs indicates the value of IVIVCs to the pharmaceutical industry. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies during the formulation development as the main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers. It supports and/or validates the use of dissolution methods and specification settings. This is because the IVIVC includes in vivo relevance to in vitro dissolution specifications. It can also assist in quality control for certain scale-up and post-approval changes (SUPAC). With the proliferation of modified-release products, it becomes necessary to examine the concept of IVIVC in greater depth. Investigations of IVIVC are increasingly becoming an integral part of extended release drug development. There must be some in vitro means of assuring that each batch of the same product will perform identically in vivo. This review article represents the FDA guidance, development, evaluation, and validation of an IVIVC to grant biowaivers, and to set dissolution specifications for oral dosage forms, biopharmaceutics classification systems (BCS), BCS biowaivers, application of BCS in IVIVC development and concept of mapping. The importance of dissolution media and methodology and pharmacokinetic studies in the context of IVIVC has been highlighted. The review also covers the literature examples of IVIVCs

  11. Implementing California's Law on Assisted Dying.

    PubMed

    Mishra, Ruchika

    2017-03-01

    On October 5, 2015, Governor Jerry Brown approved bill ABX2 15, the End of Life Option Act, making California the fifth state in the country to allow physician-assisted dying. The law was modeled after Oregon's 1997 Death with Dignity Act. When the legislative special session ended on March 10, 2016, California health care providers had only ninety days to respond to the state mandate before the law would take effect, on June 9, 2016. Experience with the law so far suggests several challenges with implementation.

  12. Do imaginary companions die? An exploratory study.

    PubMed

    Kastenbaum, Robert; Fox, Lynn

    Adults in this exploratory study usually recalled that their childhood imaginary companions faded away or were dismissed as other options for social interaction became more appealing. However, eight participants reported that their IC had died. Analysis of these deaths offers a glimpse of the child's talent for transitional thought processes that navigate between the emerging constraints of logic and the continuing appeal of fantasy. It is suggested that young children are testing the limits and possibilities of what it means to be "real" at the same time they are trying to puzzle out "alive" and "dead."

  13. Die Schokoladen-Diät

    NASA Astrophysics Data System (ADS)

    Ehrhardt, Matthias

    Schlankheitskuren sind einerseits ein soziales Phänomen, aber auch ein großer Zweig der Nahrungsmittelindustrie. Die Industrie bietet dabei verschiedene Produkte an, wie Diätlebensmittel, Nahrungsergänzungsmittel, Sportkleidung und -ausrüstung, Übungsvideos und -bücher, usw. Allerdings ist es bekanntermaßen sehr schwer, das einmal erreichte Wunschgewicht auch langfristig zu halten. Häufig tritt dabei der so genannte Jojo-Effekt auf, so dass man schließlich nach der Diät mehr wiegt als vorher.

  14. Die swell as an objective in the design of polymer extrusion dies

    NASA Astrophysics Data System (ADS)

    Siegbert, Roland; Behr, Marek; Elgeti, Stefanie

    2016-10-01

    This paper focuses on developing a suitable objective function for the inverse form of profile extrusion die design. First, the problem is motivated by introducing the extrusion die design process. After describing how Computer Aided Engineering enhances the traditional design process, a set of applicable objective functions is introduced. The main criteria for identifying the most suitable are computational applicability, robustness and smoothness of the functional. After discussing the results of several simulations, an objective function is proposed for the implementation in an existing optimization framework utilizing parameter-based optimization.

  15. DIE Deflection Modeling: Empirical Validation and Tech Transfer

    SciTech Connect

    R. Allen Miller

    2003-05-28

    This report summarizes computer modeling work that was designed to help understand how the die casting die and machine contribute to parting plane separation during operation. Techniques developed in earlier research (8) were applied to complete a large computational experiment that systematically explored the relationship between the stiffness of the machine platens and key dimensional and structural variables (platen area covered, die thickness, platen thickness, thickness of insert and the location of the die with respect to the platen) describing the die/machine system. The results consistently show that there are many significant interactions among the variables and it is the interactions, more than the individual variables themselves, which determine the performance of the machine/die system. That said, the results consistently show that it is the stiffness of the machine platens that has the largest single impact on die separation.

  16. In vivo microsampling to capture the elusive exposome

    NASA Astrophysics Data System (ADS)

    Bessonneau, Vincent; Ings, Jennifer; McMaster, Mark; Smith, Richard; Bragg, Leslie; Servos, Mark; Pawliszyn, Janusz

    2017-03-01

    Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies.

  17. In vivo red cell destruction by anti-Lu6

    SciTech Connect

    Issitt, P.D.; Valinsky, J.E.; Marsh, W.L.; DiNapoli, J.; Gutgsell, N.S. )

    1990-03-01

    An example is presented of an IgG1, anti-Lu6, that reacted by indirect antiglobulin test and was capable of destroying antigen-positive red cells in vivo. Two methods for the measurement of red cell survival, {sup 51}Cr labeling and flow cytometry, gave the same result: 20 percent of the test dose of Lu:6 red cells was destroyed in the first hour after injection and 80 percent in the first 24 hours. The clinical relevance of the antibody was correctly predicted by an in vitro monocyte monolayer assay. The finding that this example of anti-Lu6 was clinically significant should not be taken to mean that all antibodies directed against high-incidence Lutheran and Lutheran system-related antigens will behave similarly. When such antibodies are encountered, in vivo and/or in vitro studies to assess their clinical significance are necessary before rare blood is used for transfusion.

  18. In Vivo Flow Cytometry: A Horizon of Opportunities

    PubMed Central

    Tuchin, Valery V.; Tárnok, Attila; Zharov, Vladimir P.

    2012-01-01

    Flow cytometry has been a fundamental tool of biological discovery for many years. Invasive extraction of cells from a living organism, however, may lead to changes in cell properties and prevents studying cells in their native environment. These problems can be overcome by use of in vivo flow cytometry which provides detection and imaging of circulating normal and abnormal cells directlyin blood or lymph flow. The goal of this mini-review is to provide a brief history, features and challenges of this new generation of flow cytometry methods and instruments. Spectrum of possibilities of in vivo flow cytometry in biological science (e.g., cell metabolism, immune function, or apoptosis) and medical fields (e.g., cancer, infection, cardiovascular disorder) including integrated photoacoustic-photothermal theranostics of circulating abnormal cells are discussed with focus on recent advances of this new platform. PMID:21915991

  19. Visualizing how T cells collect activation signals in vivo.

    PubMed

    Moreau, Hélène D; Bousso, Philippe

    2014-02-01

    A decade ago the first movies depicting T cell behavior in vivo with the help of two-photon microscopy were generated. These initial experiments revealed that T cells migrate rapidly and randomly in secondary lymphoid organs at steady state and profoundly alter their behavior during antigen recognition, establishing both transient and stable contacts with antigen-presenting cells (APCs). Since then, in vivo imaging has continuously improved our understanding of T cell activation. In particular, recent studies uncovered how T cells may be guided in their search for the best APCs. Additionally, the development of more sophisticated fluorescent tools has permitted not only to visualize T cell-APC contacts but also to probe their functional impact on T cell activation. These recent progresses are providing new insights into how T cells sense antigen, collect activation signals during distinct types of interaction and integrate information over successive encounters.

  20. Intravascular micropump for augmented liver perfusion: first in vivo experience.

    PubMed

    Havlík, R; Kerkhoffs, W; Jiao, L R; Schumacher, O; Reul, H; Habib, N

    2001-05-01

    The aim of this study was to assess the in vivo performance of a new microaxial rotary blood pump developed for long-term intraportal implantation. The pump, measuring 7 mm in diameter, has a single stage impeller and is powered by a microelectric motor. The pump was implanted into the portal vein in 13 large white pigs under general anesthesia. All animals recovered after the portal pump implantation, and they were observed until the pump failed. The 2 longest running pumps performed for 40 and 36 h, respectively. Either thrombus formation or technical problems, especially in the bearings, were the main causes of pump failure during the experiment. No local or systemic adverse effects were observed during the portal pumping period. Full recovery of the animals following intraportal pump implantation was achieved. However, further technical improvements to the pump are required to maintain a longer performance in vivo.

  1. DNA methylation remodeling in vitro and in vivo

    PubMed Central

    Clark, Amander T

    2015-01-01

    In mammals, global DNA demethylation in vivo occurs in the pre-implantation embryo and in primordial germ cells (PGCs) where it is hypothesized to create a blank slate or “tabula rasa” upon which new DNA methylation patterns are written. However, global DNA demethylation in vivo is far from complete with a small number of loci protected from demethylation. Failure to demethylate, or overt demethylation results in compromised differentiation. Recent work has shown that reversion of primed human pluripotent stem cells to the naïve state leads to unbridled DNA demethylation which has unknown consequences on the quality differentiated cells created in vitro. Taken together understanding DNA methylation remodeling is critical for understanding the epigenetic foundations of life, and the quality of stem cells for regenerative medicine. PMID:26451496

  2. In vivo photoacoustic imaging of model of port wine stains.

    PubMed

    Yuan, Kaihua; Yuan, Yi; Gu, Ying; Gao, Jianhua; Xing, Da

    2012-01-01

    Port wine stains are categorized as a benign capillary vascular malformation, which is hard to cure. In this paper, a photoacoustic microscopy system, which integrated a two-dimensional scanning galvanometer, an objective lens and a focused ultrasound transducer, was designed for noninvasive imaging of blood vessels of port wine stains model in vivo. Cock comb was chosen as the port wine stains model in the experiment. The blood vessels in x-y plane and x-z plane were imaged clearly. Experimental results demonstrate that photoacoustic microscopy can image the blood vessels of port wine stains model in vivo with high contrast and high resolution. It has the potential for clinical applications in detecting the blood vessels in port wine stains skin.

  3. 3D bioprinting and its in vivo applications.

    PubMed

    Hong, Nhayoung; Yang, Gi-Hoon; Lee, JaeHwan; Kim, GeunHyung

    2017-01-20

    The purpose of 3D bioprinting technology is to design and create functional 3D tissues or organs in situ for in vivo applications. 3D cell-printing, or additive biomanufacturing, allows the selection of biomaterials and cells (bioink), and the fabrication of cell-laden structures in high resolution. 3D cell-printed structures have also been used for applications such as research models, drug delivery and discovery, and toxicology. Recently, numerous attempts have been made to fabricate tissues and organs by using various 3D printing techniques. However, challenges such as vascularization are yet to be solved. This article reviews the most commonly used 3D cell-printing techniques with their advantages and drawbacks. Furthermore, up-to-date achievements of 3D bioprinting in in vivo applications are introduced, and prospects for the future of 3D cell-printing technology are discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.

  4. Linear topology confers in vivo gene transfer activity to polyethylenimines.

    PubMed

    Brissault, B; Leborgne, C; Guis, C; Danos, O; Cheradame, H; Kichler, A

    2006-01-01

    Although polyethylenimines (PEIs) are frequently used transfection agents, it is still unclear which of their properties are required for efficient gene delivery. This is even more striking when working in vivo since some PEIs are able to generate significant gene expression, whereas others are not. To facilitate a rational development of compounds with improved transfection activities, studies aimed at identifying the properties involved in the transfection process seem indispensable. In the present work, we investigated how transfection with linear PEI of 22 kDa allows for high reporter gene expression in lungs after intravenous injection, whereas the branched PEI of 25 kDa does not. To this end, we synthesized L-PEI derivatives that are intermediates between linear and branched PEIs. Our results show that the topology plays a crucial role in obtaining in vivo reporter gene expression, whereas the content of primary, secondary, and tertiary amines is only of minor importance.

  5. Chemiluminescence detection from sonodynamic action in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    He, Yonghong; Xing, Da; Yan, Guihong; Ueda, Ken-ichi

    2001-10-01

    In this work, chemiluminescence method was engaged for the first time to detect the active oxygen spices during sonocynamic action both in vitro and in vivo. We used CLA derivatives, which can efficiently react with singlet oxygen (1O2) or superoxide anion (O2-) to emit light, and luminol, which can be oxidized by a variety of free radicals to emit photons, to real-timely detect oxygen free radical formation in the sonosensitization of two sonosensitizer ATX-70 and HpD. The results show that 1O2 is involved in the sonosensitization. The mechanism of sonosensitizing was discussed. In vivo experiments, tumor imaging by sonodynamic chemiluminescence detection methods was established. This method could have potential applications in clinics for early-stage tumor diagnosis.

  6. Type C botulinum toxin causes degeneration of motoneurons in vivo.

    PubMed

    Zhao, Li-Chun; Yang, Bo; Wang, Rengang; Lipton, Stuart A; Zhang, Dongxian

    2010-01-06

    All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death. Rapid treatment with anti-BoNT antibodies can prevent progression, but recovery still requires weeks on a ventilator. Even after recovery, there is a potential for persistent fatigue in some cases of botulism even years after the insult, possibly because of motoneuron dropout for previously unknown reasons. Unique among BoNTs, the C-type (BoNT/C) cleaves two proteins involved in neurotransmitter release, syntaxin and SNAP-25, and induces apoptotic cell death in cultured cerebellar neurons. It is not clear, however, whether BoNT/C also affects neurons that encounter toxin in vivo, namely motoneurons. Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies.

  7. pHluorin-based in vivo assay for hydrolase screening.

    PubMed

    Schuster, Sascha; Enzelberger, Markus; Trauthwein, Harald; Schmid, Rolf D; Urlacher, Vlada B

    2005-05-01

    pHluorin, a pH-sensitive mutant of green fluorescent protein (GFP), acts as a sensor for intracellular pH shifts, triggered by hydrolytic enzymes. This principle was used to develop a pHluorin-based in vivo assay for hydrolase screening. The presented assay was evaluated for Escherichia coli (E. coli) cells, producing heterologous pHluorin and an esterase from Geobacillus stearothermophilus which is considered as a model hydrolase. Subsequently, the utility of this detection system was also demonstrated with recombinantly expressed hydantoinase and amidase in E. coli. This in vivo assay also shows capability for readout with flow cytometric devices. Population shifts of pHluorin-expressing E. coli cells were easily recognized due to pH changes caused by substrate hydrolysis.

  8. In Vivo Clearance and Toxicity of Monodisperse Iron Oxide Nanocrystals

    PubMed Central

    Gu, Luo; Fang, Ronnie H.; Sailor, Michael J.; Park, Ji-Ho

    2012-01-01

    Thermal decomposition of organometallic precursors have been found to generate highly crystalline iron oxide (IO) nanocrystals that display superior MR contrast and lower polydispersity than IO nanocrystals synthesized by aqueous precipitation. In the present study, the in vivo characteristics of IO nanocrystals prepared by the thermal decomposition route and then coated with a phospholipid containing a pendant poly(ethylene glycol) chain are examined. The size and surface chemistry of the IO nanocrystal influences the biodistibution, the rate of biodegradation and bioclearance, and the biodegradation products. We conclude that the in vivo fate of PEGylated monodisperse IO nanocrystals and the iron, phospholipid, and oleic acid biodegradation products may influence the cellular environments in the organs and blood that can determine their safety in the body. PMID:22646927

  9. Real-time in vivo cancer diagnosis using Raman spectroscopy.

    PubMed

    Wang, Wenbo; Zhao, Jianhua; Short, Michael; Zeng, Haishan

    2015-07-01

    Raman spectroscopy has becoming a practical tool for rapid in vivo tissue diagnosis. This paper provides an overview on the latest development of real-time in vivo Raman systems for cancer detection. Instrumentation, data handling, as well as oncology applications of Raman techniques were covered. Optic fiber probes designs for Raman spectroscopy were discussed. Spectral data pre-processing, feature extraction, and classification between normal/benign and malignant tissues were surveyed. Applications of Raman techniques for clinical diagnosis for different types of cancers, including skin cancer, lung cancer, stomach cancer, oesophageal cancer, colorectal cancer, cervical cancer, and breast cancer, were summarized. Schematic of a real-time Raman spectrometer for skin cancer detection. Without correction, the image captured on CCD camera for a straight entrance slit has a curvature. By arranging the optic fiber array in reverse orientation, the curvature could be effectively corrected.

  10. Spectroscopic research on purple sulphur bacteria Chromatium sp. in vivo

    NASA Astrophysics Data System (ADS)

    Milukov, Anton S.; Patsayeva, Svetlana V.; Rostovtseva, Elena L.; Yuzhakov, Viktor I.

    2006-05-01

    Phototrophic purple sulphur bacteria represent an important constituent of coastal zone biota and a crucial link of sulphur cycling in the nature. Purple bacteria are widespread in the environment occurring almost in every water basin and also in soil. The spectroscopic research was performed in vivo on purple sulphur bacteria Chromatium sp. in different culture development stages and illumination conditions during culture growth. Possibilities of purple bacteria quantification in vivo using absorbance and fluorescence intensities are described. The experiments revealed the possibility of application of the intensities ratio of porphyrin pigments emission to cell blue fluorescence for the estimation of the culture physiological status. These findings may be used for improvement of remote sensing techniques of ecological monitoring.

  11. Engineering Cell Fate for Tissue Regeneration by In Vivo Transdifferentiation.

    PubMed

    de Lázaro, I; Kostarelos, K

    2016-02-01

    Changes in cell identity occur in adult mammalian organisms but are rare and often linked to disease. Research in the last few decades has thrown light on how to manipulate cell fate, but the conversion of a particular cell type into another within a living organism (also termed in vivo transdifferentiation) has only been recently achieved in a limited number of tissues. Although the therapeutic promise of this strategy for tissue regeneration and repair is exciting, important efficacy and safety concerns will need to be addressed before it becomes a reality in the clinical practice. Here, we review the most relevant in vivo transdifferentiation studies in adult mammalian animal models, offering a critical assessment of this potentially powerful strategy for regenerative medicine.

  12. In vivo microsampling to capture the elusive exposome

    PubMed Central

    Bessonneau, Vincent; Ings, Jennifer; McMaster, Mark; Smith, Richard; Bragg, Leslie; Servos, Mark; Pawliszyn, Janusz

    2017-01-01

    Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies. PMID:28266605

  13. Data sources for in vivo molecular profiling of human phenotypes.

    PubMed

    Cardozo, Timothy; Gupta, Priyanka; Ni, Eric; Young, Lauren M; Tivon, Doreen; Felsovalyi, Klara

    2016-11-01

    Molecular profiling of human diseases has been approached at the genetic (DNA), expression (RNA), and proteomic (protein) levels. An important goal of these efforts is to map observed molecular patterns to specific, mechanistic organic entities, such as loci in the genome, individual RNA molecules or defined proteins or protein assemblies. Importantly, such maps have been historically approached in the more intuitive context of a theoretical individual cell, but diseases are better described in reality using an in vivo framework, namely a library of several tissue-specific maps. In this article, we review the existing data atlases that can be used for this purpose and identify critical gaps that could move the field forward from cellular to in vivo dimensions. WIREs Syst Biol Med 2016, 8:472-484. doi: 10.1002/wsbm.1354 For further resources related to this article, please visit the WIREs website.

  14. In vivo versus ex vivo CRISPR therapies for retinal dystrophy

    PubMed Central

    Bakondi, Benjamin

    2017-01-01

    SUMMARY Two therapeutic paths have been proposed to treat inherited retinal dystrophy using clustered regularly interspaced short palindromic repeats (CRISPR). One strategy is to genetically correct patient cells ex vivo for autologous transplant, whereas the second is to modify cells in vivo by delivering CRISPR effectors to the retina. The feasibility of both editing strategies has been demonstrated within three years of CRISPR’s adaptation to mammalian systems. However, the functional integration of transplanted cells into host retinae has been a long-standing challenge that currently represents the 2025 moonshot of the National Eye Institute’s Audacious Goals Initiative. The clinical translatability of each path is discussed with regard to current investigations and whether cell replacement can be circumvented by in vivo editing. PMID:28163772

  15. In vivo microsampling to capture the elusive exposome.

    PubMed

    Bessonneau, Vincent; Ings, Jennifer; McMaster, Mark; Smith, Richard; Bragg, Leslie; Servos, Mark; Pawliszyn, Janusz

    2017-03-07

    Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies.

  16. Near-infrared Molecular Probes for In Vivo Imaging

    PubMed Central

    Zhang, Xuan; Bloch, Sharon; Akers, Walter; Achilefu, Samuel

    2012-01-01

    Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo because of the low absorption of biological molecules in this region. This Unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications. PMID:22470154

  17. In vivo recordings of brain activity using organic transistors

    PubMed Central

    Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G.

    2013-01-01

    In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications. PMID:23481383

  18. Nanoscale imaging of caveolin-1 membrane domains in vivo.

    PubMed

    Gabor, Kristin A; Kim, Dahan; Kim, Carol H; Hess, Samuel T

    2015-01-01

    Light microscopy enables noninvasive imaging of fluorescent species in biological specimens, but resolution is generally limited by diffraction to ~200-250 nm. Many biological processes occur on smaller length scales, highlighting the importance of techniques that can image below the diffraction limit and provide valuable single-molecule information. In recent years, imaging techniques have been developed which can achieve resolution below the diffraction limit. Utilizing one such technique, fluorescence photoactivation localization microscopy (FPALM), we demonstrated its ability to construct super-resolution images from single molecules in a living zebrafish embryo, expanding the realm of previous super-resolution imaging to a living vertebrate organism. We imaged caveolin-1 in vivo, in living zebrafish embryos. Our results demonstrate the successful image acquisition of super-resolution images in a living vertebrate organism, opening several opportunities to answer more dynamic biological questions in vivo at the previously inaccessible nanoscale.

  19. New models for analyzing mast cell functions in vivo.

    PubMed

    Reber, Laurent L; Marichal, Thomas; Galli, Stephen J

    2012-12-01

    In addition to their well-accepted role as critical effector cells in anaphylaxis and other acute IgE-mediated allergic reactions, mast cells (MCs) have been implicated in a wide variety of processes that contribute to disease or help to maintain health. Although some of these roles were first suggested by analyses of MC products or functions in vitro, it is critical to determine whether, and under which circumstances, such potential roles actually can be performed by MCs in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products during biological responses in vivo, and comments on some of the similarities and differences in the results obtained with these newer versus older models of MC deficiency.

  20. 19F MRI for quantitative in vivo cell tracking

    PubMed Central

    Srinivas, Mangala; Heerschap, Arend; Ahrens, Eric T.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2010-01-01

    Cellular therapy, including stem cell transplants and dendritic cell vaccines, is typically monitored for dosage optimization, accurate delivery and localization using non-invasive imaging, of which magnetic resonance imaging (MRI) is a key modality. 19F MRI retains the advantages of MRI as an imaging modality, while allowing direct detection of labelled cells for unambiguous identification and quantification, unlike typical metal-based contrast agents. Recent developments in 19F MRI-based in vivo cell quantification, the existing clinical use of 19F compounds and current explosive interest in cellular therapeutics have brought 19F imaging technology closer to clinical application. We review the application of 19F MRI to cell tracking, discussing intracellular 19F labels, cell labelling and in vivo quantification, as well as the potential clinical use of 19F MRI. PMID:20427096

  1. [Antitumoral effect of xenogenic substances in vivo and in vitro].

    PubMed

    Munder, P G; Stiefel, T; Widmann, K H; Theurer, K

    1982-04-01

    The proliferation of various tumour cells was inhibited in vivo and in vitro after application of/or incubation with xenogeneic liver tissue. The development of s.c.-implanted meth-A-sarcoma was blocked by the prophylactic injection of these preparations. In addition firmly established tumours regressed under therapy. Preparations obtained from xenogeneic organs like thymus, placenta or brain had a similar antitumor activity. A mixture of various xenogeneic tissues from different species had a much higher therapeutic efficiency. In the Meth-A-system the xenogeneic material surpassed the antineoplastic effect of rather high doses of cyclophosphamide. The preparations showed no side-effects in mice and rats. These results were supported by experiments in tissue culture. This new antitumour activity of xenogeneic tissues in vivo is interpreted as mediated by an increased host defense. The results in tissue culture however, indicate also a direct regulatory effect on cells.

  2. Fluorescence spectral imaging of dihydroxyacetone on skin in vivo.

    PubMed

    Forest, Susan E; Grothaus, Jeff T; Ertel, Keith D; Rader, Charlie; Plante, Janyl

    2003-05-01

    Dihydroxyacetone (DHA) has been proposed as a potential alternative to dansyl chloride for use as a fluorescence marker on skin to assess stratum corneum turnover time in vivo. However, the fluorescence from DHA on skin has not been adequately studied. To address this void, a noninvasive, noncontact spectral imaging system is used to characterize the fluorescence spectrum of DHA on skin in vivo and to determine the optimal wavelengths over which to collect the DHA signal that minimizes the contributions from skin autofluorescence. The DHA-skin fluorescence signal dominates the 580-680 nm region of the visible spectrum when excited with ultraviolet radiation in the 320-400 nm wavelength region (UVA). An explanation of the time-dependent spectral features is proposed in terms of DHA polymerization and binding to skin.

  3. In Vivo study of naturally deformed Escherichia coli bacteria.

    PubMed

    Tavaddod, Sharareh; Naderi-Manesh, Hossein

    2016-06-01

    A combination of light-microscopy and image processing has been applied to study naturally deformed Escherichia coli under in vivo condition and at the order of sub-pixel high-resolution accuracy. To classify deflagellated non-dividing E. coli cells to the rod-shape and bent-shape, a geometrical approach has been applied. From the analysis of the geometrical data which were obtained of image processing, we estimated the required effective energy for shaping a rod-shape to a bent-shape with the same size. We evaluated the energy of deformation in the naturally deformed bacteria with minimum cell manipulation, under in vivo condition, and with minimum influence of any external force, torque and pressure. Finally, we have also elaborated on the possible scenario to explain how naturally deformed bacteria are formed from initial to final-stage.

  4. Applying the ARRIVE Guidelines to an In Vivo Database

    PubMed Central

    Karp, Natasha A.; Meehan, Terry F.; Morgan, Hugh; Mason, Jeremy C.; Blake, Andrew; Kurbatova, Natalja; Smedley, Damian; Jacobsen, Julius; Mott, Richard F.; Iyer, Vivek; Matthews, Peter; Melvin, David G.; Wells, Sara; Flenniken, Ann M.; Masuya, Hiroshi; Wakana, Shigeharu; White, Jacqueline K.; Lloyd, K. C. Kent; Reynolds, Corey L.; Paylor, Richard; West, David B.; Svenson, Karen L.; Chesler, Elissa J.; de Angelis, Martin Hrabě; Tocchini-Valentini, Glauco P.; Sorg, Tania; Herault, Yann; Parkinson, Helen; Mallon, Ann-Marie; Brown, Steve D. M.

    2015-01-01

    The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future. PMID:25992600

  5. Improved in vivo stability of actinium-225 macrocyclic complexes.

    PubMed

    Deal, K A; Davis, I A; Mirzadeh, S; Kennel, S J; Brechbiel, M W

    1999-07-29

    The favorable nuclear properties of actinium-225 ((225)Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free (225)Ac, a series of ligands were evaluated for stability in vivo. Loss of (225)Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and (225)Ac-HEHA showed exceptional stability in vivo. (225)Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the (225)Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.

  6. Mobile Genetic Elements: In Silico, In Vitro, In Vivo

    PubMed Central

    Arkhipova, Irina R.; Rice, Phoebe A.

    2016-01-01

    Mobile genetic elements (MGEs), also called transposable elements (TEs), represent universal components of most genomes and are intimately involved in nearly all aspects of genome organization, function, and evolution. However, there is currently a gap between fast-paced TE discovery in silico, stimulated by exponential growth of comparative genomic studies, and a limited number of experimental models amenable to more traditional in vitro and in vivo studies of structural, mechanistic, and regulatory properties of diverse MGEs. Experimental and computational scientists came together to bridge this gap at a recent conference, “Mobile Genetic Elements: in silico, in vitro, in vivo,” held at the Marine Biological Laboratory (MBL) in Woods Hole, MA, USA. PMID:26822117

  7. Applying the ARRIVE Guidelines to an In Vivo Database.

    PubMed

    Karp, Natasha A; Meehan, Terry F; Morgan, Hugh; Mason, Jeremy C; Blake, Andrew; Kurbatova, Natalja; Smedley, Damian; Jacobsen, Julius; Mott, Richard F; Iyer, Vivek; Matthews, Peter; Melvin, David G; Wells, Sara; Flenniken, Ann M; Masuya, Hiroshi; Wakana, Shigeharu; White, Jacqueline K; Lloyd, K C Kent; Reynolds, Corey L; Paylor, Richard; West, David B; Svenson, Karen L; Chesler, Elissa J; de Angelis, Martin Hrabě; Tocchini-Valentini, Glauco P; Sorg, Tania; Herault, Yann; Parkinson, Helen; Mallon, Ann-Marie; Brown, Steve D M

    2015-05-01

    The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future.

  8. Variables influencing the frictional behaviour of in vivo human skin.

    PubMed

    Veijgen, N K; Masen, M A; van der Heide, E

    2013-12-01

    In the past decades, skin friction research has focused on determining which variables are important to affect the frictional behaviour of in vivo human skin. Until now, there is still limited knowledge on these variables. This study has used a large dataset to identify the effect of variables on the human skin, subject characteristics and environmental conditions on skin friction. The data are obtained on 50 subjects (34 males and 16 females). Friction measurements represent the friction between in vivo human skin and an aluminium sample, assessed on three anatomical locations. The coefficient of friction increased significantly (p<0.05) with increasing age, increasing ambient temperature and increasing relative air humidity. A significant inversely proportional relationship was found between friction and both the amount of hair present on the skin and the height of the subject. Other outcome variables in this study were the hydration of the skin and the skin temperature.

  9. Silver Nanoplate Contrast Agents for In Vivo Molecular Photoacoustic Imaging

    PubMed Central

    Homan, Kimberly A.; Souza, Michael; Truby, Ryan; Luke, Geoffrey P.; Green, Christopher; Vreeland, Erika; Emelianov, Stanislav

    2012-01-01

    Silver nanoplates are introduced as a new photoacoustic contrast agent that can be easily functionalized for molecular photoacoustic imaging in vivo. Methods are described for synthesis, functionalization, and stabilization of silver nanoplates using biocompatible (“green”) reagents. Directional antibody conjugation to the nanoplate surface is presented along with proof of molecular sensitivity in vitro with pancreatic cancer cells. Cell viability tests show the antibody-conjugated silver nanoplates to be nontoxic at concentrations up to 1 mg/ml. Furthermore, the silver nanoplates' potential for in vivo application as a molecularly sensitive photoacoustic contrast agent is demonstrated using an orthotopic mouse model of pancreatic cancer. Results of these studies suggest that the synthesized silver nanoplates are well suited for a host of biomedical imaging and sensing applications. PMID:22188516

  10. Applications of nuclear technologies for in-vivo elemental analysis

    SciTech Connect

    Cohn, S.H.; Ellis, K.J.; Vartsky, D.; Wielopolski, L.

    1982-01-01

    Measurement facilities developed, to date, include a unique whole-body-counter, (WBC); a total-body neutron-activation facility (TBNAA); and a partial-body activation facility (PBNAA). A variation of the prompt-gamma neutron-activation technique for measuring total-body nitrogen was developed to study body composition of cancer patients and the effect of nutritional regimens on the composition. These new techniques provide data in numerous clinical studies not previously amenable to investigation. The development and perfection of these techniques provide unique applications of radiation and radioisotopes to the early diagnosis of certain diseases and the evaluation of therapeutic programs. The PBNAA technique has been developed and calibrated for in-vivo measurement of metals. Development has gone forward on prompt-gamma neutron activation for the measurement of cadmium, x-ray fluorescence (XRF) for measurement of iron. Other techniques are being investigated for in-vivo measurement of metals such as silicon and beryllium.

  11. Nanoparticle PEBBLE sensors in live cells and in vivo.

    PubMed

    Lee, Yong-Eun Koo; Smith, Ron; Kopelman, Raoul

    2009-01-01

    Nanoparticle sensors have been developed for real-time imaging and dynamic monitoring, both in live cells and in vivo, of molecular and ionic components, constructs, forces, and dynamics observed during biological, chemical, and physical processes. With their biocompatible small size and inert matrix, nanoparticle sensors have been successfully applied to noninvasive real-time measurements of analytes and fields in cells and in rodents, with spatial, temporal, physical, and chemical resolution. This review describes the diverse designs of nanoparticle sensors for ions and small molecules, physical fields, and biological features, as well as the characterization, properties, and applications of these nanosensors to in vitro and in vivo measurements. Their floating as well as localization abilities in biological media are captured by the acronym PEBBLE: photonic explorer for bioanalysis with biologically localized embedding.

  12. In vivo platforms for analysis of HIV persistence and eradication.

    PubMed

    Garcia, J Victor

    2016-02-01

    HIV persistence in patients undergoing antiretroviral therapy is a major impediment to the cure of HIV/AIDS. The molecular and cellular mechanisms underlying HIV persistence in vivo have not been fully elucidated. This lack of basic knowledge has hindered progress in this area. The in vivo analysis of HIV persistence and the implementation of curative strategies would benefit from animal models that accurately recapitulate key aspects of the human condition. This Review summarizes the contribution that humanized mouse models of HIV infection have made to the field of HIV cure research. Even though these models have been shown to be highly informative in many specific areas, their great potential to serve as excellent platforms for discovery in HIV pathogenesis and treatment has yet to be fully developed.

  13. Label-free oxygen-metabolic photoacoustic microscopy in vivo

    NASA Astrophysics Data System (ADS)

    Yao, Junjie; Maslov, Konstantin I.; Zhang, Yu; Xia, Younan; Wang, Lihong V.

    2011-07-01

    Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO2) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO2 in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO2 does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.

  14. In vivo heat shock protects rat myocardial mitochondria.

    PubMed

    Bornman, L; Steinmann, C M; Gericke, G S; Polla, B S

    1998-05-29

    Heat shock (HS)/stress proteins (HSP) provide protection from a variety of stresses other than HS, including oxidative stress and mitochondria have been implicated as the target of HS-related protection in stressed cultured cells. Here we investigated whether mitochondria also are targets for the HS-mediated protection in vivo. Sprague Dawley rats were exposed, or not, to HS (41 degrees C, 15 min). After a 21 h recovery period, hearts were excised and perfused with or without H2O2 (0.15 mM). Myocardial mitochondria were then isolated, and their oxygen consumption was analyzed. HS prevented H2O2-induced alterations in state 3 respiration while increasing the expression of Hsp70 and heme oxygenase (HO). Thus, in vivo HS protects rat myocardial mitochondrial respiration against the deleterious effects of oxidative injury, a protection relating to Hsp70 and/or HO and targeting state 3 respiration.

  15. Famine versus feast: understanding the metabolism of tumors in vivo

    PubMed Central

    Mayers, Jared R.; Vander Heiden, Matthew G.

    2015-01-01

    To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. PMID:25639751

  16. Non-contact intracellular binding of chloroplasts in vivo

    NASA Astrophysics Data System (ADS)

    Li, Yuchao; Xin, Hongbao; Liu, Xiaoshuai; Li, Baojun

    2015-06-01

    Non-contact intracellular binding and controllable manipulation of chloroplasts in vivo was demonstrated using an optical fiber probe. Launching a 980-nm laser beam into a fiber, which was placed about 3 μm above the surface of a living plant (Hydrilla verticillata) leaf, enabled stable binding of different numbers of chloroplasts, as well as their arrangement into one-dimensional chains and two-dimensional arrays inside the leaf without damaging the chloroplasts. Additionally, the formed chloroplast chains were controllably transported inside the living cells. The optical force exerted on the chloroplasts was calculated to explain the experimental results. This method provides a flexible method for studying intracellular organelle interaction with highly organized organelle-organelle contact in vivo in a non-contact manner.

  17. In vivo photoacoustic imaging of osteosarcoma on animal model

    NASA Astrophysics Data System (ADS)

    Yu, Menglei; Ye, Fei; Hu, Jun

    2011-01-01

    Osteosarcoma is the commonest primary malignant tumor of bone, and the second highest cause of cancer-related death in the paediatric age group. Although there are several methods for osteosarcoma detection, e.g. X-ray, CT, MRI and bone scan, they are not satisfied methods because they can hardly detect osteosarcoma in early stage. Photoacoustic imaging (PAI) is an emerging hybrid imaging modality that is noninvasive, nonionizing, with high sensitivity, satisfactory imaging depth and good temporal and spatial resolution. In order to explore this new method to detect osteosarcoma, we established SD rat models with osteosarcoma and utilized PAI to reconstruct the osteosarcoma image in vivo. This is the first time detecting osteosarcoma in vivo using PAI, and the results suggested that PAI has potential clinical application for detecting osteosarcoma in the early stage.

  18. Die-target for dynamic powder consolidation

    DOEpatents

    Flinn, J.E.; Korth, G.E.

    1985-06-27

    A die/target is disclosed for consolidation of a powder, especially an atomized rapidly solidified metal powder, to produce monoliths by the dynamic action of a shock wave, especially a shock wave produced by the detonation of an explosive charge. The die/target comprises a rectangular metal block having a square primary surface with four rectangular mold cavities formed therein to receive the powder. The cavities are located away from the geometrical center of the primary surface and are distributed around such center while also being located away from the geometrical diagonals of the primary surface to reduce the action of reflected waves so as to avoid tensile cracking of the monoliths. The primary surface is covered by a powder retention plate which is engaged by a flyer plate to transmit the shock wave to the primary surface and the powder. Spawl plates are adhesively mounted on other surfaces of the block to act as momentum traps so as to reduce reflected waves in the block. 4 figs.

  19. Die-target for dynamic powder consolidation

    DOEpatents

    Flinn, John E.; Korth, Gary E.

    1986-01-01

    A die/target is disclosed for consolidation of a powder, especially an atomized rapidly solidified metal powder, to produce monoliths by the dynamic action of a shock wave, especially a shock wave produced by the detonation of an explosive charge. The die/target comprises a rectangular metal block having a square primary surface with four rectangular mold cavities formed therein to receive the powder. The cavities are located away from the geometrical center of the primary surface and are distributed around such center while also being located away from the geometrical diagonals of the primary surface to reduce the action of reflected waves so as to avoid tensile cracking of the monoliths. The primary surface is covered by a powder retention plate which is engaged by a flyer plate to transmit the shock wave to the primary surface and the powder. Spawl plates are adhesively mounted on other surfaces of the block to act as momentum traps so as to reduce reflected waves in the block.

  20. The dying child and surviving family members.

    PubMed

    Shrier, D K

    1980-12-01

    This overview of death and dying focuses on the dying child and surviving family members. Children's concepts of death at different developmental stages are reviewed. These range from an inability to distinguish death from other forms of separation prior to age 3, through partial concepts of death until, by age 10 to 15 years, children are able to conceptualize death as universal, inevitable and final. The importance of adults assisting in the child's growing comprehension of death is stressed. The stages of grief and mourning, as outlined by Kubler-Ross, are reviewed from the perspective of the child and family: denial, anger, bargaining, depression and acceptance. Recognition is given to the variations in coping styles among different family members. The special circumstances related to the death of an infant and the impact of the death of a child on the surviving siblings are discussed. Specific helpful interventions to assist families in coping with mourning are described. The death of a child remains one of the most painful and difficult events for a family and its physician to accept.

  1. Dying or living?: The double bind.

    PubMed

    Longhofer, J

    1980-06-01

    Describing the behaviors of terminally ill patients, their families and those charged with their care has received considerable attention during the past decade. This study of comprehensive cancer treatment and research facility indicates that the prevailing theory is limited to explanation at the intra-psychic level. In her work with hundreds of terminal cases, Dr. Elizabeth Kubler-Ross found that patients typically progress through five stages: 1) denial, 2) anger, 3) bargaining, 4) depression, and 5) acceptance. She concludes that the majority of her patients die in a stage of acceptance--a state of equanimity. Recently, scholars have claimed that this five stage scheme has limited applicability and may in fact contribute to the formalization of a dying person's behavior. This preliminary report proposes that the stage theory, if it has any descriptive validity, becomes meaningful only when used to describe behaviors occurring among patients, families, and medical practitioners. A plausible explanation of these behaviors is accomplished by examination of communication patterns containing the structure of paradox or double bind. Patients are forced to perceive realities about their physical conditions not as they appear to them, but as they are defined by those in their environment. This paper explores these communication patterns in relation to the structure of social relationships and the specific contents of messages being transmitted and received.

  2. [The debate about the right to die].

    PubMed

    Beca, Juan Pablo; Ortiz, Armando; Solar, Sebastián

    2005-05-01

    The Right to Die is a debatable issue and some basic notions need to be clarified to discuss it. Death needs to be recognized as part of human life. The goal of medicine is to avoid pain and alleviate suffering, to prevent premature death and when this is not possible, to let it occur peacefully. The concept of euthanasia is unclear, which increases the confusion on end-of-life topics. The term euthanasia should be used only when referring to medical acts performed to produce the patient's death, with the intention of terminating his/her suffering. It is what is usually called "active" euthanasia, which can be voluntary or involuntary. It is essential to understand the difference between producing and allowing death. This will permit timely decisions about limiting or withdrawing treatments, that can be disproportionate or that are only prolonging suffering. Limiting treatments does not mean to abandon the patient but rather to redefine his needs, such as pain treatment, prevention of complications, and relief of suffering. The ethic rationale for these decisions is the respect to the dignity of human life, and the estimation of proportionality or futility of each treatment. The physician's duty with the patient at the end of his life is to assist him in dying according to his values and to minimize his distress.

  3. Dying, mourning, and spirituality: a psychological perspective.

    PubMed

    Marrone, R

    1999-09-01

    Based in an unfortunate tradition that stretches back in time to Watson's behaviorism and Freud's psychoanalysis, psychology has tended to reject and to pathologize matters of the spirit. In the past 30 years, however, with the advent of what has been termed the cognitive revolution, psychology has greatly expanded the scope of its subject matter. Psychologists and thanatologists have begun to unravel the cognitive underpinnings of our assumptive world and the transformation of those underpinnings in times of crisis and stress. This article examines the cognitive basis of the spiritual experience and the use of cognitive assimilation, accommodation strategies during the process of mourning the death of a loved one, as well as during the process of living our own dying. Of special importance to mental health professionals and clergy, new research on dying, mourning, and spirituality suggests that the specific ways in which people rediscover meaning--such as belief in traditional religious doctrine, the afterlife, reincarnation, philanthropy, or a spiritual order to the universe--may be less important than the process itself. In other words, in the midst of dealing with profound loss in our lives, the ability to reascribe meaning to a changed world through spiritual transformation, religious conversion, or existential change may be more significant than the specific content by which that need is filled.

  4. Probing Tumor Microenvironment with in Vivo Phage Display

    DTIC Science & Technology

    2013-07-01

    Vivo Phage Display PRINCIPAL INVESTIGATOR: Kazuki N. Sugahara, M.D., Ph.D...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Probing Tumor Microenvironment with In Vivo Phage Display 5b. GRANT NUMBER W81XWH-12-1-0174 5c...cells and the matrix. The goal of our group is to make technical improvements in our phage display system, and find peptides that target carcinoma

  5. Studying tumor metastasis by in vivo imaging and flow cytometer

    NASA Astrophysics Data System (ADS)

    Wei, Xunbin; Guo, Jin; Liu, Guangda; Li, Yan; Chen, Yun; Zhang, Li; Tan, Yuan; Chen, Tong; Gu, Zhenqin; Wang, Chen

    2009-02-01

    Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. This ranges from 15,000 cases in the United States to more than a 250,000 in China. About 80% of people with primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help, one third of the patients have cancer that has not progressed beyond the liver. Primary liver cancer (hepatocellular carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. HCC may metastasize to the lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor-the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real-time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  6. RNA nanotechnology for computer design and in vivo computation.

    PubMed

    Qiu, Meikang; Khisamutdinov, Emil; Zhao, Zhengyi; Pan, Cheryl; Choi, Jeong-Woo; Leontis, Neocles B; Guo, Peixuan

    2013-10-13

    Molecular-scale computing has been explored since 1989 owing to the foreseeable limitation of Moore's law for silicon-based computation devices. With the potential of massive parallelism, low energy consumption and capability of working in vivo, molecular-scale computing promises a new computational paradigm. Inspired by the concepts from the electronic computer, DNA computing has realized basic Boolean functions and has progressed into multi-layered circuits. Recently, RNA nanotechnology has emerged as an alternative approach. Owing to the newly discovered thermodynamic stability of a special RNA motif (Shu et al. 2011 Nat. Nanotechnol. 6, 658-667 (doi:10.1038/nnano.2011.105)), RNA nanoparticles are emerging as another promising medium for nanodevice and nanomedicine as well as molecular-scale computing. Like DNA, RNA sequences can be designed to form desired secondary structures in a straightforward manner, but RNA is structurally more versatile and more thermodynamically stable owing to its non-canonical base-pairing, tertiary interactions and base-stacking property. A 90-nucleotide RNA can exhibit 4⁹⁰ nanostructures, and its loops and tertiary architecture can serve as a mounting dovetail that eliminates the need for external linking dowels. Its enzymatic and fluorogenic activity creates diversity in computational design. Varieties of small RNA can work cooperatively, synergistically or antagonistically to carry out computational logic circuits. The riboswitch and enzymatic ribozyme activities and its special in vivo attributes offer a great potential for in vivo computation. Unique features in transcription, termination, self-assembly, self-processing and acid resistance enable in vivo production of RNA nanoparticles that harbour various regulators for intracellular manipulation. With all these advantages, RNA computation is promising, but it is still in its infancy. Many challenges still exist. Collaborations between RNA nanotechnologists and computer

  7. How are base excision DNA repair pathways deployed in vivo?

    PubMed Central

    Thapar, Upasna; Demple, Bruce

    2017-01-01

    Since the discovery of the base excision repair (BER) system for DNA more than 40 years ago, new branches of the pathway have been revealed at the biochemical level by in vitro studies. Largely for technical reasons, however, the confirmation of these subpathways in vivo has been elusive. We review methods that have been used to explore BER in mammalian cells, indicate where there are important knowledge gaps to fill, and suggest a way to address them. PMID:28357058

  8. In vivo characterization of developing chronic pancreatitis in rats.

    PubMed

    Glawe, Claudia; Emmrich, Jörg; Sparmann, Gisela; Vollmar, Brigitte

    2005-02-01

    Despite numerous experimental and clinical investigations, there is no unifying concept on pathophysiology and pathogenesis of chronic pancreatitis. Defining the interplay between pancreatic microcirculation and parenchymal tissue, we will provide a basis for the better understanding of pancreatic fibrogenesis using in vivo high-resolution multifluorescence microscopy in dibutyltin chloride (DBTC)-exposed rats. Pancreatic microcirculation at days 3 and 7 after DBTC revealed leukocyte activation with a two-fold higher fraction of rolling cells and a nine- to 10-fold increase of cells firmly adherent to the endothelial lining, followed by subsequent transendothelial migration into tissue, as given by chloracetate esterase histology. In vivo staining of acinar tissue with bisbenzimide presented single cells exhibiting nuclear chromatin condensation and fragmentation. Apoptotic cell death was confirmed by immunohistochemical staining for active caspase-3 as well as by TUNEL analysis. Necrotic cells were found dispersed throughout the exocrine tissue under observation. Both modes of cell death were found highest in extent at days 3 and 7 with 15-20 cells/mm2, but progressively decreased below 10 cells/mm2 up to 28 days after DBTC. By means of in vivo microscopy yellow-green autofluorescent collagen deposits were found at day 7 and progressively increased up to approximately 12% at day 28 after DBTC. Concomitantly, density of capillaries progressively decreased and capillaries failing to conduct blood flow became apparent. Present on-line analysis indicates an early inflammatory response with acinar cell death, most probably triggering progression of disease with collagen deposition, capillary rarefication and manifestation of perfusion failure. These temporal and spatial multiparameter measurements of the in vivo microenvironment provide new insights into the pathological processes of pancreatic fibrogenesis.

  9. An in vivo screening system to identify tumorigenic genes.

    PubMed

    Ihara, T; Hosokawa, Y; Kumazawa, K; Ishikawa, K; Fujimoto, J; Yamamoto, M; Muramkami, T; Goshima, N; Ito, E; Watanabe, S; Semba, K

    2017-04-06

    Screening for oncogenes has mostly been performed by in vitro transformation assays. However, some oncogenes might not exhibit their transforming activities in vitro unless putative essential factors from in vivo microenvironments are adequately supplied. Here, we have developed an in vivo screening system that evaluates the tumorigenicity of target genes. This system uses a retroviral high-efficiency gene transfer technique, a large collection of human cDNA clones corresponding to ~70% of human genes and a luciferase-expressing immortalized mouse mammary epithelial cell line (NMuMG-luc). From 845 genes that were highly expressed in human breast cancer cell lines, we focused on 205 genes encoding membrane proteins and/or kinases as that had the greater possibility of being oncogenes or drug targets. The 205 genes were divided into five subgroups, each containing 34-43 genes, and then introduced them into NMuMG-luc cells. These cells were subcutaneously injected into nude mice and monitored for tumor development by in vivo imaging. Tumors were observed in three subgroups. Using DNA microarray analyses and individual tumorigenic assays, we found that three genes, ADORA2B, PRKACB and LPAR3, were tumorigenic. ADORA2B and LPAR3 encode G-protein-coupled receptors and PRKACB encodes a protein kinase A catalytic subunit. Cells overexpressing ADORA2B, LPAR3 or PRKACB did not show transforming phenotypes in vitro, suggesting that transformation by these genes requires in vivo microenvironments. In addition, several clinical data sets, including one for breast cancer, showed that the expression of these genes correlated with lower overall survival rate.

  10. Grueneisen relaxation photoacoustic microscopy in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Ma, Jun; Shi, Junhui; Hai, Pengfei; Zhou, Yong; Wang, Lihong V.

    2016-03-01

    Optical-resolution photoacoustic microscopy (OR-PAM) can achieve submicron lateral resolution by tightly focusing the excitation light, while the axial resolution is still limited by the frequency bandwidth of the ultrasonic transducer. The Grueneisen relaxation effect, in which the Grueneisen parameter changes within the thermal relaxation time following a laser impulse heating, can provide excellent axial resolution due to its optical sectioning property. Based on this effect, Grueneisen relaxation photoacoustic microscopy (GR-PAM) was developed and demonstrated ex vivo. Here, we present for the first time in vivo imaging of mouse brains with improved axial resolution based on GR-PAM. An intensity-modulated continuous-wave (CW) 532 nm laser thermally heated the in-focus absorber. Another 532 nm pulsed laser, which is aligned confocally with the CW laser, generated the photoacoustic (PA) signal from the absorber. The difference between the amplitudes of the photoacoustic signals with and without heating was used for image reconstruction. The achieved axial resolution is ~12.5 µm, which is fivefold better than the acoustically determined value for a 20 MHz-bandwidth ultrasound transducer. The system was demonstrated by imaging a blood-filled tube ex vivo and blood vessels of mouse brains in vivo. The blood-filled tube diameter obtained from the PA image by GR-PAM is 105 µm, which is much closer to its actual diameter (100 µm) than the value from conventional OR-PAM (160 µm). This axial resolution improvement was further validated in imaging mouse brains in vivo, and yielded significantly narrower axial profiles of the vessels. This in vivo demonstration of imaging by GR-PAM might inspire more applications in PA biomedical imaging and sensing.

  11. Complex spectral OCT in human eye imaging in vivo

    NASA Astrophysics Data System (ADS)

    Targowski, Piotr; Wojtkowski, Maciej; Kowalczyk, Andrzej; Bajraszewski, Tomasz; Szkulmowski, Maciej; Gorczyńska, Iwona

    2004-01-01

    Complex spectral optical coherence tomography in comparison to spectral optical coherence tomography produces images free of parasitic terms with extended measurement range. This technique requires stability of the object during at least three consecutive measurements. In this paper we present how to improve this technique to make measurements less sensitive to involuntary eye movements. The first images of human skin and anterior chamber of the eye in vivo based on complex spectral optical coherence tomography are presented.

  12. Hepatic Dipeptidyl Peptidase-4 Controls Pharmacokinetics of Vildagliptin In Vivo.

    PubMed

    Asakura, Mitsutoshi; Fukami, Tatsuki; Nakajima, Miki; Fujii, Hideaki; Atsuda, Koichiro; Itoh, Tomoo; Fujiwara, Ryoichi

    2017-02-01

    The main route of elimination of vildagliptin, which is an inhibitor of dipeptidyl peptidase-4 (DPP-4), in humans is cyano group hydrolysis to produce a carboxylic acid metabolite M20.7. Our in vitro study previously demonstrated that DPP-4 itself greatly contributed to the hydrolysis of vildagliptin in mouse, rat, and human livers. To investigate whether hepatic DPP-4 contributes to the hydrolysis of vildagliptin in vivo, in the present study, we conducted in vivo pharmacokinetics studies of vildagliptin in mice coadministered with vildagliptin and sitagliptin, which is another DPP-4 inhibitor, and also in streptozotocin (STZ)-induced diabetic mice. The area under the plasma concentration-time curve (AUC) value of M20.7 in mice coadministered with vildagliptin and sitagliptin was significantly lower than that in mice administered vildagliptin alone (P < 0.01). Although plasma DPP-4 expression level was increased 1.9-fold, hepatic DPP-4 activity was decreased in STZ-induced diabetic mice. The AUC values of M20.7 in STZ-induced diabetic mice were lower than those in control mice (P < 0.01). Additionally, the AUC values of M20.7 significantly positively correlated with hepatic DPP-4 activities in the individual mice (Rs = 0.943, P < 0.05). These findings indicated that DPP-4 greatly contributed to the hydrolysis of vildagliptin in vivo and that not plasma, but hepatic DPP-4 controlled pharmacokinetics of vildagliptin. Furthermore, enzyme assays of 23 individual human liver samples showed that there was a 3.6-fold interindividual variability in vildagliptin-hydrolyzing activities. Predetermination of the interindividual variability of hepatic vildagliptin-hydrolyzing activity might be useful for the prediction of blood vildagliptin concentrations in vivo.

  13. In vivo real-time volumetric synthetic aperture ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Bouzari, Hamed; Rasmussen, Morten F.; Brandt, Andreas H.; Stuart, Matthias B.; Nikolov, Svetoslav; Jensen, Jørgen A.

    2015-03-01

    Synthetic aperture (SA) imaging can be used to achieve real-time volumetric ultrasound imaging using 2-D array transducers. The sensitivity of SA imaging is improved by maximizing the acoustic output, but one must consider the limitations of an ultrasound system, both technical and biological. This paper investigates the in vivo applicability and sensitivity of volumetric SA imaging. Utilizing the transmit events to generate a set of virtual point sources, a frame rate of 25 Hz for a 90° × 90° field-of-view was achieved. data were obtained using a 3.5 MHz 32 × 32 elements 2-D phased array transducer connected to the experimental scanner (SARUS). Proper scaling is applied to the excitation signal such that intensity levels are in compliance with the U.S. Food and Drug Administration regulations for in vivo ultrasound imaging. The measured Mechanical Index and spatial-peak-temporal-average intensity for parallel beam-forming (PB) are 0.83 and 377.5mW/cm2, and for SA are 0.48 and 329.5mW/cm2. A human kidney was volumetrically imaged with SA and PB techniques simultaneously. Two radiologists for evaluation of the volumetric SA were consulted by means of a questionnaire on the level of details perceivable in the beam-formed images. The comparison was against PB based on the in vivo data. The feedback from the domain experts indicates that volumetric SA images internal body structures with a better contrast resolution compared to PB at all positions in the entire imaged volume. Furthermore, the autocovariance of a homogeneous area in the in vivo SA data, had 23.5% smaller width at the half of its maximum value compared to PB.

  14. RNA nanotechnology for computer design and in vivo computation

    PubMed Central

    Qiu, Meikang; Khisamutdinov, Emil; Zhao, Zhengyi; Pan, Cheryl; Choi, Jeong-Woo; Leontis, Neocles B.; Guo, Peixuan

    2013-01-01

    Molecular-scale computing has been explored since 1989 owing to the foreseeable limitation of Moore's law for silicon-based computation devices. With the potential of massive parallelism, low energy consumption and capability of working in vivo, molecular-scale computing promises a new computational paradigm. Inspired by the concepts from the electronic computer, DNA computing has realized basic Boolean functions and has progressed into multi-layered circuits. Recently, RNA nanotechnology has emerged as an alternative approach. Owing to the newly discovered thermodynamic stability of a special RNA motif (Shu et al. 2011 Nat. Nanotechnol. 6, 658–667 (doi:10.1038/nnano.2011.105)), RNA nanoparticles are emerging as another promising medium for nanodevice and nanomedicine as well as molecular-scale computing. Like DNA, RNA sequences can be designed to form desired secondary structures in a straightforward manner, but RNA is structurally more versatile and more thermodynamically stable owing to its non-canonical base-pairing, tertiary interactions and base-stacking property. A 90-nucleotide RNA can exhibit 490 nanostructures, and its loops and tertiary architecture can serve as a mounting dovetail that eliminates the need for external linking dowels. Its enzymatic and fluorogenic activity creates diversity in computational design. Varieties of small RNA can work cooperatively, synergistically or antagonistically to carry out computational logic circuits. The riboswitch and enzymatic ribozyme activities and its special in vivo attributes offer a great potential for in vivo computation. Unique features in transcription, termination, self-assembly, self-processing and acid resistance enable in vivo production of RNA nanoparticles that harbour various regulators for intracellular manipulation. With all these advantages, RNA computation is promising, but it is still in its infancy. Many challenges still exist. Collaborations between RNA nanotechnologists and computer

  15. Transcutaneous Raman Spectroscopy of Murine Bone In Vivo

    PubMed Central

    Schulmerich, Matthew V.; Cole, Jacqueline H.; Kreider, Jaclynn M.; Esmonde-White, Francis; Dooley, Kathryn A.; Goldstein, Steven A.; Morris, Michael D.

    2009-01-01

    Raman spectroscopy can provide valuable information about bone tissue composition in studies of bone development, biomechanics, and health. In order to study the Raman spectra of bone in vivo, instrumentation that enhances the recovery of subsurface spectra must be developed and validated. Five fiber-optic probe configurations were considered for transcutaneous bone Raman spectroscopy of small animals. Measurements were obtained from the tibia of sacrificed mice, and the bone Raman signal was recovered for each probe configuration. The configuration with the optimal combination of bone signal intensity, signal variance, and power distribution was then evaluated under in vivo conditions. Multiple in vivo transcutaneous measurements were obtained from the left tibia of 32 anesthetized mice. After collecting the transcutaneous Raman signal, exposed bone measurements were collected and used as a validation reference. Multivariate analysis was used to recover bone spectra from transcutaneous measurements. To assess the validity of the transcutaneous bone measurements cross-correlations were calculated between standardized spectra from the recovered bone signal and the exposed bone measurements. Additionally, the carbonate-to-phosphate height ratios of the recovered bone signals were compared to the reference exposed bone measurements. The mean cross-correlation coefficient between the recovered and exposed measurements was 0.96, and the carbonate-to-phosphate ratios did not differ significantly between the two sets of spectra (p > 0.05). During these first systematic in vivo Raman measurements, we discovered that probe alignment and animal coat color influenced the results and thus should be considered in future probe and study designs. Nevertheless, our noninvasive Raman spectroscopic probe accurately assessed bone tissue composition through the skin in live mice. PMID:19281644

  16. In vivo EMG biofeedback in violin and viola pedagogy.

    PubMed

    LeVine, W R; Irvine, J K

    1984-06-01

    In vivo EMG biofeedback was found to be an effective pedagogical tool for removing unwanted left-hand tension in nine violin and viola players. Improvement occurred rapidly and persisted throughout a 5-month follow-up period. Further studies will be necessary to assess the effect of biofeedback independent of placebo effects. The brevity of the method and the magnitude of improvement warrant further investigation.

  17. Direct detection of alpha synuclein oligomers in vivo

    PubMed Central

    2013-01-01

    Background Rat models of Parkinson’s disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo. Results Viral coinjection resulted in widespread VenusYFP signal within the nigrostriatal pathway, including cell bodies in the substantia nigra and synaptic accumulation in striatal terminals, suggestive of in vivo alpha-synuclein oligomers formation. Transduced rats showed alpha-synuclein induced dopaminergic neuron loss in the substantia nigra, the appearance of dystrophic neurites, and gliosis in the striatum. Moreover, we have applied in vivo imaging techniques in the living mouse to directly image alpha-synuclein oligomers in the cortex. Conclusion We have developed a unique animal model that provides a tool for the Parkinson’s disease research community with which to directly detect alpha- synuclein oligomers in vivo and screen therapeutic approaches targeting alpha-synuclein oligomers. PMID:24252244

  18. Interferon induces natural killer cell blastogenesis in vivo

    NASA Technical Reports Server (NTRS)

    Biron, C. A.; Sonnenfeld, G.; Welsh, R. M.

    1984-01-01

    Interferon (IFN), types beta and gamma, and IFN inducers polyinosinic-polycytidylic acid and lymphocytic choriomeningitis virus, all stimulated the generation of blast-natural killer (NK) cells in mouse spleens, Blast-NK cells were characterized on the basis of size, 3H-thymidine uptake, and NK cell markers These data indicate that in addition to augmenting NK cell-mediated lysis, IFN may regulate NK cell proliferation in vivo.

  19. Are rare-earth nanoparticles suitable for in vivo applications?

    PubMed

    Liu, Chunyan; Hou, Yi; Gao, Mingyuan

    2014-10-29

    Rare earth (RE) nanoparticles have attracted considerable attention due to their unique optical and magnetic properties associated with f-electrons. The recent accomplishments in RE nanoparticle synthesis have aroused great interest of scientists to further explore their biomedical applications. This Research News summarizes recent achievements in controlled synthesis of magnetic and luminescent RE nanoparticles, surface modification, and toxicity studies of RE nanomaterials, and highlights state-of-the-art in in vivo applications of RE nanoparticles.

  20. Tracking Origins of Prostate Cancer: An Innovative in Vivo Modeling

    DTIC Science & Technology

    2014-11-01

    could express specifically in prostate under PB- Cre4 control, and could label normal, hyperplasic, neoplastic and malignant carcinoma cells . More...propose to develop an innovative and hitherto not attempted in vivo prostate cancer model that will delineate the exact cell of origin through...different stages of prostate cancer development and progression. We propose to study possible cell (s) of origin for prostate cancer by combinatorial

  1. Targeted erythropoietin selectively stimulates red blood cell expansion in vivo

    PubMed Central

    Burrill, Devin R.; Vernet, Andyna; Collins, James J.; Silver, Pamela A.; Way, Jeffrey C.

    2016-01-01

    The design of cell-targeted protein therapeutics can be informed by natural protein–protein interactions that use cooperative physical contacts to achieve cell type specificity. Here we applied this approach in vivo to the anemia drug erythropoietin (EPO), to direct its activity to EPO receptors (EPO-Rs) on red blood cell (RBC) precursors and prevent interaction with EPO-Rs on nonerythroid cells, such as platelets. Our engineered EPO molecule was mutated to weaken its affinity for EPO-R, but its avidity for RBC precursors was rescued via tethering to an antibody fragment that specifically binds the human RBC marker glycophorin A (huGYPA). We systematically tested the impact of these engineering steps on in vivo markers of efficacy, side effects, and pharmacokinetics. huGYPA transgenic mice dosed with targeted EPO exhibited elevated RBC levels, with only minimal platelet effects. This in vivo selectivity depended on the weakening EPO mutation, fusion to the RBC-specific antibody, and expression of huGYPA. The terminal plasma half-life of targeted EPO was ∼28.3 h in transgenic mice vs. ∼15.5 h in nontransgenic mice, indicating that huGYPA on mature RBCs acted as a significant drug sink but did not inhibit efficacy. In a therapeutic context, our targeting approach may allow higher restorative doses of EPO without platelet-mediated side effects, and also may improve drug pharmacokinetics. These results demonstrate how rational drug design can improve in vivo specificity, with potential application to diverse protein therapeutics. PMID:27114509

  2. Ranking the in vivo toxicity of nanomaterials in Drosophila melanogaster

    NASA Astrophysics Data System (ADS)

    Vecchio, G.; Galeone, A.; Malvindi, M. A.; Cingolani, R.; Pompa, P. P.

    2013-09-01

    In this work, we propose a quantitative assessment of nanoparticles toxicity in vivo. We show a quantitative ranking of several types of nanoparticles (AuNPs, AgNPs, cadmium-based QDs, cadmium-free QDs, and iron oxide NPs, with different coating and/or surface chemistries), providing a categorization of their toxicity outcomes. This strategy may offer an innovative high-throughput screening tool of nanomaterials, of potential and broad interest to the nanoscience community.

  3. How are base excision DNA repair pathways deployed in vivo?

    PubMed

    Thapar, Upasna; Demple, Bruce

    2017-01-01

    Since the discovery of the base excision repair (BER) system for DNA more than 40 years ago, new branches of the pathway have been revealed at the biochemical level by in vitro studies. Largely for technical reasons, however, the confirmation of these subpathways in vivo has been elusive. We review methods that have been used to explore BER in mammalian cells, indicate where there are important knowledge gaps to fill, and suggest a way to address them.

  4. In Vivo Measurement of Drug Efficacy in Breast Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0386 TITLE: In Vivo Measurement of Drug Efficacy in Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Randy J. Giedt CONTRACTING...Measurement of Drug Efficacy in Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0386 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Randy J...and utilizing intravital methods for studying drug and nanoparticle function in mouse breast cancer models. We hypothesize that, firstly, we can

  5. Multiplexed aberration measurement for deep tissue imaging in vivo

    PubMed Central

    Wang, Chen; Liu, Rui; Milkie, Daniel E.; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

    2014-01-01

    We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large imaging volume. PMID:25128976

  6. Directed evolution of artificial metalloenzymes for in vivo metathesis.

    PubMed

    Jeschek, Markus; Reuter, Raphael; Heinisch, Tillmann; Trindler, Christian; Klehr, Juliane; Panke, Sven; Ward, Thomas R

    2016-09-29

    The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions. Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions. For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist: repurposing natural metalloenzymes for abiotic transformations; in silico metalloenzyme (re-)design; and incorporation of abiotic cofactors into proteins. The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein. This limits the throughput of genetic optimization schemes applied to artificial metalloenzymes and their applicability in vivo to expand natural metabolism. Here we report the compartmentalization and in vivo evolution of an artificial metalloenzyme for olefin metathesis, which represents an archetypal organometallic reaction without equivalent in nature. Building on previous work on an artificial metallohydrolase, we exploit the periplasm of Escherichia coli as a reaction compartment for the 'metathase' because it offers an auspicious environment for artificial metalloenzymes, mainly owing to low concentrations of inhibitors such as glutathione, which has recently been identified as a major inhibitor. This strategy facilitated the assembly of a functional metathase in vivo and its directed evolution with substantially increased throughput compared to conventional approaches that rely on purified protein variants. The evolved metathase compares favourably with commercial catalysts, shows activity for different metathesis substrates and can be further evolved in

  7. Measuring In Vivo Free Radical Production by the Outer Retina

    PubMed Central

    Berkowitz, Bruce A.; Bredell, Bryce X.; Davis, Christopher; Samardzija, Marijana; Grimm, Christian; Roberts, Robin

    2015-01-01

    Purpose Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-μm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). Methods Low-dose sodium iodate–treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl−/− mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and α-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). Results In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2-month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. Conclusions Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo. PMID:26670830

  8. Capacitive Extensometer Particularly Suited for Measuring in Vivo Bone Strain

    NASA Technical Reports Server (NTRS)

    Perusek, Gail P. (Inventor)

    2000-01-01

    The present invention provides for in vivo measurements of the principal strain magnitudes and directions, and maximum shear strain that occurs in a material, such as human bone, when it is loaded (or subjected to a load). In one embodiment the invention includes a capacitive delta extensometer arranged with six sensors in a three piece configuration, with each sensor of each pair spaced apart from each other by 120 degrees.

  9. RF Attenuation Characteristics for In Vivo Wireless Healthcare Chip

    NASA Astrophysics Data System (ADS)

    Yamada, Tomohiro; Uezono, Takumi; Okada, Kenichi; Masu, Kazuya; Oki, Akio; Horiike, Yasuhiro

    2005-07-01

    We investigate a wireless communication system for an in vivo healthcare chip. In this paper, we present measured attenuation characteristics through the human body at several frequencies. In the measurement, we use physiological saline and fresh meat instead of a real human body. From the measured results, we found that 13.56 MHz has an attenuation of 47 dB and is suitable for the proposed system.

  10. Quantitative In Vivo Imaging of Breast Tumor Extracellular Matrix

    DTIC Science & Technology

    2010-05-01

    backscattering of the forward propagating SHG. The propagation of light in turbid media can be well modeled by Monte Carlo simulation of the paths that...propagating SHG. The propagation of light in turbid media can be well modeled by Monte Carlo simulation of the paths that photons make as they travel...below). Fig. 1. Experimental setup for in vivo measurement of collagen SHG F/B ratio 2 SHG Back Scattering and Monte Carlo Simulation Using

  11. Near-Infrared Fluorescent Nanoprobes for in Vivo Optical Imaging

    PubMed Central

    Quek, Chai-Hoon; Leong, Kam W.

    2012-01-01

    Near-infrared (NIR) fluorescent probes offer advantages of high photon penetration, reduced light scattering and minimal autofluorescence from living tissues, rendering them valuable for noninvasive mapping of molecular events, assessment of therapeutic efficacy, and monitoring of disease progression in animal models. This review provides an overview of the recent development of the design and optical property of the different classes of NIR fluorescent nanoprobes associated with in vivo imaging applications.

  12. Directed evolution of artificial metalloenzymes for in vivo metathesis

    NASA Astrophysics Data System (ADS)

    Jeschek, Markus; Reuter, Raphael; Heinisch, Tillmann; Trindler, Christian; Klehr, Juliane; Panke, Sven; Ward, Thomas R.

    2016-09-01

    The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions. Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions. For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist: repurposing natural metalloenzymes for abiotic transformations; in silico metalloenzyme (re-)design; and incorporation of abiotic cofactors into proteins. The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein. This limits the throughput of genetic optimization schemes applied to artificial metalloenzymes and their applicability in vivo to expand natural metabolism. Here we report the compartmentalization and in vivo evolution of an artificial metalloenzyme for olefin metathesis, which represents an archetypal organometallic reaction without equivalent in nature. Building on previous work on an artificial metallohydrolase, we exploit the periplasm of Escherichia coli as a reaction compartment for the ‘metathase’ because it offers an auspicious environment for artificial metalloenzymes, mainly owing to low concentrations of inhibitors such as glutathione, which has recently been identified as a major inhibitor. This strategy facilitated the assembly of a functional metathase in vivo and its directed evolution with substantially increased throughput compared to conventional approaches that rely on purified protein variants. The evolved metathase compares favourably with commercial catalysts, shows activity for different metathesis substrates and can be further evolved in

  13. In vitro and in vivo approaches to study osteocyte biology.

    PubMed

    Kalajzic, Ivo; Matthews, Brya G; Torreggiani, Elena; Harris, Marie A; Divieti Pajevic, Paola; Harris, Stephen E

    2013-06-01

    Osteocytes, the most abundant cell population of the bone lineage, have been a major focus in the bone research field in recent years. This population of cells that resides within mineralized matrix is now thought to be the mechanosensory cell in bone and plays major roles in the regulation of bone formation and resorption. Studies of osteocytes had been impaired by their location, resulting in numerous attempts to isolate primary osteocytes and to generate cell lines representative of the osteocytic phenotype. Progress has been achieved in recent years by utilizing in vivo genetic technology and generation of osteocyte directed transgenic and gene deficiency mouse models. We will provide an overview of the current in vitro and in vivo models utilized to study osteocyte biology. We discuss generation of osteocyte-like cell lines and isolation of primary osteocytes and summarize studies that have utilized these cellular models to understand the functional role of osteocytes. Approaches that attempt to selectively identify and isolate osteocytes using fluorescent protein reporters driven by regulatory elements of genes that are highly expressed in osteocytes will be discussed. In addition, recent in vivo studies utilizing overexpression or conditional deletion of various genes using dentin matrix protein (Dmp1) directed Cre recombinase are outlined. In conclusion, evaluation of the benefits and deficiencies of currently used cell lines/genetic models in understanding osteocyte biology underlines the current progress in this field. The future efforts will be directed towards developing novel in vitro and in vivo models that would additionally facilitate in understanding the multiple roles of osteocytes.

  14. Advances in fiber optic sensors for in-vivo monitoring

    NASA Astrophysics Data System (ADS)

    Baldini, Francesco; Mignani, Anna G.

    1995-09-01

    Biomedical fiber-optic sensors are attractive for the measurement of both physical and chemical parameters as well as for spectral measurements directly performed on the patient. An overview of fiber-optic sensors for in vivo monitoring is given, with particular attention to the advantages that these sensors are able to offer in different fields of application such as cardiovascular and intensive care, angiology, gastroenterology, ophthalmology, oncology, neurology, dermatology, and dentistry.

  15. Regulated GDNF Delivery in Vivo Using Neural Stem Cells

    DTIC Science & Technology

    2006-04-01

    which do not kill cell bodies within the striatum but induce retrograde death of dopamine bodies in the brain stem showed a level of survival and...Neural Stem Cells PRINCIPAL INVESTIGATOR: Clive Svendsen, Ph.D. CONTRACTING ORGANIZATION: University of Wisconsin...Regulated GDNF Delivery in Vivo Using Neural Stem Cells 5b. GRANT NUMBER DAMD17-03-1-0122 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

  16. Regulated GDNF Delivery In Vivo using Neural Stem Cells

    DTIC Science & Technology

    2005-04-01

    attached as Appendix 2. Body Task 1. To produce rat and monkey neural stem cells which secrete GDNF under an inducible promoter. a. Assess and optimize GDNF...AD Award Number: DAMD17-03-1-0122 TITLE: Regulated GDNF Delivery In Vivo Using Neural Stem Cells PRINCIPAL INVESTIGATOR: Clive N. Svendsen, Ph.D...analysis of 4 rats for PET. This system is now ready for the new stem cell transplants and carrying out the experiments outlined in year three which

  17. NIR fluorescent ytterbium compound for in vivo fluorescence molecular imaging.

    PubMed

    Aita, Kazuki; Temma, Takashi; Kuge, Yuji; Seki, Koh-ichi; Saji, Hideo

    2010-01-01

    We have developed a new NIR fluorescent probe based on an ytterbium(III) (E)-1-(pyridin-2-yl-diazenyl)naphthalen-2-ol (PAN) complex. This probe emits near-infrared luminescence derived from the Yb ion through excitation of the PAN moiety with visible light (lambda(ex)= 530 nm, lambda(em)= 975 nm). The results support the possible utility of the probe for in vivo fluorescence molecular imaging.

  18. A Guide to Studying Human Hair Follicle Cycling In Vivo.

    PubMed

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

    2016-01-01

    Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.

  19. In vivo nanoneurotoxicity screening using oxidative stress and neuroinflammation paradigms

    PubMed Central

    Kim, Youngsoon; Kong, Seong Deok; Chen, Li-Han; Pisanic, Thomas R.; Jin, Sungho; Shubayev, Veronica I.

    2013-01-01

    Iron oxide nanoparticles (IONPs) are promising neuroimaging agents and molecular cargo across neurovascular barriers. Development of intrinsically safe IONP chemistries requires a robust in vivo nanoneurotoxicity screening model. Herein, we engineered four IONPs of different surface and core chemistries: DMSA-Fe2O3, DMSA-Fe3O4, PEG-Fe3O4 and PEG-Au-Fe3O4. Capitalizing on the ability of the peripheral nervous system to recruit potent immune cells from circulation, we characterized a spatiotemporally controlled platform for the study of in vivo nanobiointerfaces with hematogenous immune cells, neuroglial and neurovascular units after intraneural IONP delivery into rat sciatic nerve. SQUID magnetometry and histological iron stain were used for IONP tracking. Among the IONPs, DMSA-Fe2O3 NPs were potent pro-apoptotic agents in nerve, with differential ability to regulate oxidative stress, inflammation and apoptotic signaling in neuroglia, macrophages, lymphocytes and endothelial cells. This platform aims to facilitate the development of predictive paradigms of nanoneurotoxicity based on mechanistic investigation of relevant in vivo bio-nanointerfaces. PMID:23669369

  20. In vivo dosimetry with silicon diodes in total body irradiation

    NASA Astrophysics Data System (ADS)

    Oliveira, F. F.; Amaral, L. L.; Costa, A. M.; Netto, T. G.

    2014-02-01

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments.

  1. In vivo cultivation of tumor cells in hollow fibers.

    PubMed

    Hollingshead, M G; Alley, M C; Camalier, R F; Abbott, B J; Mayo, J G; Malspeis, L; Grever, M R

    1995-01-01

    Advancement of potential anti-cancer agents from "discovery" in an in vitro screen to pre-clinical development requires a demonstration of in vivo efficacy in one or more animal models of neoplastic disease. Most such models require considerable materials in terms of laboratory animals and test compound as well as substantial amounts of time (and cost) to determine whether a given experimental agent or series of agents have even minimal anti-tumor activity. The present study was initiated to assess the feasibility of employing an alternate methodology for preliminary in vivo evaluations of therapeutic efficacy. Results of experimentation to date demonstrate that a hollow fiber encapsulation/implantation methodology provides quantitative indices of drug efficacy with minimum expenditures of time and materials. Following further pharmacologic calibrations, the hollow fiber technique is anticipated (a) to identify compounds having moderate to prominent anti-cancer activity and (b) to facilitate the identification of sensitive tumor cell line "targets" and optimal or near-optimal treatment regimens for subsequent testing using standard in vivo solid tumor models. The potential suitability of this methodology is demonstrated with several standard anti-neoplastic agents.

  2. Pyrimethamine nanosuspension with improved bioavailability: in vivo pharmacokinetic studies.

    PubMed

    Dhapte, Vividha; Kadam, Vivek; Pokharkar, Varsha

    2013-10-01

    Pyrimethamine is a standard antiprotozoal drug recommended for prophylaxis and treatment of malarial infections. Limited bioavailability, slow onset of action, and life-threatening side effects restrict its use. Hence, in the present study, pyrimethamine nanosuspension was prepared with the objective to improve its dissolution rate and pharmacokinetic profile. Stable pyrimethamine nanosuspension with submicron particle size was prepared by nanoprecipitation and high-pressure homogenization techniques. Nanosizing and stabilizers modified the surface characteristics of drug particles resulting in considerable increase in the dissolution rate. The in vivo pharmacokinetic studies of the prepared nanosuspension were carried out and compared with plain pyrimethamine suspension and marketed pyrimethamine suspension. The in vivo pharmacokinetic profiling of pyrimethamine nanosuspension in rats showed higher AUC0-24 h and C max compared to the plain and marketed pyrimethamine suspensions. In contrast to its plain and marketed formulation, pyrimethamine nanosuspension showed rapid onset of action (T max 0.5 h vs. 2 h). Also, the low volume of distribution and reduced elimination half-life of the developed nanosuspension can lead to reduced side effects. Thus, improved in vitro-in vivo kinetics indicated that nanosuspension proved to be a suitable strategy for elevating the therapeutic profile of pyrimethamine.

  3. Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration.

    PubMed

    Hansen, H H; Schmid, P C; Bittigau, P; Lastres-Becker, I; Berrendero, F; Manzanares, J; Ikonomidou, C; Schmid, H H; Fernández-Ruiz, J J; Hansen, H S

    2001-09-01

    Endogenous cannabinoid receptor ligands (endocannabinoids) may rescue neurons from glutamate excitotoxicity. As these substances also accumulate in cultured immature neurons following neuronal damage, elevated endocannabinoid concentrations may be interpreted as a putative neuroprotective response. However, it is not known how glutamatergic insults affect in vivo endocannabinoid homeostasis, i.e. N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), as well as other constituents of their lipid families, N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs), respectively. Here we employed three in vivo neonatal rat models characterized by widespread neurodegeneration as a consequence of altered glutamatergic neurotransmission and assessed changes in endocannabinoid homeostasis. A 46-fold increase of cortical NAE concentrations (anandamide, 13-fold) was noted 24 h after intracerebral NMDA injection, while less severe insults triggered by mild concussive head trauma or NMDA receptor blockade produced a less pronounced NAE accumulation. By contrast, levels of 2-AG and other 2-MAGs were virtually unaffected by the insults employed, rendering it likely that key enzymes in biosynthetic pathways of the two different endocannabinoid structures are not equally associated to intracellular events that cause neuronal damage in vivo. Analysis of cannabinoid CB(1) receptor mRNA expression and binding capacity revealed that cortical subfields exhibited an up-regulation of these parameters following mild concussive head trauma and exposure to NMDA receptor blockade. This may suggest that mild to moderate brain injury may trigger elevated endocannabinoid activity via concomitant increase of anandamide levels, but not 2-AG, and CB(1) receptor density.

  4. A Statistical Model for In Vivo Neuronal Dynamics

    PubMed Central

    Surace, Simone Carlo; Pfister, Jean-Pascal

    2015-01-01

    Single neuron models have a long tradition in computational neuroscience. Detailed biophysical models such as the Hodgkin-Huxley model as well as simplified neuron models such as the class of integrate-and-fire models relate the input current to the membrane potential of the neuron. Those types of models have been extensively fitted to in vitro data where the input current is controlled. Those models are however of little use when it comes to characterize intracellular in vivo recordings since the input to the neuron is not known. Here we propose a novel single neuron model that characterizes the statistical properties of in vivo recordings. More specifically, we propose a stochastic process where the subthreshold membrane potential follows a Gaussian process and the spike emission intensity depends nonlinearly on the membrane potential as well as the spiking history. We first show that the model has a rich dynamical repertoire since it can capture arbitrary subthreshold autocovariance functions, firing-rate adaptations as well as arbitrary shapes of the action potential. We then show that this model can be efficiently fitted to data without overfitting. We finally show that this model can be used to characterize and therefore precisely compare various intracellular in vivo recordings from different animals and experimental conditions. PMID:26571371

  5. A crystal-clear zebrafish for in vivo imaging

    PubMed Central

    Antinucci, Paride; Hindges, Robert

    2016-01-01

    The larval zebrafish (Danio rerio) is an excellent vertebrate model for in vivo imaging of biological phenomena at subcellular, cellular and systems levels. However, the optical accessibility of highly pigmented tissues, like the eyes, is limited even in this animal model. Typical strategies to improve the transparency of zebrafish larvae require the use of either highly toxic chemical compounds (e.g. 1-phenyl-2-thiourea, PTU) or pigmentation mutant strains (e.g. casper mutant). To date none of these strategies produce normally behaving larvae that are transparent in both the body and the eyes. Here we present crystal, an optically clear zebrafish mutant obtained by combining different viable mutations affecting skin pigmentation. Compared to the previously described combinatorial mutant casper, the crystal mutant lacks pigmentation also in the retinal pigment epithelium, therefore enabling optical access to the eyes. Unlike PTU-treated animals, crystal larvae are able to perform visually guided behaviours, such as the optomotor response, as efficiently as wild type larvae. To validate the in vivo application of crystal larvae, we performed whole-brain light-sheet imaging and two-photon calcium imaging of neural activity in the retina. In conclusion, this novel combinatorial pigmentation mutant represents an ideal vertebrate tool for completely unobstructed structural and functional in vivo investigations of biological processes, particularly when imaging tissues inside or between the eyes. PMID:27381182

  6. The DOE in-vivo phantom library program

    SciTech Connect

    Olsen, P.C.

    1993-12-31

    The use of improved in vivo bioassay calibration phantoms in recent years has led to significant advances in the detection capabilities of in vivo counting laboratories, and increased ability to cross-calibrate various systems and laboratories for standardization purposes in DOE programs. The cost of these phantoms are significant, though, and this inhibits successful intercomparisons for improving calibrations. A recent CIRRPC Workshop on Internal Dosimetry in April 1992 recommended establishing intercomparison programs for in vivo measurements and improved phantom designs. Improved phantoms, developed at PNL with NIST-traceable source reference material loadings, proven solid tissue substitutes, and extensive documentation on construction, activity, and physical and chemical composition are available through a newly operational library. These phantoms use original LLNL molds and existing BOMAB phantom shells, but with improved tissue substitutes. All phantom materials have been extensively tested for their chemical, physical, and radiation transmission properties, and are tailored for identical transmission characteristics at the photon energies of concern. PNL has been pursuing approval from NIST for {open_quotes}certification{close_quotes} of these phantoms. The DOE Phantom Library loans organ, whole-body, and through cooperation with USTR, an Am-241 skeletal phantom to DOE contractor laboratories without cost. Only the price of shipping the phantom is requested. This paper will discuss the operation of the library, the current and planned holdings, the quality of phantom construction, and planning for NIST cooperation in certifying these phantoms.

  7. Nanosensor aided photoacoustic measurement of pH in vivo

    NASA Astrophysics Data System (ADS)

    Ray, Aniruddha; Yoon, Hyung Ki; Kopelman, Raoul; Wang, Xueding

    2013-03-01

    pH plays a critical role in many aspects of cell and tissues physiology. Lower pH is also a typical characteristic of arthritic joints and tumor tissues. These pH anomalies are also exploited in different drug delivery mechanisms. Here we present, a new method of pH sensing in vivo using spectroscopic photoacoustic measurements facilitated by pH sensitive nanosensors. The nanosensors consist of Seminaphtharhodafluor (SNARF), a pH sensitive dye, encapsulated in a specially designed polyacrylamide hydrogel matrix with a hydrophobic core. The photoacoustic intensity ratio between the excitation wavelengths of 585nm and 565nm increases in the pH range from 6.0 to 8.0 and is used to determine the pH of the local environment. These nanosensors are biodegradable, biocompatible, have a long plasma lifetime and can be targeted to any type of cells or tissues by surface modification using proper targeting moieties. The encapsulation of the dye prevents the interaction of the dye with proteins in plasma and also reduces the dye degradation. The SNARF dye in its free form loses 90% of its absorbance in presence of albumin, a protein found in abundance in plasma, and this has severely limited its adaptation to in vivo environments. In comparison, the SNARF nanosensors lose only 16% of their absorbance in the same environment. We employ these nanosensors to demonstrate the feasibility of pH sensing in vivo through photoacoustic measurements on a rat joint model.

  8. In vivo histamine voltammetry in the mouse premammillary nucleus.

    PubMed

    Samaranayake, Srimal; Abdalla, Aya; Robke, Rhiannon; Wood, Kevin M; Zeqja, Anisa; Hashemi, Parastoo

    2015-06-07

    Histamine plays a major role in the mediation of allergic reactions such as peripheral inflammation. This classical monoamine is also a neurotransmitter involved in the central nervous system but its role in this context is poorly understood. Studying histamine neurotransmission is important due to its implications in many neurological disorders. The sensitivity, selectivity and high temporal resolution of fast scan cyclic voltammetry (FSCV) offer many advantages for studying electroactive neurotransmitters. Histamine has previously been studied with FSCV; however, the lack of a robust Faradaic electrochemical signal makes it difficult to selectively identify histamine in complex media, as found in vivo. In this work, we optimize an electrochemical waveform that provides a stimulation-locked and unique electrochemical signal towards histamine. We describe in vitro waveform optimization and a novel in vivo physiological model for stimulating histamine release in the mouse premammillary nucleus via stimulation of the medial forebrain bundle. We demonstrate that a robust signal can be used to effectively identify histamine and characterize its in vivo kinetics.

  9. Studying Neutrophil Migration In Vivo Using Adoptive Cell Transfer.

    PubMed

    Miyabe, Yoshishige; Kim, Nancy D; Miyabe, Chie; Luster, Andrew D

    2016-01-01

    Adoptive cell transfer experiments can be used to study the roles of cell trafficking molecules on the migratory behavior of specific immune cell populations in vivo. Chemoattractants and their G protein-coupled seven-transmembrane-spanning receptors regulate migration of cells in vivo, and dysregulated expression of chemoattractants and their receptors is implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. We have used adoptive neutrophil transfer to define the contributions of chemoattractant receptors, cytokines, and activation receptors expressed on neutrophils that critically regulate their entry into the inflamed joint. In this review, we describe the procedure of neutrophil adoptive transfer to study the influence of neutrophil-specific receptors or mediators upon the their recruitment into the joint using the K/BxN model of inflammatory arthritis as a model of how adoptive cell transfer studies can be used to study immune cell migration in vivo.

  10. Infrared neural stimulation of human spinal nerve roots in vivo

    PubMed Central

    Cayce, Jonathan M.; Wells, Jonathon D.; Malphrus, Jonathan D.; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B.; Konrad, Peter E.; Jansen, E. Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Abstract. Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23  J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09  J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID:26157986

  11. Aspartame induces angiogenesis in vitro and in vivo models.

    PubMed

    Yesildal, F; Aydin, F N; Deveci, S; Tekin, S; Aydin, I; Mammadov, R; Fermanli, O; Avcu, F; Acikel, C H; Ozgurtas, T

    2015-03-01

    Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation (p < 0.001). In addition, in vivo rat model of skin wound-healing study showed that aspartame group had better healing than control group, and this was statistically significant at p < 0.05. There was a slight proliferative effect of aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases.

  12. In vivo imaging of IFT in Chlamydomonas flagella.

    PubMed

    Lechtreck, Karl F

    2013-01-01

    Intraflagellar transport (IFT) is a specialized intracellular transport which is required for the assembly and maintenance of cilia and eukaryotic flagella. IFT protein particles move bidirectionally along the flagella in the space between the flagellar membrane and the axonemal doublets. The particles consist of more than 20 different polypeptides and are transported by kinesin-2 from the cell body to the flagellar tip and by cytoplasmic dynein back to the cell body. Chlamydomonas reinhardtii is unique in that IFT can be visualized by two distinct microscopic approaches: differential interference contrast (DIC) and tracking of fluorescently tagged IFT proteins. In vivo imaging of IFT is critical to determine, for example, the role of individual proteins in the IFT pathway and how flagellar proteins are transported by IFT. Here, the microscopic requirements and the procedures for the imaging of IFT by DIC and by total internal reflection fluorescence microscopy will be described. Kymograms, graphical representations of spatial position over time, provide a convenient way to analyze in vivo recordings of IFT. In the future, multicolor in vivo imaging of IFT and its cargoes will be used to understand how flagella are assembled, maintained, and repaired.

  13. Circulation times of cancer cells by in vivo flow cytometry

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Li, Yan; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. Hepatocellular carcinoma may metastasize to lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed. A recently developed "in vivo flow cytometer" combined with real-time confocal fluorescence imaging are used to assess spreading and the circulation kinetics of liver tumor cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labeled cells in vivo in real time without extracting blood sample. We have measured the depletion kinetics of two related human HCC cell lines, high-metastatic HCCLM3 cells and low-metastatic HepG2 cells, which were from the same origin and obtained by repetitive screenings in mice. >60% HCCLM3 cells are depleted within the first hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In comparison, <40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide insights into early metastasis processes.

  14. Systemic Inhibition of CREB is Well-tolerated in vivo

    PubMed Central

    Li, Bingbing X.; Gardner, Ryan; Xue, Changhui; Qian, David Z.; Xie, Fuchun; Thomas, George; Kazmierczak, Steven C.; Habecker, Beth A.; Xiao, Xiangshu

    2016-01-01

    cAMP-response element binding protein (CREB) is a nuclear transcription factor activated by multiple extracellular signals including growth factors and hormones. These extracellular cues activate CREB through phosphorylation at Ser133 by various protein serine/threonine kinases. Once phosphorylated, it promotes its association with transcription coactivators CREB-binding protein (CBP) and its paralog p300 to activate CREB-dependent gene transcription. Tumor tissues of different origins have been shown to present overexpression and/or overactivation of CREB, indicating CREB as a potential cancer drug target. We previously identified 666-15 as a potent inhibitor of CREB with efficacious anti-cancer activity both in vitro and in vivo. Herein, we investigated the specificity of 666-15 and evaluated its potential in vivo toxicity. We found that 666-15 was fairly selective in inhibiting CREB. 666-15 was also found to be readily bioavailable to achieve pharmacologically relevant concentrations for CREB inhibition. Furthermore, the mice treated with 666-15 showed no evidence of changes in body weight, complete blood count, blood chemistry profile, cardiac contractility and tissue histologies from liver, kidney and heart. For the first time, these results demonstrate that pharmacological inhibition of CREB is well-tolerated in vivo and indicate that such inhibitors should be promising cancer therapeutics. PMID:27694829

  15. Favipiravir elicits antiviral mutagenesis during virus replication in vivo

    PubMed Central

    Arias, Armando; Thorne, Lucy; Goodfellow, Ian

    2014-01-01

    Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses. DOI: http://dx.doi.org/10.7554/eLife.03679.001 PMID:25333492

  16. Organelle acidification negatively regulates vacuole membrane fusion in vivo

    PubMed Central

    Desfougères, Yann; Vavassori, Stefano; Rompf, Maria; Gerasimaite, Ruta; Mayer, Andreas

    2016-01-01

    The V-ATPase is a proton pump consisting of a membrane-integral V0 sector and a peripheral V1 sector, which carries the ATPase activity. In vitro studies of yeast vacuole fusion and evidence from worms, flies, zebrafish and mice suggested that V0 interacts with the SNARE machinery for membrane fusion, that it promotes the induction of hemifusion and that this activity requires physical presence of V0 rather than its proton pump activity. A recent in vivo study in yeast has challenged these interpretations, concluding that fusion required solely lumenal acidification but not the V0 sector itself. Here, we identify the reasons for this discrepancy and reconcile it. We find that acute pharmacological or physiological inhibition of V-ATPase pump activity de-acidifies the vacuole lumen in living yeast cells within minutes. Time-lapse microscopy revealed that de-acidification induces vacuole fusion rather than inhibiting it. Cells expressing mutated V0 subunits that maintain vacuolar acidity were blocked in this fusion. Thus, proton pump activity of the V-ATPase negatively regulates vacuole fusion in vivo. Vacuole fusion in vivo does, however, require physical presence of a fusion-competent V0 sector. PMID:27363625

  17. Single-cell analysis of endothelial morphogenesis in vivo.

    PubMed

    Yu, Jianxin A; Castranova, Daniel; Pham, Van N; Weinstein, Brant M

    2015-09-01

    Vessel formation has been extensively studied at the tissue level, but the difficulty in imaging the endothelium with cellular resolution has hampered study of the morphogenesis and behavior of endothelial cells (ECs) in vivo. We are using endothelial-specific transgenes and high-resolution imaging to examine single ECs in zebrafish. By generating mosaics with transgenes that simultaneously mark endothelial nuclei and membranes we are able to definitively identify and study the morphology and behavior of individual ECs during vessel sprouting and lumen formation. Using these methods, we show that developing trunk vessels are composed of ECs of varying morphology, and that single-cell analysis can be used to quantitate alterations in morphology and dynamics in ECs that are defective in proper guidance and patterning. Finally, we use single-cell analysis of intersegmental vessels undergoing lumen formation to demonstrate the coexistence of seamless transcellular lumens and single or multicellular enclosed lumens with autocellular or intercellular junctions, suggesting that heterogeneous mechanisms contribute to vascular lumen formation in vivo. The tools that we have developed for single EC analysis should facilitate further rigorous qualitative and quantitative analysis of EC morphology and behavior in vivo.

  18. A guide to studying human hair follicle cycling in vivo

    PubMed Central

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A.; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan

    2015-01-01

    Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. PMID:26763421

  19. A Historically Significant Shield for In Vivo Measurements

    SciTech Connect

    Lynch, Timothy P.

    2007-08-01

    Due to the ubiquitous nature of ionizing radiation, in vivo measurement systems designed to measure low levels of radionuclides in people are usually enclosed within a high density shield. Lead, steel, earth, and water are just some of the materials that have been and are being used to shield the detectors from radiations of cosmic, atmospheric, and terrestrial origin. At many Department of Energy sites, the counting room shields are constructed of pre-world War II steel to reduce the background levels to achieve measurements with low minimum detectable activities (MDA). This is one example of what is commonly called low background steel in the in vivo industry vernacular. The name arises from the fact the steel was manufactured prior to the beginning of atmospheric testing of nuclear weapons in the 1940s. Consequently, the steel is not likely to be contaminated with fission or activation products from fallout. For high energy photons (600 keV In Vivo Radioassay and Research Facility (IVRRF) in Richland, Washington.

  20. In vivo engineering of organs: the bone bioreactor.

    PubMed

    Stevens, Molly M; Marini, Robert P; Schaefer, Dirk; Aronson, Joshua; Langer, Robert; Shastri, V Prasad

    2005-08-09

    Treatment of large defects requires the harvest of fresh living bone from the iliac crest. Harvest of this limited supply of bone is accompanied by extreme pain and morbidity. This has prompted the exploration of other alternatives to generate new bone using traditional principles of tissue engineering, wherein harvested cells are combined with porous scaffolds and stimulated with exogenous mitogens and morphogens in vitro and/or in vivo. We now show that large volumes of bone can be engineered in a predictable manner, without the need for cell transplantation and growth factor administration. The crux of the approach lies in the deliberate creation and manipulation of an artificial space (bioreactor) between the tibia and the periosteum, a mesenchymal layer rich in pluripotent cells, in such a way that the body's healing mechanism is leveraged in the engineering of neotissue. Using the "in vivo bioreactor" in New Zealand White rabbits, we have engineered bone that is biomechanically identical to native bone. The neobone formation followed predominantly an intramembraneous path, with woven bone matrix subsequently maturing into fully mineralized compact bone exhibiting all of the histological markers and mechanical properties of native bone. We harvested the bone after 6 weeks and transplanted it into contralateral tibial defects, resulting in complete integration after 6 weeks with no apparent morbidity at the donor site. Furthermore, in a proof-of-principle study, we have shown that by inhibiting angiogenesis and promoting a more hypoxic environment within the "in vivo bioreactor space," cartilage formation can be exclusively promoted.

  1. Resurrection of DNA Function In Vivo from an Extinct Genome

    PubMed Central

    Pask, Andrew J.; Behringer, Richard R.; Renfree, Marilyn B.

    2008-01-01

    There is a burgeoning repository of information available from ancient DNA that can be used to understand how genomes have evolved and to determine the genetic features that defined a particular species. To assess the functional consequences of changes to a genome, a variety of methods are needed to examine extinct DNA function. We isolated a transcriptional enhancer element from the genome of an extinct marsupial, the Tasmanian tiger (Thylacinus cynocephalus or thylacine), obtained from 100 year-old ethanol-fixed tissues from museum collections. We then examined the function of the enhancer in vivo. Using a transgenic approach, it was possible to resurrect DNA function in transgenic mice. The results demonstrate that the thylacine Col2A1 enhancer directed chondrocyte-specific expression in this extinct mammalian species in the same way as its orthologue does in mice. While other studies have examined extinct coding DNA function in vitro, this is the first example of the restoration of extinct non-coding DNA and examination of its function in vivo. Our method using transgenesis can be used to explore the function of regulatory and protein-coding sequences obtained from any extinct species in an in vivo model system, providing important insights into gene evolution and diversity. PMID:18493600

  2. Portable XRF Technology to Quantify Pb in Bone In Vivo

    PubMed Central

    Specht, Aaron James; Weisskopf, Marc; Nie, Linda Huiling

    2014-01-01

    Lead is a ubiquitous toxicant. Bone lead has been established as an important biomarker for cumulative lead exposures and has been correlated with adverse health effects on many systems in the body. K-shell X-ray fluorescence (KXRF) is the standard method for measuring bone lead, but this approach has many difficulties that have limited the widespread use of this exposure assessment method. With recent advancements in X-ray fluorescence (XRF) technology, we have developed a portable system that can quantify lead in bone in vivo within 3 minutes. Our study investigated improvements to the system, four calibration methods, and system validation for in vivo measurements. Our main results show that the detection limit of the system is 2.9 ppm with 2 mm soft tissue thickness, the best calibration method for in vivo measurement is background subtraction, and there is strong correlation between KXRF and portable LXRF bone lead results. Our results indicate that the technology is ready to be used in large human population studies to investigate adverse health effects of lead exposure. The portability of the system and fast measurement time should allow for this technology to greatly advance the research on lead exposure and public/environmental health. PMID:26317033

  3. Rod-shaped nanocrystals elicit neuronal activity in vivo.

    PubMed

    Malvindi, Maria Ada; Carbone, Luigi; Quarta, Alessandra; Tino, Angela; Manna, Liberato; Pellegrino, Teresa; Tortiglione, Claudia

    2008-10-01

    The development of novel nanomaterials has raised great interest in efforts to evaluate their effect on biological systems, ranging from single cells to whole animals. In particular, there exists an open question regarding whether nanoparticles per se can elicit biological responses, which could interfere with the phenomena they are intended to measure. Here it is reported that challenging the small cnidaria Hydra vulgaris in vivo with rod-shaped semiconductor nanoparticles, also known as quantum rods (QRs), results in an unexpected tentacle-writhing behavior, which is Ca(2+) dependent and relies on the presence of tentacle neurons. Due to the absence of surface functionalization of the QRs with specific ligands, and considering that spherical nanoparticles with same composition as the QRs fail to induce any in vivo behavior on the same experimental model, it is suggested that unique shape-tunable electrical properties of the QRs may account for the neuronal stimulation. This model system may represent a widely applicable tool for screening neuronal response to nanoparticles in vivo.

  4. mito-QC illuminates mitophagy and mitochondrial architecture in vivo

    PubMed Central

    McWilliams, Thomas G.; Allen, George F.G.; Tamjar, Jevgenia; Thomson, Calum; Muqit, Miratul M.K.

    2016-01-01

    Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities. PMID:27458135

  5. Infrared neural stimulation of human spinal nerve roots in vivo.

    PubMed

    Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

  6. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  7. In Vivo Monocyte Tropism of Pathogenic Feline Immunodeficiency Viruses

    PubMed Central

    Dow, Steven W.; Mathiason, Candace K.; Hoover, Edward A.

    1999-01-01

    Virus-infected monocytes rarely are detected in the bloodstreams of animals or people infected with immunodeficiency-inducing lentiviruses, yet tissue macrophages are thought to be a major reservoir of virus-infected cells in vivo. We have identified feline immunodeficiency virus (FIV) clinical isolates that are pathogenic in cats and readily transmitted vertically. We report here that five of these FIV isolates are highly monocytotropic in vivo. However, while FIV-infected monocytes were numerous in the blood of experimentally infected cats, viral antigen was not detectable in freshly isolated cells. Only after a short-term (at least 12-h) in vitro monocyte culture were FIV antigens detectable (by immunocytochemical analysis or enzyme-linked immunosorbent assay). In vitro experiments suggested that monocyte adherence provided an important trigger for virus antigen expression. In the blood of cats infected with a prototype monocytotropic isolate (FIV subtype B strain 2542), infected monocytes appeared within 2 weeks, correlating with high blood mononuclear-cell-associated viral titers and CD4 cell depletion. By contrast, infected monocytes could not be detected in the blood of cats infected with a less pathogenic FIV strain (FIV subtype A strain Petaluma). We concluded that some strains of FIV are monocytotropic in vivo. Moreover, this property may relate to virus virulence, vertical transmission, and infection of tissue macrophages. PMID:10400783

  8. In Vivo Flow Cytometry of Circulating Tumor-Associated Exosomes

    PubMed Central

    Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Jamshidi-Parsian, Azemat; Kore, Rajshekhar A.

    2016-01-01

    Circulating tumor cells (CTCs) demonstrated the potential as prognostic markers of metastatic development. However, the incurable metastasis can already be developed at the time of initial diagnosis with the existing CTC assays. Alternatively, tumor-associated particles (CTPs) including exosomes can be a more valuable prognostic marker because they can be released from the primary tumor long before CTCs and in larger amount. However, little progress has been made in high sensitivity detection of CTPs, especially in vivo. We show here that in vivo integrated photoacoustic (PA) and fluorescence flow cytometry (PAFFC) platform can provide the detection of melanoma and breast-cancer-associated single CTPs with endogenously expressed melanin and genetically engineered proteins or exogenous dyes as PA and fluorescent contrast agents. The two-beam, time-of-light PAFFC can measure the sizes of CTCs and CTPs and identify bulk and rolling CTCs and CTC clusters, with no influence on blood flow instability. This technique revealed a higher concentration of CTPs than CTCs at an early cancer stage. Because a single tumor cell can release many CTPs and in vivo PAFFC can examine the whole blood volume, PAFFC diagnostic platform has the potential to dramatically improve (up to 105-fold) the sensitivity of cancer diagnosis. PMID:27965916

  9. Novel in vivo techniques to visualize kidney anatomy and function.

    PubMed

    Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

    2015-07-01

    Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

  10. Visualization of GFP-expressing tumors and metastasis in vivo.

    PubMed

    Hoffman, R M

    2001-05-01

    We have developed mouse models of metastatic cancer with genetically fluorescent tumors that can be imaged in fresh tissue, in situ, as well as externally. To achieve this capability, we have transduced the green fluorescent protein (GFP) gene, cloned from the bioluminescent jellyfish Aequorea victoria, into a series of human and rodent cancer cell lines that were selected in vitro to stably express GFP in vivo after transplantation to metastatic rodent models. Techniques were also developed for transduction of tumors by GFP in vivo. With this fluorescent tool, we detected and visualized for the first time tumors and metastasis in fresh viable tissue or in situ in host organs down to the single-cell level. GFP tumors on the colon, prostate, breast, brain, liver, lymph nodes, lung, pancreas, bone, and other organs can also be visualized externally, transcutaneously by quantitative whole-body fluorescence optical imaging. Real-time tumor and metastatic growth and angiogenesis and inhibition by representative drugs can be imaged and quantified for rapid antitumor, antimetastatic, and antiangiogenesis drug screening. The GFP-transfected tumor cells enabled a fundamental advance in the visualization of tumor growth and metastasis in real time in vivo.

  11. An in vivo model for evaluation of the postantibiotic effect.

    PubMed

    Odenholt, I; Holm, S E; Cars, O

    1988-01-01

    A new experimental model to evaluate the postantibiotic effect (PAE) in vivo was developed using subcutaneously implanted tissue cages in rabbits with normal host defence mechanisms. The rabbits received benzylpenicillin i.v. in a dose giving a free penicillin concentration of 10 X MIC in the tissue cage fluid (TCF). A log-phase suspension of group A streptococci was injected into the tissue cages exposing them to penicillin in vivo. After 2 h bacterial samples were withdrawn, treated with penicillinase and transferred to 2 tissue cages in untreated rabbits. Simultaneously, unexposed streptococci were implanted in 2 other cages in the same animals. By repeated sampling of TCF, growth curves of the streptococci exposed to penicillin and the controls could be compared and a PAE of 1.6-2.4 h demonstrated. The PAE was of the same magnitude as that found in vitro. The model has several advantages for the demonstration of PAE in vivo: repeated samplings are easy to perform percutaneously, the effect of subinhibitory antibiotic concentrations are avoided, interindividual variations are eliminated since each animal is its own control, and the experiments can be performed in animals with undisturbed host defence mechanisms.

  12. In vivo iontophoretic delivery of salmon calcitonin across microporated skin.

    PubMed

    Vemulapalli, Viswatej; Bai, Yun; Kalluri, Haripriya; Herwadkar, Anushree; Kim, Hyun; Davis, Shawn P; Friden, Phil M; Banga, Ajay K

    2012-08-01

    The purpose of this study was to determine the effect of microneedle (MN) technology and its combination with iontophoresis (ITP) on the in vivo transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 µm) were used to porate skin prior to application of the drug, with or without ITP. Micropores created by maltose MNs were characterized by histological sectioning and calcein imaging studies, which indicated uniformity of the created micropores. In vivo studies were performed in hairless rats to assess the degree of enhancement achieved by ITP (0.2 mA/cm² for 1 h), MNs (81 MNs), and their combination. In vivo studies indicate a serum maximal concentration of 0.61 ± 0.42 ng/mL, 1.79 ± 0.72 ng/mL, and 5.51 ± 0.32 ng/mL for ITP, MNs, and combination treatment, respectively. MN treatment alone increased serum concentration 2.5-fold and the combination treatment increased the concentration ninefold as compared with iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in the highest delivery of sCT and therapeutic levels were achieved within 5 min of administration.

  13. Effect of desipramine on dopamine receptor binding in vivo

    SciTech Connect

    Suhara, Tetsuya Jikei Univ., Tokyo ); Inoue, Osamu; Kobayasi, Kaoru )

    1990-01-01

    Effect of desipramine on the in vivo binding of {sup 3}H-SCH23390 and {sup 3}H-N-methylspiperone ({sup 3}H-NMSP) in mouse striatum was studied. The ratio of radioactivity in the striatum to that in the cerebellum at 15 min after i.v. injection of {sup 3}H-SCH23390 or 45 min after injection of {sup 3}H-NMSP were used as indices of dopamine D1 or D2 receptor binding in vivo, respectively. In vivo binding of D1 and D2 receptors was decreased in a dose-dependent manner by acute treatment with desipramine (DMI). A saturation experiment suggested that the DMI-induced reduction in the binding was mainly due to the decrease in the affinity of both receptors. No direct interactions between the dopamine receptors and DMI were observed in vitro by the addition of 1 mM of DMI into striatal homogenate. Other antidepressants such as imipramine, clomipramine, maprotiline and mianserin also decreased the binding of dopamine D1 and D2 receptors. The results indicated an important role of dopamine receptors in the pharmacological effect of antidepressants.

  14. Gene repression by minimal lac loops in vivo.

    PubMed

    Bond, Laura M; Peters, Justin P; Becker, Nicole A; Kahn, Jason D; Maher, L James

    2010-12-01

    The inflexibility of double-stranded DNA with respect to bending and twisting is well established in vitro. Understanding apparent DNA physical properties in vivo is a greater challenge. Here, we exploit repression looping with components of the Escherichia coli lac operon to monitor DNA flexibility in living cells. We create a minimal system for testing the shortest possible DNA repression loops that contain an E. coli promoter, and compare the results to prior experiments. Our data reveal that loop-independent repression occurs for certain tight operator/promoter spacings. When only loop-dependent repression is considered, fits to a thermodynamic model show that DNA twisting limits looping in vivo, although the apparent DNA twist flexibility is 2- to 4-fold higher than in vitro. In contrast, length-dependent resistance to DNA bending is not observed in these experiments, even for the shortest loops constraining <0.4 persistence lengths of DNA. As observed previously for other looping configurations, loss of the nucleoid protein heat unstable (HU) markedly disables DNA looping in vivo. Length-independent DNA bending energy may reflect the activities of architectural proteins and the structure of the DNA topological domain. We suggest that the shortest loops are formed in apical loops rather than along the DNA plectonemic superhelix.

  15. Die casting die deflections: Prediction and attenuation. Final report, July 1, 1995--September 30, 1997

    SciTech Connect

    Miller, R.Allen; Ahuett-Garza, Horacio; Choudhury, Aswin K.; Dedhia, Sanjay

    1998-05-01

    The objective of this work was to develop and test die casting design evaluation techniques based on the visualization of geometric data that is related to potential defects or problems. Specifically, thickness information is used to provide insight into potential thermal problems in the part and die. Distance from the gate and a special type of animation of the fill pattern is used to provide an assessment of gate, vent and overflow locations. Techniques have been developed to convert part design information in the form of STL files to a volume-based representation called a voxel model. The use of STL files makes the process CAD system independent. Once in voxel form, methods that were developed in this work are used to identify thick regions in the part, thin regions in the part and/or die, distance from user specified entry locations (gates), and the qualitative depiction of the fill pattern. The methods were tested with a prototype implementation on the UNIX platform. The results of comparisons with numerical simulation and field reported defects were surprisingly good. The fill-related methods were also compared against short-shots and a water analog study using high speed video. The report contains the results of the testing plus detailed background material on the construction of voxel models, the methods used for displaying results, and the computational geometric reasoning methods used to create die casting-related information from the voxel model for display to the user.

  16. [From absolute necessity of dying to preventive planning of dying? The change of social and medicine debates on dying in the 1980s].

    PubMed

    Jordan, I

    2010-04-01

    International euthanasia debates focussing on "autonomous dying" in the 1980s corresponded with a general change in the health-care system: availability of new technical means with an analogous medical-ethic understanding of human suffering and dying. This change is part of a general development from "passive health consumption" to "active prevention" in our society.

  17. The dying role: its relevance to improved patient care.

    PubMed

    Noyes, R; Clancy, J

    1977-02-01

    Society is failing to meet the obligation it has to its dying members. Persons with terminal illnesses suffer isolation and neglect in hospitals, receive overzealous treatment by physicians, and are kept in ignorance of their situation by families and medical personnel. Evidence for these statements has come from observers of the medical care system and from dying patients themselves (Kübler-Ross, 1969; Reynolds and Kalish, 1974; Sudnow, 1967); In the nineteenth century it was common for persons to die in the familiar environs of their homes, surrounded by grieving families from whom they parted in a meaningful manner (Blauner, 1966). Dying persons of today no longer fill a well-defined social role. Instead, the distinction between the roles of sick and dying persons has been lost and, in the resulting confusion, the care of dying people has suffered. The purpose of this article is to clarify the distinction between the dying and sick roles, identify the signs of existing role confusion, suggest ways in which this confusion may be corrected, and show how reestablishment of the dying role can result in improved care of dying people. The important part physicians play in defining sick and dying roles will be emphasized.

  18. The Dying Role: Its Relevance to Improved Patient Care.

    PubMed

    Noyes, Russell; Clancy, John

    2016-01-01

    SOCIETY is failing to meet the obligation it has to its dying members. Persons with terminal illnesses suffer isolation and neglect in hospitals, receive overzealous treatment by physicians, and are kept in ignorance of their situation by families and medical personnel. Evidence for these statements has come from observers of the medical care system and from dying patients themselves (Kübler-Ross, 1969; Reynolds and Kalish, 1974; Sudnow, 1967). In the nineteenth century it was common for persons to die in the familiar environs of their homes, surrounded by grieving families from whom they parted in a meaningful manner (Blauner, 1966). Dying persons of today no longer fill a well-defined social role. Instead, the distinction between the roles of sick and dying persons has been lost and, in the resulting confusion, the care of dying people has suffered. The purpose of this article is to clarify the distinction between the dying and sick roles, identify the signs of existing role confusion, suggest ways in which this confusion may be corrected, and show how reestablishment of the dying role can result in improved care of dying people. The important part physicians play in defining sick and dying roles will be emphasized.

  19. In vivo Efficacy and Pharmacokinetics of Optimized Apidaecin Analogs

    PubMed Central

    Schmidt, Rico; Knappe, Daniel; Wende, Elisabeth; Ostorházi, Eszter; Hoffmann, Ralf

    2017-01-01

    Proline-rich antimicrobial peptides (PrAMPs) represent promising alternative therapeutic options for the treatment of multidrug-resistant bacterial infections. PrAMPs are predominantly active against Gram-negative bacteria by inhibiting protein expression via at least two different modes of action, i.e., blocking the ribosomal exit tunnel of 70S ribosomes (oncocin-type binding) or inhibiting the assembly of the 50S ribosomal subunit (apidaecin-type binding). The in vivo efficacy and favorable biodistribution of oncocins confirmed the therapeutic potential of short PrAMPs for the first time, whereas the in vivo evaluation of apidaecins is still limited despite the promising efficacy of apidaecin-analog Api88 in an intraperitoneal murine infection model. Here, the in vivo efficacy of apidaecin-analog Api137 was studied, which rescued all NMRI mice from a lethal intraperitoneal infection with E. coli ATCC 25922 when administered three times intraperitoneal at doses of 0.6 mg/kg starting 1 h after infection. When Api88 and Api137 were administered intravenous or intraperitoneal at doses of 5 and 20 mg/kg, their plasma levels were similarly low (<3 μg/mL) and four-fold lower than for oncocin-analog Onc72. This contradicted earlier expectation based on the very low serum stability of Api88 with a half-life time of only ~5 min compared to ~6 and ~3 h for Api137 and Onc72, respectively. Pharmacokinetic data relying on a sensitive mass spectrometry method utilizing multiple reaction monitoring and isotope-labeled peptides revealed that Api88 and Api137 were present in blood, urine, and kidney, and liver homogenates at similar levels accompanied by the same major metabolites comprising residues 1–16 and 1–17. The pretended discrepancy was solved, when all peptides were incubated in peritoneal lavage. Api137 was rapidly degraded at the C-terminus, while Api88 was rather stable despite releasing the same degradation products. Onc72 was very stable explaining its higher

  20. In vivo quantification of magnetically labelled cells by MRI relaxometry.

    PubMed

    Gimenez, Ulysse; Lajous, Hélène; El Atifi, Michèle; Bidart, Marie; Auboiroux, Vincent; Fries, Pascal Henry; Berger, François; Lahrech, Hana

    2016-11-01

    Cellular MRI, which visualizes magnetically labelled cells (cells*), is an active research field for in vivo cell therapy and tracking. The simultaneous relaxation rate measurements (R2 *, R2 , R1 ) are the basis of a quantitative cellular MRI method proposed here. U937 cells were labelled with Molday ION Rhodamine B, a bi-functional superparamagnetic and fluorescent nanoparticle (U937*). U937* viability and proliferation were not affected in vitro. In vitro relaxometry was performed in a cell concentration range of [2.5 × 10(4) -10(8) ] cells/mL. These measurements show the existence of complementary cell concentration intervals where these rates vary linearly. The juxtaposition of these intervals delineates a wide cell concentration range over which one of the relaxation rates in a voxel of an in vivo image can be converted into an absolute cell concentration. The linear regime was found at high concentrations for R1 in the range of [10(6) - 2 × 10(8) ] cells/mL, at intermediate concentrations for R2 in [2.5 × 10(5) - 5 × 10(7) ] cells/mL and at low concentrations for R2 * in [8 × 10(4) - 5 × 10(6) ] cells/mL. In vivo relaxometry was performed in a longitudinal study, with labelled U937 cells injected into a U87 glioma mouse model. Using in vitro data, maps of in vivo U937* concentrations were obtained by converting one of the in vivo relaxation rates to cell concentration maps. MRI results were compared with the corresponding optical images of the same brains, showing the usefulness of our method to accurately follow therapeutic cell biodistribution in a longitudinal study. Results also demonstrate that the method quantifies a large range of magnetically labelled cells*. Copyright © 2016 John Wiley & Sons, Ltd.