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Sample records for growth cone neck

  1. Growth cone collapse assay.

    PubMed

    Cook, Geoffrey M W; Jareonsettasin, Prem; Keynes, Roger J

    2014-01-01

    The growth cone collapse assay has proved invaluable in detecting and purifying axonal repellents. Glycoproteins/proteins present in detergent extracts of biological tissues are incorporated into liposomes, added to growth cones in culture and changes in morphology are then assessed. Alternatively purified or recombinant molecules in aqueous solution may be added directly to the cultures. In both cases after a defined period of time (up to 1 h), the cultures are fixed and then assessed by inverted phase contrast microscopy for the percentage of growth cones showing a collapsed profile with loss of flattened morphology, filopodia, and lamellipodia.

  2. Mechanochemical regulation of growth cone motility

    PubMed Central

    Kerstein, Patrick C.; Nichol IV, Robert H.; Gomez, Timothy M.

    2015-01-01

    Neuronal growth cones are exquisite sensory-motor machines capable of transducing features contacted in their local extracellular environment into guided process extension during development. Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes. However, the environment also provides mechanical support for growth cone adhesion and traction forces that stabilize leading edge protrusions. Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance. In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis. PMID:26217175

  3. Substrate Deformation Predicts Neuronal Growth Cone Advance

    PubMed Central

    Athamneh, Ahmad I.M.; Cartagena-Rivera, Alexander X.; Raman, Arvind; Suter, Daniel M.

    2015-01-01

    Although pulling forces have been observed in axonal growth for several decades, their underlying mechanisms, absolute magnitudes, and exact roles are not well understood. In this study, using two different experimental approaches, we quantified retrograde traction force in Aplysia californica neuronal growth cones as they develop over time in response to a new adhesion substrate. In the first approach, we developed a novel method, to our knowledge, for measuring traction forces using an atomic force microscope (AFM) with a cantilever that was modified with an Aplysia cell adhesion molecule (apCAM)-coated microbead. In the second approach, we used force-calibrated glass microneedles coated with apCAM ligands to guide growth cone advance. The traction force exerted by the growth cone was measured by monitoring the microneedle deflection using an optical microscope. Both approaches showed that Aplysia growth cones can develop traction forces in the 100–102 nN range during adhesion-mediated advance. Moreover, our results suggest that the level of traction force is directly correlated to the stiffness of the microneedle, which is consistent with a reinforcement mechanism previously observed in other cell types. Interestingly, the absolute level of traction force did not correlate with growth cone advance toward the adhesion site, but the amount of microneedle deflection did. In cases of adhesion-mediated growth cone advance, the mean needle deflection was 1.05 ± 0.07 μm. By contrast, the mean deflection was significantly lower (0.48 ± 0.06 μm) when the growth cones did not advance. Our data support a hypothesis that adhesion complexes, which can undergo micron-scale elastic deformation, regulate the coupling between the retrogradely flowing actin cytoskeleton and apCAM substrates, stimulating growth cone advance if sufficiently abundant. PMID:26445437

  4. The cytoskeletons of isolated, neuronal growth cones.

    PubMed

    Gordon-Weeks, P R

    1987-06-01

    We have examined by electron microscopy the cytoskeletons of growth cones isolated from neonatal rat forebrain by the method of Gordon-Weeks and Lockerbie [Gordon-Weeks and Lockerbie (1984) Neuroscience 13, 119-136]. When fixed in suspension with conventional fixatives, isolated growth cones contain a central region filled with a branching system of smooth endoplasmic reticulum and a cortical region immediately beneath the plasma membrane that is relatively free of organelles and is composed of an amorphous granular cytoplasm. The filopodia of isolated growth cones are also devoid of organelles and contain a cytoplasm that is similar in appearance to that in the cortical region. No microtubules or neurofilaments have been found in these growth cones. When isolated growth cones were prepared for electron microscopy by a method which preserves actin filaments [Boyles, Anderson and Hutcherson (1985) J. Histochem. Cytochem. 33, 1116-1128], microfilaments were found throughout the cortical cytoplasm. In the filopodia, the microfilaments were bundled together and oriented longitudinally. Filopodial microfilament bundles often extended into the body of the growth cone and could traverse it completely. Inclusion of Triton X-100 (1% v/v) in the fixative solubilized the membranes and soluble cytoplasmic proteins of growth cones, allowing an unobscured view of the microfilament cytoskeleton including the core bundle of microfilaments in filopodia. Suspended within the cytoskeleton were the coats of coated vesicles. These were particularly numerous at the broad bases of filopodia. Microfilaments bound heavy meromyosin and were cytochalasin B (2.0 X 10(-7) M) sensitive. Individual microfilaments branched and within filopodia they were extensively cross-linked by thin (7 nm) filaments. Microtubules and neurofilaments were not seen in these cytoskeletons despite the fact that the fixative contained a Ca2+ chelator. When growth cones were preincubated in taxol (14 microM) their

  5. Regulated plasmalemmal expansion in nerve growth cones.

    PubMed

    Lockerbie, R O; Miller, V E; Pfenninger, K H

    1991-03-01

    To study the mechanisms underlying plasmalemmal expansion in the nerve growth cone, a cell-free assay was developed to quantify membrane addition, using ligand binding and sealed growth cone particles isolated by subcellular fractionation from fetal rat brain. Exposed versus total binding sites of 125I-wheat germ agglutinin were measured in the absence or presence of saponin, respectively, after incubation with various agents. Ca2(+)-ionophore A23187 in the presence of Ca2+ increases the number of binding sites (Bmax) but does not change their affinity (KD), indicating that new receptors appear on the plasma membrane. Similarly, membrane depolarization by high K+ or veratridine significantly induces, in a Ca2(+)-dependent manner, the externalization of lectin binding sites from an internal pool. Morphometric analysis of isolated growth cones indicates that A23187 and high K+ treatment cause a significant reduction in a specific cytoplasmic membrane compartment, thus confirming the lectin labeling results and identifying the plasmalemmal precursor. The isolated growth cones take up gamma-amino-butyric acid and serotonin, but show no evidence for Ca2(+)-dependent transmitter release so that transmitter exocytosis is dissociated from plasmalemmal expansion. The data demonstrate that plasmalemmal expansion in the growth cone is a regulated process and identify an internal pool of precursor membrane.

  6. Regulated plasmalemmal expansion in nerve growth cones

    PubMed Central

    1991-01-01

    To study the mechanisms underlying plasmalemmal expansion in the nerve growth cone, a cell-free assay was developed to quantify membrane addition, using ligand binding and sealed growth cone particles isolated by subcellular fractionation from fetal rat brain. Exposed versus total binding sites of 125I-wheat germ agglutinin were measured in the absence or presence of saponin, respectively, after incubation with various agents. Ca2(+)-ionophore A23187 in the presence of Ca2+ increases the number of binding sites (Bmax) but does not change their affinity (KD), indicating that new receptors appear on the plasma membrane. Similarly, membrane depolarization by high K+ or veratridine significantly induces, in a Ca2(+)-dependent manner, the externalization of lectin binding sites from an internal pool. Morphometric analysis of isolated growth cones indicates that A23187 and high K+ treatment cause a significant reduction in a specific cytoplasmic membrane compartment, thus confirming the lectin labeling results and identifying the plasmalemmal precursor. The isolated growth cones take up gamma-amino-butyric acid and serotonin, but show no evidence for Ca2(+)-dependent transmitter release so that transmitter exocytosis is dissociated from plasmalemmal expansion. The data demonstrate that plasmalemmal expansion in the growth cone is a regulated process and identify an internal pool of precursor membrane. PMID:1999470

  7. GABA release from mouse axonal growth cones

    PubMed Central

    Gao, Xiao-Bing; van den Pol, Anthony N

    2000-01-01

    Using developing hypothalamic neurons from transgenic mice that express high levels of green fluorescent protein in growing axons, and an outside-out patch from mature neuronal membranes that contain neurotransmitter receptors as a sensitive detector, we found that GABA is released by a vesicular mechanism from the growth cones of developing axons prior to synapse formation. A low level of GABA release occurs spontaneously from the growth cone, and this is substantially increased by evoked action potentials. Neurotransmitters such as acetylcholine can enhance protein kinase C (PKC) activity even prior to synapse formation; PKC activation caused a substantial increase in spontaneous GABA release from the growth cone, probably acting at the axon terminal. These data indicate that GABA is secreted from axons during a stage of neuronal development when GABA is excitatory, and that neuromodulators could alter GABA release from the growing axon, potentially enabling other developing neurons of different transmitter phenotype to modulate the early actions of GABA. PMID:10718743

  8. Measurements of growth cone adhesion to culture surfaces by micromanipulation

    PubMed Central

    1994-01-01

    Neurons were grown on plastic surfaces that were untreated, or treated with polylysine, laminin, or L1 and their growth cones were detached from their culture surface by applying known forces with calibrated glass needles. This detachment force was taken as a measure of the force of adhesion of the growth cone. We find that on all surfaces, lamellipodial growth cones require significantly greater detachment force than filopodial growth cones, but this differences is, in general, due to the greater area of lamellipodial growth cones compared to filopodial growth cones. That is, the stress (force/unit area) required for detachment was similar for growth cones of lamellipodial and filopodial morphology on all surfaces, with the exception of lamellipodial growth cones on L1-treated surfaces, which had a significantly lower stress of detachment than on other surfaces. Surprisingly, the forces required for detachment (760-3,340 mudynes) were three to 15 times greater than the typical resting axonal tension, the force exerted by advancing growth cones, or the forces of retraction previously measured by essentially the same method. Nor did we observe significant differences in detachment force among growth cones of similar morphology on different culture surfaces, with the exception of lamellipodial growth cones on L1-treated surfaces. These data argue against the differential adhesion mechanism for growth cone guidance preferences in culture. Our micromanipulations revealed that the most mechanically resistant regions of growth cone attachment were confined to quite small regions typically located at the ends of filopodia and lamellipodia. Detached growth cones remained connected to the substratum at these regions by highly elastic retraction fibers. The closeness of contact of growth cones to the substratum as revealed by interference reflection microscopy (IRM) did not correlate with our mechanical measurements of adhesion, suggesting that IRM cannot be used as a

  9. Local Protein Synthesis in Axonal Growth Cones

    PubMed Central

    Šatkauskas, Saulius

    2007-01-01

    While initially thought to be essentially a developmental characteristic observed in artificial in vitro models, local protein synthesis in growth cones has been described in the adult, and more interestingly, during nerve regeneration. This emerging field is under intense investigation, revealing new functions of localized protein synthesis that include axon guidance, growth cone adaptation and sensitivity modulation at intermediate targets or axon regeneration. Here, we will review these functions and provide a short survey of the current knowledge on mechanisms of mRNA transport and regulation of localized protein synthesis. In addition, we will consider what lessons can be learned from localized protein synthesis in dendrites and what developments can be expected next in the field. This latter question relates to the crucial point of which technical strategy to adopt for an ideal and pertinent analysis of the phenomenon. PMID:19262143

  10. Biochemical pharmacology of isolated neuronal growth cones: implications for synaptogenesis.

    PubMed

    Lockerbie, R O

    1990-01-01

    The neuronal growth cone is critical to the establishment of neuronal polarity through its motile, pathfinding and target recognition properties exhibited during synaptogenesis. Subcellular fractionation procedures yielding milligram quantities of isolated growth cones has allowed for biochemical and pharmacological investigation of intrinsic growth cone components that are likely to be involved in regulation of growth cone function in neuronal development. These 'mapping' studies of growth cone components are prerequisites to elucidating the mechanisms by which extracellular factors influence the motility, adhesion and directed growth of the growth cone. For example, neurotransmitters and polypeptide growth factors which have been shown in other systems to modulate growth cone behavior are presumed to act through receptors on the growth cone, inducing second-messenger molecule formation and consequent modification and regulation of proteins effecting the response(s) of the growth cone (i.e. proteins involved in motility, adhesion and membrane turnover). In a relatively short period of time, work with the isolated growth cone preparation has identified, in independent studies, many of the elements involved in this proposed scheme of events, including transmitter receptors, second-messenger cascades, and second-messenger post-translational modifications. An obvious future goal will be to analyze in more detail the intracellular events, and the relationships between them, in the growth cone and how they transmit extracellular signals into responses such as motility and adhesivity which underly the growth cone's synaptogenic properties. It is to be expected that much of this information will come forth from experimentation with the isolated growth cone preparation.

  11. Growth cone behavior and production of traction force

    PubMed Central

    1990-01-01

    The growth cone must push its substrate rearward via some traction force in order to propel itself forward. To determine which growth cone behaviors produce traction force, we observed chick sensory growth cones under conditions in which force production was accommodated by movement of obstacles in the environment, namely, neurites of other sensory neurons or glass fibers. The movements of these obstacles occurred via three, different, stereotyped growth cone behaviors: (a) filopodial contractions, (b) smooth rearward movement on the dorsal surface of the growth cone, and (c) interactions with ruffling lamellipodia. More than 70% of the obstacle movements were caused by filopodial contractions in which the obstacle attached at the extreme distal end of a filopodium and moved only as the filopodium changed its extension. Filopodial contractions were characterized by frequent changes of obstacle velocity and direction. Contraction of a single filopodium is estimated to exert 50-90 microdyn of force, which can account for the pull exerted by chick sensory growth cones. Importantly, all five cases of growth cones growing over the top of obstacle neurites (i.e., geometry that mimics the usual growth cone/substrate interaction), were of the filopodial contraction type. Some 25% of obstacle movements occurred by a smooth backward movement along the top surface of growth cones. Both the appearance and rate of movements were similar to that reported for retrograde flow of cortical actin near the dorsal growth cone surface. Although these retrograde flow movements also exerted enough force to account for growth cone pulling, we did not observe such movements on ventral growth cone surfaces. Occasionally obstacles were moved by interaction with ruffling lamellipodia. However, we obtained no evidence for attachment of the obstacles to ruffling lamellipodia or for directed obstacle movements by this mechanism. These data suggest that chick sensory growth cones move forward by

  12. The trip of the tip: understanding the growth cone machinery.

    PubMed

    Lowery, Laura Anne; Van Vactor, David

    2009-05-01

    The central component in the road trip of axon guidance is the growth cone, a dynamic structure that is located at the tip of the growing axon. During its journey, the growth cone comprises both 'vehicle' and 'navigator'. Whereas the 'vehicle' maintains growth cone movement and contains the cytoskeletal structural elements of its framework, a motor to move forward and a mechanism to provide traction on the 'road', the 'navigator' aspect guides this system with spatial bias to translate environmental signals into directional movement. The understanding of the functions and regulation of the vehicle and navigator provides new insights into the cell biology of growth cone guidance.

  13. Cytoskeletal remodeling during growth cone-target interactions

    PubMed Central

    1993-01-01

    Reorganization of the cytoskeleton of neuronal growth cones in response to environmental cues underlies the process of axonal guidance. Most previous studies addressing cytoskeletal changes during growth cone pathfinding have focused on the dynamics of a single cytoskeletal component. We report here an investigation of homophilic growth cone- target interactions between Aplysia bag cell neurons using digitally enhanced video microscopy, which addresses dynamic interactions between actin filaments and microtubules. After physical contact of a growth cone with a physiological target, mechanical coupling occurred after a delay; and then the growth cone exerted forces on and displaced the target object. Subsequent to coupling, F-actin accumulation was observed at the target contact zone, followed by preferential microtubule extension to the same site. After successful target interactions, growth cones typically moved off highly adhesive poly-L- lysine substrates into native target cell surfaces. These events were associated with modulation of both the direction and rate of neurite outgrowth: growth cone migration was typically reoriented to a trajectory along the target interaction axis and rates of advance increased by about one order of magnitude. Directed microtubule movements toward the contact site appeared to be F-actin dependent as target site-specific microtubule extension and bundling could be reversibly randomized by micromolar levels of cytochalasin B in a characteristic manner. Our results suggest that target contacts can induce focal F-actin assembly and reorganization which, in turn, guides target site-directed microtubule redistribution. PMID:8509456

  14. Coupled local translation and degradation regulate growth cone collapse

    PubMed Central

    Deglincerti, Alessia; Colak, Dilek; Hengst, Ulrich; Liu, Yaobin; Xu, Guoqiang; Jaffrey, Samie R.

    2015-01-01

    Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, while most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signaling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses. PMID:25901863

  15. Cinder cone growth modeled after Northeast crater, Mount Etna, Sicily

    NASA Technical Reports Server (NTRS)

    Mcgetchin, T. R.; Settle, M.; Chouet, B. A.

    1974-01-01

    The structure, physical properties of ejecta, ballistics, and growth of Northeast crater, a young pyroclastic cone that originated in 1911 near the summit of Mount Etna, Sicily, were studied in order to form a model of volcano cinder cone growth. Four stages of growth were discerned: (1) a simple cone; (2) a cone with an outward-dipping talus slope; (3) destruction of rounded rim by the inward migration of the upper edge of the talus pile; and (4) extension of limits of talus pile beyond the ballistic limit of ejecta trajectories. The model is used to predict the features of lunar and Martian cones, assuming that they erupted under conditions qualitatively similar to Etna's Northeast crater.

  16. Increase in Growth Cone Size Correlates with Decrease in Neurite Growth Rate

    PubMed Central

    Ren, Yuan

    2016-01-01

    Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L-lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 μm2. The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth. PMID:27274874

  17. ERM proteins regulate growth cone responses to Sema3A

    PubMed Central

    Mintz, C. David; Carcea, Ioana; McNickle, Daniel G.; Dickson, Tracey C.; Ge, Yongchao; Salton, Stephen R.J.; Benson, Deanna L.

    2008-01-01

    Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue, Sema3A. We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1 and its co-receptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A. PMID:18651636

  18. Lipid rafts mediate chemotropic guidance of nerve growth cones.

    PubMed

    Guirland, Carmine; Suzuki, Shingo; Kojima, Masami; Lu, Bai; Zheng, James Q

    2004-04-01

    Axon guidance requires signal transduction of extracellular cues through the plasma membrane for directional motility. Here we present evidence that cholesterol- and sphingolipid-enriched membrane microdomains (lipid rafts) mediate specific guidance responses of nerve growth cones. Disruption of lipid rafts by various approaches targeting cholesterol or gangliosides selectively abolished growth cone attraction and repulsion in BDNF and netrin-1 gradients, respectively, without affecting glutamate-induced attraction. Interestingly, local raft disruption on one side of the growth cone in bath BDNF or netrin-1 produced opposite turning responses to that induced by the gradients. Raft manipulation also blocked Semaphorin 3A-induced growth cone repulsion, inhibition, and collapse. Finally, guidance responses appeared to involve raft-dependent activation of p42/p44 MAPK and ligand-induced receptor recruitment to lipid rafts. Together with the observation of asymmetric receptor-raft associations at the growth cone in guidance gradients, our findings indicate that localized signaling through membrane rafts plays a role in mediating guidance actions of extracellular cues on developing axons. PMID:15066264

  19. Deformable planning CT to cone-beam CT image registration in head-and-neck cancer

    SciTech Connect

    Hou Jidong; Guerrero, Mariana; Chen, Wenjuan; D'Souza, Warren D.

    2011-04-15

    Purpose: The purpose of this work was to implement and validate a deformable CT to cone-beam computed tomography (CBCT) image registration method in head-and-neck cancer to eventually facilitate automatic target delineation on CBCT. Methods: Twelve head-and-neck cancer patients underwent a planning CT and weekly CBCT during the 5-7 week treatment period. The 12 planning CT images (moving images) of these patients were registered to their weekly CBCT images (fixed images) via the symmetric force Demons algorithm and using a multiresolution scheme. Histogram matching was used to compensate for the intensity difference between the two types of images. Using nine known anatomic points as registration targets, the accuracy of the registration was evaluated using the target registration error (TRE). In addition, region-of-interest (ROI) contours drawn on the planning CT were morphed to the CBCT images and the volume overlap index (VOI) between registered contours and manually delineated contours was evaluated. Results: The mean TRE value of the nine target points was less than 3.0 mm, the slice thickness of the planning CT. Of the 369 target points evaluated for registration accuracy, the average TRE value was 2.6{+-}0.6 mm. The mean TRE for bony tissue targets was 2.4{+-}0.2 mm, while the mean TRE for soft tissue targets was 2.8{+-}0.2 mm. The average VOI between the registered and manually delineated ROI contours was 76.2{+-}4.6%, which is consistent with that reported in previous studies. Conclusions: The authors have implemented and validated a deformable image registration method to register planning CT images to weekly CBCT images in head-and-neck cancer cases. The accuracy of the TRE values suggests that they can be used as a promising tool for automatic target delineation on CBCT.

  20. Clinical implementation of intraoperative cone-beam CT in head and neck surgery

    NASA Astrophysics Data System (ADS)

    Daly, M. J.; Chan, H.; Nithiananthan, S.; Qiu, J.; Barker, E.; Bachar, G.; Dixon, B. J.; Irish, J. C.; Siewerdsen, J. H.

    2011-03-01

    A prototype mobile C-arm for cone-beam CT (CBCT) has been translated to a prospective clinical trial in head and neck surgery. The flat-panel CBCT C-arm was developed in collaboration with Siemens Healthcare, and demonstrates both sub-mm spatial resolution and soft-tissue visibility at low radiation dose (e.g., <1/5th of a typical diagnostic head CT). CBCT images are available ~15 seconds after scan completion (~1 min acquisition) and reviewed at bedside using custom 3D visualization software based on the open-source Image-Guided Surgery Toolkit (IGSTK). The CBCT C-arm has been successfully deployed in 15 head and neck cases and streamlined into the surgical environment using human factors engineering methods and expert feedback from surgeons, nurses, and anesthetists. Intraoperative imaging is implemented in a manner that maintains operating field sterility, reduces image artifacts (e.g., carbon fiber OR table) and minimizes radiation exposure. Image reviews conducted with surgical staff indicate bony detail and soft-tissue visualization sufficient for intraoperative guidance, with additional artifact management (e.g., metal, scatter) promising further improvements. Clinical trial deployment suggests a role for intraoperative CBCT in guiding complex head and neck surgical tasks, including planning mandible and maxilla resection margins, guiding subcranial and endonasal approaches to skull base tumours, and verifying maxillofacial reconstruction alignment. Ongoing translational research into complimentary image-guidance subsystems include novel methods for real-time tool tracking, fusion of endoscopic video and CBCT, and deformable registration of preoperative volumes and planning contours with intraoperative CBCT.

  1. Ultra-short pulses to signal neuronal growth cone machinery

    NASA Astrophysics Data System (ADS)

    Mathew, Manoj; Amat-Roldan, Ivan; Andres, Rosa; Cormack, Iain G.; Artigas, David; Soriano, Eduardo; Loza-Alvarez, Pablo

    2007-02-01

    Measurable change in the sensory motor machinery of growth cones are induced by non contact femtosecond laser. The focused laser beam with an average power of 3 mW was positioned at some distance away from the closest fillopodia of cortical neurons from primary cell cultures (mice E15). By identifying a set of preliminary parameters we were able to statistically analyze the phenomenological behavior of the fillopodia and classify the effects different conditions of laser light has on the growth cone. Results show that fillopodia become significantly biased towards the focused femtosecond laser light. The same experiment performed with continuous wave (CW) produced results which were indistinguishable from the case where there is no laser light present (placebo condition) indicating no clear effects of the CW laser light on the fillopodia at a distance. These findings show the potential for ultrashort pulsed light to become a new type of pathfinding cue for neuronal growth cones.

  2. Variability and Reliabiltiy in Axon Growth Cone Navigation Decision Making

    NASA Astrophysics Data System (ADS)

    Garnelo, Marta; Ricoult, Sébastien G.; Juncker, David; Kennedy, Timothy E.; Faisal, Aldo A.

    2015-03-01

    The nervous system's wiring is a result of axon growth cones navigating through specific molecular environments during development. In order to reach their target, growth cones need to make decisions under uncertainty as they are faced with stochastic sensory information and probabilistic movements. The overall system therefore exhibits features of whole organisms (perception, decision making, action) in the subset of a single cell. We aim to characterise growth cone navigation in defined nano-dot guidance cue environments, by using the tools of computational neuroscience to conduct ``molecular psychophysics.'' We start with a generative model of growth cone behaviour and we 1. characterise sensory and internal sources of noise contributing to behavioural variables, by combining knowledge of the underlying stochastic dynamics in cue sensing and the growth of the cytoskeleton. This enables us to 2. produce bottom-up lower limit estimates of behavioural response reliability and visualise it as probability distributions over axon growth trajectories. Given this information we can match our in silico model's ``psychometric'' decision curves with empirical data. Finally we use a Monte-Carlo approach to predict response distributions of axon trajectories from our model.

  3. Neuronal growth cones respond to laser-induced axonal damage

    PubMed Central

    Wu, Tao; Mohanty, Samarendra; Gomez-Godinez, Veronica; Shi, Linda Z.; Liaw, Lih-Huei; Miotke, Jill; Meyer, Ronald L.; Berns, Michael W.

    2012-01-01

    Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single goldfish axons in vitro. The axons underwent a localized decrease in thickness (‘thinning’) within seconds. Analysis by fluorescence and transmission electron microscopy indicated that there was no gross rupture of the cell membrane. Mitochondrial transport along the axonal cytoskeleton immediately stopped at the damage site, but recovered over several minutes. Within seconds of damage nearby growth cones extended filopodia towards the injury and were often observed to contact the damaged site. Turning of the growth cone towards the injured axon also was observed. Repair of the laser-induced damage was evidenced by recovery of the axon thickness as well as restoration of mitochondrial movement. We describe a new process of growth cone response to damaged axons. This has been possible through the interface of optics (laser subcellular surgery), fluorescence and electron microscopy, and a goldfish retinal ganglion cell culture model. PMID:21831892

  4. Evaluation of the accuracy of Cone Beam Computerized Tomography (CBCT): medical imaging technology in head and neck reconstruction

    PubMed Central

    2013-01-01

    Background With the introduction, development and commercialization of Cone Beam Computerized Tomography (CBCT) technologies in the field of head and neck reconstruction, clinicians now have increased access to the technology. Given the growth of this new user group, there is an increasing concern regarding proper use, understanding, quality and patient safety. Methods The present study was carried out to evaluate data acquisition of CBCT medical imaging technology and the accuracy of the scanning at three different machine warming times. The study also compared the accuracy of CBCT at 0.2 mm slice thickness and Computerized Tomography (CT) at 1 mm slice thickness. A control model was CT scanned at five random intervals, at 1 mm slice thickness and CBCT scanned at specialized intervals, at 0.2 mm slice thickness. The data was then converted and imported into a software program where a digital registration procedure was used to compare the average deviations of the scanned models to the control. Results The study found that there was no statistically significant difference amongst the three CBCT machine warming times. There was a statistically significant difference between CT scanning with 1 mm slice thickness and CBCT scanning with 0.2 mm slice thickness. Conclusions The accuracy of the i-CAT CBCT scans used in the present study with a parameter at voxel size 0.2, will remain consistent and reliable at any warming stage. Also the difference between the CBCT i-CAT scans and the CT scans was not clinically significant based on suggested requirements of clinicians in head and neck reconstruction. PMID:23672880

  5. Filopodial dynamics and growth cone stabilization in Drosophila visual circuit development.

    PubMed

    Özel, Mehmet Neset; Langen, Marion; Hassan, Bassem A; Hiesinger, P Robin

    2015-10-29

    Filopodial dynamics are thought to control growth cone guidance, but the types and roles of growth cone dynamics underlying neural circuit assembly in a living brain are largely unknown. To address this issue, we have developed long-term, continuous, fast and high-resolution imaging of growth cone dynamics from axon growth to synapse formation in cultured Drosophila brains. Using R7 photoreceptor neurons as a model we show that >90% of the growth cone filopodia exhibit fast, stochastic dynamics that persist despite ongoing stepwise layer formation. Correspondingly, R7 growth cones stabilize early and change their final position by passive dislocation. N-Cadherin controls both fast filopodial dynamics and growth cone stabilization. Surprisingly, loss of N-Cadherin causes no primary targeting defects, but destabilizes R7 growth cones to jump between correct and incorrect layers. Hence, growth cone dynamics can influence wiring specificity without a direct role in target recognition and implement simple rules during circuit assembly.

  6. Growth Cone Biomechanics in Peripheral and Central Nervous System Neurons

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey; Koch, Daniel; Rosoff, Will; Geller, Herbert

    2012-02-01

    The growth cone, a highly motile structure at the tip of an axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth-cone mediated guidance. We have investigated neurite outgrowth, traction forces and cytoskeletal substrate coupling on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that the biomechanics of DRG neurons are dramatically different from hippocampal, with DRG neurons displaying relatively large, steady traction forces and maximal outgrowth and forces on substrates of intermediate stiffness, while hippocampal neurons display weak, intermittent forces and limited dependence of outgrowth and forces on substrate stiffness. DRG growth cones have slower rates of retrograde actin flow and higher density of localized paxillin (a protein associated with substrate adhesion complexes) compared to hippocampal neurons, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate coupling in DRG growth cones.

  7. A quantitative study of growth cone filopodial extension.

    PubMed

    Argiro, V; Bunge, M B; Johnson, M I

    1985-01-01

    The extension of filopodia from growth cones of regenerating neurites from rat superior cervical ganglion neurons in tissue culture was studied. Cultures were grown on a thin layer of fibrous collagen and maintained in a medium containing serum and nerve growth factor. Time-lapse cinematography and computer-assisted morphometry were used to observe and measure the kinetics of extension of individual filopodia. Filopodia extended from the growth cone margin, trailing neurite, or from each other. Frequently, extension was preceded by the appearance at the cone margin of a nodule of cytoplasm which appeared dense in phase-contrast optics. Branch points between adjacent extending filopodia remained fixed with respect to the growth cone while the filopodia lengthened. The rate of extension was maximum just after initiation (0.12 +/- 0.4 micron/sec; mean +/- SD; n = 36) and declined thereafter until the filopodium collapsed. This initial rate of extension was directly correlated with the eventual length of the filopodium (r = 0.67). Filopodia of growth cones arising from embryonic neurons exhibited higher initial extension rates (range: 0.07 to 0.20 micron/sec; mean = 0.13 micron/sec) than those of postnatal neurons (range: 0.01 to 0.13 micron/sec; mean = 0.09 micron/sec). These data are discussed in relation to a model proposed by Tilney and Inoue [1982] for the extension, by distal addition of G-actin to growing filaments, of another type of elongating process filled with microfilaments, the acrosomal process of Thyone sperm.

  8. The role of cytoskeleton in organizing growth cones: a microfilament- associated growth cone component depends upon microtubules for its localization

    PubMed Central

    1989-01-01

    We are interested in the relationship between the cytoskeleton and the organization of polarized cell morphology. We show here that the growth cones of hippocampal neurons in culture are specifically stained by a monoclonal antibody called 13H9. In other systems, the antigen recognized by 13H9 is associated with marginal bands of chicken erythrocytes and shows properties of both microtubule-and microfilament- associated proteins (Birgbauer, E., and F. Solomon. 1989 J. Cell Biol. 109:1609-1620). This dual nature is manifest in hippocampal neurons as well. At early stages after plating, the antibody stains the circumferential lamellipodia that mediate initial cell spreading. As processes emerge, 13H9 staining is heavily concentrated in the distal regions of growth cones, particularly in lamellipodial fans. In these cells, the 13H9 staining is complementary to the localization of assembled microtubules. It colocalizes partially, but not entirely, with phalloidin staining of assembled actin. Incubation with nocodazole rapidly induces microtubule depolymerization, which proceeds in the distal-to-proximal direction in the processes. At the same time, a rapid and dramatic redistribution of the 13H9 staining occurs; it delocalizes along the axon shaft, becoming clearly distinct from the phalloidin staining and always remaining distal to the receding front of assembled microtubules. After longer times without assembled microtubules, no staining of 13H9 can be detected. Removal of the nocodazole allows the microtubules to reform, in an ordered proximal-to- distal fashion. The 13H9 immunoreactivity also reappears, but only in the growth cones, not in any intermediate positions along the axon, and only after the reformation of microtubules is complete. The results indicate that the antigen recognized by 13H9 is highly concentrated in growth cones, closely associated with polymerized actin, and that its proper localization depends upon intact microtubules. PMID:2677024

  9. Uptake and release of [3H]GABA by growth cones isolated from neonatal rat brain.

    PubMed

    Gordon-Weeks, P R; Lockerbie, R O; Pearce, B R

    1984-11-23

    A subcellular fraction highly enriched in neuronal growth cones was isolated from 5-day-old rat forebrain by a recently described method. The growth cone fraction was shown to have a sodium- and temperature-dependent, high-affinity (Km = 4.4 microM) uptake system for [3H]GABA. Electron microscopic autoradiography confirmed that this uptake was into growth cones since only these structures were heavily labelled with silver grains. High potassium induced the release of newly accumulated [3H]GABA from the growth cone fraction, about half of which was Ca2+-dependent. The presence of uptake and release systems for GABA in growth cones may simply reflect the development of growth cones into nerve terminals. Alternatively, these observations may indicate a role for neurotransmitter release in synaptogenesis.

  10. Use of scanning ion conductance microscopy to guide and redirect neuronal growth cones.

    PubMed

    Pellegrino, Mario; Orsini, Paolo; De Gregorio, Francesca

    2009-07-01

    Scanning ion conductance microscopy has been applied to neuronal growth cones of the leech either to image or to stimulate them. Growth cone advance was recorded in non-contact mode using a 2% ion current decrease criterion for pipette-membrane distance control. We demonstrate effective growth cone remodelling using a 5% criterion (near-scanning). Recurrent line near-scanning aligned growth cone processes along the scan line. The new membrane protrusions, marked by DiI, started a few minutes after scanning onset and progressively grew in thickness. Using scanning patterns suitable for connecting distinct growth cones, new links were consistently developed. Although the underlying mechanism is still a matter for investigation, a mechanical perturbation produced by the moving probe appeared to induce the process formation. Thanks to its deterministic and interactive features, this novel approach to guiding growth cones is a promising way to develop networks of identified neurons as well as link them with artificial structures. PMID:19447298

  11. Radixin Is Involved in Lamellipodial Stability during Nerve Growth Cone Motility

    PubMed Central

    Castelo, Leslie; Jay, Daniel G.

    1999-01-01

    Immunocytochemistry and in vitro studies have suggested that the ERM (ezrin-radixin-moesin) protein, radixin, may have a role in nerve growth cone motility. We tested the in situ role of radixin in chick dorsal root ganglion growth cones by observing the effects of its localized and acute inactivation. Microscale chromophore-assisted laser inactivation (micro-CALI) of radixin in growth cones causes a 30% reduction of lamellipodial area within the irradiated region whereas all control treatments did not affect lamellipodia. Micro-CALI of radixin targeted to the middle of the leading edge often split growth cones to form two smaller growth cones during continued forward movement (>80%). These findings suggest a critical role for radixin in growth cone lamellipodia that is similar to ezrin function in pseudopodia of transformed fibroblasts. They are consistent with radixin linking actin filaments to each other or to the membrane during motility. PMID:10233159

  12. Integrins and cAMP mediate netrin-induced growth cone collapse

    PubMed Central

    Lemons, M.L.; Abanto, M.L.; Dambrouskas, N.; Clements, C.C.; DeLoughery, Z.; Garozzo, J.; Condic, M.L.

    2013-01-01

    Growth cones integrate a remarkably complex concert of chemical cues to guide axons to their appropriate destinations. Recent work suggests that integrins contribute to axon guidance by interacting with a wide range of extracellular molecules including axon guidance molecules, by mechanisms that are not fully understood. Here, we describe an interaction between integrins and netrin-1 in growth cones that contributes to growth cone collapse. Our data show that netrin-1 causes growth cone collapse in a substratum-specific manner and is integrin-dependent. Netrin-1 causes collapse of cultured chick dorsal root ganglion (DRG) growth cones extending on high levels of laminin-1 (LN) but not growth cones extending on low levels of LN or on fibronectin. Blocking integrin function significantly decreases netrin-induced growth cone collapse on high LN. Netrin-1 and integrins interact on growth cones; netrin-1 causes integrin activation, a conformational shift to a high ligand-affinity state. Netrin-1 directly binds to integrin α3 and α6 peptides, further suggesting a netrin-integrin interaction. Interestingly, our data reveal netrin-1 increases growth cone levels of cAMP in a substratum-specific manner and that netrin-induced growth cone collapse requires increased cAMP in combination with integrin activation. Manipulations that either decrease cAMP levels or integrin activation block netrin-induced collapse. These results imply a common mechanism for growth cone collapse and novel interactions between integrins, netrin-1 and cAMP that contribute to growth cone guidance. PMID:24001590

  13. Isolation and partial characterisation of neuronal growth cones from neonatal rat forebrain.

    PubMed

    Gordon-Weeks, P R; Lockerbie, R O

    1984-09-01

    We have devised a method for the isolation of viable neuronal growth cones from neonatal rat forebrain. The method involves differential and density gradient centrifugation and exploits the relatively low buoyant density (approximately 1.018 g/cm3) of growth cones. There are no known biochemical markers for growth cones and it was necessary therefore to monitor for their presence during the isolation using transmission electron microscopy. Several criteria were used to identify isolated growth cones including the presence of filopodia, an extensive system of branching, tubular smooth endoplasmic reticulum and a region rich in microfilaments subjacent to the plasma membrane. These morphological features are similar to those of growth cones identified unequivocally in intact developing brain and in tissue culture. Electron microscopical analysis showed that greater than 90% of membrane-bound, identifiable objects in one fraction were growth cones by these criteria. The major contaminant consisted of membrane sacs and vesicles of unidentified origin. There were only small amounts of isolated rough endoplasmic reticulum and mitochondria. Isolated growth cones were roughly spherical in shape with a diameter of 1.9 +/- 0.5 micron (mean +/- 1 SD). They usually contained mitochondria, large granular vesicles and small vesicles, and occasionally contained coated vesicles, lysosomes, lamellar bodies and multivesicular bodies, and only very rarely, intermediate filaments. Occasionally, growth cones had rudimentary synapses on them. The viability of isolated growth cones was investigated by observing their behaviour in short-term culture. After a few hours in culture on poly-D-lysine-coated coverslips, growth cones flattened down and extended filopodia-like processes. This behaviour was inhibited by cytochalasin B and reversibly by cold (4 degrees C). We conclude that physiologically active growth cones can be isolated rapidly and in large numbers by the method described here.

  14. Filopodial dynamics and growth cone stabilization in Drosophila visual circuit development

    PubMed Central

    Özel, Mehmet Neset; Langen, Marion; Hassan, Bassem A; Hiesinger, P Robin

    2015-01-01

    Filopodial dynamics are thought to control growth cone guidance, but the types and roles of growth cone dynamics underlying neural circuit assembly in a living brain are largely unknown. To address this issue, we have developed long-term, continuous, fast and high-resolution imaging of growth cone dynamics from axon growth to synapse formation in cultured Drosophila brains. Using R7 photoreceptor neurons as a model we show that >90% of the growth cone filopodia exhibit fast, stochastic dynamics that persist despite ongoing stepwise layer formation. Correspondingly, R7 growth cones stabilize early and change their final position by passive dislocation. N-Cadherin controls both fast filopodial dynamics and growth cone stabilization. Surprisingly, loss of N-Cadherin causes no primary targeting defects, but destabilizes R7 growth cones to jump between correct and incorrect layers. Hence, growth cone dynamics can influence wiring specificity without a direct role in target recognition and implement simple rules during circuit assembly. DOI: http://dx.doi.org/10.7554/eLife.10721.001 PMID:26512889

  15. Subcellular Profiling Reveals Distinct and Developmentally Regulated Repertoire of Growth Cone mRNAs

    PubMed Central

    Zivraj, Krishna H.; Tung, Yi Chun Loraine; Piper, Michael; Gumy, Laura; Fawcett, James W.; Yeo, Giles S. H.; Holt, Christine E.

    2013-01-01

    Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons, yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones. Here laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An unexpectedly large pool of mRNAs defined predominant pathways in protein synthesis, oxidative phosphorylation, cancer, neurological disease, and signaling. Comparative profiling of “young” (pathfinding) versus “old” (target-arriving) Xenopus growth cones revealed that the number and complexity of transcripts increases dramatically with age. Many presynaptic protein mRNAs are present exclusively in old growth cones, suggesting that functionally related sets of mRNAs are targeted to growth cones in a developmentally regulated way. Remarkably, a subset of mRNAs was significantly enriched in the growth cone compared with the axon compartment, indicating that mechanisms exist to localize mRNAs selectively to the growth cone. Furthermore, some receptor transcripts (e.g., EphB4), present exclusively in old growth cones, were equally abundant in young and old cell bodies, indicating that RNA trafficking from the soma is developmentally regulated. Our findings show that the mRNA repertoire in growth cones is regulated dynamically with age and suggest that mRNA localization is tailored to match the functional demands of the growing axon tip as it transforms into the presynaptic terminal. PMID:21084603

  16. Collapsin response mediator protein 4 regulates growth cone dynamics through the actin and microtubule cytoskeleton.

    PubMed

    Khazaei, Mohamad R; Girouard, Marie-Pier; Alchini, Ricardo; Ong Tone, Stephan; Shimada, Tadayuki; Bechstedt, Susanne; Cowan, Mitra; Guillet, Dominique; Wiseman, Paul W; Brouhard, Gary; Cloutier, Jean Francois; Fournier, Alyson E

    2014-10-24

    Coordinated control of the growth cone cytoskeleton underlies axon extension and guidance. Members of the collapsin response mediator protein (CRMP) family of cytosolic phosphoproteins regulate the microtubule and actin cytoskeleton, but their roles in regulating growth cone dynamics remain largely unexplored. Here, we examine how CRMP4 regulates the growth cone cytoskeleton. Hippocampal neurons from CRMP4-/- mice exhibited a selective decrease in axon extension and reduced growth cone area, whereas overexpression of CRMP4 enhanced the formation and length of growth cone filopodia. Biochemically, CRMP4 can impact both microtubule assembly and F-actin bundling in vitro. Through a structure function analysis of CRMP4, we found that the effects of CRMP4 on axon growth and growth cone morphology were dependent on microtubule assembly, whereas filopodial extension relied on actin bundling. Intriguingly, anterograde movement of EB3 comets, which track microtubule protrusion, slowed significantly in neurons derived from CRMP4-/- mice, and rescue of microtubule dynamics required CRMP4 activity toward both the actin and microtubule cytoskeleton. Together, this study identified a dual role for CRMP4 in regulating the actin and microtubule growth cone cytoskeleton. PMID:25225289

  17. Live cell imaging of neuronal growth cone motility and guidance in vitro

    PubMed Central

    Suter, Daniel M.

    2013-01-01

    Summary The neuronal growth cone, a highly motile structure at the tip of neuronal processes, is an excellent model system for studying directional cell movements. While biochemical and genetic approaches unveiled molecular interactions between ligand, receptor, signaling and cytoskeleton-associated proteins controlling axonal growth and guidance, in vitro live cell imaging has emerged as a crucial approach for dissecting cellular mechanisms of growth cone motility and guidance. Important insights into these mechanisms have been gained from studies using the large growth cones elaborated by Aplysia californica neurons, an outstanding model system for live cell imaging for a number of reasons. Identified neurons can be isolated and imaged at room temperature. Aplysia growth cones are 5–10 times larger than growth cones from other species, making them suitable for quantitative high-resolution imaging of cytoskeletal protein dynamics and biophysical approaches. Lastly, protein, RNA, fluorescent probes and small molecules can be microinjected into the neuronal cell body for localization and functional studies. The following chapter describes culturing of Aplysia bag cell neurons, live cell imaging of neuronal growth cones using differential interference contrast and fluorescent speckle microscopy as well as the restrained bead interaction assay to induce adhesion-mediated growth cone guidance in vitro. PMID:21748670

  18. Distinctions in growth cone morphology and motility between monopolar and multipolar neurons in Drosophila CNS cultures.

    PubMed

    Kim, Y T; Wu, C F

    1991-04-01

    Growth cones play a central role in determining neurite extension, pathfinding and branching, and in establishing synaptic connections. This paper describes an initial characterization of growth cone morphology and behavior in dissociated larval central nervous system (CNS) cultures of Drosophila. Contrast-enhanced video images of growth cones in monopolar and multipolar neurons were characterized by employing morphometric parameters such as the number and length of filopodia, and the area and roundness of the lamellipodia. Behavior of growth cones was analyzed by a motility index and boundary flow plots originally devised for measuring motility in other cellular systems. We found that separate CNS regions yielded cultures of different major cell types with distinct neuritic patterns that could be correlated with the morphology and motility of the associated growth cones. Monopolar neurons were the major cell type in brain cultures, whereas multipolar neurons were predominant in ventral ganglion cultures. Moreover, the growth cones of monopolar neurons, which are likely to be associated with the axonal processes, differed from those of multipolar neurons, which might be related to dendritic terminals. Growth cones in monopolar neurons had larger lamellipodia of less erratic shape accompanied by fewer and shorter filopodia, and, when active, displayed much higher motility and less directionality in motion. Alternatively, these morphological and behavioral distinctions between monopolar and multipolar neurons may result from intrinsic differences in membrane adhesion and intracellular transport properties.

  19. Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

    PubMed Central

    Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla

    2013-01-01

    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549

  20. Second messengers and membrane trafficking direct and organize growth cone steering

    PubMed Central

    Tojima, Takuro; Hines, Jacob H.; Henley, John R.; Kamiguchi, Hiroyuki

    2011-01-01

    Graded distributions of extracellular cues guide developing axons toward their targets. A network of second messengers, Ca2+ and cyclic nucleotides, shapes cue-derived information into either attractive or repulsive signals that steer growth cones bidirectionally. Emerging evidence suggests that such guidance signals create a localized imbalance between exocytosis and endocytosis, which in turn redirects membrane, adhesion and cytoskeletal components asymmetrically across the growth cone to bias the direction of axon extension. These recent advances allow us to propose a unifying model of how the growth cone translates shallow gradients of environmental information into polarized activity of the steering machinery for axon guidance. PMID:21386859

  1. Absence of persistent spreading, branching, and adhesion in GAP-43- depleted growth cones

    PubMed Central

    1995-01-01

    The growth-associated protein GAP-43 is a major protein kinase C substrate of growth cones and developing nerve terminals. In the growth cone, it accumulates near the plasma membrane, where it associates with the cortical cytoskeleton and membranes. The role of GAP-43 in neurite outgrowth is not yet clear, but recent findings suggest that it may be a crucial competence factor in this process. To define the role of GAP- 43 in growth cone activity, we have analyzed neurite outgrowth and growth cone activity in primary sensory neurons depleted of GAP-43 by a specific antisense oligonucleotide procedure. Under optimal culture conditions, but in the absence of GAP-43, growth cones adhered poorly, displayed highly dynamic but unstable lamellar extensions, and were strikingly devoid of local f-actin concentrations. Upon stimulation, they failed to produce NGF-induced spreading or insulin-like growth factor-1-induced branching, whereas growth factor-induced phosphotyrosine immunoreactivity and acceleration of neurite elongation were not impaired. Unlike their GAP-43-expressing counterparts, they readily retracted when exposed to inhibitory central nervous system myelin-derived liposomes. Frequency and extent of induced retraction were attenuated by NGF. Our results indicate that GAP-43 can promote f- actin accumulation, evoked morphogenic activity, and resistance to retraction of the growth cone, suggesting that it may promote regulated neurite outgrowth during development and regeneration. PMID:7860637

  2. Signaling Mechanisms Underlying Slit2-Induced Collapse of Xenopus Retinal Growth Cones

    PubMed Central

    Piper, Michael; Anderson, Richard; Dwivedy, Asha; Weinl, Christine; van Horck, Francis; Leung, Kin Mei; Cogill, Emily; Holt, Christine

    2013-01-01

    Summary Slits mediate multiple axon guidance decisions, but the mechanisms underlying the responses of growth cones to these cues remain poorly defined. We show here that collapse induced by Slit2-conditioned medium (Slit2-CM) in Xenopus retinal growth cones requires local protein synthesis (PS) and endocytosis. Slit2-CM elicits rapid activation of translation regulators and MAP kinases in growth cones, and inhibition of MAPKs or disruption of heparan sulfate blocks Slit2-CM-induced PS and repulsion. Interestingly, Slit2-CM causes a fast PS-dependent decrease in cytoskeletal F-actin concomitant with a PS-dependent increase in the actin-depolymerizing protein cofilin. Our findings reveal an unexpected link between Slit2 and cofilin in growth cones and suggest that local translation of actin regulatory proteins contributes to repulsion. PMID:16423696

  3. The alpha-tubulin of the growth cone is predominantly in the tyrosinated form.

    PubMed

    Gordon-Weeks, P R; Lang, R D

    1988-07-01

    Growth cone cytoskeletons were prepared by detergent extraction of growth cones isolated from neonatal rat forebrain by the method of Gordon-Weeks and Lockerbie (Neuroscience, 13 (1984) 119-136). SDS-PAGE analysis of growth cone cytoskeletons revealed the presence of several major bands, identified by their mobility as actin (43 kDa Mr), myosin heavy chain (195 kDa Mr), spectrin (235 and 240 kDa Mr), and tubulin (51-54 kDa Mr). The identity of these proteins was confirmed by immunoblot analysis using specific antibodies to these proteins which further revealed that the predominant form of alpha-tubulin in the growth cone cytoskeleton and in the soluble pool of tubulin is tyrosinated at the C-terminal.

  4. Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane

    PubMed Central

    Vitriol, Eric A; Zheng, James Q

    2012-01-01

    Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to their targets. Research in the past two decades has also gained significant insight into the mechanisms by which growth cones translate extracellular signals into directional migration. This review aims to examine new progress towards understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones. PMID:22445336

  5. Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane.

    PubMed

    Vitriol, Eric A; Zheng, James Q

    2012-03-22

    Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of the neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to reach their targets. Research in the past two decades has also gained significant insight into the ways in which growth cones translate extracellular signals into directional migration. This review aims to examine new progress toward understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically, we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones.

  6. Integrin-linked kinase regulates oligodendrocyte cytoskeleton, growth cone, and adhesion dynamics.

    PubMed

    Michalski, John-Paul; Cummings, Sarah E; O'Meara, Ryan W; Kothary, Rashmi

    2016-02-01

    Integrin-linked kinase (ILK), a focal adhesion protein, brokers the link between cytoskeleton, cell membrane, and extracellular environment. Here, we demonstrate a role for ILK in laminin-2-mediated adhesion in primary murine oligodendrocytes (OLs) - with ILK loss leading to severe defects in process branching and outgrowth. These defects were partially recovered when the ILK-depleted OLs were instead grown on the non-integrin-activating substrate poly-l-lysine. Intriguingly, ILK loss on the neutral poly-l-lysine substrate led to swelling at the tips of OL processes, which we identified as enlarged growth cones. Employing the bloated ILK-depleted growth cones as template, we demonstrate the appearance of distinct cytoskeletal domains within OL growth cones bearing classic neuronal growth cone architecture. Further, microtubule organization was severely perturbed following ILK loss, with centripetal microtubule looping and failure to bundle occurring in a laminin-2-independent manner. Together, our work highlights differences in specific aspects of OL biology as driven by laminin-2-dependent or independent ILK governed mechanisms. We also reinforce the idea of OLs as growth cone bearing cells and describe the neuronal-like cytoskeleton therein. Finally, we demonstrate a role for ILK in OL growth cone maturation through microtubule regulation, the loss of which translates to decreased process length and myelin production capacity. We describe herein how different substrates fundamentally alter the oligodendrocyte's response to loss of integrin-linked kinase (ILK). On laminin-2 (Ln-2), ILK-depleted oligodendrocytes appear stunted and malformed, while on the non-integrin-activating substrate PLL branching and membrane formation are restored. We also reinforce the idea of oligodendrocytes as growth cone-bearing cells, detailing the growth cone's cytoskeletal architecture. Strikingly, loss of ILK on poly-l-lysine leads to growth cone swelling, the structure's size and

  7. Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

    PubMed Central

    Fuentes, Federico

    2009-01-01

    PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. PMID:19158394

  8. Nano-scale Topographical Studies on the Growth Cones of Nerve Cells using AFM

    NASA Astrophysics Data System (ADS)

    Durkaya, Goksel; Zhong, Lei; Rehder, Vincent; Dietz, Nikolaus

    2009-11-01

    Nerve cells are the fundamental units which are responsible for intercommunication within the nervous system. The neurites, fibrous cable-like extensions for information delivery, of nerve cells are tipped by highly motile sensory structures known as the growth cones which execute important functions; neural construction, decision making and navigation during development and regeneration of the nervous system. The highly dynamic subcomponents of the growth cones are important in neural activity. Atomic Force Microscopy (AFM) is the most powerful microscopy technique which is capable of imaging without conductivity constraint and in liquid media. AFM providing nano-scale topographical information on biological structures is also informative on the physical properties such as: elasticity, adhesion, and softness. This contribution focuses on AFM analysis of the growth cones of the nerve cells removed from the buccal ganglion of Helisoma trivolvis. The results of nano-scale topography and softness analysis on growth cone central domain, filopodia and overlying lamellopodium (veil) are presented. The subcomponents of the growth cones of different nerve cells are compared to each other. The results of the analysis are linked to the mechanical properties and internal molecular density distribution of the growth cones.

  9. [Metal artefact on head and neck cone-beam CT images].

    PubMed

    Kovacs, Miklós; Fejérdy, Pál; Dobó, Nagy Csaba

    2008-10-01

    There are only a few factors, where the properties of the CBCT is inferior compared to conventional CT. One of these properties is the low contrast resolution, which has an importance in the discrimination of different soft tissues. Another difference is the image quality degrading effect by metal objects. This latter factor has much higher importance in head and neck region CBCT application. The metal artifact is closely related to other types of artifacts, like beam-hardening and x-ray photon scattering artifacts. In some of the cases, metal artifacts can be avoided by the proper adjustment of the scanning parameters, but sometimes the problem overgrows the possibilities. The current pre- and post-processing algorithms used for the correction of different artifacts can improve the image quality, but these algorithms are not the ultimate solution to the problem. The introduction of iterative reconstruction algorithms into the CBCT market will effectively reduce the most CT artifacts, however, the spread of this algorithms are set back because of the insufficient computational power of today's PCs. Another advantage of the use of iterative algorithms is that the patient dose could be significantly reduced.

  10. Steering neuronal growth cones by shifting the imbalance between exocytosis and endocytosis.

    PubMed

    Tojima, Takuro; Itofusa, Rurika; Kamiguchi, Hiroyuki

    2014-05-21

    Extracellular molecular cues guide migrating growth cones along specific routes during development of axon tracts. Such processes rely on asymmetric elevation of cytosolic Ca(2+) concentrations across the growth cone that mediates its attractive or repulsive turning toward or away from the side with Ca(2+) elevation, respectively. Downstream of these Ca(2+) signals, localized activation of membrane trafficking steers the growth cone bidirectionally, with endocytosis driving repulsion and exocytosis causing attraction. However, it remains unclear how Ca(2+) can differentially regulate these opposite membrane-trafficking events. Here, we show that growth cone turning depends on localized imbalance between exocytosis and endocytosis and identify Ca(2+)-dependent signaling pathways mediating such imbalance. In embryonic chicken dorsal root ganglion neurons, repulsive Ca(2+) signals promote clathrin-mediated endocytosis through a 90 kDa splice variant of phosphatidylinositol-4-phosphate 5-kinase type-1γ (PIPKIγ90). In contrast, attractive Ca(2+) signals facilitate exocytosis but suppress endocytosis via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (Cdk5) that can inactivate PIPKIγ90. Blocking CaMKII or Cdk5 leads to balanced activation of both exocytosis and endocytosis that causes straight growth cone migration even in the presence of guidance signals, whereas experimentally perturbing the balance restores the growth cone's turning response. Remarkably, the direction of this resumed turning depends on relative activities of exocytosis and endocytosis, but not on the type of guidance signals. Our results suggest that navigating growth cones can be redirected by shifting the imbalance between exocytosis and endocytosis, highlighting the importance of membrane-trafficking imbalance for axon guidance and, possibly, for polarized cell migration in general.

  11. The role of Arp2/3 in growth cone actin dynamics and guidance is substrate dependent.

    PubMed

    San Miguel-Ruiz, José E; Letourneau, Paul C

    2014-04-23

    During development extrinsic guidance cues modulate the peripheral actin network in growth cones to direct axons to their targets. We wanted to understand the role of the actin nucleator Arp2/3 in growth cone actin dynamics and guidance. Since growth cones migrate in association with diverse adhesive substrates during development, we probed the hypothesis that the functional significance of Arp2/3 is substrate dependent. We report that Arp2/3 inhibition led to a reduction in the number of filopodia and growth cone F-actin content on laminin and L1. However, we found substrate-dependent differences in growth cone motility, actin retrograde flow, and guidance after Arp2/3 inhibition, suggesting that its role, and perhaps that of other actin binding proteins, in growth cone motility is substrate dependent. PMID:24760849

  12. IDENTIFICATION OF A DEVELOPMENTALLY-REGULATED PATHWAY OF MEMBRANE RETRIEVAL IN NEURONAL GROWTH CONES

    PubMed Central

    Bonanomi, Dario; Fornasiero, Eugenio F.; Valdez, Gregorio; Halegoua, Simon; Benfenati, Fabio; Menegon, Andrea; Valtorta, Flavia

    2009-01-01

    During axon navigation and upon target recognition the growth cone plasma membrane is constantly reconfigured as a result of changes in cytoskeletal and membrane dynamics. The identity and regulation of the membrane pathway(s) participating in remodeling of the growth cone surface remain elusive. Here, we identify a constitutive, high capacity plasma membrane recycling activity in the axonal growth cones which is mediated by a novel bulk endocytic pathway mechanistically related to macropinocytosis. This pathway, involving large compartments distributed at sites of intense actin-based membrane ruffling, requires phosphatidylinositol 3-kinase activity, the small GTPase Rac1 and the pinocytic chaperone Pincher. At early developmental stages, the synaptic vesicle and classical endosomal recycling pathways do not participate in the rapid retrieval of the growth cone plasma membrane. At later stages, during the onset of synaptogenesis, an intrinsic program of maturation leads to downregulation of basal bulk endocytosis and the emergence of depolarization-induced synaptic vesicle exo-endocytosis. We propose that the control of bulk membrane retrieval contributes to the homeostatic regulation of the axonal plasma membrane and growth cone remodeling during axonal outgrowth. In addition, we suggest that the downregulation of bulk endocytosis during synaptogenesis might contribute to the preservation of synaptic vesicle specificity. PMID:18940911

  13. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

    PubMed Central

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-01-01

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017

  14. Regulation of ECM degradation and axon guidance by growth cone invadosomes

    PubMed Central

    Santiago-Medina, Miguel; Gregus, Kelly A.; Nichol, Robert H.; O'Toole, Sean M.; Gomez, Timothy M.

    2015-01-01

    Invadopodia and podosomes, collectively referred to as invadosomes, are F-actin-rich basal protrusions of cells that provide sites of attachment to and degradation of the extracellular matrix. Invadosomes promote the invasion of cells, ranging from metastatic cancer cells to immune cells, into tissue. Here, we show that neuronal growth cones form protrusions that share molecular, structural and functional characteristics of invadosomes. Growth cones from all neuron types and species examined, including a variety of human neurons, form invadosomes both in vitro and in vivo. Growth cone invadosomes contain dynamic F-actin and several actin regulatory proteins, as well as Tks5 and matrix metalloproteinases, which locally degrade the matrix. When viewed using three-dimensional super-resolution microscopy, F-actin foci often extended together with microtubules within orthogonal protrusions emanating from the growth cone central domain. Finally, inhibiting the function of Tks5 both reduced matrix degradation in vitro and disrupted motoneuron axons from exiting the spinal cord and extending into the periphery. Taken together, our results suggest that growth cones use invadosomes to target protease activity during axon guidance through tissues. PMID:25564649

  15. Forces from the rear: deformed microtubules in neuronal growth cones influence retrograde flow and advancement

    NASA Astrophysics Data System (ADS)

    Rauch, Philipp; Heine, Paul; Goettgens, Barbara; Käs, Josef A.

    2013-01-01

    The directed motility of growth cones at the tip of neuronal processes is a key function in neuronal path-finding and relies on a complex system of interacting cytoskeletal components. Despite intensive research in this field, many aspects of the mechanical roles of actin structures and, in particular, of microtubules throughout this process remain unclear. Mostly, force generation is ascribed to actin-myosin-based structures such as filopodia bundles and the dynamic polymer gel within the lamellipodium. Our analysis of microtubule buckling and deformation in motile growth cones reveals that extending microtubule filaments contribute significantly to the overall protrusion force. In this study, we establish a relationship of the local variations in stored bending energy and deformation characteristics to growth cone morphology and retrograde actin flow. This implies the relevance of microtubule pushing and deformation for general neurite advancement as well as steering processes.

  16. Endocytosis-dependent desensitization and protein synthesis-dependent resensitization in retinal growth cone adaptation.

    PubMed

    Piper, Michael; Salih, Saif; Weinl, Christine; Holt, Christine E; Harris, William A

    2005-02-01

    It has been proposed that growth cones navigating through gradients adapt to baseline concentrations of guidance cues. This adaptation process is poorly understood. Using the collapse assay, we show that adaptation in Xenopus laevis retinal growth cones to the guidance cues Sema3A or netrin-1 involves two processes: a fast, ligand-specific desensitization that occurs within 2 min of exposure and is dependent on endocytosis, and a slower, ligand-specific resensitization, which occurs within 5 min and is dependent upon protein synthesis. These two phases of adaptation allow retinal axons to adjust their range of sensitivity to specific guidance cues.

  17. Endocytosis-dependent desensitization and protein synthesis–dependent resensitization in retinal growth cone adaptation

    PubMed Central

    Piper, Michael; Salih, Saif; Weinl, Christine; Holt, Christine E; Harris, William A

    2013-01-01

    It has been proposed that growth cones navigating through gradients adapt to baseline concentrations of guidance cues. This adaptation process is poorly understood. Using the collapse assay, we show that adaptation in Xenopus laevis retinal growth cones to the guidance cues Sema3A or netrin-1 involves two processes: a fast, ligand-specific desensitization that occurs within 2 min of exposure and is dependent on endocytosis, and a slower, ligand-specific resensitization, which occurs within 5 min and is dependent upon protein synthesis. These two phases of adaptation allow retinal axons to adjust their range of sensitivity to specific guidance cues. PMID:15643427

  18. Differing semaphorin 3A concentrations trigger distinct signaling mechanisms in growth cone collapse.

    PubMed

    Manns, Richard P C; Cook, Geoffrey M W; Holt, Christine E; Keynes, Roger J

    2012-06-20

    Semaphorin-3A (Sema3A) is a major guidance cue in the developing nervous system. Previous studies have revealed a dependence of responses to Sema3A on local protein synthesis (PS) in axonal growth cones, but a recent study has called this dependence into question. To understand the basis of this discrepancy we used the growth cone collapse assay on chick dorsal root ganglion neurons. We show that the dependence of growth cone collapse on protein synthesis varies according to Sema3A concentration, from near-total at low concentration (<100 ng/ml) to minimal at high concentration (>625 ng/ml). Further, we show that neuropilin-1 (NP-1) mediates both PS-dependent and PS-independent collapse. Our findings are consistent with the operation of at least two distinct Sema3A signaling pathways: one that is PS-dependent, involving mammalian target of rapamycin, and one that is PS-independent, involving GSK-3β activation and operative at all concentrations of Sema3A examined. The results provide a plausible explanation for the discrepancy in PS-dependence reported in the literature, and indicate that different signaling pathways activated within growth cones can be modulated by changing the concentration of the same guidance cue.

  19. An isolated growth cone-enriched fraction from developing rat brain has substance P binding sites.

    PubMed

    Lockerbie, R O; Beaujouan, J C; Saffroy, M; Glowinski, J

    1988-05-01

    A fraction enriched in neuronal growth cones isolated from developing rat forebrain was shown to possess binding sites for the substance P analog, Bolton-Hunter substance P [( 125I]BHSP). Specific binding of this ligand reached an equilibrium after 10 min at 20 degrees C, and was reversible and temperature-dependent. Removal of extracellular Na+ did not block but rather augmented [125I]BHSP binding suggesting that the labeled analog was not transported into the growth cone fraction. Scatchard analysis of the binding indicated a single class of non-interacting binding sites in the growth cone fraction (Kd: 257 pM; Bmax: 56 fmol/mg protein). From competition studies using substance P and other tachykinins, their rank order of potency for inhibiting [125I]BHSP binding was SP greater than physalaemin much greater than eledoisin greater than kassinin greater than NKB greater than or equal to NKA. Such order is consistent with the presence of an SP receptor (Neurokinin-1) in the growth cone fraction. The N-terminal fragments of substance P, SP1-7 and SP1-11 free acids, and the C-terminal fragment, SP7-11, were devoid of affinity for the [125I]BHSP binding site. However SP6-11 and SP1-11 methyl esters showed more potency.

  20. The Role of PI(3,4,5)P3 Signaling During Axonal Growth Cone Chemotaxis

    NASA Astrophysics Data System (ADS)

    Henle, Steven J.

    Development of the nervous system is a remarkably complex process that involves the birth of billions of neurons leading to the formation of trillions of synapses. Many biological programs underlie the formation of a functional nervous system. I focused on trying to understand the process by which a newly formed axon navigates a series of signals in the environment that guide it to a synaptic partner. At the tip of the extending neurite is a conical expansion known as the growth cone that primarily is responsible for performing this pathfinding process. In order to do so it senses the environment, and induces a program of intracellular signaling that in turn leads to directed axon extension. My work has focused on understanding this signaling machinery. I have aimed to understand the role the phosphoinositde PI(3,4,5)P3 due to the critical role it plays in amoeboid chemotaxis. I discovered that PI(3,4,5)P3 and its downstream kinase Akt define the leading edge during growth cone chemotaxis and lead to activation of a TRP (Transient Receptor Potential) channel. Furthermore, I found that the PI(3,4,5)P3 phosphatase PTEN appears to be exclusively linked to guiding growth cone migration in response to a gradient of chemorepellent. Taken together my data demonstrate that PI(3,4,5)P3 functions as a key instructive mediator of growth cone chemotaxis.

  1. Differing Semaphorin 3A concentrations trigger distinct signaling mechanisms in growth cone collapse

    PubMed Central

    Manns, Richard P.C.; Cook, Geoffrey M.W.; Holt, Christine E.; Keynes, Roger J.

    2012-01-01

    Semaphorin-3A (Sema3A) is a major guidance cue in the developing nervous system. Previous studies have revealed a dependence of responses to Sema3A on local protein synthesis (PS) in axonal growth cones, but a recent study has called this dependence into question. To understand the basis of this discrepancy we used the growth cone collapse assay on chick dorsal root ganglion (DRG) neurons. We show that the dependence of growth cone collapse on protein synthesis varies according to Sema3A concentration, from near-total at low concentration (<100ng/ml) to minimal at high concentration (>625ng/ml). Further, we show that neuropilin-1 (NP-1) mediates both PS-dependent and PS–independent collapse. Our findings are consistent with the operation of at least two distinct Sema3A signaling pathways: one that is PS-dependent, involving mammalian target of rapamycin (mTOR), and one that is PS-independent, involving GSK-3β activation and operative at all concentrations of Sema3A examined. The results provide a plausible explanation for the discrepancy in PS-dependence reported in the literature, and indicate that different signaling pathways activated within growth cones can be modulated by changing the concentration of the same guidance cue. PMID:22723695

  2. Growth cone collapse and inhibition of neurite growth by Botulinum neurotoxin C1: a t-SNARE is involved in axonal growth

    PubMed Central

    1996-01-01

    The growth cone is responsible for axonal growth, where membrane expansion is most likely to occur. Several recent reports have suggested that presynaptic proteins are involved in this process; however, the molecular mechanism details are unclear. We suggest that by cleaving a presynaptic protein syntaxin, which is essential in targeting synaptic vesicles as a target SNAP receptor (t-SNARE), neurotoxin C1 of Clostridium botulinum causes growth cone collapse and inhibits axonal growth. Video-enhanced microscopic studies showed (a) that neurotoxin C1 selectively blocked the activity of the central domain (the vesicle-rich region) at the initial stage, but not the lamellipodia in the growth cone; and (b) that large vacuole formation occurred probably through the fusion of smaller vesicles from the central domain to the most distal segments of the neurite. The total surface area of the accumulated vacuoles could explain the membrane expansion of normal neurite growth. The gradual disappearance of the surface labeling by FITC-WGA on the normal growth cone, suggesting membrane addition, was inhibited by neurotoxin C1. The experiments using the peptides derived from syntaxin, essential for interaction with VAMP or alpha-SNAP, supported the results using neurotoxin C1. Our results demonstrate that syntaxin is involved in axonal growth and indicate that syntaxin may participate directly in the membrane expansion that occurs in the central domain of the growth cone, probably through association with VAMP and SNAPs, in a SNARE-like way. PMID:8698815

  3. Quantitative genetic parameters for yield, plant growth and cone chemical traits in hop (Humulus lupulus L.)

    PubMed Central

    2014-01-01

    Background Most traits targeted in the genetic improvement of hop are quantitative in nature. Improvement based on selection of these traits requires a comprehensive understanding of their inheritance. This study estimated quantitative genetic parameters for 20 traits related to three key objectives for the genetic improvement of hop: cone chemistry, cone yield and agronomic characteristics. Results Significant heritable genetic variation was identified for α-acid and β-acid, as well as their components and relative proportions. Estimates of narrow-sense heritability for these traits (h 2  = 0.15 to 0.29) were lower than those reported in previous hop studies, but were based on a broader suite of families (108 from European, North American and hybrid origins). Narrow-sense heritabilities are reported for hop growth traits for the first time (h 2  = 0.04 to 0.20), relating to important agronomic characteristics such as emergence, height and lateral morphology. Cone chemistry and growth traits were significantly genetically correlated, such that families with more vigorous vegetative growth were associated with lower α-acid and β-acid levels. This trend may reflect the underlying population structure of founder genotypes (European and North American origins) as well as past selection in the Australian environment. Although male and female hop plants are thought to be indistinguishable until flowering, sex was found to influence variation in many growth traits, with male and female plants displaying differences in vegetative morphology from emergence to cone maturity. Conclusions This study reveals important insights into the genetic control of quantitative hop traits. The information gained will provide hop breeders with a greater understanding of the additive genetic factors which affect selection of cone chemistry, yield and agronomic characteristics in hop, aiding in the future development of improved cultivars. PMID:24524684

  4. Suppression of Radixin and Moesin Alters Growth Cone Morphology, Motility, and Process Formation In Primary Cultured Neurons

    PubMed Central

    Paglini, Gabriela; Kunda, Patricia; Quiroga, Santiago; Kosik, Kenneth; Cáceres, Alfredo

    1998-01-01

    In this study we have examined the cellular functions of ERM proteins in developing neurons. The results obtained indicate that there is a high degree of spatial and temporal correlation between the expression and subcellular localization of radixin and moesin with the morphological development of neuritic growth cones. More importantly, we show that double suppression of radixin and moesin, but not of ezrin–radixin or ezrin–moesin, results in reduction of growth cone size, disappearance of radial striations, retraction of the growth cone lamellipodial veil, and disorganization of actin filaments that invade the central region of growth cones where they colocalize with microtubules. Neuritic tips from radixin–moesin suppressed neurons displayed high filopodial protrusive activity; however, its rate of advance is 8–10 times slower than the one of growth cones from control neurons. Radixin–moesin suppressed neurons have short neurites and failed to develop an axon-like neurite, a phenomenon that appears to be directly linked with the alterations in growth cone structure and motility. Taken collectively, our data suggest that by regulating key aspects of growth cone development and maintenance, radixin and moesin modulate neurite formation and the development of neuronal polarity. PMID:9786954

  5. Semaphorin3a Enhances Endocytosis at Sites of Receptor–F-Actin Colocalization during Growth Cone Collapse

    PubMed Central

    Fournier, Alyson E.; Nakamura, Fumio; Kawamoto, Susumu; Goshima, Yoshio; Kalb, Robert G.; Strittmatter, Stephen M.

    2000-01-01

    Axonal growth cone collapse is accompanied by a reduction in filopodial F-actin. We demonstrate here that semaphorin 3A (Sema3A) induces a coordinated rearrangement of Sema3A receptors and F-actin during growth cone collapse. Differential interference contrast microscopy reveals that some sites of Sema3A-induced F-actin reorganization correlate with discrete vacuoles, structures involved in endocytosis. Endocytosis of FITC-dextran by the growth cone is enhanced during Sema3A treatment, and sites of dextran accumulation colocalize with actin-rich vacuoles and ridges of membrane. Furthermore, the Sema3A receptor proteins, neuropilin-1 and plexin, and the Sema3A signaling molecule, rac1, also reorganize to vacuoles and membrane ridges after Sema3A treatment. These data support a model whereby Sema3A stimulates endocytosis by focal and coordinated rearrangement of receptor and cytoskeletal elements. Dextran accumulation is also increased in retinal ganglion cell (RGC) growth cones, in response to ephrin A5, and in RGC and DRG growth cones, in response to myelin and phorbol-ester. Therefore, enhanced endocytosis may be a general principle of physiologic growth cone collapse. We suggest that growth cone collapse is mediated by both actin filament rearrangements and alterations in membrane dynamics. PMID:10769032

  6. Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin.

    PubMed

    Endo, Mitsuharu; Ohashi, Kazumasa; Sasaki, Yukio; Goshima, Yoshio; Niwa, Ryusuke; Uemura, Tadashi; Mizuno, Kensaku

    2003-04-01

    Growth cone motility and morphology are based on actin-filament dynamics. Cofilin plays an essential role for the rapid turnover of actin filaments by severing and depolymerizing them. The activity of cofilin is repressed by phosphorylation at Ser3 by LIM kinase (LIMK, in which LIM is an acronym of the three gene products Lin-11, Isl-1, and Mec-3) and is reactivated by dephosphorylation by phosphatases, termed Slingshot (SSH). We investigated the roles of cofilin, LIMK, and SSH in the growth cone motility and morphology and neurite extension by expressing fluorescence protein-labeled cofilin, LIMK1, SSH1, or their mutants in chick dorsal root ganglion (DRG) neurons and then monitoring live images of growth cones by time-lapse video fluorescence microscopy. The expression of LIMK1 remarkably repressed growth cone motility and neurite extension, whereas the expression of SSH1 or a nonphosphorylatable S3A mutant of cofilin enhanced these events. The fan-like shape of growth cones was disorganized by the expression of any of these proteins. The repressive effects on growth cone behavior by LIMK1 expression were significantly rescued by the coexpression of S3A-cofilin or SSH1. These findings suggest that LIMK1 and SSH1 play critical roles in controlling growth cone motility and morphology and neurite extension by regulating the activity of cofilin and may be involved in signaling pathways that regulate stimulus-induced growth cone guidance. Using various mutants of cofilin, we also obtained evidence that the actin-filament-severing activity of cofilin is critical for growth cone motility and neurite extension.

  7. Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones

    PubMed Central

    He, Yingpei; Ren, Yuan; Wu, Bingbing; Decourt, Boris; Lee, Aih Cheun; Taylor, Aaron; Suter, Daniel M.

    2015-01-01

    Src tyrosine kinases have been implicated in axonal growth and guidance; however, the underlying cellular mechanisms are not well understood. Specifically, it is unclear which aspects of actin organization and dynamics are regulated by Src in neuronal growth cones. Here, we investigated the function of Src2 and one of its substrates, cortactin, in lamellipodia and filopodia of Aplysia growth cones. We found that up-regulation of Src2 activation state or cortactin increased lamellipodial length, protrusion time, and actin network density, whereas down-regulation had opposite effects. Furthermore, Src2 or cortactin up-regulation increased filopodial density, length, and protrusion time, whereas down-regulation promoted lateral movements of filopodia. Fluorescent speckle microscopy revealed that rates of actin assembly and retrograde flow were not affected in either case. In summary, our results support a model in which Src and cortactin regulate growth cone motility by increasing actin network density and protrusion persistence of lamellipodia by controlling the state of actin-driven protrusion versus retraction. In addition, both proteins promote the formation and stability of actin bundles in filopodia. PMID:26224308

  8. Neuronal growth cone retraction relies upon proneurotrophin receptor signaling through Rac

    PubMed Central

    Deinhardt, Katrin; Kim, Taeho; Spellman, Daniel S.; Mains, Richard E.; Eipper, Betty A.; Neubert, Thomas A.; Chao, Moses V.; Hempstead, Barbara L.

    2012-01-01

    Growth of axons and dendrites is a dynamic process that involves guidance molecules, adhesion proteins, and neurotrophic factors. Although neurite extension during development has been extensively studied, the intracellular mechanisms that mediate neurite retraction are poorly understood. Here, we show that the proneurotrophin, proNGF, induces acute collapse of growth cones of cultured hippocampal neurons. This retraction is initiated by an interaction between p75NTR and the sortilin family member, SorCS2 (sortilin-related VPS10 domain containing receptor 2). Binding of proNGF to the p75NTR-SorCS2 complex induced growth cone retraction by initiating the dissociation of the guanine-nucleotide exchange factor Trio from the p75NTR- SorCS2 complex, resulting in decreased Rac activity, and consequently, growth cone collapse. The actin-bundling protein fascin also became inactivated, contributing to the destabilization and collapse of actin filaments. These results identify a bifunctional signaling mechanism by which proNGF regulates actin dynamics to modulate neuronal morphology acutely. PMID:22155786

  9. Rapid Changes in the Translatome during the Conversion of Growth Cones to Synaptic Terminals.

    PubMed

    Zhang, Kelvin Xi; Tan, Liming; Pellegrini, Matteo; Zipursky, S Lawrence; McEwen, Jason M

    2016-02-01

    A common step in the formation of neural circuits is the conversion of growth cones to presynaptic terminals. Characterizing patterns of global gene expression during this process is problematic due to the cellular diversity of the brain and the complex temporal dynamics of development. Here, we take advantage of the synchronous conversion of Drosophila photoreceptor growth cones into presynaptic terminals to explore global changes in gene expression during presynaptic differentiation. Using a tandemly tagged ribosome trap (T-TRAP) and RNA sequencing (RNA-seq) at multiple developmental times, we observed dramatic changes in coding and non-coding RNAs with presynaptic differentiation. Marked changes in the mRNA encoding transmembrane and secreted proteins occurred preferentially. The 3' UTRs of transcripts encoding synaptic proteins were preferentially lengthened, and these extended UTRs were preferentially enriched for sites recognized by RNA binding proteins. These data provide a rich resource for uncovering the regulatory logic underlying presynaptic differentiation. PMID:26832407

  10. Cyclic AMP-dependent protein phosphorylation in isolated neuronal growth cones from developing rat forebrain.

    PubMed

    Lockerbie, R O; Eddé, B; Prochiantz, A

    1989-03-01

    We have shown recently that neuronal growth cones isolated from developing rat forebrain possess an appreciable activity of adenylate cyclase, which produces cyclic AMP and can be stimulated by various neurotransmitter receptor agonists and by forskolin. To investigate cyclic AMP-mediated biochemical mechanisms in isolated growth cones, we have centered the present study on cyclic AMP-dependent protein phosphorylation. One-dimensional gel electrophoretic analysis showed that cyclic AMP analogs increased incorporation of 32P into several phosphoproteins in molecular mass ranges of 50-58 and 76-82 kilodaltons, including those of 82, 76, and 51 kilodaltons. Two-dimensional electrophoresis, using isoelectric focusing in the first dimension, resolved phosphorylated alpha- and beta-tubulin species, actin, a very acidic protein (isoelectric point 4.0) with a molecular mass of 93 kilodaltons, and two proteins (x and x') closely neighboring beta-tubulin. Two other phosphoproteins seen in the gels had molecular masses of 56 and 51 kilodaltons (respective isoelectric points, 4.5 and 4.4) and, along with the 93-kilodalton phosphoprotein, were highly enriched in the isolated growth cones. Only the tubulin and actin species were major proteins in the isolated growth cones. Cyclic AMP analogs enhanced incorporation of 32P into phosphoproteins x and x', and, as assessed by immunoprecipitation, into beta-tubulin. Peptide digest experiments suggested that phosphoproteins x and x' are unrelated to beta-tubulin. Nonequilibrium two-dimensional electrophoresis resolved many phosphoproteins, of which a 79- and 75-kilodalton doublet, a 74-kilodalton species, and a 58-kilodalton doublet showed enhanced incorporation of 32P in the presence of cyclic AMP.

  11. Growth cones isolated from developing rat forebrain: uptake and release of GABA and noradrenaline.

    PubMed

    Lockerbie, R O; Gordon-Weeks, P R; Pearce, B R

    1985-08-01

    A growth cone-enriched fraction isolated from neonatal rat forebrain was shown to accumulate gamma-amino [3H]butyric acid ([3H]-GABA) and [3H]noradrenaline ([3H]NA). Uptake of both neurotransmitters was sodium- and temperature-dependent and exhibited saturation kinetics with Km values of 17.7 microM and 4.5 microM respectively and Vmax values of 114 pmol/min/mg protein and 59 pmol/min/mg protein respectively. Electron microscopic autoradiography showed that about 50% of isolated growth cones can accumulate [3H]GABA. Inhibitor studies showed that beta-alanine was a relatively weak inhibitor of [3H]GABA uptake compared to nipecotic acid and diamino-butyric acid. Growth cone fractions preloaded with [3H]GABA and [3H]NA demonstrated a K+ (25 mM) -induced release of both neurotransmitters. Of the K+-stimulated release of [3H]GABA 50% was Ca2+-dependent, whereas the release of [3H]NA was entirely Ca2+-independent.

  12. Using plusTipTracker software to measure microtubule dynamics in Xenopus laevis growth cones.

    PubMed

    Stout, Alina; D'Amico, Salvatore; Enzenbacher, Tiffany; Ebbert, Patrick; Lowery, Laura Anne

    2014-01-01

    Microtubule (MT) plus-end-tracking proteins (+TIPs) localize to the growing plus-ends of MTs and regulate MT dynamics(1,2). One of the most well-known and widely-utilized +TIPs for analyzing MT dynamics is the End-Binding protein, EB1, which binds all growing MT plus-ends, and thus, is a marker for MT polymerization(1). Many studies of EB1 behavior within growth cones have used time-consuming and biased computer-assisted, hand-tracking methods to analyze individual MTs(1-3). Our approach is to quantify global parameters of MT dynamics using the software package, plusTipTracker(4), following the acquisition of high-resolution, live images of tagged EB1 in cultured embryonic growth cones(5). This software is a MATLAB-based, open-source, user-friendly package that combines automated detection, tracking, visualization, and analysis for movies of fluorescently-labeled +TIPs. Here, we present the protocol for using plusTipTracker for the analysis of fluorescently-labeled +TIP comets in cultured Xenopus laevis growth cones. However, this software can also be used to characterize MT dynamics in various cell types(6-8). PMID:25225829

  13. Isolated neuronal growth cones from developing rat forebrain possess adenylate cyclase activity which can be augmented by various receptor agonists.

    PubMed

    Lockerbie, R O; Hervé, D; Blanc, G; Tassin, J P; Glowinski, J

    1988-01-01

    Isolated neuronal growth cones from neonatal rat forebrain were found to contain a high specific activity of adenylate cyclase (61 pmol cyclic AMP/min/mg protein) compared to the pelleted starting homogenate (5 pmol cyclic AMP/min/mg protein). Forskolin at 10(-4) M increased adenylate cyclase activity in both the pelleted homogenate and growth cone fraction by 70 and 217 pmol cyclic AMP/min/mg protein, respectively, over basal levels. The incremental effect of forskolin was 3-fold greater in the growth cone fraction than in the pelleted homogenate. However, relative to basal levels in each of the two fractions, forskolin increased adenylate cyclase activity in the growth cone fraction by only approx. 5-fold compared to 15-fold in the pelleted homogenate. Dopamine (10(-4) M), vasoactive intestinal polypeptide (10(-6) M) and isoproterenol (10(-5) M) also augmented adenylate cyclase activity in the two fractions. In the growth cone fraction, dopamine and vasoactive intestinal polypeptide produced a stimulation over basal levels by approx. 20 pmol cyclic AMP/min/mg protein while isoproterenol produced a stimulation of approx. 10 pmol cAMP/min/mg protein. The incremental effects of these receptor agonists in the growth cone fraction are approx. 5-fold greater than in the pelleted homogenate. The dopamine-sensitive adenylate cyclase activity in the growth cone fraction could be blocked by the compound SCH23390, a selective D1 receptor antagonist. At saturating concentrations, all combinations of dopamine, vasoactive intestinal polypeptide and isoproterenol were found to be completely additive on adenylate cyclase activity in the growth cone fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. GPCR cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by LPA and S1P

    PubMed Central

    Fincher, Jarod; Whiteneck, Canaan; Birgbauer, Eric

    2014-01-01

    In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, the problem of axonal guidance. We are using the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We show that both LPA and S1P cause specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences to mouse, but very similar to Xenopus. Because LPA and S1P receptors are GPCRs, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibiting Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA and S1P induced collapse of chick retinal growth cones has a partial requirement for Gi/o. PMID:25138637

  15. The discovery of the growth cone and its influence on the study of axon guidance.

    PubMed

    Tamariz, Elisa; Varela-Echavarría, Alfredo

    2015-01-01

    For over a century, there has been a great deal of interest in understanding how neural connectivity is established during development and regeneration. Interest in the latter arises from the possibility that knowledge of this process can be used to re-establish lost connections after lesion or neurodegeneration. At the end of the XIX century, Santiago Ramón y Cajal discovered that the distal tip of growing axons contained a structure that he called the growth cone. He proposed that this structure enabled the axon's oriented growth in response to attractants, now known as chemotropic molecules. He further proposed that the physical properties of the surrounding tissues could influence the growth cone and the direction of growth. This seminal discovery afforded a plausible explanation for directed axonal growth and has led to the discovery of axon guidance mechanisms that include diffusible attractants and repellants and guidance cues anchored to cell membranes or extracellular matrix. In this review the major events in the development of this field are discussed. PMID:26029056

  16. The discovery of the growth cone and its influence on the study of axon guidance

    PubMed Central

    Tamariz, Elisa; Varela-Echavarría, Alfredo

    2015-01-01

    For over a century, there has been a great deal of interest in understanding how neural connectivity is established during development and regeneration. Interest in the latter arises from the possibility that knowledge of this process can be used to re-establish lost connections after lesion or neurodegeneration. At the end of the XIX century, Santiago Ramón y Cajal discovered that the distal tip of growing axons contained a structure that he called the growth cone. He proposed that this structure enabled the axon’s oriented growth in response to attractants, now known as chemotropic molecules. He further proposed that the physical properties of the surrounding tissues could influence the growth cone and the direction of growth. This seminal discovery afforded a plausible explanation for directed axonal growth and has led to the discovery of axon guidance mechanisms that include diffusible attractants and repellants and guidance cues anchored to cell membranes or extracellular matrix. In this review the major events in the development of this field are discussed. PMID:26029056

  17. Bidirectional interactions between NOX2-type NADPH oxidase and the F-actin cytoskeleton in neuronal growth cones.

    PubMed

    Munnamalai, Vidhya; Weaver, Cory J; Weisheit, Corinne E; Venkatraman, Prahatha; Agim, Zeynep Sena; Quinn, Mark T; Suter, Daniel M

    2014-08-01

    NADPH oxidases are important for neuronal function but detailed subcellular localization studies have not been performed. Here, we provide the first evidence for the presence of functional NADPH oxidase 2 (NOX2)-type complex in neuronal growth cones and its bidirectional relationship with the actin cytoskeleton. NADPH oxidase inhibition resulted in reduced F-actin content, retrograde F-actin flow, and neurite outgrowth. Stimulation of NADPH oxidase via protein kinase C activation increased levels of hydrogen peroxide in the growth cone periphery. The main enzymatic NADPH oxidase subunit NOX2/gp91(phox) localized to the growth cone plasma membrane and showed little overlap with the regulatory subunit p40(phox) . p40(phox) itself exhibited colocalization with filopodial actin bundles. Differential subcellular fractionation revealed preferential association of NOX2/gp91(phox) and p40(phox) with the membrane and the cytoskeletal fraction, respectively. When neurite growth was evoked with beads coated with the cell adhesion molecule apCAM, we observed a significant increase in colocalization of p40(phox) with NOX2/gp91(phox) at apCAM adhesion sites. Together, these findings suggest a bidirectional functional relationship between NADPH oxidase activity and the actin cytoskeleton in neuronal growth cones, which contributes to the control of neurite outgrowth. We have previously shown that reactive oxygen species (ROS) are critical for actin organization and dynamics in neuronal growth cones as well as neurite outgrowth. Here, we report that the cytosolic subunit p40(phox) of the NOX2-type NADPH oxidase complex is partially associated with F-actin in neuronal growth cones, while ROS produced by this complex regulates F-actin dynamics and neurite growth. These findings provide evidence for a bidirectional relationship between NADPH oxidase activity and the actin cytoskeleton in neuronal growth cones. PMID:24702317

  18. Whisker/Cone growth on the thermal control surfaces experiment no. S0069

    NASA Technical Reports Server (NTRS)

    Zwiener, James M.; Coston, James E., Jr.; Miller, Edgar R.; Mell, Richard J.; Wilkes, Donald R.

    1995-01-01

    An unusual surface 'growth' was found during scanning electron microscope (SEM) investigations of the Thermal Control Surface Experiment (TCSE) S0069 front thermal cover. This 'growth' is similar to the cone type whisker growth phenomena as studied by G. K. Wehner beginning in the 1960's. Extensive analysis has identified the most probable composition of the whiskers to be a silicate type glass. Sources of the growth material are outgassing products from the experiment and orbital atomic oxygen, which occurs naturally at the orbital altitudes of the LDEF mission in the form of neutral atomic oxygen. The highly ordered symmetry and directionality of the whiskers are attributed to the long term (5.8 year) stable flight orientation of the LDEF.

  19. Dynamic responses of Xenopus retinal ganglion cell axon growth cones to netrin-1 as they innervate their in vivo target

    PubMed Central

    Shirkey, Nicole J.; Manitt, Colleen; Zuniga, Liliana; Cohen-Cory, Susana

    2012-01-01

    Netrin-1 influences retinal ganglion cell (RGC) axon pathfinding and also participates in the branching and synaptic differentiation of mature RGC axons at their target. To investigate whether netrin also serves as an early target recognition signal in the brain, we examined the dynamic behavior of Xenopus RGC axons soon after they innervate the optic tectum. Time-lapse confocal microscopy imaging of RGC axons expressing EYFP demonstrated that netrin-1 is involved in early axon branching, as recombinant netrin-1 halted further advancement of growth cones into the tectum and induced back branching. RGC growth cones exhibited differential responses to netrin-1 that depended on the degree of differentiation of the axon and the developmental stage of the tadpole. Netrin-1 decreased the total number of branches on newly arrived RGC growth cones at the target, but increased the dynamic branching of more mature arbors at the later developmental stage. To further explore the response of axonal growth cones to netrin, Xenopus RGC axons were followed in culture by time-lapse imaging. Exposure to netrin-1 rapidly increased the forward advancement of the axon and decreased the size and expanse of the growth cone, while also inducing back branching. Taken together, the differential in vivo and in vitro responses to netrin-1 suggest that netrin alone is not sufficient to induce the cessation of growth cone advancement in the absence of a target, but can independently modulate axon branching. Collectively, our findings reveal a novel role for netrin on RGC axon branch initiation as growth cones innervate their target. PMID:21858928

  20. Ephrin-B2 elicits differential growth cone collapse and axon retraction in retinal ganglion cells from distinct retinal regions

    PubMed Central

    Petros, Timothy J.; Bryson, J. Barney; Mason, Carol

    2010-01-01

    The circuit for binocular vision and stereopsis is established at the optic chiasm, where retinal ganglion cell (RGC) axons diverge into the ipsilateral and contralateral optic tracts. In the mouse retina, ventrotemporal (VT) RGCs express the guidance receptor EphB1, which interacts with the repulsive guidance cue ephrin-B2 on radial glia at the optic chiasm to direct VT RGC axons ipsilaterally. RGCs in the ventral retina also express EphB2, which interacts with ephrin-B2, whereas dorsal RGCs express low levels of EphB receptors. To investigate how growth cones of RGCs from different retinal regions respond upon initial contact with ephrin-B2, we utilized time-lapse imaging to characterize the effects of ephrin-B2 on growth cone collapse and axon retraction in real time. We demonstrate that bath application of ephrin-B2 induces rapid and sustained growth cone collapse and axon retraction in VT RGC axons, whereas contralaterally-projecting dorsotemporal RGCs display moderate growth cone collapse and little axon retraction. Dose response curves reveal that contralaterally-projecting ventronasal axons are less sensitive to ephrin-B2 treatment compared to VT axons. Additionally, we uncovered a specific role for Rho kinase signaling in the retraction of VT RGC axons but not in growth cone collapse. The detailed characterization of growth cone behavior in this study comprises an assay for the study of Eph signaling in RGCs, and provides insight into the phenomena of growth cone collapse and axon retraction in general. PMID:20629048

  1. Insulin-like growth factor I receptors of fetal brain are enriched in nerve growth cones and contain a beta-subunit variant.

    PubMed Central

    Quiroga, S; Garofalo, R S; Pfenninger, K H

    1995-01-01

    Nerve growth cones isolated from fetal rat brain are highly enriched in a 97-kDa glycoprotein, termed beta gc, that comigrates with the beta subunit of the IGF-I receptor upon two-dimensional PAGE and is disulfide-linked to this receptor's alpha subunit. Antibodies prepared to a conserved domain shared by the insulin and IGF-I receptor beta subunits (AbP2) or to beta gc were used to study receptor distribution further. Subcellular fractionation of the fetal brain segregated most AbP2 immunoreactivity away from growth cones, whereas most beta gc immunoreactivity copurified with growth cones. Experiments involving ligand-activated receptor autophosphorylation confirmed the concentration of IGF-I but not of insulin receptors in growth cone fractions. These results indicate the enrichment of IGF-I receptors in (presumably axonal) growth cones of the differentiating neuron. Furthermore, the segregation of beta gc from AbP2 immunoreactivity suggests that such neurons express an immunochemically distinct variant of the IGF-I receptor beta subunit at the growth cone. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7753803

  2. Cone-beam CT with a flat-panel detector on a mobile C-arm: preclinical investigation in image-guided surgery of the head and neck

    NASA Astrophysics Data System (ADS)

    Siewerdsen, J. H.; Chan, Y.; Rafferty, M. A.; Moseley, D. J.; Jaffray, D. A.; Irish, J. C.

    2005-04-01

    A promising imaging platform for combined low-dose fluoroscopy and cone-beam CT (CBCT) guidance of interventional procedures has been developed in our laboratory. Based on a mobile isocentric C-arm (Siemens PowerMobil) incorporating a high-performance flat-panel detector (Varian PaxScan 4030CB), the system demonstrates sub-mm 3D spatial resolution and soft-tissue visibility with field of view sufficient for head and body sites. For pre-clinical studies in head neck tumor surgery, we hypothesize that the 3D intraoperative information provided by CBCT permits precise, aggressive techniques with improved avoidance of critical structures. The objectives include: 1) quantify improvement in surgical performance achieved with CBCT guidance compared to open and endoscopic techniques; and 2) investigate specific, challenging surgical tasks under CBCT guidance. Investigations proceed from an idealized phantom model to cadaveric specimens. A novel surgical performance evaluation method based on statistical decision theory is applied to excision and avoidance tasks. Analogous to receiver operating characteristic (ROC) analysis in medical imaging, the method quantifies surgical performance in terms of Lesion-Excised (True-Positve), Lesion-Remaining (False-Negative), Normal-Excised (False-Positive), and Normal-Remaining (True-Negative) fractions. Conservative and aggressive excision and avoidance tasks are executed in 12 cadaveric specimens with and without CBCT guidance, including: dissection through dura, preservation of posterior lamina, ethmoid air cells removal, exposure of peri-orbita, and excision of infiltrated bone in the skull base (clivus). Intraoperative CBCT data was found to dramatically improve surgical performance and confidence in the execution of such tasks. Pre-clinical investigation of this platform in head and neck surgery, as well as spinal, trauma, biopsy, and other nonvascular procedures, is discussed.

  3. FLIM FRET Visualization of Cdc42 Activation by Netrin-1 in Embryonic Spinal Commissural Neuron Growth Cones.

    PubMed

    Rappaz, Benjamin; Lai Wing Sun, Karen; Correia, James P; Wiseman, Paul W; Kennedy, Timothy E

    2016-01-01

    Netrin-1 is an essential extracellular chemoattractant that signals through its receptor DCC to guide commissural axon extension in the embryonic spinal cord. DCC directs the organization of F-actin in growth cones by activating an intracellular protein complex that includes the Rho GTPase Cdc42, a critical regulator of cell polarity and directional migration. To address the spatial distribution of signaling events downstream of netrin-1, we expressed the FRET biosensor Raichu-Cdc42 in cultured embryonic rat spinal commissural neurons. Using FLIM-FRET imaging we detected rapid activation of Cdc42 in neuronal growth cones following application of netrin-1. Investigating the signaling mechanisms that control Cdc42 activation by netrin-1, we demonstrate that netrin-1 rapidly enriches DCC at the leading edge of commissural neuron growth cones and that netrin-1 induced activation of Cdc42 in the growth cone is blocked by inhibiting src family kinase signaling. These findings reveal the activation of Cdc42 in embryonic spinal commissural axon growth cones and support the conclusion that src family kinase activation downstream of DCC is required for Cdc42 activation by netrin-1. PMID:27482713

  4. FLIM FRET Visualization of Cdc42 Activation by Netrin-1 in Embryonic Spinal Commissural Neuron Growth Cones

    PubMed Central

    Rappaz, Benjamin; Lai Wing Sun, Karen; Correia, James P.; Wiseman, Paul W.; Kennedy, Timothy E.

    2016-01-01

    Netrin-1 is an essential extracellular chemoattractant that signals through its receptor DCC to guide commissural axon extension in the embryonic spinal cord. DCC directs the organization of F-actin in growth cones by activating an intracellular protein complex that includes the Rho GTPase Cdc42, a critical regulator of cell polarity and directional migration. To address the spatial distribution of signaling events downstream of netrin-1, we expressed the FRET biosensor Raichu-Cdc42 in cultured embryonic rat spinal commissural neurons. Using FLIM-FRET imaging we detected rapid activation of Cdc42 in neuronal growth cones following application of netrin-1. Investigating the signaling mechanisms that control Cdc42 activation by netrin-1, we demonstrate that netrin-1 rapidly enriches DCC at the leading edge of commissural neuron growth cones and that netrin-1 induced activation of Cdc42 in the growth cone is blocked by inhibiting src family kinase signaling. These findings reveal the activation of Cdc42 in embryonic spinal commissural axon growth cones and support the conclusion that src family kinase activation downstream of DCC is required for Cdc42 activation by netrin-1. PMID:27482713

  5. Image Guidance During Head-and-Neck Cancer Radiation Therapy: Analysis of Alignment Trends With In-Room Cone-Beam Computed Tomography Scans

    SciTech Connect

    Zumsteg, Zachary; DeMarco, John; Lee, Steve P.; Steinberg, Michael L.; Lin, Chun Shu; McBride, William; Lin, Kevin; Wang, Pin-Chieh; Kupelian, Patrick; Lee, Percy

    2012-06-01

    Purpose: On-board cone-beam computed tomography (CBCT) is currently available for alignment of patients with head-and-neck cancer before radiotherapy. However, daily CBCT is time intensive and increases the overall radiation dose. We assessed the feasibility of using the average couch shifts from the first several CBCTs to estimate and correct for the presumed systematic setup error. Methods and Materials: 56 patients with head-and-neck cancer who received daily CBCT before intensity-modulated radiation therapy had recorded shift values in the medial-lateral, superior-inferior, and anterior-posterior dimensions. The average displacements in each direction were calculated for each patient based on the first five or 10 CBCT shifts and were presumed to represent the systematic setup error. The residual error after this correction was determined by subtracting the calculated shifts from the shifts obtained using daily CBCT. Results: The magnitude of the average daily residual three-dimensional (3D) error was 4.8 {+-} 1.4 mm, 3.9 {+-} 1.3 mm, and 3.7 {+-} 1.1 mm for uncorrected, five CBCT corrected, and 10 CBCT corrected protocols, respectively. With no image guidance, 40.8% of fractions would have been >5 mm off target. Using the first five CBCT shifts to correct subsequent fractions, this percentage decreased to 19.0% of all fractions delivered and decreased the percentage of patients with average daily 3D errors >5 mm from 35.7% to 14.3% vs. no image guidance. Using an average of the first 10 CBCT shifts did not significantly improve this outcome. Conclusions: Using the first five CBCT shift measurements as an estimation of the systematic setup error improves daily setup accuracy for a subset of patients with head-and-neck cancer receiving intensity-modulated radiation therapy and primarily benefited those with large 3D correction vectors (>5 mm). Daily CBCT is still necessary until methods are developed that more accurately determine which patients may benefit from

  6. Asymmetric endocytosis and remodeling of β1-integrin adhesions during growth cone chemorepulsion by MAG

    PubMed Central

    Hines, Jacob H.; Abu-Rub, Mohammad; Henley, John R.

    2011-01-01

    Gradients of chemorepellent factors released from myelin may impair axon pathfinding and neuro-regeneration after injury. Analogous to the process of chemotaxis in invasive tumor cells, we found that axonal growth cones of Xenopus spinal neurons modulate the functional distribution of integrin receptors during chemorepulsion induced by myelin-associated glycoprotein (MAG). A focal MAG gradient induced polarized endocytosis and concomitant asymmetric loss of β1-integrin and vinculin-containing adhesions on the repellent side during repulsive turning. Loss of symmetrical β1-integrin function was both necessary and sufficient for chemorepulsion, which required internalization by clathrin-mediated endocytosis. Induction of repulsive Ca2+ signals was necessary and sufficient for the stimulated rapid endocytosis of β1-integrin. Altogether, these findings identify β1-integrin as an important functional cargo during Ca2+-dependent rapid endocytosis stimulated by a diffusible guidance cue. Such dynamic redistribution allows the growth cone to rapidly adjust adhesiveness across its axis, an essential feature for initiating chemotactic turning. PMID:20512137

  7. A hybrid computational model to predict chemotactic guidance of growth cones

    NASA Astrophysics Data System (ADS)

    Roccasalvo, Iolanda Morana; Micera, Silvestro; Sergi, Pier Nicola

    2015-06-01

    The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood. Indeed, some emergent and counterintuitive phenomena were recently described during axon pathfinding in presence of chemical gradients. Here, a novel computational model is presented together with its ability to reproduce both regular and counterintuitive axonal behaviours. In this model, the key role of intracellular calcium was phenomenologically modelled through a non standard Gierer-Meinhardt system, as a crucial factor influencing the growth cone behaviour both in regular and complex conditions. This model was able to explicitly reproduce neuritic paths accounting for the complex interplay between extracellular and intracellular environments, through the sensing capability of the growth cone. The reliability of this approach was proven by using quantitative metrics, numerically supporting the similarity between in silico and biological results in regular conditions (control and attraction). Finally, the model was able to qualitatively predict emergent and counterintuitive phenomena resulting from complex boundary conditions.

  8. Drosophila Ten-m and Filamin Affect Motor Neuron Growth Cone Guidance

    PubMed Central

    Zheng, Lihua; Michelson, Yehudit; Freger, Vita; Avraham, Ziva; Venken, Koen J. T.; Bellen, Hugo J.; Justice, Monica J.; Wides, Ron

    2011-01-01

    The Drosophila Ten-m (also called Tenascin-major, or odd Oz (odz)) gene has been associated with a pair-rule phenotype. We identified and characterized new alleles of Drosophila Ten-m to establish that this gene is not responsible for segmentation defects but rather causes defects in motor neuron axon routing. In Ten-m mutants the inter-segmental nerve (ISN) often crosses segment boundaries and fasciculates with the ISN in the adjacent segment. Ten-m is expressed in the central nervous system and epidermal stripes during the stages when the growth cones of the neurons that form the ISN navigate to their targets. Over-expression of Ten-m in epidermal cells also leads to ISN misrouting. We also found that Filamin, an actin binding protein, physically interacts with the Ten-m protein. Mutations in cheerio, which encodes Filamin, cause defects in motor neuron axon routing like those of Ten-m. During embryonic development, the expression of Filamin and Ten-m partially overlap in ectodermal cells. These results suggest that Ten-m and Filamin in epidermal cells might together influence growth cone progression. PMID:21857973

  9. A hybrid computational model to predict chemotactic guidance of growth cones

    PubMed Central

    Roccasalvo, Iolanda Morana; Micera, Silvestro; Sergi, Pier Nicola

    2015-01-01

    The overall strategy used by growing axons to find their correct paths during the nervous system development is not yet completely understood. Indeed, some emergent and counterintuitive phenomena were recently described during axon pathfinding in presence of chemical gradients. Here, a novel computational model is presented together with its ability to reproduce both regular and counterintuitive axonal behaviours. In this model, the key role of intracellular calcium was phenomenologically modelled through a non standard Gierer-Meinhardt system, as a crucial factor influencing the growth cone behaviour both in regular and complex conditions. This model was able to explicitly reproduce neuritic paths accounting for the complex interplay between extracellular and intracellular environments, through the sensing capability of the growth cone. The reliability of this approach was proven by using quantitative metrics, numerically supporting the similarity between in silico and biological results in regular conditions (control and attraction). Finally, the model was able to qualitatively predict emergent and counterintuitive phenomena resulting from complex boundary conditions. PMID:26086936

  10. Evaluation of deformable image registration for contour propagation between CT and cone-beam CT images in adaptive head and neck radiotherapy.

    PubMed

    Li, X; Zhang, Y Y; Shi, Y H; Zhou, L H; Zhen, X

    2016-04-29

    Deformable image registration (DIR) is a critical technic in adaptive radiotherapy (ART) to propagate contours between planning computerized tomography (CT) images and treatment CT/Cone-beam CT (CBCT) image to account for organ deformation for treatment re-planning. To validate the ability and accuracy of DIR algorithms in organ at risk (OAR) contours mapping, seven intensity-based DIR strategies are tested on the planning CT and weekly CBCT images from six Head & Neck cancer patients who underwent a 6 ∼ 7 weeks intensity-modulated radiation therapy (IMRT). Three similarity metrics, i.e. the Dice similarity coefficient (DSC), the percentage error (PE) and the Hausdorff distance (HD), are employed to measure the agreement between the propagated contours and the physician delineated ground truths. It is found that the performance of all the evaluated DIR algorithms declines as the treatment proceeds. No statistically significant performance difference is observed between different DIR algorithms (p> 0.05), except for the double force demons (DFD) which yields the worst result in terms of DSC and PE. For the metric HD, all the DIR algorithms behaved unsatisfactorily with no statistically significant performance difference (p= 0.273). These findings suggested that special care should be taken when utilizing the intensity-based DIR algorithms involved in this study to deform OAR contours between CT and CBCT, especially for those organs with low contrast. PMID:27259084

  11. Substrate Availability of Mutant SPT Alters Neuronal Branching and Growth Cone Dynamics in Dorsal Root Ganglia

    PubMed Central

    Jun, Byung Kyu; Chandra, Ankush; Kuljis, Dika; Schmidt, Brian P.

    2015-01-01

    Serine palmitoyltransferase (SPT) is a key enzyme in the first step of sphingolipid biosynthesis. Mutations in the SPTLC1 gene that encodes for SPT subunits cause hereditary sensory neuropathy type 1. However, little is understood about how mutant SPT regulates mechanisms of sensory neuron and axonal growth. Using transgenic mice overexpressing the C133W SPT mutant, we found that mutant dorsal root ganglia (DRG) during growth in vitro exhibit increased neurite length and branching, coinciding with elevated expression of actin-cross-linking proteins at the neuronal growth cone, namely phosphorylated Ezrin/Radixin/Moesin. In addition, inhibition of SPT was able to reverse the mutant phenotype. Because mutant SPT preferentially uses l-alanine over its canonical substrate l-serine, we also investigated the effects of substrate availability on DRG neurons. Supplementation with l-serine or removal of l-alanine independently restored normal growth patterns in mutant SPTLC1C133W DRG. Therefore, we report that substrate availability and selectivity of SPT influence the regulation of neurite growth in DRG neurons. SIGNIFICANCE STATEMENT Hereditary sensory neuropathy type 1 is an autosomal-dominant disorder that leads to a sensory neuropathy due to mutations in the serine palmitoyltransferase (SPT) enzyme. We investigated how mutant SPT and substrate levels regulate neurite growth. Because SPT is an important enzyme in the synthesis of sphingolipids, our data are of broader significance to other peripheral and metabolic disorders. PMID:26446223

  12. Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone

    PubMed Central

    1988-01-01

    Actions of cytochalasin B (CB) on cytoskeletons and motility of growth cones from cultured Aplysia neurons were studied using a rapid flow perfusion chamber and digital video light microscopy. Living growth cones were observed using differential interference contrast optics and were also fixed at various time points to assay actin filament (F- actin) and microtubule distributions. Treatment with CB reversibly blocked motility and eliminated most of the phalloidin-stainable F- actin from the leading lamella. The loss of F-actin was nearly complete within 2-3 min of CB application and was largely reversed within 5-6 min of CB removal. The loss and recovery of F-actin were found to occur with a very distinctive spatial organization. Within 20-30 s of CB application, F-actin networks receded from the entire peripheral margin of the lamella forming a band devoid of F-actin. This band widened as F- actin receded at rates of 3-6 microns/min. Upon removal of CB, F-actin began to reappear within 20-30 s. The initial reappearance of F-actin took two forms: a coarse isotropic matrix of F-actin bundles throughout the lamella, and a denser matrix along the peripheral margin. The denser peripheral matrix then expanded in width, extending centrally to replace the coarse matrix at rates again between 3-6 microns/min. These results suggest that actin normally polymerizes at the leading edge and then flows rearward at a rate between 3-6 microns/min. CB treatment was also observed to alter the distribution of microtubules, assayed by antitubulin antibody staining. Normally, microtubules are restricted to the neurite shaft and a central growth cone domain. Within approximately 5 min after CB application, however, microtubules began extending into the lamellar region, often reaching the peripheral margin. Upon removal of CB, the microtubules were restored to their former central localization. The timing of these microtubule redistributions is consistent with their being secondary to

  13. Bidirectional interactions between NOX2-type NADPH oxidase and the F-actin cytoskeleton in neuronal growth cones

    PubMed Central

    Munnamalai, Vidhya; Weaver, Cory J.; Weisheit, Corinne E.; Venkatraman, Prahatha; Agim, Zeynep Sena; Quinn, Mark T.; Suter, Daniel M.

    2014-01-01

    NADPH oxidases are important for neuronal function but detailed subcellular localization studies have not been performed. Here, we provide the first evidence for the presence of functional NOX2-type NADPH oxidase complex in neuronal growth cones and its bidirectional relationship with the actin cytoskeleton. NADPH oxidase inhibition resulted in reduced F-actin content, retrograde F-actin flow, and neurite outgrowth. Stimulation of NADPH oxidase via protein kinase C activation increased levels of hydrogen peroxide in the growth cone periphery. The main enzymatic NADPH oxidase subunit NOX2/gp91phox localized to the growth cone plasma membrane and showed little overlap with the regulatory subunit p40phox. p40phox itself exhibited co-localization with filopodial actin bundles. Differential subcellular fractionation revealed preferential association of NOX2/gp91phox and p40phox with the membrane and the cytoskeletal fraction, respectively. When neurite growth was evoked with beads coated with the cell adhesion molecule apCAM, we observed a significant increase in co-localization of p40phox with NOX2/gp91phox at apCAM adhesion sites. Together, these findings suggest a bidirectional functional relationship between NADPH oxidase activity and the actin cytoskeleton in neuronal growth cones, which contributes to the control of neurite outgrowth. PMID:24702317

  14. Daily Image Guidance With Cone-Beam Computed Tomography for Head-and-Neck Cancer Intensity-Modulated Radiotherapy: A Prospective Study

    SciTech Connect

    Den, Robert B.; Doemer, Anthony; Kubicek, Greg; Bednarz, Greg; Galvin, James M.; Keane, William M.; Xiao Ying; Machtay, Mitchell

    2010-04-15

    Purpose: To report on a prospective clinical trial of the use of daily kilovoltage cone-beam computed tomography (CBCT) to evaluate the interfraction and residual error motion of patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. Methods and Materials: Patients were treated with intensity-modulated radiotherapy with an Elekta linear accelerator using a mounted CBCT scanner. CBCT was performed before every treatment, and translational (but not rotational) corrections were performed. At least once per week, a CBCT scan was obtained after intensity-modulated radiotherapy. Variations were measured in the medial-lateral, superoinferior, and anteroposterior dimensions, as well as in the rotation around these axes. Results: A total of 28 consecutive patients (1,013 CBCT scans) were studied. The average interfraction shift was 1.4 +- 1.4, 1.7 +- 1.9, and 1.8 +- 2.1 mm in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. The corresponding average residual error shifts were 0.7 +- 0.8, 0.9 +- 0.9, and 0.9 +- 0.9 mm. These data indicate that in the absence of daily CBCT image-guided radiotherapy, a clinical target volume to planning target volume margin of 3.9, 4.1, and 4.9 mm is needed in the medial-lateral, superoinferior, and anteroposterior dimensions, respectively. With daily CBCT, corresponding margins of 1.6, 2.5, and 1.9 mm should be acceptable. Subgroup analyses showed that larynx cancers and/or intratreatment weight loss indicate a need for slightly larger clinical target volume to planning target volume margins. Conclusion: The results of our study have shown that image-guided radiotherapy using CBCT for head-and-neck cancer is effective. These data suggest it allows a reduction in the clinical target volume to planning target volume margins by about 50%, which could facilitate future studies of dose escalation and/or improved toxicity reduction. Caution is particularly warranted for cases in which the

  15. Measurement of Mandibular Growth Using Cone-Beam Computed Tomography: A Miniature Pig Model Study

    PubMed Central

    Li, Jia-Da; Lu, Tung-Wu; Chang, Hau-Hung; Hu, Chih-Chung

    2014-01-01

    The purpose of this study was to measure the long-term growth of the mandible in miniature pigs using 3D Cone-Beam Computerized Tomography (CBCT). The mandibles of the pigs were scanned monthly over 12 months using CBCT and the 3D mandibular models were reconstructed from the data. Seventeen anatomical landmarks were identified and classified into four groups of line segments, namely anteroposterior, superoinferior, mediolateral and anteroinferior. The inter-marker distances, inter-segmental angles, volume, monthly distance changes and percentage of changes were calculated to describe mandibular growth. The total changes of inter-marker distances were normalized to the initial values. All inter-marker distances increased over time, with the greatest mean normalized total changes in the superoinferior and anteroposterior groups (p<0.05). Monthly distance changes were greatest during the first four months and then reduced over time. Percentages of inter-marker distance changes were similar among the groups, reaching half of the overall growth around the 4th month. The mandibular volume growth increased non-linearly with time, accelerating during the first five months and slowing during the remaining months. The growth of the mandible was found to be anisotropic and non-homogeneous within the bone and non-linear over time, with faster growth in the ramus than in the body. These growth patterns appeared to be related to the development of the dentition, providing necessary space for the teeth to grow upward for occlusion and for the posterior teeth to erupt. PMID:24801528

  16. Deformation and flow of membrane into tethers extracted from neuronal growth cones.

    PubMed Central

    Hochmuth, F M; Shao, J Y; Dai, J; Sheetz, M P

    1996-01-01

    Membrane tethers are extracted at constant velocity from neuronal growth cones using a force generated by a laser tweezers trap. A thermodynamic analysis shows that as the tether is extended, energy is stored in the tether as bending and adhesion energies and in the cell body as "nonlocal" bending. It is postulated that energy is dissipated by three viscous mechanisms including membrane flow, slip between the two monolayers that form the bilayer, and slip between membrane and cytoskeleton. The analysis predicts and the experiments show a linear relation between tether force and tether velocity. Calculations based on the analytical results and the experimental measurements of a tether radius of approximately 0.2 micron and a tether force at zero velocity of approximately 8 pN give a bending modulus for the tether of 2.7 x 10(-19) N.m and an extraordinarily small "apparent surface tension" in the growth cone of 0.003 mN/m, where the apparent surface tension is the sum of the far-field, in-plane tension and the energy of adhesion. Treatments with cytochalasin B and D, ethanol, and nocodazole affect the apparent surface tension but not bending. ATP depletion affects neither, whereas large concentrations of DMSO affect both. Under conditions of flow, data are presented to show that the dominant viscous mechanism comes from the slip that occurs when the membrane flows over the cytoskeleton. ATP depletion and the treatment with DMSO cause a dramatic drop in the effective viscosity. If it is postulated that the slip between membrane and cytoskeleton occurs in a film of water, then this water film has a mean thickness of only approximately 10 A. Images FIGURE 1 FIGURE 4 FIGURE 7 FIGURE 8 PMID:8770212

  17. CRMP4 and CRMP2 Interact to Coordinate Cytoskeleton Dynamics, Regulating Growth Cone Development and Axon Elongation.

    PubMed

    Tan, Minghui; Cha, Caihui; Ye, Yongheng; Zhang, Jifeng; Li, Sumei; Wu, Fengming; Gong, Sitang; Guo, Guoqing

    2015-01-01

    Cytoskeleton dynamics are critical phenomena that underpin many fundamental cellular processes. Collapsin response mediator proteins (CRMPs) are highly expressed in the developing nervous system, mediating growth cone guidance, neuronal polarity, and axonal elongation. However, whether and how CRMPs associate with microtubules and actin coordinated cytoskeletal dynamics remain unknown. In this study, we demonstrated that CRMP2 and CRMP4 interacted with tubulin and actin in vitro and colocalized with the cytoskeleton in the transition-zone in developing growth cones. CRMP2 and CRMP4 also interacted with one another coordinately to promote growth cone development and axonal elongation. Genetic silencing of CRMP2 enhanced, whereas overexpression of CRMP2 suppressed, the inhibitory effects of CRMP4 knockdown on axonal development. In addition, knockdown of CRMP2 or overexpression of truncated CRMP2 reversed the promoting effect of CRMP4. With the overexpression of truncated CRMP2 or CRMP4 lacking the cytoskeleton interaction domain, the promoting effect of CRMP was suppressed. These data suggest a model in which CRMP2 and CRMP4 form complexes to bridge microtubules and actin and thus work cooperatively to regulate growth cone development and axonal elongation.

  18. Oxygen Radicals Elicit Paralysis and Collapse of Spinal Cord Neuron Growth Cones upon Exposure to Proinflammatory Cytokines

    PubMed Central

    Kuhn, Thomas B.

    2014-01-01

    A persistent inflammatory and oxidative stress is a hallmark of most chronic CNS pathologies (Alzheimer's (ALS)) as well as the aging CNS orchestrated by the proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β). Loss of the integrity and plasticity of neuronal morphology and connectivity comprises an early step in neuronal degeneration and ultimate decline of cognitive function. We examined in vitro whether TNFα or IL-1β impaired morphology and motility of growth cones in spinal cord neuron cultures. TNFα and IL-1β paralyzed growth cone motility and induced growth cone collapse in a dose-dependent manner reflected by complete attenuation of neurite outgrowth. Scavenging reactive oxygen species (ROS) or inhibiting NADPH oxidase activity rescued loss of neuronal motility and morphology. TNFα and IL-1β provoked rapid, NOX-mediated generation of ROS in advancing growth cones, which preceded paralysis of motility and collapse of morphology. Increases in ROS intermediates were accompanied by an aberrant, nonproductive reorganization of actin filaments. These findings suggest that NADPH oxidase serves as a pivotal source of oxidative stress in neurons and together with disruption of actin filament reorganization contributes to the progressive degeneration of neuronal morphology in the diseased or aging CNS. PMID:25050325

  19. Disruption of pioneer growth cone guidance in vivo by removal of glycosyl-phosphatidylinositol-anchored cell surface proteins.

    PubMed

    Chang, W S; Serikawa, K; Allen, K; Bentley, D

    1992-02-01

    Cell surface proteins anchored to membranes via covalently attached glycosyl-phosphatidylinositol (GPI) have been implicated in neuronal adhesion, promotion of neurite outgrowth and directed cell migration. Treatment of grasshopper embryos with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme that cleaves the GPI anchor, often induced disruptions in the highly stereotyped migrations of peripheral pioneer growth cones and afferent neuron cell bodies. In distal limb regions of embryos treated with PI-PLC at early stages of pioneer axon outgrowth, growth cones lost their proximal orientation toward the central nervous system (CNS) and turned distally. Pioneer growth cones in treated limbs also failed to make a characteristic ventral turn along the trochanter-coxa (Tr-Cx) segment boundary, and instead continued to grow proximally across the boundary. Treatment at an earlier stage of development caused pre-axonogenesis Cx1 neurons to abandon their normal circumferential migration and reorient toward the CNS. None of these abnormal phenotypes were observed in limbs of untreated embryos or embryos exposed to other phospholipases that do not release GPI-anchored proteins. Incubation of embryos with PI-PLC effectively removed immunoreactivity for fasciclin I, a GPI-anchored protein expressed on a subset of neuronal surfaces. These results suggest that cell surface GPI-anchored proteins are involved in pioneer growth cone guidance and in pre-axonogenesis migration of neurons in the grasshopper limb bud in vivo.

  20. Growth of microscopic cones on titanium cathodes of sputter-ion pumps driven by sorption of large argon quantities

    SciTech Connect

    Porcelli, Tommaso; Siviero, Fabrizio; Bongiorno, Gero A.; Michelato, Paolo; Pagani, Carlo

    2015-09-15

    Microscopic cones have been observed on titanium cathodes of sputter-ion pumps (SIPs) after pump operation. The cones were studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Size and morphology of these cones are clearly correlated with the nature and the relative amount of each gas species pumped by each SIP during its working life. In particular, their growth was found to be fed by sputtering mechanisms, mostly during Ar pumping, and to be driven by the electromagnetic field applied to the Penning cells of each SIP. Experimental findings suggest that the formation and extent of such conic structures on cathode surfaces might play a leading role in the onset of phenomena typically related to the functioning of SIPs, e.g., the so-called argon instability.

  1. Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance

    PubMed Central

    Turney, Stephen G.; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B.; Goeckeler, Zoe M.; Rioux, Robert M.; Whitesides, George M.; Bridgman, Paul C.

    2016-01-01

    Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion–cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. PMID:26631553

  2. Targeting epidermal growth factor receptor for head and neck squamous cell carcinoma: still lost in translation?

    PubMed Central

    Chapman, Christopher H.; Saba, Nabil F.

    2016-01-01

    The epidermal growth factor receptor (EGFR) is preferentially expressed in head and neck squamous cell carcinoma (HNSCC), and is a promising therapeutic target. Yet other than cetuximab, no agent targeting EGFR has been approved for this disease, and none has shown benefit over the standard of care. Several randomized trials of antibody and small molecule agents have found no new indication for these agents, despite their initial promise. In this review, we examine the major clinical evidence and discuss potential future developments of translational science in this area, including use of these agents in risk-stratified subgroups, inhibition of downstream/parallel targets, and combination with immunotherapy. PMID:27004227

  3. D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

    PubMed Central

    Lankford, K L; DeMello, F G; Klein, W L

    1988-01-01

    Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators. Images PMID:3380807

  4. D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

    PubMed Central

    Lankford, K L; DeMello, F G; Klein, W L

    1988-01-01

    Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators. Images PMID:3357895

  5. Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth.

    PubMed

    Bhattacharya, Sourav; Muhammad, Naoshad; Steele, Robert; Peng, Guangyong; Ray, Ratna B

    2016-05-31

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and leading cause of cancer related mortality worldwide. Despite the advancement in treatment procedures the overall survival rate of patients has not considerably enhanced in the past few decades. Therefore, new strategies to achieve a favorable response for the improvement in the prognosis of HNSCC are urgently needed. In this study, we examined the role of bitter melon extract (BME) in HNSCC tumor microenvironment. Mouse head and neck cancer (SCCVII) cells were subcutaneously injected into the flanks of syngeneic mice. We observed that oral gavage of BME significantly inhibits the tumor growth in mice as compared to control group. Further study suggested that BME inhibits cell proliferation as evident from low expression of proliferating cell nuclear antigen (PCNA) and c-Myc in the tumors of BME fed mice as compared to that of control group. We next investigated the role of BME as an immunomodulator in HNSCC model. Forkhead box protein P3+ (FoxP3+) T cells suppress tumor immunity. Our data suggested that BME treatment decreases the infiltrating regulatory T (Treg) cells by inhibiting FoxP3+ populations in the tumors and in spleens. Additionally, BME treatment reduces Th17 cell population in the tumor. However, BME treatment did not alter Th1 and Th2 cell populations. Together, our findings offer a new insight into how bitter melon extract inhibits head and neck tumor growth by modulating cell proliferation and Treg populations, with implications for how to control tumor-infiltrating lymphocytes and tumor progression. PMID:27120805

  6. Intraoperative cone-beam CT for guidance of head and neck surgery: Assessment of dose and image quality using a C-arm prototype.

    PubMed

    Daly, M J; Siewerdsen, J H; Moseley, D J; Jaffray, D A; Irish, J C

    2006-10-01

    Cone-beam computed tomography (CBCT) with a flat-panel detector represents a promising modality for intraoperative imaging in interventional procedures, demonstrating sub-mm three-dimensional (3D) spatial resolution and soft-tissue visibility. Measurements of patient dose and in-room exposure for CBCT-guided head and neck surgery are reported, and the 3D imaging performance as a function of dose and other acquisition/reconstruction parameters is investigated. Measurements were performed on a mobile isocentric C-arm (Siemens PowerMobil) modified in collaboration with Siemens Medical Solutions (Erlangen, Germany) to provide flat-panel CBCT. Imaging dose was measured in a custom-built 16 cm cylindrical head phantom at four positions (isocenter, anterior, posterior, and lateral) as a function of kVp (80-120 kVp) and C-arm trajectory ("tube-under" and "tube-over" half-rotation orbits). At 100 kVp, for example ("tube-under" orbit), the imaging dose was 0.059 (isocenter), 0.022 (anterior), 0.10 (posterior), and 0.056 (lateral) mGy/ mAs, with scans at approximately 50 and approximately 170 mAs typical for visualization of bony and soft-tissue structures, respectively. Dose to radiosensitive structures (viz., the eyes and thyroid) were considered in particular: significant dose sparing to the eyes (a factor of 5) was achieved using a "tube-under" (rather than "tube-over") half-rotation orbit; a thyroid shield (0.5 mm Pb-equivalent) gave moderate reduction in thyroid dose due to x-ray scatter outside the primary field of view. In-room exposure was measured at positions around the operating table and up to 2 m from isocenter. A typical CBCT scan (10 mGy to isocenter) gave in-air exposure ranging from 29 mR (0.26 mSv) at 35 cm from isocenter, to <0.5 mR (<0.005 mSv) at 2 m from isocenter. Three-dimensional (3D) image quality was assessed in CBCT reconstructions of an anthropomorphic head phantom containing contrast-detail spheres (11-103 HU; 1.6-12.7 mm) and a natural human

  7. Volumetric and dosimetric assessment by cone-beam computed tomography scans in head and neck radiation therapy: a monitoring in four phases of treatment.

    PubMed

    Cozzolino, M; Fiorentino, A; Oliviero, C; Pedicini, P; Clemente, S; Califano, G; Caivano, R; Chiumento, C; Fusco, V

    2014-08-01

    Due to the anatomical changes frequently occurring during the course of head and neck (H&N) cancer radiotherapy, the dose distribution, which was actually delivered to the patient, might significantly differ from that planned. The aim of this paper is to investigate these volumetric changes and the resulting dosimetric implications on organs at risk (OARs) and clinical target volumes (CTVs) by cone beam computed tomography (CBCT) scans throughout the treatment. Ten H&N patients, treated by Intensity Modulated Radiotherapy, were analyzed. CTVs and OARs were delineated on four CBCT, acquired at the 10(th), 15(th), 20(th) and 25(th) treatment session, and then compared with the ones at planning CT. The planned beams were applied to each CBCT to recalculate the dose distribution and the corresponding dose volume histograms were compared with those generated on planning CT. To evaluate the HU discrepancies between the conventional CT and CBCT images we used a Catphan(r) 504, observing a maximum discrepancy of about 30 HU. We evaluated the impact of this HU difference in dose calculation and a not clinically relevant error, within 2.8%, was estimated. No inhomogeneity correction was used. The results showed an increased CTV mean dose (Dmean) of about 3% was found, without significant reduction in volume. Due to the parotids' shrinkage (up to 42%), significant dosimetric increases were observed: ipsilateral gland at 15th CBCT (Dmean by 18%; V30 by 31%); controlateral gland at the 10(th) CBCT (Dmean by 12.2%; V30 by 18.7%). For the larynx, a significant increase of volume was found at the 20th (15.7%) and 25th CBCT (13.3%) but it complied with dose constraint. The differences observed for the spinal cord and mandible maximum doses were not clinically relevant. In conclusion, the dosimetric analysis on CBCT can help clinicians to monitor treatment progress and to evaluate whether and when a new plan is necessary. The main benefit of replanning could be to preserve the

  8. Cyclic AMP reduces adhesion of isolated neuronal growth cones from developing rat forebrain to an astrocytic cell line from embryonic mouse striatum.

    PubMed

    Lockerbie, R O; Autillo-Touati, A; Araud, D; Seite, R; Chneiweiss, H; Glowinski, J; Prochiantz, A

    1989-01-01

    We have recently shown that isolated neuronal growth cones from developing rat forebrain possess an appreciable activity of adenylate cyclase, producing cyclic adenosine monophosphate, which can be stimulated by various neurotransmitter receptor agonists and by forskolin [Lockerbie R. O., Hervé D., Blanc G., Tassin J. P. and Glowinski J. (1988) Devl Brain Res. 38, 19-25]. In the present study, we have investigated the effect of cyclic adenosine monophosphate in an in vitro adhesion assay established between [3H]GABA-labelled isolated growth cones and a Simian virus-40 transformed astrocytic cell line from embryonic mouse striatum. Adhesion of the isolated growth cones onto the astrocytic clone increased steadily up to about 45 min before it began to level off at ca 16-18% of total [3H]GABA-labelled isolated growth cones added. Adhesion of the isolated growth cones onto the astrocytic clone was much superior to that seen on polyornithine and, in particular, on non-treated tissue culture wells. Adhesion "at plateau" was independent of both temperature and extracellular Ca2+ and was markedly reduced (ca 50%) by trypsin pre-treatment of the isolated growth cones. Pre-treatment of the isolated growth cones with either forskolin or lipophilic analogues of cyclic adenosine monophosphate attenuated adhesion in a time- and concentration-dependent manner. Approximately 30% reduction in adhesion to the astrocytic clone "at plateau" was observed after a 15 min pre-treatment of the isolated growth cones with forskolin at 10(-4) M or cyclic adenosine monophosphate analogues at 10(-3) M. A cyclic guanosine monophosphate analogue was without effect on adhesion of isolated growth cones. Scanning electron microscope analysis showed that isolated growth cones pre-treated with either cyclic adenosine monophosphate analogues or forskolin had a simpler morphology when attached to the astrocytic clone than isolated growth cones under control conditions. Pre-treatment of the isolated

  9. Amplification and Temporal Filtering during Gradient Sensing by Nerve Growth Cones Probed with a Microfluidic Assay

    PubMed Central

    Morel, Mathieu; Shynkar, Vasyl; Galas, Jean-Christophe; Dupin, Isabelle; Bouzigues, Cedric; Studer, Vincent; Dahan, Maxime

    2012-01-01

    Nerve growth cones (GCs) are chemical sensors that convert graded extracellular cues into oriented axonal motion. To ensure a sensitive and robust response to directional signals in complex and dynamic chemical landscapes, GCs are presumably able to amplify and filter external information. How these processing tasks are performed remains however poorly known. Here, we probe the signal-processing capabilities of single GCs during γ-Aminobutyric acid (GABA) directional sensing with a shear-free microfluidic assay that enables systematic measurements of the GC output response to variable input gradients. By measuring at the single molecule level the polarization of GABAA chemoreceptors at the GC membrane, as a function of the external GABA gradient, we find that GCs act as i), signal amplifiers over a narrow range of concentrations, and ii), low-pass temporal filters with a cutoff frequency independent of stimuli conditions. With computational modeling, we determine that these systems-level properties arise at a molecular level from the saturable occupancy response and the lateral dynamics of GABAA receptors. PMID:23083707

  10. An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro

    PubMed Central

    Chitsaz, Daryan; Morales, Daniel; Law, Chris; Kania, Artur

    2015-01-01

    During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs) to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as “collapsed” or “extended”. The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in ‘collapsed’ GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay. PMID:26496644

  11. Short window of opportunity for calpain induced growth cone formation after axotomy of Aplysia neurons.

    PubMed

    Gitler, Daniel; Spira, Micha E

    2002-09-15

    Our laboratory has established that local activation of calpain by a transient elevation of the free intracellular calcium concentration is crucial for the induction of growth cone (GC) formation in cultured Aplysia neurons. The mechanisms and stages in which calpain is involved in the formation of a GC are not known. We began to study these questions by determining the nature of calpain's action and the stages in which calpain activity affects the cascade of events that leads to the formation of the GC and its extension. We report that the calpain-dependent transformation of an axonal segment into a GC occurs within a narrow window of opportunity that lasts approximately 5 min. If calpain is inhibited during this window of opportunity, GC formation does not occur. Inhibition of calpain after the window of opportunity slows down the rate of lamellipodial extension but doesn't arrest it. The proteolysis of spectrin, a calpain substrate and a major component of the membrane skeleton, occurs within this window of opportunity, in agreement with the hypothesis that spectrin proteolysis is an early step in the formation of the GC. If the onset of proteolysis is deferred, spectrin remains unchanged and GC formation is compromised. We suggest that calpain participates in two different processes: it is critical for the triggering of GC formation and plays a modulatory role during the extension of the GC's lamellipodia.

  12. An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro.

    PubMed

    Chitsaz, Daryan; Morales, Daniel; Law, Chris; Kania, Artur

    2015-01-01

    During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs) to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as "collapsed" or "extended". The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in 'collapsed' GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay. PMID:26496644

  13. The Role of Rac1 in the Growth Cone Dynamics and Force Generation of DRG Neurons

    PubMed Central

    Sayyad, Wasim A.; Fabris, Paolo; Torre, Vincent

    2016-01-01

    We used optical tweezers, video imaging, immunocytochemistry and a variety of inhibitors to analyze the role of Rac1 in the motility and force generation of lamellipodia and filopodia from developing growth cones of isolated Dorsal Root Ganglia neurons. When the activity of Rac1 was inhibited by the drug EHop-016, the period of lamellipodia protrusion/retraction cycles increased and the lamellipodia retrograde flow rate decreased; moreover, the axial force exerted by lamellipodia was reduced dramatically. Inhibition of Arp2/3 by a moderate amount of the drug CK-548 caused a transient retraction of lamellipodia followed by a complete recovery of their usual motility. This recovery was abolished by the concomitant inhibition of Rac1. The filopodia length increased upon inhibition of both Rac1 and Arp2/3, but the speed of filopodia protrusion increased when Rac1 was inhibited and decreased instead when Arp2/3 was inhibited. These results suggest that Rac1 acts as a switch that activates upon inhibition of Arp2/3. Rac1 also controls the filopodia dynamics necessary to explore the environment. PMID:26766136

  14. The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines.

    PubMed

    John, Kaarthik; Lahoti, Tejas S; Wagner, Kelly; Hughes, Jarod M; Perdew, Gary H

    2014-10-01

    Previous studies in head and neck squamous cell carcinoma (HNSCC) cell lines have revealed that the Ah receptor (AHR) plays a significant role in mediating the "aggressive" phenotype of these cells, which includes enhanced inflammatory signaling (e.g., IL6) and migratory potential. Here we sought to identify putative novel targets of the AHR associated with enhanced tumor invasiveness. Global gene expression analysis identified a number of genes that are repressed upon treatment of OSC-19 or HN30 cells with an AHR antagonist. Three growth factors were targets of AHR activity; amphiregulin (AREG), epiregulin (EREG), and platelet-derived growth factor A (PDGFA) were repressed by an AHR antagonist and further examined. Quantitative PCR analysis, ELISA, and siRNA-mediated knock down of AHR revealed an attenuation of basal and/or induced levels of expression of these growth factors in two HNSCC lines, following AHR antagonism. In silico analysis revealed that these growth factors possess dioxin-like response elements. Two other AHR ligands, 6-formylindolo[3,2-b]carbazole and benzo(a)pyrene (BP) also elicited similar responses. In conclusion, this study identified AREG, EREG, and PDGFA as growth factor targets of AHR activity associated with metastatic phenotype of HNSCC cells, suggesting that attenuation of AHR activity may be a therapeutic strategy.

  15. Novel inhibitory action of tunicamycin homologues suggests a role for dynamic protein fatty acylation in growth cone-mediated neurite extension

    PubMed Central

    1994-01-01

    In neuronal growth cones, the advancing tips of elongating axons and dendrites, specific protein substrates appear to undergo cycles of posttranslational modification by covalent attachment and removal of long-chain fatty acids. We show here that ongoing fatty acylation can be inhibited selectively by long-chain homologues of the antibiotic tunicamycin, a known inhibitor of N-linked glycosylation. Tunicamycin directly inhibits transfer of palmitate to protein in a cell-free system, indicating that tunicamycin inhibition of protein palmitoylation reflects an action of the drug separate from its previously established effects on glycosylation. Tunicamycin treatment of differentiated PC12 cells or dissociated rat sensory neurons, under conditions in which protein palmitoylation is inhibited, produces a prompt cessation of neurite elongation and induces a collapse of neuronal growth cones. These growth cone responses are rapidly reversed by washout of the antibiotic, even in the absence of protein synthesis, or by addition of serum. Two additional lines of evidence suggest that the effects of tunicamycin on growth cones arise from its ability to inhibit protein long-chain acylation, rather than its previously established effects on protein glycosylation and synthesis. (a) The abilities of different tunicamycin homologues to induce growth cone collapse very systematically with the length of the fatty acyl side- chain of tunicamycin, in a manner predicted and observed for the inhibition of protein palmitoylation. Homologues with fatty acyl moieties shorter than palmitic acid (16 hydrocarbons), including potent inhibitors of glycosylation, are poor inhibitors of growth cone function. (b) The tunicamycin-induced impairment of growth cone function can be reversed by the addition of excess exogenous fatty acid, which reverses the inhibition of protein palmitoylation but has no effect on the inhibition of protein glycosylation. These results suggest an important role for

  16. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially. PMID:22617848

  17. G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1-phosphate.

    PubMed

    Fincher, Jarod; Whiteneck, Canaan; Birgbauer, Eric

    2014-01-01

    In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, i.e. the problem of axonal guidance. We used the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We showed that both LPA and S1P cause a specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences compared to the mouse but very similar to observations in Xenopus. Because LPA and S1P receptors are G-protein-coupled receptors, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibition of Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA- and S1P-induced collapse of chick retinal growth cones has a partial requirement for Gi/o. PMID:25138637

  18. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  19. Attenuation of actinomyosinII contractile activity in growth cones accelerates filopodia-guided and microtubule-based neurite elongation.

    PubMed

    Rösner, Harald; Möller, Wolfgang; Wassermann, Torsten; Mihatsch, Julia; Blum, Martin

    2007-10-24

    The myosinII-specific inhibitor blebbistatin was used to attenuate actinomyosinII contractility in E7-chicken retina explant, medulla and spinal cord neuronal cell cultures. Addition of 20-100 microM blebbistatin, a concentration range that reversibly disrupts actin stress fibers, led to a reduction of growth cone lamellipodial areas and to an elongation of filopodia within 5 to 10 min. These morphological changes were completely reversed after removing the inhibitor. In the continued presence of blebbistatin for several hours, a dose-dependent acceleration (up to 6-fold) of neurite outgrowth was observed. The rapidly elongating neuritic processes displayed narrowed growth cones with one to three long filopodia at the leading edge. At the same time, thin neuritic branches emerged in a "push"-like fashion guided by filopodial extensions. Immunocytochemical characterization of these thin sprouts revealed that they contained actin filaments, myosinIIA, phosphorylated neurofilament/tau epitopes, MAP2, NCAM-PSA, and microtubules, demonstrating that these processes presented neurites and not filopodia. The crucial involvement of microtubules in blebbistatin-induced accelerated neurite extension was confirmed by its inhibition in the presence of nocodazole or taxol. The promotion by blebbistatin of neurite outgrowth occurred on polylysine, laminin, as well as on fibronectin as substrate. The presence of the Rho/ROCK-inhibitor Y-27632 also caused a dose-dependent promotion of neurite growth which was, however, 3-fold less pronounced as compared to blebbistatin. In contrast to blebbistatin, Y-27632 led to the enlargement of growth cone lamellipodial extensions. Our data demonstrate that neurite outgrowth and branching are inversely correlated with the degree of actinomyosinII contractility which determines the speed of retrograde flow and turnover of actin filaments and, by this, microtubule extension.

  20. Stepwise Progress in Epidermal Growth Factor Receptor/Radiation Studies for Head and Neck Cancer

    SciTech Connect

    Harari, Paul M.

    2007-10-01

    The U.S. Food and Drug Administration approval of four new epidermal growth factor receptor (EGFR) inhibitors for cancer therapy (cetuximab, panitumumab, gefitinib, and erlotinib) over the last 3 years is a remarkable milestone in oncology. Indeed, molecular inhibition of EGFR signaling represents one of the most promising current arenas for the development of molecular-targeted cancer therapies. Epidermal growth factor receptor inhibitors from both the monoclonal antibody and tyrosine kinase inhibitor class have demonstrated clinical activity in the treatment of a broad spectrum of common human malignancies. For the discipline of radiation oncology, the 2006 report of a phase III trial demonstrating a survival advantage for advanced head and neck cancer patients with the addition of weekly cetuximab during a 7-week course of radiation is particularly gratifying. Indeed, this is the first phase III trial to confirm a survival advantage with the addition of a molecular-targeted agent to radiation. Furthermore, this result seems to have been achieved with only a modest increment in overall treatment toxicity and with very high compliance to the prescribed treatment regimen. Nevertheless, much remains to be learned regarding the rational integration of EGFR inhibitors into cancer treatment regimens, as well as methods to optimize the selection of patients most likely to benefit from EGFR inhibitor strategies.

  1. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed Central

    Zhang, J; Loew, L M; Davidson, R M

    1996-01-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells. PMID:8913589

  2. Negative guidance factor-induced macropinocytosis in the growth cone plays a critical role in repulsive axon turning

    PubMed Central

    Kolpak, Adrianne L.; Jiang, Jun; Guo, Daorong; Standley, Clive; Bellve, Karl; Fogarty, Kevin; Bao, Zheng-Zheng

    2009-01-01

    Macropinocytosis is a type of poorly characterized fluid-phase endocytosis which results in formation of relatively large vesicles. We report that Sonic hedgehog (Shh) protein induces macropinocytosis in the axons, through activation of a noncanonical signaling pathway including Rho GTPase and nonmuscle myosin II. Macropinocytosis induced by Shh is independent of clathrin-mediated endocytosis, but dependent on dynamin, myosin II and Rho GTPase activities. Inhibitors of macropinocytosis also abolished the negative effects of Shh on axonal growth including growth cone collapse and chemorepulsive axon turning, but not turning per se. On the other hand, activation of myosin II or treatment of phorbol ester induces macropinocytosis in the axons, elicits growth cone collapse and repulsive axon turning. Furthermore, macropinocytosis is also induced by ephrin-A2 and inhibition of dynamin abolished repulsive axon turning induced by ephrin-A2. Macropinocytosis can be induced ex vivo by high Shh, correlating with axon retraction. These results demonstrate that macropinocytosis-mediated membrane trafficking is an important cellular mechanism involved in axon chemorepulsion induced by negative guidance factors. PMID:19710302

  3. Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor.

    PubMed

    Singh, Tripti; Gupta, Nirzari A; Xu, Su; Prasad, Ram; Velu, Sadanandan E; Katiyar, Santosh K

    2015-08-28

    Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules. Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Administration of honokiol by oral gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu xenografts in athymic nude mice, which was associated with: (i) inhibition of tumor cell proliferation, (ii) induction of apoptosis, (iii) reduced expressions of cyclins and Cdks, and (iv) inhibition of EGFR signaling pathway. Molecular docking analysis of honokiol in EGFR binding site indicated that the chemotherapeutic effect of honokiol against HNSCC is mediated through its firm binding with EGFR, which is better than that of gefitinib, a commonly used drug for HNSCC treatment.

  4. Cytoskeletal social networking in the growth cone: How +TIPs mediate microtubule-actin cross-linking to drive axon outgrowth and guidance.

    PubMed

    Cammarata, Garrett M; Bearce, Elizabeth A; Lowery, Laura Anne

    2016-09-01

    The growth cone is a unique structure capable of guiding axons to their proper destinations. Within the growth cone, extracellular guidance cues are interpreted and then transduced into physical changes in the actin filament (F-actin) and microtubule cytoskeletons, providing direction and movement. While both cytoskeletal networks individually possess important growth cone-specific functions, recent data over the past several years point towards a more cooperative role between the two systems. Facilitating this interaction between F-actin and microtubules, microtubule plus-end tracking proteins (+TIPs) have been shown to link the two cytoskeletons together. Evidence suggests that many +TIPs can couple microtubules to F-actin dynamics, supporting both microtubule advance and retraction in the growth cone periphery. In addition, growing in vitro and in vivo data support a secondary role for +TIPs in which they may participate as F-actin nucleators, thus directly influencing F-actin dynamics and organization. This review focuses on how +TIPs may link F-actin and microtubules together in the growth cone, and how these interactions may influence axon guidance. © 2016 Wiley Periodicals, Inc.

  5. Lysophospholipid receptors LPA1–3 are not required for the inhibitory effects of LPA on mouse retinal growth cones

    PubMed Central

    Birgbauer, Eric; Chun, Jerold

    2016-01-01

    One of the major requirements in the development of the visual system is axonal guidance of retinal ganglion cells toward correct targets in the brain. A novel class of extracellular lipid signaling molecules, lysophospholipids, may serve as potential axon guidance cues. They signal through cognate G protein-coupled receptors, at least some of which are expressed in the visual system. Here we show that in the mouse visual system, a lysophospholipid known as lysophosphatidic acid (LPA) is inhibitory to retinal neurites in vitro when delivered extracellularly, causing growth cone collapse and neurite retraction. This inhibitory effect of LPA is both active in the nanomolar range and specific compared to the related lysophospholipid, sphingosine 1-phosphate (S1P). Knockout mice lacking three of the five known LPA receptors, LPA1–3, continue to display retinal growth cone collapse and neurite retraction in response to LPA, demonstrating that these three receptors are not required for these inhibitory effects and indicating the existence of one or more functional LPA receptors expressed on mouse retinal neurites that can mediate neurite retraction. PMID:26966392

  6. Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas

    PubMed Central

    Mineta, H; Miura, K; Ogino, T; Takebayashi, S; Misawa, K; Ueda, Y; Suzuki, I; Dictor, M; Borg, Å; Wennerberg, J

    2000-01-01

    Vascular endothelial growth factor (VEGF) has been identified as the substance that increases the permeability and proliferation of vascular endothelial cells. We examined the clinical significance of VEGF expression in 60 head and neck squamous cell carcinomas using the methods of Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and analysed the relationship between VEGF status in Western blot and tumour size, lymph-node status, histologic grade and disease-free survival (DFS) rate. Western blot analysis revealed high VEGF expressors (tumour/normal tissue density ≥ 3-fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients (57%). The results of the Western blot analysis correlated significantly with those of the RT-PCR (P= 0.00007) or immunohistochemistry (P= 0.00006). High VEGF expressors are associated with the progression of lymph-node spread (P= 0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF expressors (30%) was significantly lower than that of low VEGF expressors (78%) (P= 0.0008). Multivariate analysis showed VEGF expression and stage were independent predictors for the DFS (P= 0.045 and 0.041, respectively). VEGF expression may play an important role in progression of HNSCC. © 2000 Cancer Research Campaign PMID:10952783

  7. A Mechanism for the Polarity Formation of Chemoreceptors at the Growth Cone Membrane for Gradient Amplification during Directional Sensing

    PubMed Central

    Bouzigues, Cedric; Holcman, David; Dahan, Maxime

    2010-01-01

    Accurate response to external directional signals is essential for many physiological functions such as chemotaxis or axonal guidance. It relies on the detection and amplification of gradients of chemical cues, which, in eukaryotic cells, involves the asymmetric relocalization of signaling molecules. How molecular events coordinate to induce a polarity at the cell level remains however poorly understood, particularly for nerve chemotaxis. Here, we propose a model, inspired by single-molecule experiments, for the membrane dynamics of GABA chemoreceptors in nerve growth cones (GCs) during directional sensing. In our model, transient interactions between the receptors and the microtubules, coupled to GABA-induced signaling, provide a positive-feedback loop that leads to redistribution of the receptors towards the gradient source. Using numerical simulations with parameters derived from experiments, we find that the kinetics of polarization and the steady-state polarized distribution of GABA receptors are in remarkable agreement with experimental observations. Furthermore, we make predictions on the properties of the GC seen as a sensing, amplification and filtering module. In particular, the growth cone acts as a low-pass filter with a time constant ∼10 minutes determined by the Brownian diffusion of chemoreceptors in the membrane. This filtering makes the gradient amplification resistent to rapid fluctuations of the external signals, a beneficial feature to enhance the accuracy of neuronal wiring. Since the model is based on minimal assumptions on the receptor/cytoskeleton interactions, its validity extends to polarity formation beyond the case of GABA gradient sensing. Altogether, it constitutes an original positive-feedback mechanism by which cells can dynamically adapt their internal organization to external signals. PMID:20179770

  8. Method comparison of automated matching software-assisted cone-beam CT and stereoscopic kilovoltage x-ray positional verification image-guided radiation therapy for head and neck cancer: a prospective analysis

    NASA Astrophysics Data System (ADS)

    Fuller, Clifton D.; Scarbrough, Todd J.; Sonke, Jan-Jakob; Rasch, Coen R. N.; Choi, Mehee; Ting, Joe Y.; Wang, Samuel J.; Papanikolaou, Niko; Rosenthal, David I.

    2009-12-01

    We sought to characterize interchangeability and agreement between cone-beam computed tomography (CBCT) and digital stereoscopic kV x-ray (KVX) acquisition, two methods of isocenter positional verification currently used for IGRT of head and neck cancers (HNC). A cohort of 33 patients were near-simultaneously imaged by in-room KVX and CBCT. KVX and CBCT shifts were suggested using manufacturer software for the lateral (X), vertical (Y) and longitudinal (Z) dimensions. Intra-method repeatability, systematic and random error components were calculated for each imaging modality, as were recipe-based PTV expansion margins. Inter-method agreement in each axis was compared using limits of agreement (LOA) methodology, concordance analysis and orthogonal regression. 100 daily positional assessments were performed before daily therapy in 33 patients with head and neck cancer. Systematic error was greater for CBCT in all axes, with larger random error components in the Y- and Z-axis. Repeatability ranged from 9 to 14 mm for all axes, with CBCT showing greater repeatability in 2/3 axes. LOA showed paired shifts to agree 95% of the time within ±11.3 mm in the X-axis, ±9.4 mm in the Y-axis and ±5.5 mm in the Z-axis. Concordance ranged from 'mediocre' to 'satisfactory'. Proportional bias was noted between paired X- and Z-axis measures, with a constant bias component in the Z-axis. Our data suggest non-negligible differences in software-derived CBCT and KVX image-guided directional shifts using formal method comparison statistics. A correction was made to the first line of page 7404 of this article on 26 November 2009. The corrected electronic version is identical to the print version.

  9. Impact of targeting insulin-like growth factor signaling in head and neck cancers.

    PubMed

    Limesand, Kirsten H; Chibly, Alejandro Martinez; Fribley, Andrew

    2013-10-01

    The IGF system has been shown to have either negative or negligible impact on clinical outcomes of tumor development depending on specific tumor sites or stages. This review focuses on the clinical impact of IGF signaling in head and neck cancer, the effects of IGF targeted therapies, and the multi-dimensional role of IRS 1/2 signaling as a potential mechanism in resistance to targeted therapies. Similar to other tumor sites, both negative and positive correlations between levels of IGF-1/IGF-1-R and clinical outcomes in head and neck cancer have been reported. In addition, utilization of IGF targeted therapies has not demonstrated significant clinical benefit; therefore the prognostic impact of the IGF system on head and neck cancer remains uncertain.

  10. Cdc42 and Actin Control Polarized Expression of TI-VAMP Vesicles to Neuronal Growth Cones and Their Fusion with the Plasma MembraneV⃞

    PubMed Central

    Alberts, Philipp; Rudge, Rachel; Irinopoulou, Theano; Danglot, Lydia; Gauthier-Rouvière, Cécile; Galli, Thierry

    2006-01-01

    Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP)-mediated fusion of intracellular vesicles with the plasma membrane is crucial for neurite outgrowth, a pathway not requiring synaptobrevin-dependent exocytosis. Yet, it is not known how the TI-VAMP membrane trafficking pathway is regulated or how it is coordinated with cytoskeletal dynamics within the growth cone that guide neurite outgrowth. Here, we demonstrate that TI-VAMP, but not synaptobrevin 2, concentrates in the peripheral, F-actin-rich region of the growth cones of hippocampal neurons in primary culture. Its accumulation correlates with and depends upon the presence of F-actin. Moreover, acute stimulation of actin remodeling by homophilic activation of the adhesion molecule L1 induces a site-directed, actin-dependent recruitment of the TI-VAMP compartment. Expression of a dominant-positive mutant of Cdc42, a key regulator of cell polarity, stimulates formation of F-actin- and TI-VAMP-rich filopodia outside the growth cone. Furthermore, we report that Cdc42 activates exocytosis of pHLuorin tagged TI-VAMP in an actin-dependent manner. Collectively, our data suggest that Cdc42 and regulated assembly of the F-actin network control the accumulation and exocytosis of TI-VAMP-containing membrane vesicles in growth cones to coordinate membrane trafficking and actin remodeling during neurite outgrowth. PMID:16381811

  11. Cdc42 and actin control polarized expression of TI-VAMP vesicles to neuronal growth cones and their fusion with the plasma membrane.

    PubMed

    Alberts, Philipp; Rudge, Rachel; Irinopoulou, Theano; Danglot, Lydia; Gauthier-Rouvière, Cécile; Galli, Thierry

    2006-03-01

    Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP)-mediated fusion of intracellular vesicles with the plasma membrane is crucial for neurite outgrowth, a pathway not requiring synaptobrevin-dependent exocytosis. Yet, it is not known how the TI-VAMP membrane trafficking pathway is regulated or how it is coordinated with cytoskeletal dynamics within the growth cone that guide neurite outgrowth. Here, we demonstrate that TI-VAMP, but not synaptobrevin 2, concentrates in the peripheral, F-actin-rich region of the growth cones of hippocampal neurons in primary culture. Its accumulation correlates with and depends upon the presence of F-actin. Moreover, acute stimulation of actin remodeling by homophilic activation of the adhesion molecule L1 induces a site-directed, actin-dependent recruitment of the TI-VAMP compartment. Expression of a dominant-positive mutant of Cdc42, a key regulator of cell polarity, stimulates formation of F-actin- and TI-VAMP-rich filopodia outside the growth cone. Furthermore, we report that Cdc42 activates exocytosis of pHLuorin tagged TI-VAMP in an actin-dependent manner. Collectively, our data suggest that Cdc42 and regulated assembly of the F-actin network control the accumulation and exocytosis of TI-VAMP-containing membrane vesicles in growth cones to coordinate membrane trafficking and actin remodeling during neurite outgrowth.

  12. Further characterization of [3H]gamma-aminobutyric acid release from isolated neuronal growth cones: role of intracellular Ca2+ stores.

    PubMed

    Lockerbie, R O; Gordon-Weeks, P R

    1986-04-01

    We have recently shown that growth cones isolated from neonatal rat forebrain possess uptake and release mechanisms for the neurotransmitter gamma-aminobutyric acid. About half of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones is dependent on extracellular Ca2+. The remaining component of the [3H]gamma-aminobutyric acid release is unaffected by removal of extracellular Ca2+ and is resistant to blockade by the voltage-sensitive Ca2+-channel blocker methoxyverapamil. In the present series of experiments we have used caffeine to assess the possible role of intracellular stores of Ca2+ in supporting that component of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones that is independent of extracellular Ca2+. We have chosen caffeine because of its well established effect of releasing Ca2+ from smooth endoplasmic reticulum in muscle. We found that caffeine can release [3H]gamma-aminobutyric acid from isolated growth cones. This effect persists in Ca2+-free medium, in the presence of methoxyverapamil and in the absence of Na+. Furthermore, isobutylmethylxanthine could not substitute for caffeine suggesting that the caffeine effect is not due to phosphodiesterase inhibition and the subsequent rise in intracellular cyclic nucleotides. A combination of the mitochondrial poisons, Antimycin A and sodium azide had no effect on the release of [3H]gamma-aminobutyric acid induced either by caffeine or by high K+. We conclude that caffeine causes the release of Ca2+ from a non-mitochondrial store within the growth cone and that this Ca2+ store supports that component of the K+-induced release of [3H]gamma-aminobutyric acid that is independent of extracellular Ca2+.

  13. Uncertainties and CTV to PTV margins quantitative assessment using cone-beam CT technique in clinical application for prostate, and head and neck irradiation tumours.

    PubMed

    Juan-Senabre, X J; López-Tarjuelo, J; Conde-Moreno, A; Santos-Serra, A; Sánchez-Iglesias, A L; Quirós-Higueras, J D; de Marco Blancas, N; Calzada-Feliu, S; Ferrer-Albiach, C

    2011-11-01

    PURPOSE To evaluate the magnitude of systematic and random errors from a subset of 100 prostate and 26 head and neck (H&N) cancer patients treated with conventional conformal radiotherapy and using image-guided radiotherapy (IGRT). After treatment, the uncertainties involved and the CTV to PTV margin were evaluated. MATERIAL AND METHODS An Elekta Synergy® linear accelerator was used, taking advantage of 3D on-board computed tomography. IGRT with no-action level (NAL) protocol was applied, reporting the 3D translation and rotation corrections. A statistical study was performed to analyse systematic, random and interobserver uncertainties, and, finally, to obtain the CTV to PTV margins. RESULTS The H&N patients' uncertainties found were smaller than those of prostate patients. The CTV to PTV margins assessed, following the guidelines found in the literature, in the three dimensions of space (right-left, superior-inferior, anterior-posterior) were (5.3, 3.5, 3.2) mm for H&N and (7.3, 7.0, 9.0) mm for prostate cancer treatments. CONCLUSIONS It was found that assessing all the involved uncertainties within radiation treatments was very revealing; their quality improves using IGRT techniques and performing extensive data analysis. PMID:22082648

  14. IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer.

    PubMed

    Herbst, Roy S; Hong, Waun Ki

    2002-10-01

    Squamous cell carcinoma of the head and neck remains a clinical challenge because of the high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumors, including squamous cell carcinoma of the head and neck, is well understood; increased expression is associated with enhanced tumor invasiveness, resistance to chemotherapy, and a lower patient survival rate. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including the anti-EGFR monoclonal antibody IMC-C225, which competitively binds to the extracellular receptor site and prevents binding by the natural EGFR ligands EGF and transforming growth factor-alpha. Preclinical studies to evaluate IMC-225 in human cancer cell lines in vitro and human tumor xenografts in vivo have shown its potent antitumor activity. Clinical efficacy of IMC-C225 appears to involve multiple mechanisms, including inhibition of cell cycle progression, induction of apoptosis, inhibition of angiogenesis, inhibition of metastasis, and enhancement of the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation showed promising response rates in patients with recurrent or refractory squamous cell carcinoma of the head and neck. Phase II and III trials to examine the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m(2) loading dose, followed by weekly infusions at 250 mg/m(2).

  15. Cell Guidance on Nanogratings: A Computational Model of the Interplay between PC12 Growth Cones and Nanostructures

    PubMed Central

    Tonazzini, Ilaria; Cecchini, Marco; Micera, Silvestro

    2013-01-01

    Background Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites. Methodology/Principal Findings A synergistic procedure was used to study the mechanism of alignment of PC12 neurites with respect to the main direction of nanogratings. Finite Element simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation. After modelling all adhesions under non-spread growth cone and filopodial protrusions, the values of local stress maxima resulted from the length of filopodia. Since the stress was assumed to be the main triggering cause leading to the increase and stabilization of filopodia, the position of the local maxima was directly related to the orientation of neurites. An analytic closed form equation was then written to quantitatively assess the average ridge width needed to achieve a given neuritic alignment (R2 = 0.96), and the alignment course, when the ridge depth varied (R2 = 0.97). A computational framework was implemented within an improved free Java environment (CX3D) and in silico simulations were carried out to reproduce and predict biological experiments. No significant differences were found between biological experiments and in silico simulations (alignment, p = 0.3571; tortuosity, p = 0.2236) with a standard level of confidence (95%). Conclusions/Significance A mechanism involved in filopodial sensing of nanogratings is proposed and modelled through a synergistic use of FE models, theoretical equations and in silico simulations. This approach shows the importance of the neuritic terminal geometry, and the key role of the distribution of the adhesion constraints for the cell/substrate coupling process. Finally, the effects of the geometry of nanogratings were

  16. The dynein inhibitor Ciliobrevin D inhibits the bidirectional transport of organelles along sensory axons and impairs NGF-mediated regulation of growth cones and axon branches.

    PubMed

    Sainath, Rajiv; Gallo, Gianluca

    2015-07-01

    The axonal transport of organelles is critical for the development, maintenance, and survival of neurons, and its dysfunction has been implicated in several neurodegenerative diseases. Retrograde axon transport is mediated by the motor protein dynein. In this study, using embryonic chicken dorsal root ganglion neurons, we investigate the effects of Ciliobrevin D, a pharmacological dynein inhibitor, on the transport of axonal organelles, axon extension, nerve growth factor (NGF)-induced branching and growth cone expansion, and axon thinning in response to actin filament depolymerization. Live imaging of mitochondria, lysosomes, and Golgi-derived vesicles in axons revealed that both the retrograde and anterograde transport of these organelles was inhibited by treatment with Ciliobrevin D. Treatment with Ciliobrevin D reversibly inhibits axon extension and transport, with effects detectable within the first 20 min of treatment. NGF induces growth cone expansion, axonal filopodia formation and branching. Ciliobrevin D prevented NGF-induced formation of axonal filopodia and branching but not growth cone expansion. Finally, we report that the retrograde reorganization of the axonal cytoplasm which occurs on actin filament depolymerization is inhibited by treatment with Ciliobrevin D, indicating a role for microtubule based transport in this process, as well as Ciliobrevin D accelerating Wallerian degeneration. This study identifies Ciliobrevin D as an inhibitor of the bidirectional transport of multiple axonal organelles, indicating this drug may be a valuable tool for both the study of dynein function and a first pass analysis of the role of axonal transport.

  17. Live visualization of protein synthesis in axonal growth cones by microinjection of photoconvertible Kaede into Xenopus embryos

    PubMed Central

    Leung, Kin-Mei; Holt, Christine E

    2013-01-01

    Photoconvertible fluorescent proteins, such as Kaede, can be switched irreversibly from their native color to a new one. This property can be exploited to visualize de novo mRNA translation, because newly synthesized proteins can be distinguished from preexisting ones by their color. In this protocol, Kaede cDNA linked to the 3′ untranslated region (UTR) of β-actin is delivered into cells fated to become the retina by injection into Xenopus blastomeres. Brief exposure (6–10 s) to UV light (350–410 nm) of Kaede-positive retinal axons/growth cones efficiently converts Kaede from its native green fluorescence to red. The reappearance of the green signal reports the synthesis of new Kaede protein. This approach can be used to investigate the spatiotemporal control of translation of specific mRNAs in response to external stimuli and to test the efficiency of full-length versus mutant UTRs. The 3-d protocol can be adapted for broad use with other photoactivatable fluorescent proteins. PMID:18714300

  18. Filopodial actin bundles are not necessary for microtubule advance into the peripheral domain of Aplysia neuronal growth cones.

    PubMed

    Burnette, Dylan T; Schaefer, Andrew W; Ji, Lin; Danuser, Gaudenz; Forscher, Paul

    2007-12-01

    Filopodial actin bundles guide microtubule assembly in the growth cone peripheral (P) domain and retrograde actin-network flow simultaneously transports microtubules rearward. Therefore, microtubule-end position is determined by the sum of microtubule assembly and retrograde transport rates. However, how filopodia actually affect microtubule assembly dynamics is unknown. To address this issue we quantitatively assessed microtubule and actin dynamics before and after selective removal of filopodia. Filopodium removal had surprisingly little effect on retrograde actin-flow rates or underlying network structures, but resulted in an approximate doubling of peripheral microtubule density and deeper penetration of microtubules into the P domain. The latter stemmed from less efficient coupling of microtubules to remaining actin networks and not from a change in microtubule polymer dynamics. Loss of filopodia also resulted in increased lateral microtubule movements and a more randomized microtubule distribution in the P domain. In summary, filopodia do not seem to be formally required for microtubule advance; however, their presence ensures radial distribution of microtubules in the P domain and facilitates microtubule transport by retrograde flow. The resulting dynamic steady state has interesting implications for rapid microtubule-positioning responses in the P domain.

  19. gamma-Aminobutyric acidA (GABAA) receptors modulate [3H]GABA release from isolated neuronal growth cones in the rat.

    PubMed

    Lockerbie, R O; Gordon-Weeks, P R

    1985-04-19

    Potassium-induced release of gamma-[3H]aminobutyric acid [( 3H]GABA) from a growth cone-enriched fraction isolated from neonatal rat forebrain was inhibited by the GABA mimetic muscimol in a dose-dependent manner (IC50 15 nM). The GABA antagonist bicuculline completely reversed the effect of muscimol. Bicuculline alone slightly potentiated the K+-induced release of [3H]GABA. Baclofen, a proposed selective agonist for a bicuculline-insensitive GABAB receptor, was found to cause only a slight reduction in the K+-induced release of [3H]GABA. These results are compatible with the presence of a negative feedback mechanism mediated by GABAA receptors for controlling [3H]GABA release from growth cones of the developing rat forebrain.

  20. EMA: a developmentally regulated cell-surface glycoprotein of CNS neurons that is concentrated at the leading edge of growth cones.

    PubMed

    Baumrind, N L; Parkinson, D; Wayne, D B; Heuser, J E; Pearlman, A L

    1992-08-01

    To identify cell-surface molecules that mediate interactions between neurons and their environment during neural development, we used monoclonal antibody techniques to define a developmentally regulated antigen in the central nervous system of the mouse. The antibody we produced (2A1) immunolabels cells throughout the central nervous system; we analyzed its distribution in the developing cerebral cortex, where it is expressed on cells very soon after they complete mitosis and leave the periventricular proliferative zone. Expression continues into adult life. The antibody also labels the epithelium of the choroid plexus and the renal proximal tubules, but does not label neurons of the peripheral nervous system in the dorsal root ganglia. In dissociated cell culture of embryonic cerebral cortex, 2A1 labels the surface of neurons but not glia. Immunolabeling of neurons in tissue culture is particularly prominent on the edge of growth cones, including filopodia and the leading edge of lamellipodia, when observed with either immunofluorescence or freeze-etch immunoelectron microscopy. Immunopurification with 2A1 of a CHAPS-extracted membrane preparation from brains of neonatal mice produces a broad (32-36 kD) electrophoretic band and a less prominent 70 kD band that are sensitive to N-glycosidase but not endoglycosidase H. Thus the 2A1 antibody recognizes a developmentally regulated, neuronal cell surface glycoprotein (or glycoproteins) with complex N-linked oligosaccharide side chains. We have termed the glycoprotein antigen EMA because of its prominence on the edge membrane of growth cones. EMA is similar to the M6 antigen (Lagenaur et al: J. Neurobiol. 23:71-88, 1992) in apparent molecular weight, distribution in tissue sections, and immunoreactivity on Western blots, suggesting that the two antigens are similar or identical. Expression of EMA is a very early manifestation of neuronal differentiation; its distribution on growth cones suggests a role in mediating the

  1. Effects of crystallographic plane and co-deposited element on the growth of ion-sputter induced Si nano-cone arrays: a mechanism study

    NASA Astrophysics Data System (ADS)

    Song, Sheng-Chi; Qiu, Ying; Hao, Hong-Chen; Lu, Ming

    2015-06-01

    Self-organized Si nano-cone arrays induced by Ar+ ion sputtering on different Si crystallographic planes with different co-deposited alien atoms are investigated. The Si planes are (100), (110), and (111) ones, and the alien elements are Ta, Mo, Fe, and C, respectively. It is found that the growth of Si nano-cone arrays is insensitive to the initial crystallographic plane, but depends strongly on the co-deposited element. For the same Ar+ ion dose and sample temperature, the smaller the activation energy between the co-deposited element and Si is, the larger the average cone height and base diameter are. It is found that the preferential sputtering does not play an important role in the nano-cone formation. A model based on the concepts of classical surface-curvature-dependent sputtering yield and the formation of stationary silicide is proposed, which explains the observed results. The results of microstructural and compositional analysis support the proposed model.

  2. Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma.

    PubMed

    Slomiany, Mark G; Black, Leigh Ann; Kibbey, Megan M; Tingler, Melissa A; Day, Terry A; Rosenzweig, Steven A

    2007-04-18

    IGF-1 receptor (IGF-1R) signaling is associated with increased tumorigenesis of epithelial cancers. In light of recent epidemiological studies correlating high circulating levels of IGF-1 with increased risk of second primary tumors (SPTs) of the head and neck, we examined IGF system and epidermal growth factor receptor (EGFR) expression in human head and neck squamous cell carcinoma (HNSCC) matched pairs and a cross-section of HNSCC cell lines. Employing the latter, we demonstrated that IGF-1 stimulated S-phase transition in a PI 3-K/Akt and Erk-dependent manner in 5 of 8 cell lines, with Erk activation being dependent upon EGFR kinase activity. IGF-1 stimulated thymidine incorporation was inhibited by treatment with IGFBP-3, the IGF-1R tyrosine kinase inhibitor NVP-AEW541, or the EGFR tyrosine kinase inhibitor AG1478. Combining IGFBP-3 with NVP-AEW541 or AG1478 abrogated IGF-1 responses at 10-fold lower doses than either compound alone. These results demonstrate the potential for co-targeting the IGF system and EGFR in HNSCC.

  3. Optogenetic Control of PIP3: PIP3 Is Sufficient to Induce the Actin-Based Active Part of Growth Cones and Is Regulated via Endocytosis

    PubMed Central

    Kakumoto, Toshiyuki; Nakata, Takao

    2013-01-01

    Phosphatidylinositol-3,4,5-trisphosphate (PIP3) is highly regulated in a spatiotemporal manner and plays multiple roles in individual cells. However, the local dynamics and primary functions of PIP3 in developing neurons remain unclear because of a lack of techniques for manipulating PIP3 spatiotemporally. We addressed this issue by combining optogenetic control and observation of endogenous PIP3 signaling. Endogenous PIP3 was abundant in actin-rich structures such as growth cones and “waves”, and PIP3-rich plasma membranes moved actively within growth cones. To study the role of PIP3 in developing neurons, we developed a PI3K photoswitch that can induce production of PIP3 at specific locations upon blue light exposure. We succeeded in producing PIP3 locally in mouse hippocampal neurons. Local PIP3 elevation at neurite tips did not induce neurite elongation, but it was sufficient to induce the formation of filopodia and lamellipodia. Interestingly, ectopic PIP3 elevation alone activated membranes to form actin-based structures whose behavior was similar to that of growth-cone-like “waves”. We also found that endocytosis regulates effective PIP3 concentration at plasma membranes. These results revealed the local dynamics and primary functions of PIP3, providing fundamental information about PIP3 signaling in neurons. PMID:23951027

  4. The Disruption of the Cytoskeleton during Semaphorin 3A induced Growth Cone Collapse Correlates with Differences in Actin Organization and Associated Binding Proteins

    PubMed Central

    Brown, Jacquelyn A; Bridgman, Paul C

    2010-01-01

    Repulsive guidance cues induce growth cone collapse or collapse and retraction. Collapse results from disruption and loss of the actin cytoskeleton. Actin rich regions of growth cones contain binding proteins that influence filament organization, such as Arp2/3, cortactin, and fascin, but little is known about the role that these proteins play in collapse. Here we show that Semaphorin 3A (Sema 3A), which is repulsive to mouse dorsal root ganglion neurons, has unequal effects on actin binding proteins and their associated filaments. The immunofluorescence staining intensity of Arp-2 and cortactin decreases relative to total protein, while in unextracted growth cones fascin increases. Fascin and myosin IIB staining redistribute and show increased overlap. The degree of actin filament loss during collapse correlates with filament superstructures detected by rotary shadow electron microscopy. Collapse results in the loss of branched f-actin meshworks, while actin bundles are partially retained to varying degrees. Taken together with the known affects of Sema 3A on actin, this suggests a model for collapse that follows a sequence; depolymerization of actin meshworks followed by partial depolymerization of fascin associated actin bundles and their movement to the neurite to complete collapse. The relocated fascin associated actin bundles may provide the substrate for actomyosin contractions that produce retraction. PMID:19513995

  5. Differentiation of neuronal growth cones: specialization of filopodial tips for adhesive interactions.

    PubMed Central

    Tsui, H C; Lankford, K L; Klein, W L

    1985-01-01

    Adhesive contacts made by filopodia of developing neurons are important in neurite growth and in the formation of synaptic junctions. In the present work, filopodial interactions of cultured chicken retina neurons were studied by using video-enhanced contrast, differential interference contrast (VEC-DIC) microscopy and the high-voltage electron microscope (HVEM). Use of the HVEM to examine whole mounts of fixed cells showed that filopodia in older cultures developed an appearance that might be expected of nascent synapses, becoming enlarged at their endings and accumulating organelles resembling synaptic vesicles. VEC-DIC microscopy, used to observe the motility and adhesive properties of filopodia in living cells, showed there was a particularly high affinity between filopodia tips. Contacting filopodia typically repositioned themselves so they could attach at a tip-to-tip position, occasionally bending as much as 90 degrees to achieve this preferred orientation. Interacting filopodia frequently remained together as they pushed or pulled on each other, moved laterally together, or stretched tightly and underwent intense vibratory movements. Such linked motility occurred even when apparent gaps existed between the filopodia. Examination of these gaps with the HVEM revealed filamentous structures linking the apposed membranes. The filamentous links were 10-13 nm in diameter and 30-100 nm long. Although it has not yet been established that the filaments reflect the native configuration of the interconnecting materials, the structures seem likely to be associated with the strongly adhesive behavior of the filopodial tips. The possible significance of these structural and functional properties of filopodia tips to axon growth and synapse formation is discussed. Images PMID:3865227

  6. Dual Role of Herpes Simplex Virus 1 pUS9 in Virus Anterograde Axonal Transport and Final Assembly in Growth Cones in Distal Axons

    PubMed Central

    Boadle, Ross A.

    2015-01-01

    ABSTRACT The herpes simplex virus type 1 (HSV-1) envelope protein pUS9 plays an important role in virus anterograde axonal transport and spread from neuronal axons. In this study, we used both confocal microscopy and transmission electron microscopy (TEM) to examine the role of pUS9 in the anterograde transport and assembly of HSV-1 in the distal axon of human and rat dorsal root ganglion (DRG) neurons using US9 deletion (US9−), repair (US9R), and wild-type (strain F, 17, and KOS) viruses. Using confocal microscopy and single and trichamber culture systems, we observed a reduction but not complete block in the anterograde axonal transport of capsids to distal axons as well as a marked (∼90%) reduction in virus spread from axons to Vero cells with the US9 deletion viruses. Axonal transport of glycoproteins (gC, gD, and gE) was unaffected. Using TEM, there was a marked reduction or absence of enveloped capsids, in varicosities and growth cones, in KOS strain and US9 deletion viruses, respectively. Capsids (40 to 75%) in varicosities and growth cones infected with strain 17, F, and US9 repair viruses were fully enveloped compared to less than 5% of capsids found in distal axons infected with the KOS strain virus (which also lacks pUS9) and still lower (<2%) with the US9 deletion viruses. Hence, there was a secondary defect in virus assembly in distal axons in the absence of pUS9 despite the presence of key envelope proteins. Overall, our study supports a dual role for pUS9, first in anterograde axonal transport and second in virus assembly in growth cones in distal axons. IMPORTANCE HSV-1 has evolved mechanisms for its efficient transport along sensory axons and subsequent spread from axons to epithelial cells after reactivation. In this study, we show that deletion of the envelope protein pUS9 leads to defects in virus transport along axons (partial defect) and in virus assembly and egress from growth cones (marked defect). Virus assembly and exit in the neuronal

  7. TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis

    PubMed Central

    Qin, Xing; Yan, Ming; Zhang, Jianjun; Wang, Xu; Shen, Zongze; Lv, Zhongjing; Li, Zhihui; Wei, Wenyi; Chen, Wantao

    2016-01-01

    The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target. PMID:26857387

  8. Surface orientation affects the direction of cone growth by Leptolyngbya sp. strain C1, a likely architect of coniform structures Octopus Spring (Yellowstone National Park).

    PubMed

    Reyes, Kristina; Gonzalez, Nicolas I; Stewart, Joshua; Ospino, Frank; Nguyen, Dickie; Cho, David T; Ghahremani, Nahal; Spear, John R; Johnson, Hope A

    2013-02-01

    Laminated, microbially produced stromatolites within the rock record provide some of the earliest evidence for life on Earth. The chemical, physical, and biological factors that lead to the initiation of these organosedimentary structures and shape their morphology are unclear. Modern coniform structures with morphological features similar to stromatolites are found on the surface of cyanobacterial/microbial mats. They display a vertical element of growth, can have lamination, can be lithified, and observably grow with time. To begin to understand the microbial processes and interactions required for cone formation, we determined the phylogenetic composition of the microbial community of a coniform structure from a cyanobacterial mat at Octopus Spring, Yellowstone National Park, and reconstituted coniform structures in vitro. The 16S rRNA clone library from the coniform structure was dominated by Leptolyngbya sp. Other cyanobacteria and heterotrophic bacteria were present in much lower abundance. The same Leptolyngbya sp. identified in the clone library was also enriched in the laboratory and could produce cones in vitro. When coniform structures were cultivated in the laboratory, the initial incubation conditions were found to influence coniform morphology. In addition, both the angle of illumination and the orientation of the surface affected the angle of cone formation demonstrating how external factors can influence coniform, and likely, stromatolite morphology.

  9. Metformin suppresses growth of human head and neck squamous cell carcinoma via global inhibition of protein translation

    PubMed Central

    Sikka, Arron; Kaur, Manjinder; Agarwal, Chapla; Deep, Gagan

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer in the world; the main risk factors are alcohol and tobacco use. Advancements in therapies have yet to improve the prognosis of HNSCC. the connection between diabetes and cancer is being recognized, and metformin has been shown to decrease cancer incidence in diabetic patients. Accordingly, here, for the first time, we investigated metformin's efficacy on the growth and viability of human HNSCC FaDU and Detroit 562 cells. our results show that metformin treatment (5–20 mM) dose-dependently inhibits the growth of both cell lines. In FaDU cells, metformin caused 18–57% and 35–81% growth inhibition after 48 and 72 h treatments, respectively. Similarly, in Detroit 562 cells, 48 and 72 h metformin treatment resulted in 20–57% and 33–82% inhibition, respectively. Mechanistically, metformin caused G1 arrest, which coincided with a decrease in the protein levels of Cdks (2, 4 and 6), cyclins (D1 and e) and Cdk inhibitors (p15, p16, p18 and p27) but no change in p19 and p21. Metformin also decreased the levels of oncogenic proteins Skp2 and β-Trcp. In other studies, metformin decreased the phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites but drastically increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results in global translational inhibition. In summary, the observed wide spectrum of mechanistic effects of metformin on HNSCC cells provides support for the anticancer capability of the drug and its potential use in future therapies. PMID:22421144

  10. Differential diagnostic value of computed tomography perfusion combined with vascular endothelial growth factor expression in head and neck lesions

    PubMed Central

    WANG, JIE; TANG, ZUOHUA; WANG, SHUYI; ZENG, WENJIAO; QIAN, WEN; WU, LINGJIE; WANG, WENZHONG; LUO, JIANFENG

    2016-01-01

    There are numerous types of head and neck lesions (HNLs), and conventional computed tomography (CT) has low specificity and sensitivity in the definitive and differential diagnosis of HNLs. The aim of the present study was to evaluate the value of perfusion CT (CTP) combined with vascular endothelial growth factor (VEGF) expression in the differentiation between malignant and benign HNLs. In total, 41 HNLs, which were pathologically confirmed, underwent CTP and VEGF expression analysis. All lesions were divided into three groups: Group A, benign hypovascular lesions; Group B, benign hypervascular lesions; and Group C, malignant lesions. Time density curve (TDC) and CTP parameters [maximum intensity projection (MIP), blood volume (BV), blood flow (BF), mean transit time and capillary permeability] were analyzed. The association between perfusion measurements and VEGF was assessed using Pearson's correlation. TDCs were classified into three types, and type I was more frequently identified in benign tumors (Groups A and B) compared with malignant tumors (Group C) (P=0.003). Malignant tumors primarily had a TDC of type II and III. MIP, BF and BV were all significantly higher in Groups B and C compared to Group A (P<0.01). VEGF expression of malignant tumors was significantly higher than benign tumors (P=0.007). No correlation was identified between VEGF and any CTP parameter. The present findings suggest that CTP combined with VEGF may differentiate between malignant and benign HNLs, and between benign hypovascular and hypervascular lesions. PMID:27123114

  11. The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones.

    PubMed

    Hinna, Katja Hvid; Rich, Karen; Fex-Svenningsen, Åsa; Benedikz, Eirikur

    2015-01-01

    A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A's role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity.

  12. The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones

    PubMed Central

    Hinna, Katja Hvid; Rich, Karen; Fex-Svenningsen, Åsa; Benedikz, Eirikur

    2015-01-01

    A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A’s role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity. PMID:26148198

  13. Axl mediates acquired resistance of head and neck cancer cells to the epidermal growth factor receptor inhibitor erlotinib.

    PubMed

    Giles, Keith M; Kalinowski, Felicity C; Candy, Patrick A; Epis, Michael R; Zhang, Priscilla M; Redfern, Andrew D; Stuart, Lisa M; Goodall, Gregory J; Leedman, Peter J

    2013-11-01

    Elevated expression and activity of the epidermal growth factor receptor (EGFR) is associated with development and progression of head and neck cancer (HNC) and a poor prognosis. Clinical trials with EGFR tyrosine kinase inhibitors (e.g., erlotinib) have been disappointing in HNC. To investigate the mechanisms mediating resistance to these agents, we developed an HNC cell line (HN5-ER) with acquired erlotinib resistance. In contrast to parental HN5 HNC cells, HN5-ER cells exhibited an epithelial-mesenchymal (EMT) phenotype with increased migratory potential, reduced E-cadherin and epithelial-associated microRNAs (miRNA), and elevated vimentin expression. Phosphorylated receptor tyrosine kinase profiling identified Axl activation in HN5-ER cells. Growth and migration of HN5-ER cells were blocked with a specific Axl inhibitor, R428, and R428 resensitized HN5-ER cells to erlotinib. Microarray analysis of HN5-ER cells confirmed the EMT phenotype associated with acquired erlotinib resistance, and identified activation of gene expression associated with cell migration and inflammation pathways. Moreover, increased expression and secretion of interleukin (IL)-6 and IL-8 in HN5-ER cells suggested a role for inflammatory cytokine signaling in EMT and erlotinib resistance. Expression of the tumor suppressor miR-34a was reduced in HN5-ER cells and increasing its expression abrogated Axl expression and reversed erlotinib resistance. Finally, analysis of 302 HNC patients revealed that high tumor Axl mRNA expression was associated with poorer survival (HR = 1.66, P = 0.007). In summary, our results identify Axl as a key mediator of acquired erlotinib resistance in HNC and suggest that therapeutic inhibition of Axl by small molecule drugs or specific miRNAs might overcome anti-EGFR therapy resistance. PMID:24026012

  14. Existence of benefit finding and posttraumatic growth in people treated for head and neck cancer: a systematic review.

    PubMed

    Harding, Sam; Sanipour, Fatimeh; Moss, Timothy

    2014-01-01

    Background. The impact of head and neck cancer (HNC) in long-term survivors differs widely among individuals, and a significant number of them suffer from the negative effects of disease, whereas others report significant positive effect. This systematic review investigated the evidence the implications of treatment for HNC and subsequent development of Benefit Finding (BF) or Posttraumatic Growth (PTG). Purpose. To understand how differing medical, psychological and social characteristics of HNC may lead to BF/PTG and subsequently inform post-treatment interventions to encourage positive outcomes. Method. In February 2012, five databases including Pubmed, and Psych Info, were searched, for peer-reviewed English-language publications. Search strings included key words pertaining to HNC, BF, and PTG. One thousand three hundred and sixty three publications were identified, reviewed, and reduced following Cochrane guidelines and inclusion/exclusion criteria specified by a group of maxillofacial consultants and psychologists. Publications were then quality assessed using the CASP Cohort Critical Appraisal tool. Findings. Five manuscripts met the search and selection criteria, and were sourced for review. All studies were identified as being level IIb evidence which is a medium level of quality. The majority of studies investigated benefit finding (80%) and were split between recruiting participant via cancer clinics and postal survey. They focused on the medical, psychological and social characteristics of the patient following completion of treatment for HNC. Conclusion. Demographic factors across the papers showed similar patterns of relationships across BF and PTG; that higher education/qualification and cohabitation/marriage are associated with increased BF/PTG. Similarly, overlap with disease characteristics and psychosocial factors where hope and optimism were both positively correlated with increased reported BF/PTG.

  15. Existence of benefit finding and posttraumatic growth in people treated for head and neck cancer: a systematic review

    PubMed Central

    Sanipour, Fatimeh; Moss, Timothy

    2014-01-01

    Background. The impact of head and neck cancer (HNC) in long-term survivors differs widely among individuals, and a significant number of them suffer from the negative effects of disease, whereas others report significant positive effect. This systematic review investigated the evidence the implications of treatment for HNC and subsequent development of Benefit Finding (BF) or Posttraumatic Growth (PTG). Purpose. To understand how differing medical, psychological and social characteristics of HNC may lead to BF/PTG and subsequently inform post-treatment interventions to encourage positive outcomes. Method. In February 2012, five databases including Pubmed, and Psych Info, were searched, for peer-reviewed English-language publications. Search strings included key words pertaining to HNC, BF, and PTG. One thousand three hundred and sixty three publications were identified, reviewed, and reduced following Cochrane guidelines and inclusion/exclusion criteria specified by a group of maxillofacial consultants and psychologists. Publications were then quality assessed using the CASP Cohort Critical Appraisal tool. Findings. Five manuscripts met the search and selection criteria, and were sourced for review. All studies were identified as being level IIb evidence which is a medium level of quality. The majority of studies investigated benefit finding (80%) and were split between recruiting participant via cancer clinics and postal survey. They focused on the medical, psychological and social characteristics of the patient following completion of treatment for HNC. Conclusion. Demographic factors across the papers showed similar patterns of relationships across BF and PTG; that higher education/qualification and cohabitation/marriage are associated with increased BF/PTG. Similarly, overlap with disease characteristics and psychosocial factors where hope and optimism were both positively correlated with increased reported BF/PTG. PMID:24688840

  16. IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer.

    PubMed

    Herbst, R S; Kim, E S; Harari, P M

    2001-07-01

    Squamous cell carcinoma (SCC) of the head and neck (H&N) remains a clinical challenge due to its high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumours (including SCC of the H&N) is well understood; increased expression is associated with enhanced tumour invasion, resistance to chemotherapy and decreased patient survival. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including an anti-EGFR monoclonal antibody (mAb), IMC-C225, which competitively binds to the extracellular receptor site to prevent binding by natural EGFR ligands (EGF and TGF-alpha). Preclinical studies evaluating this chimeric mAb in human cancer cell lines in vitro and human tumour xenografts in vivo have demonstrated its potent antitumour activity. The clinical efficacy of IMC-C225 appears to involve multiple anticancer mechanisms, including inhibition of cell cycle progression, induction of apoptosis, anti-angiogenesis, inhibition of metastasis and its ability to enhance the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation for SCC of the H&N demonstrate excellent response rates in patients with recurrent or refractory disease. Phase II and III trials examining the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well-tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m2 loading dose, followed by weekly infusions of 250 mg/m2.

  17. EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease.

    PubMed

    Brennaman, Leann H; Moss, Marcia L; Maness, Patricia F

    2014-01-01

    EphrinA/EphA-dependent axon repulsion is crucial for synaptic targeting in developing neurons but downstream molecular mechanisms remain obscure. Here, it is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10 to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced ADAM10 activity to promote ectodomain shedding of polysialic acid-NCAM in cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3 kinase activity as shown in HEK293T cells transfected with dominant negative ADAM10 and kinase-inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at a sequence within the E-F loop of the second fibronectin type III domain (Leu(671) -Lys(672) /Ser(673) -Leu(674) ) identified by mass spectrometry. Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3-induced shedding of NCAM in HEK293T cells. EphrinA5-induced growth cone collapse was dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM. Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely impacts synapse development, and may lead to excess NCAM shedding when disrupted, as implicated in neurodevelopmental disorders such as schizophrenia. PSA-NCAM and ephrinA/EphA3 coordinately regulate inhibitory synapse development. Here, we have found that ephrinA5 stimulates EphA3 kinase and ADAM10 activity to promote PSA-NCAM cleavage at a site in its second FNIII repeat, which regulates ephrinA5-induced growth cone collapse in GABAergic and non-GABAergic neurons. These findings identify a new regulatory mechanism which may contribute to inhibitory connectivity.

  18. Targeting Cancer Stem Cell Plasticity Through Modulation of Epidermal Growth Factor and Insulin-Like Growth Factor Receptor Signaling in Head and Neck Squamous Cell Cancer

    PubMed Central

    Leong, Hui Sun; Chong, Fui Teen; Sew, Pui Hoon; Lau, Dawn P.; Wong, Bernice H.; Teh, Bin-Tean

    2014-01-01

    Emerging data suggest that cancer stem cells (CSCs) exist in equilibrium with differentiated cells and that stochastic transitions between these states can account for tumor heterogeneity and drug resistance. The aim of this study was to establish an in vitro system that recapitulates stem cell plasticity in head and neck squamous cell cancers (HNSCCs) and identify the factors that play a role in the maintenance and repopulation of CSCs. Tumor spheres were established using patient-derived cell lines via anchorage-independent cell culture techniques. These tumor spheres were found to have higher aldehyde dehydrogenase (ALD) cell fractions and increased expression of Kruppel-like factor 4, SRY (sex determining region Y)-box 2, and Nanog and were resistant to γ-radiation, 5-fluorouracil, cisplatin, and etoposide treatment compared with monolayer culture cells. Monolayer cultures were subject to single cell cloning to generate clones with high and low ALD fractions. ALDHigh clones showed higher expression of stem cell and epithelial-mesenchymal transition markers compared with ALDLow clones. ALD fractions, representing stem cell fractions, fluctuated with serial passaging, equilibrating at a level specific to each cell line, and could be augmented by the addition of epidermal growth factor (EGF) and/or insulin. ALDHigh clones showed increased EGF receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) phosphorylation, with increased activation of downstream pathways compared with ALDLow clones. Importantly, blocking these pathways using specific inhibitors against EGFR and IGF-1R reduced stem cell fractions drastically. Taken together, these results show that HNSCC CSCs exhibit plasticity, with the maintenance of the stem cell fraction dependent on the EGFR and IGF-1R pathways and potentially amenable to targeted therapeutics. PMID:25024430

  19. Presence of a Large β(1-3)Glucan Linked to Chitin at the Saccharomyces cerevisiae Mother-Bud Neck Suggests Involvement in Localized Growth Control

    PubMed Central

    Blanco, Noelia; Arroyo, Javier

    2012-01-01

    Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of β(1-3)glucan, may help to suppress cell wall growth at the neck by competing with β(1-6)glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to β(1-3)glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, β(1-3)glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the β(1-3)glucan of buds, where growth occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the β(1-3)glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with β(1-3)glucan. PMID:22366124

  20. Presence of a large β(1-3)glucan linked to chitin at the Saccharomyces cerevisiae mother-bud neck suggests involvement in localized growth control.

    PubMed

    Cabib, Enrico; Blanco, Noelia; Arroyo, Javier

    2012-04-01

    Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of β(1-3)glucan, may help to suppress cell wall growth at the neck by competing with β(1-6)glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to β(1-3)glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, β(1-3)glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the β(1-3)glucan of buds, where growth occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the β(1-3)glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with β(1-3)glucan.

  1. [Fiddler's neck].

    PubMed

    Knierim, C; Goertz, W; Reifenberger, J; Homey, B; Meller, S

    2013-10-01

    The fiddler's neck is an uncommon variant of acne mechanica in violinists and violists. It is a single firm red-brown dermal nodule usually on the left side of neck. This special form of acne mechanica represents a therapeutic challenge since the triggering mechanical factors persist, unless they can be corrected by changes in positioning or modifications of the chin pad. A 72-year-old woman who had played the violin since childhood presented with a red-brown nodule on her neck for 18 months. Cushioning provided no relief. Excision of the affected area with primary closure represented one therapeutic option. Further supportive measures include improved posture to reduce the pressure between skin and instrument and interposing a neck cloth. PMID:23989244

  2. Neck pain

    MedlinePlus

    A common cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such activities include: Bending over a desk for hours Having poor posture while watching TV or ...

  3. Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers.

    PubMed

    Herbst, Roy S; Langer, Corey J

    2002-02-01

    Epidermal growth factor receptor is one of four receptors critical to cellular proliferation, differentiation, and survival, and is widely expressed in malignant tissue, particularly in squamous cell carcinoma of the head and neck. Expression has been associated with malignant progression, inhibition of apoptosis, neoplastic angiogenesis, enhanced metastatic potential, and both chemoresistance and radioresistance. IMC-C225 is a chimeric monoclonal antibody that targets extracellular epidermal growth factor receptor; it has shown both in vitro and in vivo antitumor activity in tumor cells lines expressing epidermal growth factor receptor, including heightened radiation response in vitro in cultured human squamous cell carcinoma and enhancement of taxane- and platinum-induced cytotoxicity in non-small cell lung cancer xenografts. In A431 head and neck squamous cell xenografts, IMC-C225 administered both before and after radiation therapy yields a radiation enhancement factor of 3.62, attributable to both tumor necrosis and antiangiogenesis. In phase I pharmacokinetic studies, IMC-C225 has a long half-life, lending itself to convenient weekly administration. It has shown a favorable toxicity profile, limited primarily to allergic and dermatologic reactions, the latter characterized by a self-limited, sterile, acneiform rash. Anaphylaxis is rare. Standard treatment entails a loading dose of 400 mg/m(2) at week 1, followed by a maintenance dose of 250 mg/m(2) weekly. An ongoing phase III international multicenter, randomized study in locally advanced squamous cell carcinoma of the head and neck is evaluating therapeutic radiation therapy, either alone or in conjunction with IMC-C225. In a pilot trial, six of nine patients with platinum-exposed squamous cell carcinoma of the head and neck exhibited objective response. In an ongoing phase II trial in patients with stable or progressive disease on platinum-based therapy, the preliminary response rate is approximately 20

  4. The effect of the Naked Neck genotype (Nana), feeding and outdoor rearing on growth and carcass characteristics of free range broilers in a hot climate.

    PubMed

    de Almeida, André Martinho; Zuber, Urs

    2010-01-01

    Alternative poultry production with special reference to free range broilers has increased significantly since the nineties in many regions of the world. Numerous factors influence the productive performance of this type of broilers: genotype (namely the use of naked neck animals), feeding and access to an outdoor area. The aim of this paper is to study the influence of each of these factors on the productive performance of free range broilers under commercial rearing conditions. A total of 3200, day old chicks of both sexes from naked neck and normally feathered genotypes were used in this trial. After a joint initiation phase, animals were divided into four different treatments with the combination of two concentrates (high vs low energy content) and management (access to outside park or not). Experiment lasted a total of 12 weeks. Live weight date was recorded weekly and a samples of animals from the trial were sacrificed at the age of 8, 10 and 12 weeks, when carcass characteristics were determined. Besides sex, the only factor that seems to affect growth characteristics was genotype as naked neck animals had poorer growth rates than normally feathered. No effect was detected on carcass yields and percentages of carcass components for any of the variables. From the data presented in this trial the practises associated with free range production are of relative inconsequence to the technical animal production parameters and can only be justified by a pressing need to differentiate these products from standard poultry products in what concerns both welfare issues and meat characteristics. The results also indicate that genetic material from alternative poultry production in Europe can be a useful option in poultry production development projects in the tropics.

  5. Whiskers, cones and pyramids created in sputtering by ion bombardment

    NASA Technical Reports Server (NTRS)

    Wehner, G. K.

    1979-01-01

    A thorough study of the role which foreign atoms play in cone formation during sputtering of metals revealed many experimental facts. Two types of cone formation were distinquished, deposit cones and seed cones. Twenty-six combinations of metals for seed cone formation were tested. The sputtering yield variations with composition for combinations which form seed cones were measured. It was demonstrated that whisker growth becomes a common occurrence when low melting point material is sputter deposited on a hot nonsputtered high melting point electrode.

  6. The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.

    PubMed

    Mohamed, Ahmed M; Boudreau, Jeffrey R; Yu, Fabian P S; Liu, Jun; Chin-Sang, Ian D

    2012-01-01

    The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.

  7. Neck Pain

    MedlinePlus

    ... get better. No 7. Did you have a whiplash-type injury in the past, or do you have pain and/or stiffness every day in your neck, hands, knees, hips or other joints? Yes Your pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

  8. Neck pain

    PubMed Central

    2008-01-01

    Introduction Non-specific neck pain has a postural or mechanical basis and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but may become chronic in about 10% of people. Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident, although this varies between countries. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for people with non-specific neck pain without severe neurological deficit? What are the effects of treatments for acute whiplash injury? What are the effects of treatments for chronic whiplash injury? What are the effects of treatments for neck pain with radiculopathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 91 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of the evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, biofeedback, drug treatments (analgesics, antidepressants, epidural steroid injections, muscle relaxants, non-steroidal anti-inflammatory drugs [NSAIDs]), early mobilisation, early return to normal activity, exercise, heat or cold, manipulation (alone or plus exercise), mobilisation, multimodal treatment, patient education, percutaneous radiofrequency neurotomy

  9. An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer.

    PubMed

    Colley, Helen E; Muthana, Munitta; Danson, Sarah J; Jackson, Lucinda V; Brett, Matthew L; Harrison, Joanne; Coole, Sean F; Mason, Daniel P; Jennings, Luke R; Wong, Melanie; Tulasi, Vamshi; Norman, Dennis; Lockey, Peter M; Williams, Lynne; Dossetter, Alexander G; Griffen, Edward J; Thompson, Mark J

    2015-12-10

    A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.

  10. The Use of Epidermal Growth Factor Receptor Monoclonal Antibodies in Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Russell, Jeffery S.; Colevas, A. Dimitrios

    2012-01-01

    Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal antibodies may demonstrate multi-target epitope recognition, enhanced immune cell stimulation, or conjugation with radioisotopes in order to improve clinical outcomes. Identification of the specific patient subset that would optimally benefit from anti-EGFR monoclonal antibodies remains an elusive goal. PMID:23150825

  11. Growth inhibition and apoptosis by an active component of OK-432, a streptococcal agent, via Toll-like receptor 4 in human head and neck cancer cell lines.

    PubMed

    Tano, Tomoyuki; Okamoto, Masato; Kan, Shin; Nakashiro, Koh-ichi; Shimodaira, Shigetaka; Yamashita, Naomi; Kawakami, Yutaka; Hamakawa, Hiroyuki

    2012-08-01

    Toll-like receptor 4 (TLR4) plays a significant role in cancer therapy as receptors of bacteria-derived immunotherapeutic agents such as OK-432, a streptococcal immunotherapeutic agent. In addition, recent reports demonstrated that TLRs, including TLR4, are also expressed in cancer cells as well as in immunocompetent cells. It is a problem in cancer therapy that the immunoadjuvant may activate survival signals such as nuclear factor (NF)-κB or mitogen-activated protein kinases (MAPKs) in cancer cells via TLRs. In the current study, we investigated responsiveness of human head and neck cancer cell lines against TLR4 ligands, OK-PSA, an active component of OK-432, and a lipopolysaccharide (LPS). Stimulation with LPS or OK-PSA resulted in the activation of NF-κB in these cell lines expressing TLR4 and MD-2 that is a significant coreceptor for TLR4 signaling. Interestingly, OK-PSA induced cell-growth inhibition, while LPS enhanced the proliferation of the cancer cells. OK-PSA induced NF-κB activation more slowly than that induced by LPS. In addition, phosphorylation of p38 MAPK by OK-PSA was only slight compared with that by LPS. OK-PSA also induced apoptosis of the cancer cells mediated by the activation of caspase 1, 3 and 8 in a p53-independent manner. These findings strongly suggest that active components of OK-432 may elicit anti-cancer effects via enhancing host immunity as well as via directly inducing the growth inhibition and apoptosis of head and neck cancer cells through TLR4 signal.

  12. The cone dystrophies.

    PubMed

    Simunovic, M P; Moore, A T

    1998-01-01

    The cone dystrophies are a heterogeneous group of inherited disorders that result in dysfunction of the cone photoreceptors and sometimes their post-receptoral pathways. The major clinical features of cone dystrophy are photophobia, reduced visual acuity and abnormal colour vision. Ganzfeld electroretinography shows reduced or absent cone responses. On the basis of their natural history, the cone dystrophies may be broadly divided into two groups: stationary and progressive cone dystrophies. The stationary cone dystrophies have received more attention, and subsequently our knowledge of their molecular genetic, psychophysical and clinical characteristics is better developed. Various methods of classification have been proposed for the progressive cone dystrophies, but none is entirely satisfactory, largely because the underlying disease mechanisms are poorly understood. Multidisciplinary studies involving clinical assessment, molecular genetics, electrophysiology and psychophysics should lead to an improved understanding of the pathogenesis of these disorders.

  13. Cold knife cone biopsy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003910.htm Cold knife cone biopsy To use the sharing features on this page, please enable JavaScript. A cold knife cone biopsy (conization) is surgery to remove ...

  14. LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer)

    PubMed Central

    Simonik, Elizabeth A.; Cai, Ying; Kimmelshue, Katherine N.; Brantley-Sieders, Dana M.; Loomans, Holli A.; Andl, Claudia D.; Westlake, Grant M.; Youngblood, Victoria M.; Chen, Jin; Yarbrough, Wendell G.; Brown, Brandee T.; Nagarajan, Lalitha; Brandt, Stephen J.

    2016-01-01

    Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease. First, we found that the relative abundance of LMO4, LDB1, and the two SSBPs correlated very significantly in a panel of human HNSCC cell lines. Second, expression of these proteins in tumor primaries and lymph nodes involved by metastasis were concordant in 3 of 3 sets of tissue. Third, using a Matrigel invasion and organotypic reconstruct assay, CRISPR/Cas9-mediated deletion of LDB1 in the VU-SCC-1729 cell line, which is highly invasive of basement membrane and cellular monolayers, reduced tumor cell invasiveness and migration, as well as proliferation on tissue culture plastic. Finally, inactivation of the LDB1 gene in these cells decreased growth and vascularization of xenografted human tumor cells in vivo. These data show that LMO4, LDB1, and SSBP2 and/or SSBP3 regulate metastasis, proliferation, and angiogenesis in HNSCC and provide the first evidence that SSBPs control LMO4 and LDB1 protein abundance in a cancer context. PMID:27780223

  15. Lack of Association of Tumor Necrosis Factor-α G-308A and Transforming Growth Factor-β1 C-509T Polymorphisms in Patients with Deep Neck Space Infections.

    PubMed

    Jevtović-Stoimenov, T; Despotović, M; Pešić, Z; Cosić, A

    2013-12-01

    Deep neck space infections are defined as infections that spread along the fascial planes and spaces of the head and neck. Even in the era of antibiotics, these infections can and have been potentially life-threatening conditions. The role of single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) genes in deep neck infections has not been studied. Thus, the aim of this study was to investigate the distribution of the TNF-α G-308A and TGF-β1 C-509T polymorphisms in patients suffering from infections of deep neck spaces and to determine the correlation of these polymorphisms with the values of inflammation markers [C-reactive protein (CRP) and white blood cell (WBC) count]. A total of 41 patients with infections of deep neck spaces and 44 healthy controls were screened for TNF-α G-308A and TGF-β1 C-509T polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The distribution of the TNF-α G-308A genotype in patients did not reveal statistically significant correlation compared to con-trols (p = 0.483, χ(2) = 0.491) as well as the distribution of the TGF-β1 C-509T genotypes (p = 0.644, χ(2) = 0.725). The distribution of TNF-α -308 and TGF-β1 -509 alleles was not significantly different in patients compared to controls. Moreover, CRP levels and WBC counts were not associated with TNF-α G-308A and TGF-β1 C-509T promoter polymorphisms in patients with deep neck infections. In conclusion, our study suggests that the TNF-α G-308A and TGF-β1 C-509T polymorphisms are not associated with infections of deep neck spaces.

  16. Hyaluronic acid-paclitaxel conjugate inhibits growth of human squamous cell carcinomas of the head and neck via a hyaluronic acid-mediated mechanism.

    PubMed

    Galer, Chad E; Sano, Daisuke; Ghosh, Sukhen C; Hah, Jeong H; Auzenne, Edmund; Hamir, Amirali N; Myers, Jeffrey N; Klostergaard, Jim

    2011-11-01

    Chemotherapeutic regimens incorporating taxanes significantly improve outcomes for patients with squamous cell carcinomas of the head and neck (SCCHN). However, treatment with taxanes is limited by toxicities, including bone marrow suppression and peripheral neuropathies. We proposed that conjugating taxanes to targeting carrier molecules would increase antitumor efficacy and decrease toxicity. The cell surface proteoglycan, CD44, is expressed on most SCCHNs, and we hypothesized that it is an attractive candidate for targeted therapy via its natural ligand, hyaluronic acid (HA). We determined whether HA-paclitaxel conjugates were able to decrease tumor growth and improve survival in orthotopic nude mouse human SCCHN xenograft models. HA-paclitaxel concentration-dependent growth inhibition of human SCCHN cell lines OSC-19 and HN5 in vitro, very similarly to free paclitaxel treatment. Tumor cell uptake of FITC-labeled HA-paclitaxel was significantly blocked with free HA, indicating the dependence of uptake on CD44. HA-paclitaxel administered intravenously once per week for three weeks at 120 mg/kg paclitaxel equivalents, far above the paclitaxel maximum tolerated dose, exerted superior tumor growth control to that of paclitaxel in both orthotopic OSC-19-luciferase and HN5 xenograft models in vivo. Mouse survival following HA-paclitaxel administration was prolonged compared with that of controls in mice implanted with either of these xenografts. Mice treated with HA-paclitaxel displayed increased TUNEL(+) cells in tumor tissue, as well as markedly reduced microvessel density compared to those treated with free paclitaxel. No acute histopathological changes were observed in mice treated with HA-paclitaxel. Thus, we conclude that HA-paclitaxel effectively inhibits tumor growth in human SCCHN xenografts via an HA-mediated mechanism and this conjugate should be considered for further preclinical development for this disease.

  17. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth.

    PubMed

    Hassan, Christopher E; Webster, Thomas J

    2016-01-01

    Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs) were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC) and human dermal fibroblast (HDF) cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 μg rSeNP/mL media for 1-3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 μg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20-55 μg rSeNP/mL media. Observations showed that doses of rSeNP <5 μg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. PMID:27536104

  18. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth

    PubMed Central

    Hassan, Christopher E; Webster, Thomas J

    2016-01-01

    Given their low toxicity and natural presence in the human diet, selenium nanoparticles have been established as potential candidates for the treatment of numerous cancers. Red-allotrope selenium nanoparticles (rSeNPs) were synthesized and characterized in this study. Head and neck squamous cell carcinoma (HNSCC) and human dermal fibroblast (HDF) cells were cultured and exposed to rSeNPs at concentrations ranging from 0.01 to 100 μg rSeNP/mL media for 1–3 days. The toxicity of rSeNP toward HNSCC and HDFs was analyzed. Results indicated that the particles were approximately four times as cytotoxic toward HNSCC compared to HDFs, with their respective IC50 values at 19.22 and 59.61 μg rSeNP/mL media. Using statistical analysis, an effective dosage range for killing HNSCC cells while simultaneously minimizing damage to HDFs over a 3-day incubation period was established at 20–55 μg rSeNP/mL media. Observations showed that doses of rSeNP <5 μg rSeNP/mL media resulted in cell proliferation. Transmission electron microscopy images of HNSCC and HDF cells, both treated with rSeNPs, revealed that the rSeNPs became localized in the cytoplasm near the lysosomes and mitochondria. Analysis of cell morphology showed that the rSeNPs primarily induced HNSCC apoptosis. Collectively, these results indicated that rSeNPs are a promising option for treating HNSCC without adversely affecting healthy cells and without resorting to the use of harmful chemotherapeutics. PMID:27536104

  19. Mechanisms of growth cone repulsion

    PubMed Central

    Krull, Catherine E

    2010-01-01

    Research conducted in the last century suggested that chemoattractants guide cells or their processes to appropriate locations during development. Today, we know that many of the molecules involved in cellular guidance can act as chemorepellents that prevent migration into inappropriate territories. Here, we review some of the early seminal experiments and our current understanding of the underlying molecular mechanisms. PMID:20711492

  20. [Neck appendages--branchiogenic surplus malformations (choristoma)].

    PubMed

    Stieler, W; Senff, H; Mensing, H

    1988-09-01

    Congenital cartilaginous rests of the neck are branchiogenic surplus malformations that are very rare. They arise from epithelial growth in a false place and frequently contain elastic cartilage. Congenital cartilaginous rests of the neck are only rarely associated with other congenital malformations.

  1. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age.

    PubMed

    Wang, Xiao-Fang; Duan, Yunbo; Beck, Thomas J; Seeman, Ego

    2005-06-01

    The structural basis of racial and sex differences in femoral neck (FN) fragility in old age was assessed in a cross-sectional study of 829 healthy Chinese and 1181 healthy Caucasian subjects aged 18 to 93 years in Melbourne, Australia. We measured FN bone mineral density (BMD), periosteal diameter, and estimated endocortical diameter, cortical thickness, volumetric BMD (vBMD), section modulus, and buckling ratio using dual X-ray absorptiometry. Racial and sex differences in structural and strength indices were adjusted for age, bone length and body weight and were expressed in standard deviation (SD) unit. In young adulthood, Chinese women had a 0.85 SD narrower FN, a 0.47 SD thinner cortex and a 0.79 SD shorter FN axis length (FNAL) than Caucasian women. Across age, Chinese and Caucasian women had similar increments in endocortical and periosteal diameters and similar decrements in cortical thickness and vBMD (both approximately 20%). In young adult males, FN periosteal diameter did not differ by race, but cortical thickness was 0.35 SD lower in Chinese than Caucasians. Across age, increments in periosteal and endocortical diameters were less in Chinese than Caucasian men so cortical thickness and vBMD diminished less in Chinese than in Caucasian men. In both races, young adult women had narrower FN than men. As Chinese women had a greater increment in periosteal diameter than Chinese men across age, the sex difference in FN periosteal diameter established in young adulthood diminished in old age. As Caucasian men had a greater increment in periosteal diameter than Caucasian women, the sex difference in FN periosteal diameter established in young adulthood increased with age. In old age, for both sexes, Chinese had a higher fracture risk in bending than Caucasians, but a lower fracture risk by buckling. For both races, women had a higher fracture risk in bending than men. Racial and sexual dimorphism in the absolute and relative behavior of the periosteal and

  2. The role of collapsing and cone rafting on eruption style changes and final cone morphology: Los Morados scoria cone, Mendoza, Argentina

    NASA Astrophysics Data System (ADS)

    Németh, Karoly; Risso, Corina; Nullo, Francisco; Kereszturi, Gabor

    2011-06-01

    Payún Matru Volcanic Field is a Quaternary monogenetic volcanic field that hosts scoria cones with perfect to breached morphologies. Los Morados complex is a group of at least four closely spaced scoria cones (Los Morados main cone and the older Cones A, B, and C). Los Morados main cone was formed by a long lived eruption of months to years. After an initial Hawaiian-style stage, the eruption changed to a normal Strombolian, conebuilding style, forming a cone over 150 metres high on a northward dipping (˜4°) surface. An initial cone gradually grew until a lava flow breached the cone's base and rafted an estimated 10% of the total volume. A sudden sector collapse initiated a dramatic decompression in the upper part of the feeding conduit and triggered violent a Strombolian style eruptive stage. Subsequently, the eruption became more stable, and changed to a regular Strombolian style that partially rebuilt the cone. A likely increase in magma flux coupled with the gradual growth of a new cone caused another lava flow outbreak at the structurally weakened earlier breach site. For a second time, the unstable flank of the cone was rafted, triggering a second violent Strombolian eruptive stage which was followed by a Hawaiian style lava fountain stage. The lava fountaining was accompanied by a steady outpour of voluminous lava emission accompanied by constant rafting of the cone flank, preventing the healing of the cone. Santa Maria is another scoria cone built on a nearly flat pre-eruption surface. Despite this it went through similar stages as Los Morados main cone, but probably not in as dramatic a manner as Los Morados. In contrast to these examples of large breached cones, volumetrically smaller cones, associated to less extensive lava flows, were able to heal raft/collapse events, due to the smaller magma output and flux rates. Our evidence shows that scoria cone growth is a complex process, and is a consequence of the magma internal parameters (e.g. volatile

  3. Study of Microorganism Growth Pattern in Nasal Pack of Patients Visiting the Department of ENT, Head and Neck Surgery.

    PubMed

    Shrestha, I; Pokharel, M; Dhakal, A; Amatya, R Cm; Madhup, S; Sherchan, J B

    2015-01-01

    Background Nasal packs are utilized nearly by otorhinolaryngologists for controlling epistaxis and post nasal procedures. Complications have been reported due to them; therefore the use of antibiotics is a common practice among otorhinolaryngologists. Objective To detect microbiological flora associated with nasal packing and find evidence to support the benefit of systemic antibiotics with it. Method A prospective, analytical study was conducted on 51 patients presenting to the Department of ENT, KUSMS from June to September 2015 who required nasal packing. Approval of the local Institutional review committee (IRC) was taken. The mid part of the pack was collected in a sterile bottle under aseptic technique and sent to microbiology department. Specimen collection, culture, identification tests were done according to the guidelines by American Society for Microbiology. Data were collected using the individual patient records and Microsoft Office Excel 2007. Statistical analysis was performed with SPSS 16.0. Result Among the 51 cultures; 33 (64.7%) were positive. In 18 (35.3%) cultures no organism was grown. Statistical analysis did not show significance between duration of pack kept with microbial growth (p=0.051) or the type of pack kept (p=0.212) .It showed significance with foul smell of the pack to the growth (p <0.001). Conclusion Microbiological flora was associated with nasal pack. Antibiotic soaked nasal packs have lesser incidence of positive bacterial growth when compared with plain nasal packs. Nasal packs kept for less than 48 hours have lesser incidence of positive bacterial growth when compared with nasal packs kept for more than 48 hours. Therefore, administering systemic antibiotics in cases when we plan to keep the pack for longer duration is recommended. PMID:27423279

  4. Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling.

    PubMed

    Jia, Lifeng; Song, Qi; Zhou, Chenyang; Li, Xiaoming; Pi, Lihong; Ma, Xiuru; Li, Hui; Lu, Xiuying; Shen, Yupeng

    2016-01-01

    Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients. PMID:26784960

  5. Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model

    PubMed Central

    Selvi, Ruthrotha B.; Swaminathan, Amrutha; Chatterjee, Snehajyoti; Shanmugam, Muthu K.; Li, Feng; Ramakrishnan, Gowsica B.; Siveen, Kodappully Sivaraman; Chinnathambi, Arunachalam; Zayed, M. Emam; Alharbi, Sulaiman Ali; Basha, Jeelan; Bhat, Akshay; Vasudevan, Madavan; Dharmarajan, Arunasalam; Sethi, Gautam; Kundu, Tapas K.

    2015-01-01

    Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down-regulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing. PMID:26517526

  6. Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling

    PubMed Central

    Jia, Lifeng; Song, Qi; Zhou, Chenyang; Li, Xiaoming; Pi, Lihong; Ma, Xiuru; Li, Hui; Lu, Xiuying; Shen, Yupeng

    2016-01-01

    Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients. PMID:26784960

  7. Effects of Water Restriction on the Growth Performance, Carcass Characteristics and Organ Weights of Naked Neck and Ovambo Chickens of Southern Africa

    PubMed Central

    Chikumba, N.; Chimonyo, M.

    2014-01-01

    In semi-arid areas of Southern Africa, dehydration can compromise the performance and welfare of local chickens, particularly during the growing period when confinement is curtailed and birds are left to scavenge for feed and water. The effect of water restriction on the growth performance was compared in Naked Neck (NNK) and Ovambo (OVB) chickens that are predominant in Southern Africa. A total of 54 eight-wk-old pullets each of NNK and OVB chickens with an initial average weight of 641±10 g/bird were randomly assigned to three water intake treatments, each having six birds for 8 wk. The water restriction treatments were ad libitum, 70% of ad libitum and 40% of ad libitum intake. Nine experimental pens with a floor space of 3.3 m2 per strain were used. The pens were housed in an open-sided house with cement floor deep littered with a 20 cm layer of untreated wood shavings. Feed was provided ad libitum. Average daily water intake (ADWI), BW at 16 weeks of age (FBW), ADG, ADFI, feed conversion ratio (FCR) and water to feed ratios (WFR) were determined. Ovambo chickens had superior (p<0.05) FBW, ADG and ADWI than NNK chickens. Body weight of birds at 16 weeks of age, ADG, ADFI, ADWI, and WFR declined progressively (p<0.05) with increasing severity of water restriction while FCR values increased (p<0.05) as the severity of water restriction increased. Naked Neck chickens had better FCR at the 40% of ad libitum water intake level than Ovambo chickens. The dressing percentage per bird was higher in water restricted birds than those on ad libitum water consumption, irrespective of strain. Heart weight was significantly lower in birds on 40% of ad libitum water intake than those on ad libitum and 70% of ad libitum water intake, respectively. In conclusion, NNK chickens performed better than OVB chickens under conditions of water restriction and would be ideal to raise for meat and egg production in locations where water shortages are a major challenge. PMID:25050039

  8. Effects of water restriction on the growth performance, carcass characteristics and organ weights of naked neck and ovambo chickens of southern Africa.

    PubMed

    Chikumba, N; Chimonyo, M

    2014-07-01

    In semi-arid areas of Southern Africa, dehydration can compromise the performance and welfare of local chickens, particularly during the growing period when confinement is curtailed and birds are left to scavenge for feed and water. The effect of water restriction on the growth performance was compared in Naked Neck (NNK) and Ovambo (OVB) chickens that are predominant in Southern Africa. A total of 54 eight-wk-old pullets each of NNK and OVB chickens with an initial average weight of 641±10 g/bird were randomly assigned to three water intake treatments, each having six birds for 8 wk. The water restriction treatments were ad libitum, 70% of ad libitum and 40% of ad libitum intake. Nine experimental pens with a floor space of 3.3 m(2) per strain were used. The pens were housed in an open-sided house with cement floor deep littered with a 20 cm layer of untreated wood shavings. Feed was provided ad libitum. Average daily water intake (ADWI), BW at 16 weeks of age (FBW), ADG, ADFI, feed conversion ratio (FCR) and water to feed ratios (WFR) were determined. Ovambo chickens had superior (p<0.05) FBW, ADG and ADWI than NNK chickens. Body weight of birds at 16 weeks of age, ADG, ADFI, ADWI, and WFR declined progressively (p<0.05) with increasing severity of water restriction while FCR values increased (p<0.05) as the severity of water restriction increased. Naked Neck chickens had better FCR at the 40% of ad libitum water intake level than Ovambo chickens. The dressing percentage per bird was higher in water restricted birds than those on ad libitum water consumption, irrespective of strain. Heart weight was significantly lower in birds on 40% of ad libitum water intake than those on ad libitum and 70% of ad libitum water intake, respectively. In conclusion, NNK chickens performed better than OVB chickens under conditions of water restriction and would be ideal to raise for meat and egg production in locations where water shortages are a major challenge. PMID:25050039

  9. WE-G-18A-03: Cone Artifacts Correction in Iterative Cone Beam CT Reconstruction

    SciTech Connect

    Yan, H; Folkerts, M; Jiang, S; Jia, X; Wang, X; Bai, T; Lu, W

    2014-06-15

    Purpose: For iterative reconstruction (IR) in cone-beam CT (CBCT) imaging, data truncation along the superior-inferior (SI) direction causes severe cone artifacts in the reconstructed CBCT volume images. Not only does it reduce the effective SI coverage of the reconstructed volume, it also hinders the IR algorithm convergence. This is particular a problem for regularization based IR, where smoothing type regularization operations tend to propagate the artifacts to a large area. It is our purpose to develop a practical cone artifacts correction solution. Methods: We found it is the missing data residing in the truncated cone area that leads to inconsistency between the calculated forward projections and measured projections. We overcome this problem by using FDK type reconstruction to estimate the missing data and design weighting factors to compensate the inconsistency caused by the missing data. We validate the proposed methods in our multi-GPU low-dose CBCT reconstruction system on multiple patients' datasets. Results: Compared to the FDK reconstruction with full datasets, while IR is able to reconstruct CBCT images using a subset of projection data, the severe cone artifacts degrade overall image quality. For head-neck case under a full-fan mode, 13 out of 80 slices are contaminated. It is even more severe in pelvis case under half-fan mode, where 36 out of 80 slices are affected, leading to inferior soft-tissue delineation. By applying the proposed method, the cone artifacts are effectively corrected, with a mean intensity difference decreased from ∼497 HU to ∼39HU for those contaminated slices. Conclusion: A practical and effective solution for cone artifacts correction is proposed and validated in CBCT IR algorithm. This study is supported in part by NIH (1R01CA154747-01)

  10. Irradiation-Induced Regulation of Plasminogen Activator Inhibitor Type-1 and Vascular Endothelial Growth Factor in Six Human Squamous Cell Carcinoma Lines of the Head and Neck

    SciTech Connect

    Artman, Tuuli; Schilling, Daniela; Multhoff, Gabriele

    2010-02-01

    Purpose: It has been shown that plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are involved in neo-angiogenesis. The aim of this study was to investigate the irradiation-induced regulation of PAI-1 and VEGF in squamous cell carcinomas of the head and neck (SCCHN) cell lines of varying radiation sensitivity. Methods and Materials: Six cell lines derived from SCCHN were investigated in vitro. The colorimetric AlamarBlue assay was used to detect metabolic activity of cell lines during irradiation as a surrogate marker for radiation sensitivity. PAI-1 and VEGF secretion levels were measured by enzyme-linked immunosorbent assay 24, 48, and 72 h after irradiation with 0, 2, 6, and 10 Gy. The direct radioprotective effect of exogenous PAI-1 was measured using the clonogenic assay. For regulation studies, transforming growth factor-beta1 (TGF-beta1), hypoxia-inducible factor-1alpha (HIF-1alpha), hypoxia-inducible factor-2alpha (HIF-2alpha), or both HIF-1alpha and HIF-2alpha were downregulated using siRNA. Results: Although baseline levels varied greatly, irradiation led to a comparable dose-dependent increase in PAI-1 and VEGF secretion in all six cell lines. Addition of exogenous stable PAI-1 to the low PAI-1-expressing cell lines, XF354 and FaDu, did not lead to a radioprotective effect. Downregulation of TGF-beta1 significantly decreased VEGF secretion in radiation-sensitive XF354 cells, and downregulation of HIF-1alpha and HIF-2alpha reduced PAI-1 and VEGF secretion in radiation-resistant SAS cells. Conclusions: Irradiation dose-dependently increased PAI-1 and VEGF secretion in all SCCHN cell lines tested regardless of their basal levels and radiation sensitivity. In addition, TGF-beta1 and HIF-1alpha could be partly responsible for VEGF and PAI-1 upregulation after irradiation.

  11. The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro

    SciTech Connect

    Li, Qiang; Song, Xin-mao; Ji, Yang-yang; Jiang, Hui; Xu, Lin-gen

    2013-11-01

    Highlights: •AZD8055 induces significant cytotoxic effects in cultured HNSCC cells. •AZD8055 blocks mTORC1 and mTORC2 activation in cultured HNSCC cells. •JNK activation is required for AZD8055-induced HNSCC cell death. •AZD8055 inhibits Hep-2 cell growth in vivo, and was more efficient than rapamycin. -- Abstract: The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.

  12. Cone Health and Retinoids.

    PubMed

    Kono, Masahiro

    2015-01-01

    Cones are photoreceptor cells used for bright light and color vision. Retinoids are vitamin A derivatives, one of which is the 11-cis aldehyde form that serves as the chromophore for both cone and rod visual pigments. In the visual disease, Type 2 Leber congenital amaurosis (LCA2), 11-cis-retinal generation is inhibited or abolished. Work by others has shown that patients with LCA2 have symptoms consistent with degenerating cones. In mouse models for LCA2, early cone degeneration is readily apparent: cone opsins and other proteins associated with the outer segment are delocalized and cell numbers decline rapidly within the first month. Rods would appear normal morphologically and functionally, if not for the absence of chromophore. Supplementation of mouse models of LCA2 with cis-retinoids has been shown to slow loss of cone photoreceptor cells if mice were maintained in darkness. Thus, 11-cis-retinal appears not only to have a role in the light response reaction but also to promote proper trafficking of the cone opsins and maintain viable cones. PMID:26310171

  13. Cone sampling array models

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J., Jr.; Poirson, Allen

    1987-01-01

    A model is described for positioning cones in the retina. Each cone has a circular disk of influence, and the disks are tightly packed outward from the center. This model has three parameters that can vary with eccentricity: the mean radius of the cone disk, the standard deviation of the cone disk radius, and the standard deviation of postpacking jitter. Estimates for these parameters out to 1.6 deg are found by using measurements reported by Hirsch and Hylton (1985) and Hirsch and Miller (1987) of the positions of the cone inner segments of an adult macaque. The estimation is based on fitting measures of variation in local intercone distances, and the fit to these measures is good.

  14. Progressive cone dystrophy.

    PubMed Central

    Ripps, H; Noble, K G; Greenstein, V C; Siegel, I M; Carr, R E

    1987-01-01

    Psychophysical, reflectometric, and electrophysiological studies were performed on four members of a dominant pedigree with progressive cone dystrophy. The two youngest individuals were asymptomatic at the initial examination, and none of the subjects complained of problems associated with night vision. Absent or grossly reduced cone-mediated ERG responses revealed the widespread loss of cone function. Moderate elevations (1 log unit) in absolute threshold together with reductions in rhodopsin levels in the midperipheral retina provided evidence of a mild impairment of the rod system also, although not to the degree seen in a cone-rod dystrophy. The progressive nature of the disease was apparent from the case histories and the changes in visual performance that occurred on re-test after a 5-year interval. Likewise, the results of incremental threshold measurements at several retinal loci suggested that peripheral cones may be affected earlier and more severely than those in the central retina. PMID:3502298

  15. S-cone psychophysics.

    PubMed

    Smithson, Hannah E

    2014-03-01

    We review the features of the S-cone system that appeal to the psychophysicist and summarize the celebrated characteristics of S-cone mediated vision. Two factors are emphasized: First, the fine stimulus control that is required to isolate putative visual mechanisms and second, the relationship between physiological data and psychophysical approaches. We review convergent findings from physiology and psychophysics with respect to asymmetries in the retinal wiring of S-ON and S-OFF visual pathways, and the associated treatment of increments and decrements in the S-cone system. Beyond the retina, we consider the lack of S-cone projections to superior colliculus and the use of S-cone stimuli in experimental psychology, for example to address questions about the mechanisms of visually driven attention. Careful selection of stimulus parameters enables psychophysicists to produce entirely reversible, temporary, "lesions," and to assess behavior in the absence of specific neural subsystems. PMID:24759446

  16. Intraoperative fluorescence delineation of head and neck cancer with a fluorescent anti-epidermal growth factor receptor nanobody.

    PubMed

    van Driel, P B A A; van der Vorst, J R; Verbeek, F P R; Oliveira, S; Snoeks, T J A; Keereweer, S; Chan, B; Boonstra, M C; Frangioni, J V; van Bergen en Henegouwen, P M P; Vahrmeijer, A L; Lowik, C W G M

    2014-06-01

    Intraoperative near-infrared (NIR) fluorescence imaging is a technology with high potential to provide the surgeon with real-time visualization of tumors during surgery. Our study explores the feasibility for clinical translation of an epidermal growth factor receptor (EGFR)-targeting nanobody for intraoperative imaging and resection of orthotopic tongue tumors and cervical lymph node metastases. The anti-EGFR nanobody 7D12 and the negative control nanobody R2 were conjugated to the NIR fluorophore IRDye800CW (7D12-800CW and R2-800CW). Orthotopic tongue tumors were induced in nude mice using the OSC-19-luc2-cGFP cell line. Tumor-bearing mice were injected with 25 µg 7D12-800CW, R2-800CW or 11 µg 800CW. Subsequently, other mice were injected with 50 or 75 µg of 7D12-800CW. The FLARE imaging system and the IVIS spectrum were used to identify, delineate and resect the primary tumor and cervical lymph node metastases. All tumors could be clearly identified using 7D12-800CW. A significantly higher tumor-to-background ratio (TBR) was observed in mice injected with 7D12-800CW compared to mice injected with R2-800CW and 800CW. The highest average TBR (2.00 ± 0.34 and 2.72 ± 0.17 for FLARE and IVIS spectrum, respectively) was observed 24 hr after administration of the EGFR-specific nanobody. After injection of 75 µg 7D12-800CW cervical lymph node metastases could be clearly detected. Orthotopic tongue tumors and cervical lymph node metastases in a mouse model were clearly identified intraoperatively using a recently developed fluorescent EGFR-targeting nanobody. Translation of this approach to the clinic would potentially improve the rate of radical surgical resections.

  17. The color cone.

    PubMed

    Logvinenko, Alexander D

    2015-02-01

    While the notion of a color cone can be found in writings of Maxwell, Helmholtz, Grassmann, and other scientists of the nineteenth century, it has not been clearly defined as yet. In this paper, the color cone is understood as the set of points in the cone excitation space produced by all possible lights. The spectral curve representing all the monochromatic lights is shown not to entirely belong to the color cone boundary, since its ends turn into the color cone interior. The monochromatic lights represented by the fragment of the spectral curve lying on the color cone boundary make up what is called the effective visible spectrum. The color cone is shown to be a convex hull of the conical surface through the fragment of the spectral curve representing the effective visible spectrum. The effective visible spectrum ends are shown to be determined by the photopigment spectral absorbance being independent of the prereceptor filters (e.g., the spectral transmittance of the lense and macular pigment).

  18. Integrating Epidermal Growth Factor Receptor Assay With Clinical Parameters Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Chung, Christine H.; Hammond, Elizabeth M.; Trotti, Andy M.; Wang Huijun; Spencer, Sharon; Zhang Huazhong; Cooper, Jay; Jordan, Richard; Rotman, Marvin H.; Ang, K. Kian

    2011-10-01

    Purpose: Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial. Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density). Results: This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a fivefold difference in the risk of LRR. Conclusions: Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation.

  19. 2017 Eclipse Shadow Cones

    NASA Video Gallery

    A solar eclipse occurs when the Moon's shadow falls on the Earth. The shadow comprises two concentric cones called the umbra and the penumbra. Within the smaller, central umbra, the Sun is complete...

  20. Lunar cinder cones.

    PubMed

    McGetchin, T R; Head, J W

    1973-04-01

    Data on terrestrial eruptions of pyroclastic material and ballistic considerations suggest that in the lunar environment (vacuum and reduced gravity) low-rimmed pyroclastic rings are formed rather than the high-rimmed cinder cones so abundant on the earth. Dark blanketing deposits in the Taurus-Littrow region (Apollo 17 landing area) are interpreted as being at least partly composed of lunar counterparts of terrestrial cinder cones.

  1. Lunar cinder cones.

    NASA Technical Reports Server (NTRS)

    Mcgetchin, T. R.; Head, J. W.

    1973-01-01

    Data on terrestrial eruptions of pyroclastic material and ballistic considerations suggest that in the lunar environment (vacuum and reduced gravity) low-rimmed pyroclastic rings are formed rather than the high-rimmed cinder cones so abundant on the earth. Dark blanketing deposits in the Taurus-Littrow region (Apollo 17 landing area) are interpreted as being at least partly composed of lunar counterparts of terrestrial cinder cones.

  2. Head, Neck, and Oral Cancer

    MedlinePlus

    ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ... Neck and Oral Pathology Head, Neck and Oral Pathology Close to 42,000 Americans will be diagnosed ...

  3. Neck Injuries and Disorders

    MedlinePlus

    ... too long. Sometimes you can strain your neck muscles from sleeping in an awkward position or overdoing it during exercise. Falls or accidents, including car accidents, are another common cause of neck pain. ...

  4. Head and Neck Cancer

    MedlinePlus

    Head and neck cancer includes cancers of the mouth, nose, sinuses, salivary glands, throat, and lymph nodes in the ... swallowing A change or hoarseness in the voice Head and neck cancers are twice as common in men. Using ...

  5. [Deep neck infections].

    PubMed

    Nowak, Katarzyna; Szyfter, Witold

    2006-01-01

    Deep neck infection is relatively rare but potentially life threatening complication of common oropharyngeal infections. This retrospective study was aimed at analyzing the occurrence of complications, diagnostic methods and proper management of deep neck infection. A review was conducted in 32 cases who were diagnosed as having deep neck infection from 1995 to 2005. The causes of deep neck infections were tonsillitis (16 cases), tooth diseases (6 cases), paratonsillar abscess (4 cases), parotitis (1 case), pussy lymphonodes after tonsillectomy (2 cases), pussy congenital neck cyst (1 case), chronic otitis media (1 case), parotitis (1 case), foreign body of the esophagus (1 case). All the puss bacterial cultivation were positive. All the patients were treated by different ways of chirurgical drainage and use of large dosage of antibiotics. Deep neck infection should be suspected in patients with long lasting fever and painful swelling of the neck and treatment should begin quick as possible. PMID:17152800

  6. [Deep neck infections].

    PubMed

    Nowak, Katarzyna; Szyfter, Witold

    2006-01-01

    Deep neck infection is relatively rare but potentially life threatening complication of common oropharyngeal infections. This retrospective study was aimed at analyzing the occurrence of complications, diagnostic methods and proper management of deep neck infection. A review was conducted in 32 cases who were diagnosed as having deep neck infection from 1995 to 2005. The causes of deep neck infections were tonsillitis (16 cases), tooth diseases (6 cases), paratonsillar abscess (4 cases), parotitis (1 case), pussy lymphonodes after tonsillectomy (2 cases), pussy congenital neck cyst (1 case), chronic otitis media (1 case), parotitis (1 case), foreign body of the esophagus (1 case). All the puss bacterial cultivation were positive. All the patients were treated by different ways of chirurgical drainage and use of large dosage of antibiotics. Deep neck infection should be suspected in patients with long lasting fever and painful swelling of the neck and treatment should begin quick as possible.

  7. The cone dysfunction syndromes

    PubMed Central

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  8. Why rods and cones?

    PubMed

    Lamb, T D

    2016-02-01

    Under twenty-first-century metropolitan conditions, almost all of our vision is mediated by cones and the photopic system, yet cones make up barely 5% of our retinal photoreceptors. This paper looks at reasons why we additionally possess rods and a scotopic system, and asks why rods comprise 95% of our retinal photoreceptors. It considers the ability of rods to reliably signal the arrival of individual photons of light, as well as the ability of the retina to process these single-photon signals, and it discusses the advantages that accrue. Drawbacks in the arrangement, including the very slow dark adaptation of scotopic vision, are also considered. Finally, the timing of the evolution of cone and rod photoreceptors, the retina, and the camera-style eye is summarised.

  9. Cap protects aircraft nose cone

    NASA Technical Reports Server (NTRS)

    Bryan, C. F., Jr.; Bryan, D. C.

    1981-01-01

    Inexpensive, easily fabricated cap protects aircraft nose cone from erosion. Made of molded polycarbonate, cap has been flight tested at both subsonic and supesonic speeds. Its strength and erosion characteristics are superior to those of fiberglass cones.

  10. Magma supply rates inferred from cinder cone volumes

    NASA Astrophysics Data System (ADS)

    Bemis, K. G.; Borgia, A.; Neri, M.; Kervyn, M.

    2010-12-01

    Revisiting the question of how cinder cones grow suggests the possibility of inferring magma supply rates from cinder cones sizes. We start with a conceptual model of cinder cone growth: (1) Eruption volume flux increases rapidly and then decreases exponentially. (2) Cinder cones get steeper during the initiation of the eruption and then maintain a constant steepness. (3) The initial basal diameter varies with volume flux into the cone. Based on these constraints, we propose a general form for the relationship between cinder cone volume and magma supply rate: V = Q(exp(-t/b)/b - exp(-t/a)/a), where V is volume (in m3), Q is the maximum potential magma flux (in m3/s), t is time (in s), a is a damping factor (in s) controlling the decline in volume flux, and b is a factor controlling the initial increase in volume flux. Then we use the data available on the growth of cinder cones from four modern eruptions to show the relevance of our model and to constrain the supply curves. All four modern cones (Paricutin, Mexico which erupted 1943-1974; Tolbachik, Kamchatka which erupted in 1975-1976; Cono del Laghetto, Mount Etna, Italy which formed in 2001; and a small cone on the summit of Oldoinyo Lengai, Tanzania, which formed during the 2007 eruption) show the basic growth pattern: initial rapid growth followed by declining growth (Figure 1). The regression results yeild the following magma supply rates: The southern Tolbachik cones have the largest predicted magma supply at ~100 m3/s. Paricutin and Laghetto are around 9 m3/s. The Oldoinyo Lengai cone has a magma supply of ~0.5 m3/s. The northern Tolbachik cone has the lowest magma supply of ~0.1 m3/s. In contrast, the damping factor a is generally on the order of 107 (it varies from 8 x 106 at southern Tolbachik to 4 x 107 at northern Tolbachik). The parameter b controlling the initial increase is generally small (<1). The predicted magma supply does not seem to be very sensitive to either parameter. Thus we suggest that

  11. Forgotten triangles of neck.

    PubMed

    Singh, Manpreet; Vashistha, Arpit; Chaudhary, Manoj; Kaur, Gagandeep

    2016-01-01

    The purpose of this manuscript is to add some more information in the present scientific literature on these nearly forgotten triangles of surgical importance. The neck is an area that lends itself to anatomical geometry, such as triangles. Many triangles of the neck have been described, and some are well-known, yet, some have been nearly forgotten, i.e., Lesser's triangle, Farabeuf triangle, Pirogoff's triangle, and Beclard's triangle. From the anatomic and surgical point of view, the neck is an amazingly interesting place. It is like a connection where crucial functional units meet and pass. Added surgical landmarks are always helpful to the surgeon while dealing with the neck. Described triangles of neck in this article are always reliable and constant landmarks for head and neck surgeons. PMID:27563614

  12. American Head and Neck Society

    MedlinePlus

    American Head & Neck Society Mission Statement: Advance Education, Research, and Quality of Care for the head and neck oncology patient. American Head & Neck Society | AHNS The mission of the AHNS is ...

  13. Chainsaw penetrating neck injury.

    PubMed

    Brown, A F

    1995-06-01

    A case of chainsaw injury to the neck is described. Previous reports in the English language are exceedingly rare. A brief discussion of safety features on chain saws is followed by a review of selective vs. mandatory surgical exploration in penetrating neck trauma, including the role of ancillary diagnostic tests.

  14. Light cone matrix product

    SciTech Connect

    Hastings, Matthew B

    2009-01-01

    We show how to combine the light-cone and matrix product algorithms to simulate quantum systems far from equilibrium for long times. For the case of the XXZ spin chain at {Delta} = 0.5, we simulate to a time of {approx} 22.5. While part of the long simulation time is due to the use of the light-cone method, we also describe a modification of the infinite time-evolving bond decimation algorithm with improved numerical stability, and we describe how to incorporate symmetry into this algorithm. While statistical sampling error means that we are not yet able to make a definite statement, the behavior of the simulation at long times indicates the appearance of either 'revivals' in the order parameter as predicted by Hastings and Levitov (e-print arXiv:0806.4283) or of a distinct shoulder in the decay of the order parameter.

  15. Perfusion Estimated With Rapid Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlates Inversely With Vascular Endothelial Growth Factor Expression and Pimonidazole Staining in Head-and-Neck Cancer: A Pilot Study

    SciTech Connect

    Donaldson, Stephanie B.; Betts, Guy; Bonington, Suzanne C.; Homer, Jarrod J.; Slevin, Nick J.; Kershaw, Lucy E.; Valentine, Helen; West, Catharine M.L.; Buckley, David L.

    2011-11-15

    Purpose: To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. Methods and Materials: Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. Results: Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). Conclusions: Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.

  16. Shatter cones: Diagnostic impact signatures

    NASA Astrophysics Data System (ADS)

    McHone, J. F.; Dietz, R. S.

    Uniquely fractured target rocks known as shatter cones are associated with more than one half the world's 120 or so presently known impact structures. Shatter cones are a form of tensile rock failure in which a positive conical plug separates from a negative outer cup or mold and delicate ornaments radiating from an apex are preserved on surfaces of both portions. Although distinct, shatter cones are sometimes confused with other striated geologic features such as ventifacts, stylolites, cone-in-cone, slickensides, and artificial blast plumes. Complete cones or solitary cones are rare, occurrences are usually as swarms in thoroughly fractured rock. Shatter cones may form in a zone where an expanding shock wave propagating through a target decays to form an elastic wave. Near this transition zone, the expanding primary wave may strike a pebble or other inhomogeneity whose contrasting transmission properties produce a scattered secondary wave. Interference between primary and secondary scattered waves produce conical stress fields with axes perpendicular to the plane of an advancing shock front. This model supports mechanism capable of producing such shatter cone properties as orientation, apical clasts, lithic dependence, and shock pressure zonation. Although formational mechanics are still poorly understood, shatter cones have become the simplest geologic field criterion for recognizing astroblemes (ancient terrestrial impact structures).

  17. Shatter cones: Diagnostic impact signatures

    NASA Technical Reports Server (NTRS)

    Mchone, J. F.; Dietz, R. S.

    1988-01-01

    Uniquely fractured target rocks known as shatter cones are associated with more than one half the world's 120 or so presently known impact structures. Shatter cones are a form of tensile rock failure in which a positive conical plug separates from a negative outer cup or mold and delicate ornaments radiating from an apex are preserved on surfaces of both portions. Although distinct, shatter cones are sometimes confused with other striated geologic features such as ventifacts, stylolites, cone-in-cone, slickensides, and artificial blast plumes. Complete cones or solitary cones are rare, occurrences are usually as swarms in thoroughly fractured rock. Shatter cones may form in a zone where an expanding shock wave propagating through a target decays to form an elastic wave. Near this transition zone, the expanding primary wave may strike a pebble or other inhomogeneity whose contrasting transmission properties produce a scattered secondary wave. Interference between primary and secondary scattered waves produce conical stress fields with axes perpendicular to the plane of an advancing shock front. This model supports mechanism capable of producing such shatter cone properties as orientation, apical clasts, lithic dependence, and shock pressure zonation. Although formational mechanics are still poorly understood, shatter cones have become the simplest geologic field criterion for recognizing astroblemes (ancient terrestrial impact structures).

  18. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis.

    PubMed Central

    Patel, V; Senderowicz, A M; Pinto, D; Igishi, T; Raffeld, M; Quintanilla-Martinez, L; Ensley, J F; Sausville, E A; Gutkind, J S

    1998-01-01

    Flavopiridol (HMR 1275) has been identified recently as a novel antineoplastic agent in the primary screen conducted by the Developmental Therapeutics Program, National Cancer Institute. Flavopiridol inhibits most cyclin-dependent kinases (cdks) and displays unique anticancer properties. Here, we investigated whether this compound was effective against head and neck squamous cell carcinomas (HNSCC). Exposure of HNSCC cells to flavopiridol diminished cdc2 and cdk2 activity and potently inhibited cell proliferation (IC50 43-83 nM), which was concomitant with the appearance of cells with a sub-G1 DNA content. Moreover, DNA fragmentation and TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labeling) reaction confirmed that flavopiridol induces apoptosis in all cell lines, even on certain HNSCC cells that are insensitive to apoptosis to DNA-damaging agents (gamma-irradiation and bleomycin). A tumorigenic HNSCC cell line was used to assess the effect of flavopiridol in vivo. Treatment (5 mg/kg per day, intraperitoneally) for 5 d led to the appearance of apoptotic cells in the tumor xenografts and caused a 60-70% reduction in tumor size, which was sustained over a period of 10 wk. Flavopiridol treatment also resulted in a remarkable reduction of cyclin D1 expression in HNSCC cells and tumor xenografts. Our data indicate that flavopiridol exerts antitumor activity in HNSCC, and thus it can be considered a suitable candidate drug for testing in the treatment of refractory carcinomas of the head and neck. PMID:9802881

  19. Cone rod dystrophies.

    PubMed

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  20. Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo.

    PubMed

    Duffey, D C; Chen, Z; Dong, G; Ondrey, F G; Wolf, J S; Brown, K; Siebenlist, U; Van Waes, C

    1999-07-15

    We demonstrated recently that constitutive expression of proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in head and neck squamous cell carcinoma is correlated with activation of transcription factor nuclear factor (NF)-kappaB/Rel A (p50/p65), which binds the promoter region within each of the genes encoding this repertoire of cytokines. NF-kappaB can be activated after signal-dependent phosphorylation and degradation of inhibitor-kappaBalpha and has been reported to promote cell survival and growth. In the present study, we expressed a phosphorylation site mutant of inhibitor-kappaBalpha (IkappaBalphaM) in head and neck squamous cell carcinoma lines UM-SCC-9, -11B, and -38 to determine the effect of inhibition of NF-kappaB on cytokine expression, cell survival in vitro, and growth in vivo. After transfection with IKBalphaM, only a few UM-SCC-9 clones were obtained that stably expressed the mutant IkappaB, suggesting that expression of a mutant IkappaBalpha may affect survival of the transfected UM-SCC cell lines. After cotransfection of IkappaBalphaM with a Lac-Z reporter, we found that the number of surviving beta-galactosidase-positive cells in the three cell lines was reduced by 70-90% when compared with controls transfected with vector lacking the insert. In UM-SCC-9 cells that stably expressed IkappaBalphaM, inhibition of constitutive and tumor necrosis factor-a induced NF-kappaB activation, and production of all four cytokines was observed. Although UM-SCC-9 IkappaBalphaM-transfected cells proliferated at the same rate as vector-transfected cells in vitro, a significant reduction in growth of tumor xenografts was observed in SCID mice in vivo. The decreased growth of UM-SCC-9 IkappaBalphaM-transfected tumor cells accompanied decreased immunohistochemical detection of the activated form of NF-kappaB in situ. These results provide evidence that NF-KB and IkappaBalpha play an important role in

  1. Increase in neuropilin-1 on the surface of growth cones and putative raft domains in neuronal NG108-15 cells co-cultured with vascular smooth muscle SM-3 cells.

    PubMed

    Yoshimura, Ryoichi; Kyuka, Ayumi; Jinno, Miwa; Nishio, Satomi; Matsusaka, Mamoru; Nishida, Tomoki; Endo, Yasuhisa

    2015-04-01

    The mechanisms underlying autonomic innervation to its targets involve various chemical factors, but have not yet been elucidated in detail. We constructed a co-culture system of neuronal cells and vascular smooth muscle cells to investigate the mechanisms underlying innervation of the vasculature. A co-culture with the vascular smooth muscle cell line, SM-3 significantly promoted cell viability, neurite extension, and neuropilin-1 (Nrp-1) mRNA expression in the cholinergic neuronal cell line, NG108-15. Furthermore, immunocytochemistry with or without a detergent treatment revealed that a co-culture with SM-3 cells or culturing with the conditioned medium of SM-3 cells translocated Nrp-1 onto the cell surface of growth cones rather than varicosities of NG108-15 cells. Immunofluorescent microscopy combined with a cold detergent treatment or cholesterol depletion revealed that Nrp-1 accumulated in putative raft domains in the plasma membrane of NG108-15 cells co-cultured with SM-3 cells. The results of the present study suggest that some soluble factors from smooth muscle cells may affect the localization of Nrp-1 in cholinergic neuronal cells, which may, in turn, be involved in the autonomic innervation of blood vessels.

  2. Deep neck space infections.

    PubMed

    Beasley, D J; Amedee, R G

    1995-05-01

    The incidence of deep neck space infections has dramatically decreased since the advent of antibiotics, but with delayed treatment they carry the potential for significant morbidity and mortality. Odontogenic infections with involvement of the submandibular space are the most common source of deep neck space infections in adults, whereas in the pediatric population the most common cause is acute tonsillitis with involvement of the peritonsillar space. The newest group of patients at risk for deep neck space infections are intravenous drug abusers who inject the major vessels of the neck. Knowledge of neck spaces and fascial relationships is important in understanding the presentation, treatment, and complications of deep neck space infections. The spaces, which are created by various fasciae of the head and neck, are only potential spaces in that under normal conditions they cannot be examined clinically or radiographically. As the spaces are invaded by bacteria, a cellulitis or abscess occurs, and this infection may travel through paths of least resistance from one space to another.

  3. Facial dysmorphology in the neglected paediatric head and neck burn.

    PubMed

    Katsaros, J; David, D J; Griffin, P A; Moore, M H

    1990-03-01

    The morphological distortion of the facial skeleton induced by untreated paediatric burns of the head and neck reinforces the theories of craniofacial growth and the modern principles of acute burn management and post-burn facial reconstruction.

  4. Head and Neck Cancer

    MedlinePlus

    ... head and neck cancer. Poor oral and dental hygiene . Poor care of the mouth and teeth has ... sore throat Foul mouth odor not explained by hygiene Hoarseness or change in voice Nasal obstruction or ...

  5. Torticollis (wry neck) (image)

    MedlinePlus

    Torticollis is a form of dystonia (prolonged muscle contractions) in which the neck muscles, particularly the sternocleidomastoid muscle, contract involuntarily causing the head to turn. Torticollis may occur without known cause (idiopathic), be genetic ( ...

  6. TCGA head Neck

    Cancer.gov

    Investigators with The Cancer Genome Atlas (TCGA) Research Network have discovered genomic differences – with potentially important clinical implications – in head and neck cancers caused by infection with the human papillomavirus (HPV).

  7. Talar neck fractures.

    PubMed

    Berlet, G C; Lee, T H; Massa, E G

    2001-01-01

    Clinical management of talar neck fractures is complex and fraught with complications. As Gaius Julius Caesar stated: "The die is cast"; often the outcome of a talar neck fracture is determined at the time of injury. The authors believe, however, that better results can be achieved by following some simple guidelines. The authors advocate prompt and precise anatomic surgical reduction, preferring the medial approach with secondary anterolateral approach. Preservation of blood supply can be achieved by a thorough understanding of vascular pathways and efforts to stay within appropriate surgical intervals. The authors advocate bone grafting of medial neck comminution (if present) to prevent varus malalignment and rigid internal fixation to allow for joint mobilization postoperatively. These guidelines may seem simple, but when dealing with the complexity of talar neck fractures, the foot and ankle surgeon needs to focus and rely on easily grasped concepts to reduce poor outcomes. PMID:11465133

  8. Ultrasound of the neck.

    PubMed

    Koischwitz, D; Gritzmann, N

    2000-09-01

    Sonography, when performed by an experienced examiner, can be used for evaluation of many pathologies in the head and neck area. Some benign neck lesions, such as cysts, lipomas, carotid body tumors, and hyperplastic lymph nodes, have typical sonomorphology. Sonography has an accuracy rate of about 90% in cervical lymph node staging and can delineate subclinical lymph node recurrences. It is the method of choice for evaluation of tumor infiltrations of the wall of the great vessels. Salivary gland tumors in the superficial lobe can be delineated completely by sonography. Salivary stones can be detected and localized. Carcinoma of the tongue and floor of the mouth with T1 and T2 staging can be assessed by US. The use and contribution of color Doppler sonography for the assessment of pathologic entities in the neck is a method under clinical investigation. US-guided fine-needle aspiration biopsy of lymph nodes and tumors of the salivary glands is easy to perform and is characterized by high sensitivity and specificity. To perform US examinations of the head and neck area of the highest quality the examiner should be familiar with the anatomy of the head and neck, be informed about the clinical problem, and have experience in the interpretation of abnormal US findings. US of the head and neck area is one of the most difficult sonographic examinations and should be performed by an experienced physician.

  9. The Holographic Entropy Cone

    SciTech Connect

    Bao, Ning; Nezami, Sepehr; Ooguri, Hirosi; Stoica, Bogdan; Sully, James; Walter, Michael

    2015-09-21

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phase space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.

  10. The Holographic Entropy Cone

    DOE PAGESBeta

    Bao, Ning; Nezami, Sepehr; Ooguri, Hirosi; Stoica, Bogdan; Sully, James; Walter, Michael

    2015-09-21

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phasemore » space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.« less

  11. Making An Impact: Shatter Cones

    ERIC Educational Resources Information Center

    Blank, Lisa M.; Plautz, Michael R.; Crews, Jeffrey W.

    2004-01-01

    In 1990, a group of geologists discovered a large number of shatter cones in southwestern Montana. Shatter cones are a type of metamorphosed rock often found in impact structures (the remains of a crater after a meteor impact and years of Earth activity). Scientists have discovered only 168 impact craters around the world. If rocks could talk,…

  12. Evaluation of otoscope cone cleaning and disinfection procedures commonly used in veterinary medical practices: a pilot study.

    PubMed

    Newton, Heide M; Rosenkrantz, Wayne S; Muse, Russell; Griffin, Craig E

    2006-04-01

    The objective of this study was to evaluate the relative efficacy of otoscope cone cleaning and disinfection methods commonly used in veterinary practices. Using sterile technique, 60 new gas-sterilized 4-mm otoscope cones were inoculated with a broth culture of 1.5 billion Pseudomonas aeruginosa bacteria per mL then allowed to dry for 10 min. Six study groups of 10 cones each were created. Group 1 served as positive control and received no cleaning or disinfection. Group 2 cones were wiped with sterile cotton-tipped applicators and gauze then rinsed with water. Group 3 cones were wiped with 70% isopropyl alcohol. Group 4 cones were scrubbed in a speculum cleaner with Cetylcide II solution (Cetylite Industries, Inc., Pennsauken, NJ). Groups 5 and 6 cones were soaked for 20 min in Cetylcide II and chlorhexidine gluconate 2% solutions, respectively. Using sterile technique and after 10-15 min drying time, the cones were swabbed in a consistent pattern, and samples were submitted for quantitative culture. Culture results showed no growth from cones soaked in Cetylcide II or chlorhexidine solutions. Two of the 10 cones wiped with alcohol, 3/10 cones wiped then rinsed with water, and 3/10 cones scrubbed with the speculum cleaner showed growth of P. aeruginosa. All (10/10) cones in the control group showed heavy growth of P. aeruginosa. These results show that P. aeruginosa can survive on otoscope cones cleaned and disinfected by several commonly used methods. Further study is needed to determine practical and optimal cleaning and disinfection methods for otoscope cones.

  13. CT angiography - head and neck

    MedlinePlus

    Computed tomography angiography - brain; CTA - skull; CTA - cranial; TIA-CTA head; Stroke-CTA head; Computed tomography angiography - neck; CTA - neck; Vertebral artery - CTA; Carotid artery stenosis - CTA; ...

  14. Skeletal dosimetry in cone beam computed tomography

    SciTech Connect

    Walters, B. R. B.; Ding, G. X.; Kramer, R.; Kawrakow, I.

    2009-07-15

    Cone beam computed tomography (CBCT) is a relatively new patient imaging technique that has proved invaluable for treatment target verification and patient positioning during image-guided radiotherapy (IGRT). It has been shown that CBCT results in additional dose to bone that may amount to 10% of the prescribed dose. In this study, voxelized human phantoms, FAX06 (adult female) and MAX06 (adult male), are used together with phase-space data collected from a realistic model of a CBCT imager to calculate dose in the red bone marrow (RBM) and bone surface cells (BSCs), the two organs at risk within the bone spongiosa, during simulated head and neck, chest and pelvis CBCT scans. The FAX06/MAX06 phantoms model spongiosa based on micro-CT images, filling the relevant phantom voxels, which are 0.12x0.12x0.12 cm{sup 3}, with 17x17x17 {mu}m{sup 3} microvoxels to form a micromatrix of trabecular bone and bone marrow. FAX06/MAX06 have already been implemented in an EGSnrc-based Monte Carlo code to simulate radiation transport in the phantoms; however, this study required significant modifications of the code to allow use of phase-space data from a simulated CBCT imager as a source and to allow scoring of total dose, RBM dose and BSC dose on a voxel-by-voxel basis. In simulated CBCT scans, the BSC dose is significantly greater than the dose to other organs at risk. For example, in a simulated head and neck scan, the average BSC dose is 25% higher than the average dose to eye lens ({approx}8.3 cGy), and 80% greater than the average dose to brain (5.7 cGy). Average dose to RBM, on the other hand, is typically only {approx}50% of the average BSC dose and less than the dose to other organs at risk (54% of the dose to eye lens and 76% of dose to brain in a head and neck scan). Thus, elevated dose in bone due to CBCT results in elevated BSC dose. This is potentially of concern when using CBCT in conjunction with radiotherapy treatment.

  15. Stereotactic Body Radiotherapy for Head and Neck Tumors

    ClinicalTrials.gov

    2016-04-18

    Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Salivary Gland Cancer; Head and Neck Sarcoma; Paraganglioma of Head and Neck; Chordoma of Head and Neck; Chondrosarcoma of Head and Neck; Angiofibroma of Head and Neck

  16. Rootless cone eruption processes informed by dissected tephra deposits and conduits

    NASA Astrophysics Data System (ADS)

    Reynolds, P.; Brown, R. J.; Thordarson, T.; Llewellin, E. W.; Fielding, K.

    2015-09-01

    Rootless cones result from the explosive interaction between lava flows and underlying water-saturated sediment or volcaniclastic deposits. Rootless explosions can represent a significant far-field hazard during basaltic eruptions, but there are few detailed studies of their deposits. A rootless cone field in the 8.5 Ma Ice Harbor flow field of the Columbia River Basalt Province, NW USA, is revealed by sections through rootless conduit and cone structures. The Ice Harbor lava flow hosting the rootless cones was emplaced across a floodplain or lacustrine environment that had recently been mantled by a layer of silicic volcanic ash from a major explosive eruption. Our observations indicate a two-stage growth model for the rootless cones: (1) initial explosions generated sediment-rich tephra emplaced by fallout and pyroclastic density currents and (2) later weaker explosions that generated spatter-rich fountains. Variable explosive activity resulted in a wide range of pyroclast morphologies and vesicularities. Cross-sections through funnel-shaped conduits also show how the conduits were constructed and stabilised. The growth model is consistent with decreasing water availability with time, as inferred for rootless cones described in Iceland. The Ice Harbor rootless cones provide further lithological data to help distinguish between rootless cone-derived tephra and tephra generated above an erupting dyke.

  17. Hyperparathyroidism after neck irradiation.

    PubMed

    Christmas, T J; Chapple, C R; Noble, J G; Milroy, E J; Cowie, A G

    1988-09-01

    A retrospective review of 1550 cases of hyperparathyroidism (HPT) treated surgically over a 30-year period reveals a past history of exposure to neck irradiation in 10 cases (0.7 per cent). The indication for radiotherapy was benign disease in nine and papillary thyroid carcinoma in one case. The mean interval between radiation exposure and the detection of HPT was 32 years (range 3-63 years). Patients treated with radioactive iodine alone developed HPT after a mean of 5 years while the interval for those treated with external beam therapy alone was a mean of 44 years. The parathyroid histology was adenoma in six cases, carcinoma in three cases and nodular hyperplasia in one case. All patients had coincident benign thyroid disease apart from one that had previously had papillary carcinoma and another with follicular carcinoma. Neck irradiation has been shown to confer an increased risk of HPT due to parathyroid adenoma and carcinoma. Radiotherapy for benign disease has generally been abandoned and these cases demonstrate a further contra-indication for the use of neck irradiation.

  18. Shatter cones: (Mis)understood?

    PubMed Central

    Osinski, Gordon R.; Ferrière, Ludovic

    2016-01-01

    Meteorite impact craters are one of the most common geological features in the solar system. An impact event is a near-instantaneous process that releases a huge amount of energy over a very small region on a planetary surface. This results in characteristic changes in the target rocks, from vaporization and melting to solid-state effects, such as fracturing and shock metamorphism. Shatter cones are distinctive striated conical fractures that are considered unequivocal evidence of impact events. They are one of the most used and trusted shock-metamorphic effects for the recognition of meteorite impact structures. Despite this, there is still considerable debate regarding their formation. We show that shatter cones are present in several stratigraphic settings within and around impact structures. Together with the occurrence of complete and “double” cones, our observations are most consistent with shatter cone formation due to tensional stresses generated by scattering of the shock wave due to heterogeneities in the rock. On the basis of field mapping, we derive the relationship Dsc = 0.4 Da, where Dsc is the maximum spatial extent of in situ shatter cones, and Da is the apparent crater diameter. This provides an important, new, more accurate method to estimate the apparent diameter of eroded complex craters on Earth. We have reestimated the diameter of eight well-known impact craters as part of this study. Finally, we suggest that shatter cones may reduce the strength of the target, thus aiding crater collapse, and that their distribution in central uplifts also records the obliquity of impact. PMID:27532050

  19. Shatter cones: (Mis)understood?

    PubMed

    Osinski, Gordon R; Ferrière, Ludovic

    2016-08-01

    Meteorite impact craters are one of the most common geological features in the solar system. An impact event is a near-instantaneous process that releases a huge amount of energy over a very small region on a planetary surface. This results in characteristic changes in the target rocks, from vaporization and melting to solid-state effects, such as fracturing and shock metamorphism. Shatter cones are distinctive striated conical fractures that are considered unequivocal evidence of impact events. They are one of the most used and trusted shock-metamorphic effects for the recognition of meteorite impact structures. Despite this, there is still considerable debate regarding their formation. We show that shatter cones are present in several stratigraphic settings within and around impact structures. Together with the occurrence of complete and "double" cones, our observations are most consistent with shatter cone formation due to tensional stresses generated by scattering of the shock wave due to heterogeneities in the rock. On the basis of field mapping, we derive the relationship D sc = 0.4 D a, where D sc is the maximum spatial extent of in situ shatter cones, and D a is the apparent crater diameter. This provides an important, new, more accurate method to estimate the apparent diameter of eroded complex craters on Earth. We have reestimated the diameter of eight well-known impact craters as part of this study. Finally, we suggest that shatter cones may reduce the strength of the target, thus aiding crater collapse, and that their distribution in central uplifts also records the obliquity of impact.

  20. Shatter cones: (Mis)understood?

    PubMed

    Osinski, Gordon R; Ferrière, Ludovic

    2016-08-01

    Meteorite impact craters are one of the most common geological features in the solar system. An impact event is a near-instantaneous process that releases a huge amount of energy over a very small region on a planetary surface. This results in characteristic changes in the target rocks, from vaporization and melting to solid-state effects, such as fracturing and shock metamorphism. Shatter cones are distinctive striated conical fractures that are considered unequivocal evidence of impact events. They are one of the most used and trusted shock-metamorphic effects for the recognition of meteorite impact structures. Despite this, there is still considerable debate regarding their formation. We show that shatter cones are present in several stratigraphic settings within and around impact structures. Together with the occurrence of complete and "double" cones, our observations are most consistent with shatter cone formation due to tensional stresses generated by scattering of the shock wave due to heterogeneities in the rock. On the basis of field mapping, we derive the relationship D sc = 0.4 D a, where D sc is the maximum spatial extent of in situ shatter cones, and D a is the apparent crater diameter. This provides an important, new, more accurate method to estimate the apparent diameter of eroded complex craters on Earth. We have reestimated the diameter of eight well-known impact craters as part of this study. Finally, we suggest that shatter cones may reduce the strength of the target, thus aiding crater collapse, and that their distribution in central uplifts also records the obliquity of impact. PMID:27532050

  1. Selective uptake and imaging of aptamer- and antibody-conjugated hollow nanospheres targeted to epidermal growth factor receptors overexpressed in head and neck cancer.

    PubMed

    Melancon, Marites Pasuelo; Zhou, Min; Zhang, Rui; Xiong, Chiyi; Allen, Peter; Wen, Xiaoxia; Huang, Qian; Wallace, Michael; Myers, Jeffrey N; Stafford, R Jason; Liang, Dong; Ellington, Andrew D; Li, Chun

    2014-05-27

    The purpose of this study was to compare the binding affinity and selective targeting of aptamer- and antibody-coated hollow gold nanospheres (HAuNS) targeted to epidermal growth factor receptors (EGFR). EGFR-targeting aptamers were conjugated to HAuNS (apt-HAuNS) by attaching a thiol-terminated single-stranded DNA to the HAuNS and then adding the complementary RNA targeted to EGFR. Apt-HAuNS was characterized in terms of size, surface charge, absorption, and number of aptamers per particle. The in vivo pharmacokinetics, in vivo biodistribution, and micro-SPECT/CT imaging of (111)In-labeled apt-HAuNS and anti-EGFR antibody (C225)-conjugated HAuNS were evaluated in nude mice bearing highly malignant human OSC-19 oral tumors. (111)In-labeled PEG-HAuNS was used as a control (n = 5/group). Apt-HAuNS did not have an altered absorbance profile or size (λmax = 800 nm; diameter = 55 nm) compared to C225-HAuNS or PEG-HAuNS. The surface charge became more negative upon conjugation of the aptamer (-51.4 vs -19.0 for PEG-HAuNS and -25.0 for C225-HAuNS). The number of aptamers/particle was ∼250. In vitro cell binding and in vivo biodistribution showed selective binding of the apt-HAuNS to EGFR. μSPECT/CT imaging confirmed that there was more tumor uptake of apt-HAuNS than C225-HAuNS. Aptamer is a promising ligand for image-guided delivery of nanoparticles for treatment of tumor cells overexpressing EGFR.

  2. RP cone-rod degeneration.

    PubMed Central

    Heckenlively, J R

    1987-01-01

    A group of patients with progressive retinal degeneration and visual field loss, who meet the basic definition of RP were investigated to better define the relationship of the findings on the ERG with clinical characteristics such as visual field size, presence or absence of scotomata or pseudo-altitudinal defects on visual field, amount of night blindness; and presence or absence of macular or optic nerve changes. These studies suggest that cone-rod degeneration patients of the RP type go through the following stages; early, the ERG has a definite cone-rod pattern where the rod ERG is larger than the cone ERG while both are abnormal. As the disease advances, there is more of a reduction in the scotopic ERG such that both the rod and cone ERGs become nearly equal. As the disease further progresses the ERG becomes non-recordable on single-flash technique, but there is good residual rod function and the final rod threshold remains good until the visual field is reduced, typically less than 10 degrees with the IV-4 isopter. Finally with advanced disease the patient becomes night blind and generally becomes very difficult to distinguished from patients who have advanced rod-cone degeneration. While it may seem logical to find that visual field size correlates with various ERG parameters; this has not been as consistent a finding in patients with rod-cone degeneration in the author's experience. The analysis shows several new pieces of information about visual field changes in cone-rod degeneration; enlarged blind spots are seen earlier in cases which have recordable cone-rod patterns (group I), and pseudo-altitudinal changes are more likely to occur in autosomal recessive patients. Patients with macular lesions and central scotomata had larger amplitudes than patients with normal appearing maculae and no central scotomata. Patients with temporal optic atrophy had an earlier onset of symptoms and significant correlation with both photopic a- and b-waves and bright flash

  3. Cone Penetrometer N Factor Determination Testing Results

    SciTech Connect

    Follett, Jordan R.

    2014-03-05

    This document contains the results of testing activities to determine the empirical 'N Factor' for the cone penetrometer in kaolin clay simulant. The N Factor is used to releate resistance measurements taken with the cone penetrometer to shear strength.

  4. Interventional radiology neck procedures.

    PubMed

    Zabala Landa, R M; Korta Gómez, I; Del Cura Rodríguez, J L

    2016-05-01

    Ultrasonography has become extremely useful in the evaluation of masses in the head and neck. It enables us to determine the anatomic location of the masses as well as the characteristics of the tissues that compose them, thus making it possible to orient the differential diagnosis toward inflammatory, neoplastic, congenital, traumatic, or vascular lesions, although it is necessary to use computed tomography or magnetic resonance imaging to determine the complete extension of certain lesions. The growing range of interventional procedures, mostly guided by ultrasonography, now includes biopsies, drainages, infiltrations, sclerosing treatments, and tumor ablation. PMID:27138033

  5. Interventional radiology neck procedures.

    PubMed

    Zabala Landa, R M; Korta Gómez, I; Del Cura Rodríguez, J L

    2016-05-01

    Ultrasonography has become extremely useful in the evaluation of masses in the head and neck. It enables us to determine the anatomic location of the masses as well as the characteristics of the tissues that compose them, thus making it possible to orient the differential diagnosis toward inflammatory, neoplastic, congenital, traumatic, or vascular lesions, although it is necessary to use computed tomography or magnetic resonance imaging to determine the complete extension of certain lesions. The growing range of interventional procedures, mostly guided by ultrasonography, now includes biopsies, drainages, infiltrations, sclerosing treatments, and tumor ablation.

  6. Drugs Approved for Head and Neck Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Head and Neck Cancer This page ... and neck cancer that are not listed here. Drugs Approved for Head and Neck Cancer Abitrexate (Methotrexate) ...

  7. Head and Neck Cancer: Symptoms and Signs

    MedlinePlus

    ... Symptoms and Signs Request Permissions Print to PDF Head and Neck Cancer - Symptoms and Signs Approved by the Cancer. ... Cancer Research and Advocacy Survivorship Blog About Us Head and Neck Cancer Guide Cancer.Net Guide Head and Neck ...

  8. Transient wake and trajectory of free falling cones with various apex angles

    NASA Astrophysics Data System (ADS)

    Jin, Yaqing; Hamed, Ali M.; Chamorro, Leonardo P.

    2015-11-01

    The early free-fall stages of cones with a density ratio 1.18 and apex angles of 30°, 45°, 60°, and 90° were studied using a wireless 3-axis gyroscope and accelerometer to describe the cone 3D motions, while the induced flow in the near wake was captured using particle image velocimetry. The Reynolds number based on the cone diameter and the velocity at which the cone reaches the first local velocity maximum is found to set the limit between two distinctive states. Before this Re is reached the departure from the vertical path and cone rotations are insignificant, while relatively rapid growth is observed after this Re. Sequences of vertical velocity, swirling strength, LES-decomposed velocity, and pressure fields shows the formation and growth of a large and initially symmetric recirculation bubble at the cone base and highlights the presence of a symmetric 3D vortex rollup dominating the near-wake in the early stages of the fall. Later, the shear layer at the edge of the wake manifests in the shedding of Kelvin-Helmholtz vortices that, due to the nature of the recirculation bubble, reorganize to constitute a part of the rollup. Later in the fall, the wake loses its symmetry and shows a high population of vortical structures leading to turbulence. The asymmetric wake leads to strong interactions between the flow field and the cone creating complex feedback loops.

  9. [Femoral neck fracture].

    PubMed

    Gierer, P; Mittlmeier, T

    2015-03-01

    The incidence of femoral neck fractures increases exponentially with rising age. Young patients are rarely affected but when they are it is mostly due to high energy accidents, whereas older patients suffer from femoral neck fractures by low energy trauma due to osteoporotic changes of the bone mineral density. Treatment options have not essentially changed over the last few years. Non-operative treatment may be a choice in non-dislocated and impacted fractures. Due to the high risk of secondary fracture displacement prophylactic screw osteosynthesis is recommended even in Garden type I fractures. Osteosynthetic fracture stabilization with cannulated screws or angle stable sliding screws, is usually applied in non-displaced fractures and fractures in younger patients. Older patients need rapid mobilization after surgery; therefore, total hip arthroplasty and hemiarthroplasty are commonly used with a low incidence of secondary complications. In addition to sufficient operative treatment a guideline conform osteoprosis therapy should be initiated for the prophylaxis of further fractures and patients should undertake a suitable rehabilitation.

  10. Journey of water in pine cones

    PubMed Central

    Song, Kahye; Yeom, Eunseop; Seo, Seung-Jun; Kim, Kiwoong; Kim, Hyejeong; Lim, Jae-Hong; Joon Lee, Sang

    2015-01-01

    Pine cones fold their scales when it rains to prevent seeds from short-distance dispersal. Given that the scales of pine cones consist of nothing but dead cells, this folding motion is evidently related to structural changes. In this study, the structural characteristics of pine cones are studied on micro-/macro-scale using various imaging instruments. Raindrops fall along the outer scales to the three layers (bract scales, fibers and innermost lignified structure) of inner pine cones. However, not all the layers but only the bract scales get wet and then, most raindrops move to the inner scales. These systems reduce the amount of water used and minimize the time spent on structural changes. The result shows that the pine cones have structural advantages that could influence the efficient motion of pine cones. This study provides new insights to understand the motion of pine cones and would be used to design a novel water transport system. PMID:25944117

  11. Journey of water in pine cones

    NASA Astrophysics Data System (ADS)

    Song, Kahye; Yeom, Eunseop; Seo, Seung-Jun; Kim, Kiwoong; Kim, Hyejeong; Lim, Jae-Hong; Joon Lee, Sang

    2015-05-01

    Pine cones fold their scales when it rains to prevent seeds from short-distance dispersal. Given that the scales of pine cones consist of nothing but dead cells, this folding motion is evidently related to structural changes. In this study, the structural characteristics of pine cones are studied on micro-/macro-scale using various imaging instruments. Raindrops fall along the outer scales to the three layers (bract scales, fibers and innermost lignified structure) of inner pine cones. However, not all the layers but only the bract scales get wet and then, most raindrops move to the inner scales. These systems reduce the amount of water used and minimize the time spent on structural changes. The result shows that the pine cones have structural advantages that could influence the efficient motion of pine cones. This study provides new insights to understand the motion of pine cones and would be used to design a novel water transport system.

  12. Disclinations, e-cones, and their interactions in extensible sheets.

    PubMed

    Chopin, Julien; Kudrolli, Arshad

    2016-05-11

    We investigate the nucleation, growth, and spatial organization of topological defects with a ribbon shaped elastic sheet which is stretched and twisted. Singularities are found to spontaneously arrange in a triangular lattice in the form of vertices connected by stretched ridges that result in a self-rigidified structure. The vertices are shown to be negative disclinations or e-cones which occur in sheets with negative Gaussian curvature, in contrast with d-cones in sheets with zero-Gaussian curvature. We find the growth of the wrinkled width of the ribbon to be consistent with a far-from-threshold approach assuming a compression-free base state. The system is found to show a transition from a regime where the wavelength is given by the ribbon geometry, to where it is given by its elasticity as a function of the ratio of the applied tension to the elastic modulus and cross-sectional area of the ribbon.

  13. Head and neck squamous cell carcinoma: new translational therapies.

    PubMed

    Prince, Anthony; Aguirre-Ghizo, Julio; Genden, Eric; Posner, Marshall; Sikora, Andrew

    2010-01-01

    Head and neck squamous cell carcinoma includes cancers of the mouth, throat, larynx, and lymph nodes of the neck. Although early disease is amenable to single-modality treatment with surgery or radiation, patients with advanced disease have a dramatically worse prognosis, despite potentially morbid/toxic treatment regimens involving surgery, radiation, chemotherapy, or all 3 modalities. The present review seeks to provide an overview of current understanding and treatment of head and neck squamous cell carcinoma for the nonspecialist clinician or basic/translational researcher, followed by an overview of major translational approaches to the treatment of head and neck squamous cell carcinoma. Translational research topics addressed include targeted molecular therapy, immunotherapy, minimally invasive robotic surgery, and ablation of dormant/residual tumor cells. Despite the many potentially promising avenues of head and neck squamous cell carcinoma research, only 2 new treatment approaches (antiepidermal growth factor receptor therapy and robotic surgery) have been approved by the US Food and Drug Administration in the past 30 years. Focused research programs involving integrated teams of clinicians, basic scientists, and translational clinician-researchers have the potential to accelerate discovery and change treatment paradigms for patients with head and neck cancer. PMID:21105129

  14. Evaluation of Radiation Dose and Image Quality for the Varian Cone Beam Computed Tomography System

    SciTech Connect

    Cheng, Harry C.Y.; Wu, Vincent W.C.; Liu, Eva S.F.; Kwong, Dora L.W.

    2011-05-01

    Purpose: To compare the image quality and dosimetry on the Varian cone beam computed tomography (CBCT) system between software Version 1.4.13 and Version 1.4.11 (referred to as 'new' and 'old' protocols, respectively, in the following text). This study investigated organ absorbed dose, total effective dose, and image quality of the CBCT system for the head-and-neck and pelvic regions. Methods and Materials: A calibrated Farmer chamber and two standard cylindrical Perspex CT dosimetry phantoms with diameter of 16 cm (head phantom) and 32 cm (body phantom) were used to measure the weighted cone-beam computed tomography dose index (CBCTDIw) of the Varian CBCT system. The absorbed dose of different organs was measured in a female anthropomorphic phantom with thermoluminescent dosimeters (TLD) and the total effective dose was estimated according to International Commission on Radiological Protection (ICRP) Publication 103. The dose measurement and image quality were studied for head-and-neck and pelvic regions, and comparison was made between the new and old protocols. Results: The values of the new CBCTDIw head-and-neck and pelvic protocols were 36.6 and 29.4 mGy, respectively. The total effective doses from the new head-and-neck and pelvic protocols were 1.7 and 8.2 mSv, respectively. The absorbed doses of lens for the new 200{sup o} and old 360{sup o} head-and-neck protocols were 3.8 and 59.4 mGy, respectively. The additional secondary cancer risk from daily CBCT might be up to 2.8%. Conclusions: The new Varian CBCT provided volumetric information for image guidance with acceptable image quality and lower radiation dose. This imaging tool gave a better standard for patient daily setup verification.

  15. [Grading of head and neck neoplasms].

    PubMed

    Agaimy, A; Weichert, W

    2016-07-01

    Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e. g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e. g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed. PMID:27342593

  16. Phase I trial of dacomitinib, a pan-human epidermal growth factor receptor (HER) inhibitor, with concurrent radiotherapy and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (XDC-001).

    PubMed

    Prawira, Amy; Brana-Garcia, Irene; Spreafico, Anna; Hope, Andrew; Waldron, John; Razak, Albiruni R Abdul; Chen, Eric X; Jang, Raymond; O'Sullivan, Brian; Giuliani, Meredith; Bayley, Andrew; Cho, John; Wang, Lisa; Perez-Ordonez, Bayardo; Weinreb, Ilan; Siu, Lillian L; Hansen, Aaron R

    2016-10-01

    Background Curative-intent, non-surgical treatment options for locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) include radiotherapy with/without chemotherapy or radiotherapy with cetuximab. This single institution phase I dose escalation trial tested the pan-human epidermal growth factor receptor (HER) oral tyrosine kinase inhibitor, dacomitinib, in combination with standard cisplatin-based chemoradiotherapy. Methods Patients received oral dacomitinib once daily at 3 protocol-defined dose levels (15 mg, 30 mg, and 45 mg). Cisplatin was given intravenously at 100 mg/m(2) every 3 weeks. Radiotherapy was delivered using intensity modulated radiation therapy (IMRT) to a dose of 70Gy in 35 daily fractions to the primary and nodal disease. Dose escalation was performed using a standard 3 + 3 design. Results Twelve patients with LA-SCCHN were enrolled between January 2013 and August 2014. No dose limiting toxicities (DLTs) were observed in the 15 mg and 30 mg dose levels. In the 45 mg dose level, one of four evaluable patients developed a DLT with intolerable grade 2 diarrhea requiring discontinuation of therapy. Adverse events (AEs) attributed to dacomitinib alone include diarrhea, hypertension, and acneiform and maculopapular rash. The most common non-hematological AEs include weight loss, diarrhea, dry mouth, mucositis, nausea, hypoalbuminemia, and hyponatremia. Frequency and severity of AEs did not increase with increasing dose levels of dacomitinib. All patients completed the full course of radiotherapy on schedule and the median dose of cisplatin was 200 mg/m(2), which is comparable to historical standards. Of the 10 patients evaluable for response, 1 patient relapsed with metastatic disease. Conclusions The triple combination has a tolerable side effect profile and dose levels 15 mg and 30 mg were cleared safely. The addition of dacomitinib did not preclude delivery of standard chemoradiotherapy. Studies testing the

  17. Inside the cone of protection

    SciTech Connect

    Stahmann, J.R.

    1983-01-01

    Although lightning cones of protection and cones of attraction have been used for over 100 years, much confusion still remains as to their effectiveness, particularly as applied to personnel protection. At Kennedy Space Center, a 1:1 cone of protection with a straight side is standard for structure or equipment protection. However, at the launch pad, where a 400-foot lightning lightning rod on top of an insulating mast is used for pad lightning protection, the idea developed that personnel within a 400-foot radius of this mast would be safe from lightning and those outside it would not. Since it is obvious that a person 395 feet (120.4 m.) from the mast is only slightly safer than one at 405 feet (123.5 m.), an investigation was initiated to calculate the probabilities of a person being struck by lightning as he moves closer to the mast inside the cone of protection. Since the risk does not go to zero outside the structure, the risk level can then be estimated. To arrive at the expected strike frequency, it was necessary to measure the strike frequencies at KSC. Krider and others have found a mean area density of cloud-to-ground lightning at KSC of about 4.6 + or - 3.1 flashes per sq km per month in the summer. An overall frequency is estimated as about 20 flashes per sq km per year. With these data, the risk of exposure at various distances from the lightning mast can be calculated. Assuming continuous exposure during thunderstorms, this risk varies from about one strike per person in 1,400 years near the tower to one stroke per person in 300 years at about 400 foot (122 m.).

  18. Cardiac cone-beam CT

    SciTech Connect

    Manzke, Robert . E-mail: robert.manzke@philips.com

    2005-10-15

    This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net.

  19. Prescriptionless light-cone integrals

    NASA Astrophysics Data System (ADS)

    Suzuki, A. T.; Schmidt, A. G. M.

    2000-01-01

    Perturbative quantum gauge field theory as seen within the perspective of physical gauge choices such as the light-cone gauge entails the emergence of troublesome poles of the type (k\\cdot n)^{-α} in the Feynman integrals. These come from the boson field propagator, where α = 1,2,\\cdots and n^{μ} is the external arbitrary four-vector that defines the gauge proper. This becomes an additional hurdle in the computation of Feynman diagrams, since any graph containing internal boson lines will inevitably produce integrands with denominators bearing the characteristic gauge-fixing factor. How one deals with them has been the subject of research over decades, and several prescriptions have been suggested and tried in the course of time, with failures and successes. However, a more recent development at this fronteer which applies the negative dimensional technique to compute light-cone Feynman integrals shows that we can altogether dispense with prescriptions to perform the calculations. An additional bonus comes to us attached to this new technique, in that not only it renders the light-cone prescriptionless but, by the very nature of it, it can also dispense with decomposition formulas or partial fractioning tricks used in the standard approach to separate pole products of the type (k\\cdot n)^{-α}[(k-p)\\cdot n]^{-β} (β = 1,2,\\cdots ). In this work we demonstrate how all this can be done.

  20. Bursting the Taylor cone bubble

    NASA Astrophysics Data System (ADS)

    Pan, Zhao; Truscott, Tadd

    2014-11-01

    A soap bubble fixed on a surface and placed in an electric field will take on the shape of a cone rather than constant curvature (dome) when the electrical field is not present. The phenomenon was introduced by J. Zeleny (1917) and studied extensively by C.T. Wilson & G.I. Taylor (1925). We revisit the Taylor cone problem by studying the deformation and bursting of soap bubbles in a point charge electric field. A single bubble takes on the shape of a cone in the electric field and a high-speed camera equipped with a micro-lens is used to observe the unsteady dynamics at the tip. Rupture occurs as a very small piece of the tip is torn away from the bubble toward the point charge. Based on experiments, a theoretical model is developed that predicts when rupture should occur. This study may help in the design of foam-removal techniques in engineering and provide a better understanding of an electrified air-liquid interface.

  1. Organization of the human trichromatic cone mosaic.

    PubMed

    Hofer, Heidi; Carroll, Joseph; Neitz, Jay; Neitz, Maureen; Williams, David R

    2005-10-19

    Using high-resolution adaptive-optics imaging combined with retinal densitometry, we characterized the arrangement of short- (S), middle- (M), and long- (L) wavelength-sensitive cones in eight human foveal mosaics. As suggested by previous studies, we found males with normal color vision that varied in the ratio of L to M cones (from 1.1:1 to 16.5:1). We also found a protan carrier with an even more extreme L:M ratio (0.37:1). All subjects had nearly identical S-cone densities, indicating independence of the developmental mechanism that governs the relative numerosity of L/M and S cones. L:M cone ratio estimates were correlated highly with those obtained in the same eyes using the flicker photometric electroretinogram (ERG), although the comparison indicates that the signal from each M cone makes a larger contribution to the ERG than each L cone. Although all subjects had highly disordered arrangements of L and M cones, three subjects showed evidence for departures from a strictly random rule for assigning the L and M cone photopigments. In two retinas, these departures corresponded to local clumping of cones of like type. In a third retina, the L:M cone ratio differed significantly at two retinal locations on opposite sides of the fovea. These results suggest that the assignment of L and M pigment, although highly irregular, is not a completely random process. Surprisingly, in the protan carrier, in which X-chromosome inactivation would favor L- or M-cone clumping, there was no evidence of clumping, perhaps as a result of cone migration during foveal development. PMID:16237171

  2. Fundamental conical defects: The d-cone, its e-cone, and its p-cone

    NASA Astrophysics Data System (ADS)

    Seffen, Keith A.

    2016-07-01

    We consider well-known surface disclinations by cutting, joining, and folding pieces of paper card. The resulting shapes have a discrete, folded vertex whose geometry is described easily by Gauss's mapping, in particular, we can relate the degree of angular excess, or deficit, to the size of fold line rotations by the area enclosed by the vector diagram of these rotations. This is well known for the case of a so-called "d-cone" of zero angular deficit, and we formulate the same for a general disclination. This method allows us to observe kinematic properties in a meaningful way without needing to consider equilibrium. Importantly, the simple vector nature of our analysis shows that some disclinations are primitive; and that other types, such as d-cones, are amalgamations of them.

  3. Fundamental conical defects: The d-cone, its e-cone, and its p-cone.

    PubMed

    Seffen, Keith A

    2016-07-01

    We consider well-known surface disclinations by cutting, joining, and folding pieces of paper card. The resulting shapes have a discrete, folded vertex whose geometry is described easily by Gauss's mapping, in particular, we can relate the degree of angular excess, or deficit, to the size of fold line rotations by the area enclosed by the vector diagram of these rotations. This is well known for the case of a so-called "d-cone" of zero angular deficit, and we formulate the same for a general disclination. This method allows us to observe kinematic properties in a meaningful way without needing to consider equilibrium. Importantly, the simple vector nature of our analysis shows that some disclinations are primitive; and that other types, such as d-cones, are amalgamations of them. PMID:27575208

  4. Transition on elliptic cones at Mach 8

    NASA Astrophysics Data System (ADS)

    Huntley, Mark Bradford

    2000-10-01

    Flow visualizations of boundary layer transition on two sharp-nosed elliptic cones at Mach 8 are presented. The elliptic cone is a relevant three-dimensional flow field since it represents a generic hypersonic lifting vehicle shape. Experiments utilize carbon dioxide enhanced Filtered Rayleigh scattering to produce planar single-shot and motion picture images. CO2 is injected into the flow upstream of the tunnel stagnation chamber and subsequently condenses into nanoscale clusters during the nozzle expansion process. The clusters sublimate as they enter the hot boundary layer, and Rayleigh images capture the interface that exists between the regions of condensed (freestream) and sublimated (boundary layer) carbon dioxide. Boundary layers ranging from laminar to late-transitional in character are imaged using streamwise, spanwise, and planform laser sheet orientations. Characteristics of observed instabilities are quantified using pdf profiles, power spectrum analysis, and autocorrelation results derived from single-shot images. A new MHz-rate imaging system is also used to produce motion pictures images and volumetric reconstructions of the boundary layer. The pressure gradient and associated crossflow from the major axis to the minor axis of the cone causes increased growth and subsequent early transition of the centerline boundary layer. The convection velocity and temporal evolution of structures appearing on both the centerline and off-axis regions is studied using cross correlation procedures. Volumetric image sets of the centerline reveal hairpin structures characteristic of the early stages of subsonic turbulent spot formation. In the off-axis regions, planform single-shot images reveal a pattern of finger-like crests in the boundary layer. At higher Reynolds numbers the breakdown of these crests involves the formation of a series of chain-like structures. The behavior appears qualitatively similar to visualizations of crossflow vortex breakdown in

  5. Isolating prompt photons with narrow cones

    NASA Astrophysics Data System (ADS)

    Catani, S.; Fontannaz, M.; Guillet, J. Ph.; Pilon, E.

    2013-09-01

    We discuss the isolation of prompt photons in hadronic collisions by means of narrow isolation cones and the QCD computation of the corresponding cross sections. We reconsider the occurence of large perturbative terms with logarithmic dependence on the cone size and their impact on the fragmentation scale dependence. We cure the apparent perturbative violation of unitarity for small cone sizes, which had been noticed earlier in next-to-leading-order (NLO) calculations, by resumming the leading logarithmic dependence on the cone size. We discuss possible implications regarding the implementation of some hollow cone variants of the cone criterion, which simulate the experimental difficulty to impose isolation inside the region filled by the electromagnetic shower that develops in the calorimeter.

  6. Cone Penetrometer Off-Surface Sensor

    SciTech Connect

    Smail, T.R.; French, p.J.; Huffman, R.K.; Hebert, P.S.

    1999-10-20

    Cone penetrometer technology accounts for approximately 50 percent of the subsurface drilling done at the Savannah River Site. This technology provides a means of collecting data for use in the characterization of the subsurface. The cone penetrometer consists of a steel cone attached to a pipe column that is hydraulically inserted into the ground. To allow researchers to accurately measure subsurface properties, without the inherent problems of cone penetrometer equipment, the Savannah River Technology Center has developed the Cone Penetrometer Off-Surface Sensor (CPOSS). The CPOSS design consists of a knife-blade mechanism mounted along the surface of a module capable of attaching to existing cone penetrometer equipment and being deployed at depths of up to 200 feet. CPOSS development is the subject of this report.

  7. Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations.

    PubMed

    Gardner, J C; Michaelides, M; Hardcastle, A J

    2016-05-25

    X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.

  8. Acute disposition of neck injuries.

    PubMed

    Cooper, Leslie

    2005-02-01

    Neck injuries can be some of the most serious and anxiety-producing injuries that occur during sporting events. It is important for the team physician to be prepared for the care of these injuries and be able to identify some of the more serious injuries. Proper care of these injuries can be life saving and prevent further injury and permanent disability. This article reviews the principles of management and latest evidence for acute neck injuries.

  9. Ionic emission from Taylor cones

    NASA Astrophysics Data System (ADS)

    Castro Reina, Sergio

    Electrified Taylor cones have been seen as an efficient way to generate thrust for space propulsion. Especially the pure ionic regime (PIR) combines a very high specific impulse (thrust per unit mass) and efficiency, which is very important to reduce fuel transportation costs. The PIR has been primarily based on electrosprays of liquid metals [Swatik and Hendricks 1968, Swatik 1969]. However, emissions dominated by or containing exclusively ions have also been observed from nonmetallic purely ionic substances, initially sulfuric acid [Perel et al. 1969], and more recently room temperature molten salts referred to as ionic liquids (ILs) [Romero-Sanz et al. 2003]. The recent use of the liquid metal ion source (LMIS) with ILs, becoming this "new" source to be known as ionic liquid ion source (ILIS) [Lozano and Martinez-Sanchez 2005], has shown important differences on the emission from Taylor cones with the traditional hollow capillary. This new source seems to be more flexible than the capillary [Paulo, Sergio, carlos], although its low emission level (low thrust) is an important drawback from the space propulsion point of view. Throughout the thesis I have studied some aspects of the ionic emission from ionic liquid Taylor cones and the influence of the properties of the liquids and the characteristic of source on the emission. I have unraveled the reason why ILIS emits such low currents (˜200 nA) and found a way to solve this problem increasing the current up to capillary levels (˜1000 nA) [Castro and Fernandez de la Mora 2009]. I have also tried to reduce ion evaporation while reducing the emitted droplet size in order to increase the thrust generated while keeping the efficiency relatively high and I have measured the energy of evaporation of several cations composing ionic liquids, mandatory step to understand ionic evaporation.

  10. Nested-cone transformer antenna

    DOEpatents

    Ekdahl, C.A.

    1991-05-28

    A plurality of conical transmission lines are concentrically nested to form an output antenna for pulsed-power, radio-frequency, and microwave sources. The diverging conical conductors enable a high power input density across a bulk dielectric to be reduced below a breakdown power density at the antenna interface with the transmitting medium. The plurality of cones maintain a spacing between conductors which minimizes the generation of high order modes between the conductors. Further, the power input feeds are isolated at the input while enabling the output electromagnetic waves to add at the transmission interface. Thus, very large power signals from a pulse rf, or microwave source can be radiated. 6 figures.

  11. Nested-cone transformer antenna

    DOEpatents

    Ekdahl, Carl A.

    1991-01-01

    A plurality of conical transmission lines are concentrically nested to form n output antenna for pulsed-power, radio-frequency, and microwave sources. The diverging conical conductors enable a high power input density across a bulk dielectric to be reduced below a breakdown power density at the antenna interface with the transmitting medium. The plurality of cones maintain a spacing between conductors which minimizes the generation of high order modes between the conductors. Further, the power input feeds are isolated at the input while enabling the output electromagnetic waves to add at the transmission interface. Thus, very large power signals from a pulse rf, or microwave source can be radiated.

  12. Persistence of a Cervical Neck Mass, Not Just the Lymphoma

    PubMed Central

    Zaarour, Mazen; Ibrahim, Uroosa; Saouma, Samer; Liu, Ying; Kong, Fanyi; Atallah, Jean Paul

    2016-01-01

    Actinomycosis is a rare, chronic granulomatous infection caused by gram-positive, anaerobic to microaerophilic branching filamentous bacteria. In the cervicofacial region, it usually presents as an enlarging neck mass. It remains a diagnostic challenge due to the fact that cultures show no growth in more than 50% of cases. We report a case of a 67-year-old patient known to have a neck mass secondary to lymphoma in which the neck mass persisted despite therapy. Upon evaluation, the diagnosis of culture-negative actinomycosis was based on histopathology findings, and the patient received antibiotic therapy. We will discuss the diagnosis and pathology of actinomycosis, attempting to explore the relationship between actinomycosis and lymphoid malignancy.  PMID:27699142

  13. Persistence of a Cervical Neck Mass, Not Just the Lymphoma

    PubMed Central

    Zaarour, Mazen; Ibrahim, Uroosa; Saouma, Samer; Liu, Ying; Kong, Fanyi; Atallah, Jean Paul

    2016-01-01

    Actinomycosis is a rare, chronic granulomatous infection caused by gram-positive, anaerobic to microaerophilic branching filamentous bacteria. In the cervicofacial region, it usually presents as an enlarging neck mass. It remains a diagnostic challenge due to the fact that cultures show no growth in more than 50% of cases. We report a case of a 67-year-old patient known to have a neck mass secondary to lymphoma in which the neck mass persisted despite therapy. Upon evaluation, the diagnosis of culture-negative actinomycosis was based on histopathology findings, and the patient received antibiotic therapy. We will discuss the diagnosis and pathology of actinomycosis, attempting to explore the relationship between actinomycosis and lymphoid malignancy. 

  14. Identification of appropriate cone length to avoid positive cone margin in high grade cervical intraepithelial neoplasia

    PubMed Central

    Tsuda, Naotake; Nishio, Shin; Ushijima, Kimio

    2016-01-01

    Objective To identify key factors for predicting positive cone margin and appropriate cone length. Methods We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. Results Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut-off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. Conclusion We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length. PMID:27401478

  15. The structure and emplacement of cinder cone fields

    NASA Technical Reports Server (NTRS)

    Settle, M.

    1979-01-01

    The paper examines the structure and emplacement of cinder cone fields. Terrestrial cinder cone fields occur in volcanic provinces upon the flanks of major volcanoes or within relatively flat-lying volcanic fields. Measurements of cone shape and distribution were made in three volcano cone fields and three platform cone fields, and it was found that modal average values of cone basal diameter are on the order of 300 to 400 m within volcano cone fields and 900 to 1000 m within platform cone fields. The average morphometric parameters for the six fields indicate that cone diameter is positively correlated with cone separation distance, and that the size and spacing of cinder cones formed on the flanks of volcanoes is less than the size and spacing of cones constructed in volcanic fields.

  16. Panoramic cone beam computed tomography

    SciTech Connect

    Chang Jenghwa; Zhou Lili; Wang Song; Clifford Chao, K. S.

    2012-05-15

    Purpose: Cone-beam computed tomography (CBCT) is the main imaging tool for image-guided radiotherapy but its functionality is limited by a small imaging volume and restricted image position (imaged at the central instead of the treatment position for peripheral lesions to avoid collisions). In this paper, the authors present the concept of ''panoramic CBCT,'' which can image patients at the treatment position with an imaging volume as large as practically needed. Methods: In this novel panoramic CBCT technique, the target is scanned sequentially from multiple view angles. For each view angle, a half scan (180 deg. + {theta}{sub cone} where {theta}{sub cone} is the cone angle) is performed with the imaging panel positioned in any location along the beam path. The panoramic projection images of all views for the same gantry angle are then stitched together with the direct image stitching method (i.e., according to the reported imaging position) and full-fan, half-scan CBCT reconstruction is performed using the stitched projection images. To validate this imaging technique, the authors simulated cone-beam projection images of the Mathematical Cardiac Torso (MCAT) thorax phantom for three panoramic views. Gaps, repeated/missing columns, and different exposure levels were introduced between adjacent views to simulate imperfect image stitching due to uncertainties in imaging position or output fluctuation. A modified simultaneous algebraic reconstruction technique (modified SART) was developed to reconstruct CBCT images directly from the stitched projection images. As a gold standard, full-fan, full-scan (360 deg. gantry rotation) CBCT reconstructions were also performed using projection images of one imaging panel large enough to encompass the target. Contrast-to-noise ratio (CNR) and geometric distortion were evaluated to quantify the quality of reconstructed images. Monte Carlo simulations were performed to evaluate the effect of scattering on the image quality and

  17. Cone penetrometer demonstration standard startup review checklist

    SciTech Connect

    KRIEG, S.A.

    1998-11-09

    Startup readiness for the Cone Penetrometer Demonstration in AX Tank Farm will be verified through the application of a Standard Startup Review Checklist. This is a listing of those items essential to demonstrating readiness to start the Cone Penetrometer Demonstration in AX Tank Farm.

  18. System design description cone penetrometer system

    SciTech Connect

    Seda, R.Y., Westinghouse Hanford

    1996-08-12

    The system design description documents in detail the design of the cone penetrometer system. The systems includes the cone penetrometer physical package, raman spectroscopy package and moisture sensor package. Information pertinent to the system design, development, fabrication and testing is provided.

  19. Recoverin depletion accelerates cone photoresponse recovery

    PubMed Central

    Zang, Jingjing; Keim, Jennifer; Kastenhuber, Edda; Gesemann, Matthias; Neuhauss, Stephan C. F.

    2015-01-01

    The neuronal Ca2+-binding protein Recoverin has been shown to regulate phototransduction termination in mammalian rods. Here we identify four recoverin genes in the zebrafish genome, rcv1a, rcv1b, rcv2a and rcv2b, and investigate their role in modulating the cone phototransduction cascade. While Recoverin-1b is only found in the adult retina, the other Recoverins are expressed throughout development in all four cone types, except Recoverin-1a, which is expressed only in rods and UV cones. Applying a double flash electroretinogram (ERG) paradigm, downregulation of Recoverin-2a or 2b accelerates cone photoresponse recovery, albeit at different light intensities. Exclusive recording from UV cones via spectral ERG reveals that knockdown of Recoverin-1a alone has no effect, but Recoverin-1a/2a double-knockdowns showed an even shorter recovery time than Recoverin-2a-deficient larvae. We also showed that UV cone photoresponse kinetics depend on Recoverin-2a function via cone-specific kinase Grk7a. This is the first in vivo study demonstrating that cone opsin deactivation kinetics determine overall photoresponse shut off kinetics. PMID:26246494

  20. Increase in cone biomass and terpenophenolics in hops ( Humulus lupulus L.) by treatment with prohexadione-calcium.

    PubMed

    Kavalier, Adam R; Pitra, Nicholi J; Koelling, Jared M; Coles, Mark C; Kennelly, Edward J; Matthews, Paul D

    2011-06-22

    Humulus lupulus L. (hop), a specialty crop bred for flavor characteristics of the inflorescence, is an essential ingredient in beer. Hop inflorescences, commonly known as hop cones, contain terpenophenolic compounds, which are important for beer flavoring and of interest in biomedical research. Hop breeders focus their efforts on increasing cone biomass and terpenophenolic content. As an alternative to traditional breeding, hops were treated with prohexadione-calcium (Pro-Ca), a growth inhibitor previously shown to have positive agronomic effects in several crops. Application of Pro-Ca to hop plants during cone maturation induced increases in cone biomass production by 1.5-19.6% and increased terpenophenolic content by 9.1-87.3%; however, some treatments also induced significant decreases in terpenophenolic content. Induced changes in cone biomass production and terpenophenolic accumulation were most dependent on cultivar and the developmental stage at which plants were treated. PMID:21598976

  1. Unique characteristics of cones in Central Elysium Planitia, Mars

    NASA Astrophysics Data System (ADS)

    Noguchi, Rina; Kurita, Kei

    2015-06-01

    Martian magmatism within recent several hundreds of millions years is still controversial. Central Elysium Planitia (CEP) is suspected as a site of the latest magmatism on Mars, but hot debates have been caused as for the origin of this flat plain. Cones in CEP are expected to be a key to resolve this controversy. In previous works, there are 2 models proposed for the origin of CEP cones: volcanic rootless cone (e.g. Jaeger et al., 2007) and periglacial pingo (e.g. Burr et al., 2002; Page et al., 2009). In this study, we described detail morphology, distribution and size of CEP cones by using high-resolution images and topographic data. CEP cones are classified into 3 morphological types: Single Cone (SC), Double Cone (DC), and Lotus Fruit Cone (LC). DC has an inner cone in the summit crater of the outer cone, and LC has several inner cones in the summit crater of the outer cone. Several cones have moat structure around the edifice with peripheral rise. DCs and LCs are located in very flat areas of Athabasca Valles in the vicinity of Cerberus Fossae, while SCs distribute in the entire region of CEP. We compared CEP cones with terrestrial rootless cones and pingos in aerial photos. In Lake Myvatn, Iceland, there exist rootless cones which resemble DCs and LCs in CEP. Based on the similarities with terrestrial analogies, we concluded that the most feasible origin of CEP cones is rootless cones.

  2. Primate Short-Wavelength Cones Share Molecular Markers with Rods

    PubMed Central

    Craft, Cheryl M.; Huang, Jing; Possin, Daniel E.; Hendrickson, Anita

    2015-01-01

    Macaca, Callithrix jacchus marmoset monkey, Pan troglodytes chim- panzee and human retinas were examined to define if short wavelength (S) cones share molecular markers with L&M cone or rod photoreceptors. S cones showed consistent differences in their immunohistochemical staining and expression levels compared to L&M cones for “rod” Arrestin1 (S-Antigen), “cone” Arrestin4, cone alpha transducin, and Calbindin. Our data verify a similar pattern of expression in these primate retinas and provide clues to the structural divergence of rods and S cones versus L&M cones, suggesting S cone retinal function is “intermediate” between them. PMID:24664680

  3. Gravity duals of boundary cones

    NASA Astrophysics Data System (ADS)

    Camps, Joan

    2016-09-01

    The replica trick defines Rényi entropies as partition functions on conically singular geometries. We discuss their gravity duals: regular bulk solutions to the Einstein equations inducing conically singular metrics at the boundary. When the conical singularity is supported on a flat or spherical surface, these solutions are rewritings of the hyperbolic black hole. For more general shapes, these solutions are new. We construct them perturbatively in a double expansion in the distance and strength of the conical singularity, and extract the vacuum polarisation due to the cone. Recent results about the structure of logarithmic divergences of Rényi entropies are reproduced — in particular, f b ≠ f c . We discuss in detail the dynamical resolution of the singularity in the bulk. This resolution is in agreement with a previous proposal, and indicates a non-minimal settling to the `splitting problem': an apparent ambiguity in the holographic entropy formula of certain theories with higher derivatives.

  4. Elastic cone for Chinese calligraphy

    NASA Astrophysics Data System (ADS)

    Cai, Fenglei; Li, Haisheng

    2014-01-01

    The brush plays an important role in creating Chinese calligraphy. We regard a single bristle of a writing brush as an elastic rod and the brush tuft absorbing ink as an elastic cone, which naturally deforms according to the force exerted on it when painting on a paper, and the brush footprint is formed by the intersection region between the deformed tuft and the paper plane. To efficiently generate brush strokes, this paper introduces interpolation and texture mapping approach between two adjacent footprints, and automatically applies bristle-splitting texture to the stroke after long-time painting. Experimental results demonstrate that our method is effective and reliable. Users can create realistic calligraphy in real time.

  5. Loss-cone instability: Wave saturation by particle trapping

    SciTech Connect

    Zaslavsky, A.; Krafft, C.; Volokitin, A.

    2007-12-15

    The nonlinear mechanisms governing the interactions between whistler or lower hybrid waves and loss-cone type particles' distributions in magnetized plasmas are of great importance if one considers the major role that waves of frequency below the electron cyclotron frequency play in space and thermonuclear fusion plasmas. Up to now, most of the numerical simulations have been devoted to study the nonlinear processes at work when the plasma is weakly relativistic and when the anisotropy of the particles' distributions leads to the so-called maser instability. However, in many interesting cases, the particles' energies are sufficiently weak to ensure the validity of the nonrelativistic approximation. In this framework, the paper studies the interaction at normal cyclotron resonances between lower hybrid waves and electron distributions presenting loss-cone like features. A theoretical Hamiltonian model and a corresponding numerical symplectic code are used to evidence and to explain the nonlinear mechanisms at work at the saturation stage of the loss-cone instability. Moreover, simple analytical expressions and scaling laws have been derived for the linear growth rates and the wave amplitude at saturation.

  6. Deep space infections of neck.

    PubMed

    Kaluskar, S; Bajaj, P; Bane, P

    2007-03-01

    A retrospective study was performed on fourteen cases of deep cervical space infections in the neck admitted for diagnosis and treatment to the ENT Department, during a period of seven years from 1989-1997. Of the fourteen, four patients had Ludwig's angina and of the fourteen, one had a very serious complication resulting in death. Early diagnosis and adequate treatment were of paramount importance. The role of tracheostomy and management of airway in deep cervical space infections of the neck is discussed to gether with bacteriology, antibiotic treatment and surgical management.

  7. [Head and neck cancer--history].

    PubMed

    Woźniak, Anna; Szyfter, Krzysztof; Szyfter, Witold; Florek, Ewa

    2012-01-01

    According to epidemiological data head and neck cancers constitute for 12% of all malignancies in the world. It is estimated that a total of 400 000 cases of the mouth and throat and of 160 000 cases of laryngeal cancer, 300 000 people die each year. History of head and neck cancers developed and underwent many changes at the turn of the century. Treatment, pathogenesis and possessed state of knowledge on the subject has changed. Starting from the ancient times there were texts on how to treat and examine patients. The Edwin Smith and Ebers Papyrus are two of the oldest medical documents describing the treatment of cancer patients. Hippocrates was the first person who used the word "cancer" and probably he was the first who divided the tumors into benign and malignant. In a document known as the Doctrine of Hippocrates he described skin cancer and cancer treatments. Over the next centuries, medical science did not develop because of religious concerns about autopsy and surgical procedures. The 17th century is a period in which there were a lot of new information about how to treat such oral cancer. Cancer of the tongue was removed by cauterization, which in the 18th century was replaced by the use of surgical instruments. In the same age glossectomy has been accepted as the treatment of choice performed in the treatment of cancer. The 19th century brought a major breakthrough in the treatment of surgical, diagnostic, anesthetic techniques and understanding of the pathological mechanisms. Histological evaluation of tumors has become mandatory and standard practice in the assessment of cancer. Laryngectomy and neck lymph nodes removal has become commonplace. Modified Radical Neck Dissection (MRND), became popularized as another cancer treatment technique. Describing ways to treat cancer, radiotherapy can not be ignored - there are several new techniques such as Intensity Modulated Radiotherapy (IMRT) and hypofractionation currently used. Chemotherapy and the

  8. Neck pain or spasms - self care

    MedlinePlus

    ... chronic pain . Some with ongoing neck pain take narcotics to control the pain . It is best if only one health care provider is prescribing your narcotic pain medicines. If you have chronic neck pain, ...

  9. Pseudopathologic fracture of the femoral neck

    SciTech Connect

    Pope, T.L. Jr.; Keats, T.E.; Goldner, R.; Stelling, C.B.; Logan, M.

    1981-11-01

    We have seen two cases of traumatic subcapital fractures of the femoral neck which resembled pathologic fractures on plain radiography. We have named this entity pseudopathologic fracture of the femoral neck and offer suggestions for why it occurs.

  10. Anthropomorphic dummy neck modeling and injury considerations.

    PubMed

    Deng, Y C

    1989-02-01

    This study investigates the modeling of the Hybrid III dummy head and neck system and its response under impulsive loading. Two neck models were proposed, one rigid, one flexible; both give satisfactory head kinematics upon comparing to minisled test results. The flexible neck model provides a more detailed understanding of the Hybrid III neck structure behavior. It indicates that the Hybrid III neck has a torque response similar to a human neck but has higher shear response. During flexion whiplash, the torque at the occipital condyle reverses its direction at about 25 ms after impact. Since concussion may be related to the head angular acceleration, which reaches its peak value in the first 25 ms, it might be necessary to extend the existing human torque-rotation corridor to include the neck response in this region. For flexion whiplash impact, simulation results indicated that the neck injury threshold is reached before exceeding the head injury threshold as the impact velocity is increased.

  11. Thyroid Hormone Signaling and Cone Photoreceptor Viability.

    PubMed

    Ma, Hongwei; Ding, Xi-Qin

    2016-01-01

    Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and apoptosis. In the retina, TH signaling plays a central role in cone opsin expression. TH signaling inhibits S opsin expression, stimulates M opsin expression, and promotes dorsal-ventral opsin patterning. TH signaling has also been associated with cone photoreceptor viability. Treatment with thyroid hormone triiodothyronine (T3) or induction of high T3 by deleting the hormone-inactivating enzyme type 3 iodothyronine deiodinase (DIO3) causes cone death in mice. This effect is reversed by deletion of the TH receptor (TR) gene. Consistent with the T3 treatment effect, suppressing TH signaling preserves cones in mouse models of retinal degeneration. The regulation of cone survival by TH signaling appears to be independent of its regulatory role in cone opsin expression. The mechanism by which TH signaling regulates cone viability remains to be identified. The current understanding of TH signaling regulation in photoreceptor viability suggests that suppressing TH signaling locally in the retina may represent a novel strategy for retinal degeneration management. PMID:26427466

  12. Modal content of living human cone photoreceptors

    PubMed Central

    Liu, Zhuolin; Kocaoglu, Omer P.; Turner, Timothy L.; Miller, Donald T.

    2015-01-01

    Decades of experimental and theoretical investigations have established that photoreceptors capture light based on the principles of optical waveguiding. Yet considerable uncertainty remains, even for the most basic prediction as to whether photoreceptors support more than a single waveguide mode. To test for modal behavior in human cone photoreceptors in the near infrared, we took advantage of adaptive-optics optical coherence tomography (AO-OCT, λc = 785 nm) to noninvasively image in three dimensions the reflectance profile of cones. Modal content of reflections generated at the cone inner segment and outer segment junction (IS/OS) and cone outer segment tip (COST) was examined over a range of cone diameters in 1,802 cones from 0.6° to 10° retinal eccentricity. Second moment analysis in conjunction with theoretical predictions indicate cone IS and OS have optical properties consistent of waveguides, which depend on segment diameter and refractive index. Cone IS was found to support a single mode near the fovea (≤3°) and multiple modes further away (>4°). In contrast, no evidence of multiple modes was found in the cone OSs. The IS/OS and COST reflections share a common optical aperture, are most circular near the fovea, show no orientation preference, and are temporally stable. We tested mode predictions of a conventional step-index fiber model and found that in order to fit our AO-OCT results required a lower estimate of the IS refractive index and introduction of an IS focusing/tapering effect. PMID:26417509

  13. The Cone-specific Visual Cycle

    PubMed Central

    Wang, Jin-Shan; Kefalov, Vladimir J

    2010-01-01

    Cone photoreceptors mediate our daytime vision and function under bright and rapidly-changing light conditions. As their visual pigment is destroyed in the process of photoactivation, the continuous function of cones imposes the need for rapid recycling of their chromophore and regeneration of their pigment. The canonical retinoid visual cycle through the retinal pigment epithelium cells recycles chromophore and supplies it to both rods and cones. However, shortcomings of this pathway, including its slow rate and competition with rods for chromophore, have led to the suggestion that cones might use a separate mechanism for recycling of chromophore. In the past four decades biochemical studies have identified enzymatic activities consistent with recycling chromophore in the retinas of cone-dominant animals, such as chicken and ground squirrel. These studies have led to the hypothesis of a cone-specific retina visual cycle. The physiological relevance of these studies was controversial for a long time and evidence for the function of this visual cycle emerged only in very recent studies and will be the focus of this review. The retina visual cycle supplies chromophore and promotes pigment regeneration only in cones but not in rods. This pathway is independent of the pigment epithelium and instead involves the Müller cells in the retina, where chromophore is recycled and supplied selectively to cones. The rapid supply of chromophore through the retina visual cycle is critical for extending the dynamic range of cones to bright light and for their rapid dark adaptation following exposure to light. The importance of the retina visual cycle is emphasized also by its preservation through evolution as its function has now been demonstrated in species ranging from salamander to zebrafish, mouse, primate, and human. PMID:21111842

  14. Dose calculation using megavoltage cone-beam CT

    SciTech Connect

    Morin, Olivier . E-mail: Morin@radonc17.ucsf.edu; Chen, Josephine; Aubin, Michele; Gillis, Amy; Aubry, Jean-Francois; Bose, Supratik; Chen Hong; Descovich, Martina; Xia Ping; Pouliot, Jean

    2007-03-15

    Purpose: To demonstrate the feasibility of performing dose calculation on megavoltage cone-beam CT (MVCBCT) of head-and-neck patients in order to track the dosimetric errors produced by anatomic changes. Methods and Materials: A simple geometric model was developed using a head-size water cylinder to correct an observed cupping artifact occurring with MVCBCT. The uniformity-corrected MVCBCT was calibrated for physical density. Beam arrangements and weights from the initial treatment plans defined using the conventional CT were applied to the MVCBCT image, and the dose distribution was recalculated. The dosimetric inaccuracies caused by the cupping artifact were evaluated on the water phantom images. An ideal test patient with no observable anatomic changes and a patient imaged with both CT and MVCBCT before and after considerable weight loss were used to clinically validate MVCBCT for dose calculation and to determine the dosimetric impact of large anatomic changes. Results: The nonuniformity of a head-size water phantom ({approx}30%) causes a dosimetric error of less than 5%. The uniformity correction method developed greatly reduces the cupping artifact, resulting in dosimetric inaccuracies of less than 1%. For the clinical cases, the agreement between the dose distributions calculated using MVCBCT and CT was better than 3% and 3 mm where all tissue was encompassed within the MVCBCT. Dose-volume histograms from the dose calculations on CT and MVCBCT were in excellent agreement. Conclusion: MVCBCT can be used to estimate the dosimetric impact of changing anatomy on several structures in the head-and-neck region.

  15. Electrical coupling between cones in turtle retina.

    PubMed Central

    Detwiler, P B; Hodgkin, A L

    1979-01-01

    1. The electrical coupling between cones of known spectral sensitivity in the peripheral part of the turtle's retina was studied by passing current through a micro-electrode inserted into one cone and recording with a second micro-electrode inserted into a neighbouring cone. 2. Spatial sensitivity profiles were determined by recording flash responses to a long narrow strip of light which was moved across the impaled cones in orthogonal directions. These measurements gave both the length constant lambda of electrical spread in the cone network and the separation of the two cones. 3. The cone separation determined from the spatial profiles agreed closely with that measured directly by injecting a fluorescent dye into two cones. 4. The length constant lambda varied from 18 to 39 micron with a mean of 25 micron for red-sensitive cones and 26 micron for green-sensitive cones. 5. The majority of cone pairs studied were electrically coupled provided they had the same spectral sensitivity and were separated by less than 60 micron: thirty-two out of thirty-six red-red pairs, two out of two green-green pairs, none out of eight red-green pairs: no blue cones were observed. 6. The strength of electrical coupling was expressed as a mutual resistance defined as the voltage in one cell divided by the current flowing into the other. Mutual resistances decreased from a maximum value of about 30 M omega at separations close to zero to 0.2 M omega, the lower limit of detectable coupling at separations of about 60 micron. Mutual resistances were always positive and were independent of which cell was directly polarized. The coupling seemed to be ohmic and any rectification or non-linearity probably arose in the cone membranes rather than in the coupling resistances. 7. The results were analysed in terms of the Lamb & Simon (1977) theories of square and hexagonal lattices, which approximate to the continuous sheet model except in the case of the cone to which current is applied. 8. The

  16. Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2016-06-28

    Cancer of Head; Cancer of Head and Neck; Cancer of Neck; Cancer of the Head; Cancer of the Head and Neck; Cancer of the Neck; Head and Neck Cancer; Head Cancer; Head Neoplasms; Head, Neck Neoplasms; Neck Cancer; Neck Neoplasms; Neoplasms, Head; Neoplasms, Head and Neck; Neoplasms, Neck; Neoplasms, Upper Aerodigestive Tract; UADT Neoplasms; Upper Aerodigestive Tract Neoplasms

  17. Measurement for natural dental neck data of normal adults and its clinical significance on guiding implant restoration

    PubMed Central

    Sun, Mingxu; Gu, Fang; Wang, Junjun; Zhou, Chengyuan; Xia, Junnan; Qin, Hongwei; Yang, Jianjun

    2015-01-01

    Objective: Provide reference basis for the clinical implant restoration to select implant diameter through measuring each data of 7 teeth in the dental neck of bilateral upper and lower jaws of the young volunteers with normal dentition. Methods: Select 30 healthy young volunteers with complete dentition but no malocclusion, take cone beam CT (CBCT), measure the mesiodistal and buccolingual distance of the tooth root at 1.5 mm from 14 teeth (bilateral upper and lower jaws) to alveolar crest, trace out the outline of each tooth neck in this layer, calculate the cross sectional area and roundness of each tooth neck according to pixel value calibration, and then carry out statistical processing. Results: Complete the data collection and processing of mesiodistal length, buccolingual width, cross sectional area, and cross sectional roundness of the dental neck at 1.5 mm from these seven teeth of the bilateral upper and lower jaws to the alveolar crest of 30 volunteers, and calculate the mean value, variance, and reference value range of medical science of each index. Conclusion: CBCT can effectively obtain the image information of the dental neck. Through mimics 10.0 and Photoshop CS3, it is possible to accurately calculate the dental neck length and width, and cross sectional area of each tooth according to CBCT image information. This result can provide reference basis for the implant restoration of the clinical teeth. PMID:26628955

  18. Evaluation of the Painful Dual Taper Modular Neck Stem Total Hip Arthroplasty: Do They All Require Revision?

    PubMed

    Kwon, Young-Min

    2016-07-01

    Although dual taper modular-neck total hip arthroplasty (THA) design with additional neck-stem modularity has the potential to optimize hip biomechanical parameters by facilitating adjustments of leg length, femoral neck version and offset, there is increasing concern regarding this stem design as a result of the growing numbers of adverse local tissue reactions due to fretting and corrosion at the neck-stem taper junction. Implant factors such as taper cone angle, taper surface roughness, taper contact area, modular neck taper metallurgy, and femoral head size play important roles in influencing extent of taper corrosion. There should be a low threshold to conduct a systematic clinical evaluation of patients with dual-taper modular-neck stem THA using systematic risk stratification algorithms as early recognition and diagnosis will ensure prompt and appropriate treatment. Although specialized tests such as metal ion analysis and cross-sectional imaging modalities such as metal artifact reduction sequence magnetic resonance imaging (MARS MRI) are useful in optimizing clinical decision-making, overreliance on any single investigative tool in the clinical decision-making process for revision surgery should be avoided. PMID:27118353

  19. Neck pain after minor neck trauma--is it always neck sprain?

    PubMed

    Chong, C L; Ooi, S B

    2000-06-01

    We report a patient who had headache and neck pain after whiplash injury and subsequently developed cerebellar infarction due to vertebral artery dissection. This patient's pain was out of proportion to his apparent injury and it was a clue to the final diagnosis. Gross motor examination for cord injury may not be adequate for patients with minor neck trauma. Detailed cranial nerve and cerebellar examination should be performed for detection of circulatory insufficiency. Discharge advice for patients should also include that of stroke or transient ischaemic attack.

  20. Inhibition of STAT3 by Niclosamide Synergizes with Erlotinib against Head and Neck Cancer

    PubMed Central

    Li, Rui; You, Shuo; Hu, Zhongliang; Chen, Zhuo G.; Sica, Gabriel L.; Khuri, Fadlo R.; Curran, Walter J.; Shin, Dong M.; Deng, Xingming

    2013-01-01

    Epidermal growth factor receptor (EGFR) is extensively expressed in head and neck cancer. However, EGFR-targeted therapy has only modest efficacy in head and neck cancer, through mechanisms that are not fully understood. Here, we found that inhibition of EGFR by erlotinib stimulated phosphorylation and activation of STAT3 leading to increased Bcl2/Bcl-XL expression in head and neck cancer cells, which may dampen the therapeutic efficacy of erlotinib against head and neck cancer. Erlotinib-enhanced STAT3 phosphorylation results, at least in part, from suppression of its physiological phosphatase, PTPMeg2. Specific knockdown of STAT3 by RNA interference significantly sensitized head and neck cancer cells to erlotinib treatment. Pharmacological inhibition of STAT3 by niclosamide not only blocked erlotinib-stimulated STAT3 phosphorylation but also synergistically repressed head and neck cancer growth in vitro and in vivo. Combined inhibition of EGFR and STAT3 by erlotinib and niclosamide more effectively induced apoptosis in tumor tissues without toxicity for normal tissues. Based on our findings, treatment with erlotinib combined with niclosamide may offer an effective therapeutic approach to improve the prognosis of head and neck cancer. PMID:24019973

  1. Large-sized tubular graphite cones with nanotube tips

    SciTech Connect

    Shang, N.G.; Jiang, X.

    2005-10-17

    Tubular graphite cones (TGCs) have been grown on planar steel substrates by microwave plasma-assisted chemical vapor deposition with a high concentration of methane and at a high substrate temperature. The largest TGCs can reach 110 {mu}m in length and 10 {mu}m in diameter at the root. Unique TGCs terminated in long extruding carbon nanotube tips are realized. Scanning micro-Raman spectroscopy of individual TGCs shows a high crystallinity of the tips and more disordered structure of the roots. A possible growth mechanism of TGCs is presented.

  2. Distribution and specificity of S-cone ("blue cone") signals in subcortical visual pathways.

    PubMed

    Martin, Paul R; Lee, Barry B

    2014-03-01

    We review here the distribution of S-cone signals and properties of S-cone recipient receptive fields in subcortical pathways. Nearly everything we know about S-cone signals in the subcortical visual system comes from the study of visual systems in cats and primates (monkeys); in this review, we concentrate on results from macaque and marmoset monkeys. We discuss segregation of S-cone recipient (blue-on and blue-off) receptive fields in the dorsal lateral geniculate nucleus and describe their receptive field properties. We treat in some detail the question of detecting weak S-cone signals as an introduction for newcomers to the field. Finally, we briefly consider the question on how S-cone signals are distributed among nongeniculate targets. PMID:24555883

  3. Distribution and specificity of S-cone ("blue cone") signals in subcortical visual pathways.

    PubMed

    Martin, Paul R; Lee, Barry B

    2014-03-01

    We review here the distribution of S-cone signals and properties of S-cone recipient receptive fields in subcortical pathways. Nearly everything we know about S-cone signals in the subcortical visual system comes from the study of visual systems in cats and primates (monkeys); in this review, we concentrate on results from macaque and marmoset monkeys. We discuss segregation of S-cone recipient (blue-on and blue-off) receptive fields in the dorsal lateral geniculate nucleus and describe their receptive field properties. We treat in some detail the question of detecting weak S-cone signals as an introduction for newcomers to the field. Finally, we briefly consider the question on how S-cone signals are distributed among nongeniculate targets.

  4. Misidentification of Mycobacterium fortuitum in an immunocompetent patient presenting with a unilateral neck mass

    PubMed Central

    Kanzara, Todd; Hall, Andy; Namnyak, Simon; Owa, Tony

    2014-01-01

    A 31-year-old African man with a blameless medical history presented with an enlarging neck swelling of 6 months duration. He was systemically well with normal heamatobiochemistry. MRI of the neck demonstrated abnormal signalling in the subcutaneous fat overlying the posterior spinal muscles in the midline and the left sternocleidomastoid muscle. Scanty growth of Rhodococcus equi was reported from a turbid fine needle aspirate of the neck on two separate occasions. The swelling progressed despite numerous antibiotic combinations which necessitated surgical debridement. Analysis of debrided tissue using 16S rDNA surprisingly identified Mycobacterium fortuitum, not R equi, thereby resolving our diagnostic conundrum. PMID:24744071

  5. Nonlinear Resonance Cones and Converging Plasma Blobs

    NASA Astrophysics Data System (ADS)

    Agmon, Nathan; Pribyl, Patrick; Gekelman, Walter; Wise, Joe; Katz, Cami; Ha, Chis; Baker, Bob

    2013-10-01

    Electric field resonance cones have been shown to create density disturbances in cold, magnetized plasmas. Two circular antennas in the LAPTAG experimental plasma device were used to create converging, nonlinear resonance cones. The nonlinear electrostatic field is produced by large amplitude RF (ERF/nkTe >> 1). A movable probe, powered by a computerized motor and consisting of three mutually orthogonal electric dipoles, is used to measure the electric field of the cones which become distorted at large amplitudes. A 2D movable Langmuir probe was used to determine localized density perturbations after turn-off of the RF power. A density blob moving at 3-5 times the ion sound speed has been observed to propagate away (for at least 20 cm) from the focus of the cone. Two ring antennas produced colliding blobs. The physics of the collision will be described. Work performed at the Basic Plasma Science Facility supported by DOE and NSF.

  6. Some inversion formulas for the cone transform

    NASA Astrophysics Data System (ADS)

    Terzioglu, Fatma

    2015-11-01

    Several novel imaging applications have lead recently to a variety of Radon type transforms, where integration is made over a family of conical surfaces. We call them cone transforms (in 2D they are also called V-line or broken ray transforms). Most prominently, they are present in the so called Compton camera imaging that arises in medical diagnostics, astronomy, and lately in homeland security applications. Several specific incarnations of the cone transform have been considered separately. In this paper, we address the most general (and overdetermined) cone transform, obtain integral relations between cone and Radon transforms in {{{R}}}n, and a variety of inversion formulas. In many applications (e.g., in homeland security), the signal to noise ratio is very low. So, if overdetermined data is collected (as in the case of Compton imaging), attempts to reduce the dimensionality might lead to essential elimination of the signal. Thus, our main concentration is on obtaining formulas involving overdetermined data.

  7. Homologies among Coniferophyte cones: further observations

    NASA Astrophysics Data System (ADS)

    Grauvogel-Stamm, Léa; Galtier, Jean

    1998-04-01

    A reinvestigation of the Triassic conifer pollen cone of Darneya shows evidence that clusters of pollen sacs are attached (adnate), at regular intervals, to the upper side of the stalk and that the distribution of stomata is restricted to the apical part of the abaxial side of the peltate scale. These features and others, such as the commissure visible on the stalk and the scale, suggest a dual nature of the male scale complex of Darneya which therefore is interpreted as an abaxial bract fused with an adaxial fertile shoot bearing several clusters of pollen sacs. This conifer pollen cone is thus considered as a compound strobilus (inflorescence) homologous with the female cone of the conifers and therefore with the cones, both male and female, of the cordaites.

  8. Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers

    PubMed Central

    2012-01-01

    Background The purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer. Methods We retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60-70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy. Results Neck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post-radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC. Conclusions The neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy. PMID:22313843

  9. DEFORMATION OF SCORIA CONE BY CONDUIT PRESSURIZATION

    SciTech Connect

    E.S. Gaffney; B. Damjanac; D. Krier; G. Valentine

    2005-08-26

    A simplified mechanical model is used to simulate the deformation of a scoria cone due to pressurization of magma in a feeder conduit. The scoria cone is modeled as consisting of a cone of stabilized scoria with an axial region of loose scoria (height h{sub 1}), all overlying a vertically oriented cylindrical conduit intruded into rhyolite tuff country rock. For our analyses, the conduit is filled with basalt magma, usually with the upper length (h{sub 2}) solidified. The style of deformation of the cone depends on both h{sub 1} and h{sub 2}. If magma is prevented from hydrofracturing out of the conduit (as, for example, might be the case if the magma is surrounded by a solidified, but plastically deformable layer acting as a gasket backed up by the brittle country rock) pressures in the magma can build to 10s of MPa. When h{sub 1} is 100 m, not unusual for a small isolated basaltic cinder cone, the magma pressure needed to destabilize the cone when molten magma extends all the way to the original ground surface (h{sub 2} = 0) is only about one-third of the pressure when the upper part of the conduit is solidified (h{sub 2} = 25m). In the former case, almost the entire upper third of the cone is at failure in tension when the configuration becomes unstable. In the latter case, small portions of the surface of the cone are failing in tension when instability occurs, but a large volume in the central core of the cone is failing in shear or compressions. These results may provide insight into the status of volcanic plumbing, either past or present, beneath scoria cones. Field observations at the Lathrop Wells volcano in southern Nevada identify structures at the outer edge just below the crater rim that appear to be inward-dipping listric normal faults. This may indicate that, near the end of its active stage, the cone was close to failing in this fashion. A companion paper suggests that such a failure could have been quite energetic had it occurred.

  10. Electron-cyclotron maser instability driven by a loss-cone distribution

    SciTech Connect

    Lau, Y.Y.; Chu, K.

    1983-01-24

    It is shown that the electron-cyclotron maser instabilities may readily be excited in a plasma with a loss-cone distribution when the electron temperature exceeds a few tens of kiloelectronvolts. The growth rate is typically a few percent of the electron-cyclotron frequency. The appearance of the instability can be avoided by proper control of the plasma density.

  11. Microspectrophotometric evidence for cone monochromacy in sharks

    NASA Astrophysics Data System (ADS)

    Hart, Nathan Scott; Theiss, Susan Michelle; Harahush, Blake Kristin; Collin, Shaun Patrick

    2011-03-01

    Sharks are apex predators, and their evolutionary success is in part due to an impressive array of sensory systems, including vision. The eyes of sharks are well developed and function over a wide range of light levels. However, whilst close relatives of the sharks—the rays and chimaeras—are known to have the potential for colour vision, an evolutionary trait thought to provide distinct survival advantages, evidence for colour vision in sharks remains equivocal. Using single-receptor microspectrophotometry, we measured the absorbance spectra of visual pigments located in the retinal photoreceptors of 17 species of shark. We show that, while the spectral tuning of the rod (wavelength of maximum absorbance, λmax 484-518 nm) and cone (λmax 532-561 nm) visual pigments varies between species, each shark has only a single long-wavelength-sensitive cone type. This suggests that sharks may be cone monochromats and, therefore, potentially colour blind. Whilst cone monochromacy on land is rare, it may be a common strategy in the marine environment: many aquatic mammals (whales, dolphins and seals) also possess only a single, green-sensitive cone type. It appears that both sharks and marine mammals may have arrived at the same visual design by convergent evolution. The spectral tuning of the rod and cone pigments of sharks is also discussed in relation to their visual ecology.

  12. Design of a trichromatic cone array.

    PubMed

    Garrigan, Patrick; Ratliff, Charles P; Klein, Jennifer M; Sterling, Peter; Brainard, David H; Balasubramanian, Vijay

    2010-02-01

    Cones with peak sensitivity to light at long (L), medium (M) and short (S) wavelengths are unequal in number on the human retina: S cones are rare (<10%) while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens. Meanwhile, total information represented by the cone mosaic remained relatively insensitive to L/M proportions. Thus, the observed cone array design along with a long-wavelength accommodated lens provides a selective advantage: it is maximally informative. PMID:20168996

  13. Cone Tracing for Furry Object Rendering.

    PubMed

    Qin, Hao; Chai, Menglei; Hou, Qiming; Ren, Zhong; Zhou, Kun

    2014-08-01

    We present a cone-based ray tracing algorithm for high-quality rendering of furry objects with reflection, refraction and defocus effects. By aggregating many sampling rays in a pixel as a single cone, we significantly reduce the high supersampling rate required by the thin geometry of fur fibers. To reduce the cost of intersecting fur fibers with cones, we construct a bounding volume hierarchy for the fiber geometry to find the fibers potentially intersecting with cones, and use a set of connected ribbons to approximate the projections of these fibers on the image plane. The computational cost of compositing and filtering transparent samples within each cone is effectively reduced by approximating away in-cone variations of shading, opacity and occlusion. The result is a highly efficient ray tracing algorithm for furry objects which is able to render images of quality comparable to those generated by alternative methods, while significantly reducing the rendering time. We demonstrate the rendering quality and performance of our algorithm using several examples and a user study. PMID:26357369

  14. Crowding in the S-cone pathway.

    PubMed

    Coates, Daniel R; Chung, Susana T L

    2016-05-01

    The spatial extent of interference from nearby object or contours (the critical spacing of "crowding") has been thoroughly characterized across the visual field, typically using high contrast achromatic stimuli. However, attempts to link this measure with known properties of physiological pathways have been inconclusive. The S-cone pathway, with its ease of psychophysical isolation and known anatomical characteristics, offers a unique tool to gain additional insights into crowding. In this study, we measured the spatial extent of crowding in the S-cone pathway at several retinal locations using a chromatic adaptation paradigm. S-cone crowding was evident and extensive, but its spatial extent changed less markedly as a function of retinal eccentricity than the extent found using traditional achromatic stimuli. However, the spatial extent agreed with that of low contrast achromatic stimuli matched for isolated resolvability. This suggests that common cortical mechanisms mediate the crowding effect in the S-cone and achromatic pathway, but contrast is an important factor. The low contrast of S-cone stimuli makes S-cone vision more acuity-limited than crowding-limited.

  15. Microspectrophotometric evidence for cone monochromacy in sharks.

    PubMed

    Hart, Nathan Scott; Theiss, Susan Michelle; Harahush, Blake Kristin; Collin, Shaun Patrick

    2011-03-01

    Sharks are apex predators, and their evolutionary success is in part due to an impressive array of sensory systems, including vision. The eyes of sharks are well developed and function over a wide range of light levels. However, whilst close relatives of the sharks-the rays and chimaeras-are known to have the potential for colour vision, an evolutionary trait thought to provide distinct survival advantages, evidence for colour vision in sharks remains equivocal. Using single-receptor microspectrophotometry, we measured the absorbance spectra of visual pigments located in the retinal photoreceptors of 17 species of shark. We show that, while the spectral tuning of the rod (wavelength of maximum absorbance, λ(max) 484-518 nm) and cone (λ(max) 532-561 nm) visual pigments varies between species, each shark has only a single long-wavelength-sensitive cone type. This suggests that sharks may be cone monochromats and, therefore, potentially colour blind. Whilst cone monochromacy on land is rare, it may be a common strategy in the marine environment: many aquatic mammals (whales, dolphins and seals) also possess only a single, green-sensitive cone type. It appears that both sharks and marine mammals may have arrived at the same visual design by convergent evolution. The spectral tuning of the rod and cone pigments of sharks is also discussed in relation to their visual ecology. PMID:21212930

  16. Microspectrophotometric evidence for cone monochromacy in sharks.

    PubMed

    Hart, Nathan Scott; Theiss, Susan Michelle; Harahush, Blake Kristin; Collin, Shaun Patrick

    2011-03-01

    Sharks are apex predators, and their evolutionary success is in part due to an impressive array of sensory systems, including vision. The eyes of sharks are well developed and function over a wide range of light levels. However, whilst close relatives of the sharks-the rays and chimaeras-are known to have the potential for colour vision, an evolutionary trait thought to provide distinct survival advantages, evidence for colour vision in sharks remains equivocal. Using single-receptor microspectrophotometry, we measured the absorbance spectra of visual pigments located in the retinal photoreceptors of 17 species of shark. We show that, while the spectral tuning of the rod (wavelength of maximum absorbance, λ(max) 484-518 nm) and cone (λ(max) 532-561 nm) visual pigments varies between species, each shark has only a single long-wavelength-sensitive cone type. This suggests that sharks may be cone monochromats and, therefore, potentially colour blind. Whilst cone monochromacy on land is rare, it may be a common strategy in the marine environment: many aquatic mammals (whales, dolphins and seals) also possess only a single, green-sensitive cone type. It appears that both sharks and marine mammals may have arrived at the same visual design by convergent evolution. The spectral tuning of the rod and cone pigments of sharks is also discussed in relation to their visual ecology.

  17. Photonic Landau levels on cones

    NASA Astrophysics Data System (ADS)

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-05-01

    We present the first experimental realization of a bulk magnetic field for optical photons. By using a non-planar ring resonator, we induce an image rotation on each round trip through the resonator. This results in a Coriolis/Lorentz force and a centrifugal anticonfining force, the latter of which is cancelled by mirror curvature. Using a digital micromirror device to control both amplitude and phase, we inject arbitrary optical modes into our resonator. Spatial- and energy- resolved spectroscopy tracks photonic eigenstates as residual trapping is reduced, and we observe photonic Landau levels as the eigenstates become degenerate. We show that there is a conical geometry of the resulting manifold for photon dynamics and present a measurement of the local density of states that is consistent with Landau levels on a cone. While our work already demonstrates an integer quantum Hall material composed of photons, we have ensured compatibility with strong photon-photon interactions, which will allow quantum optical studies of entanglement and correlation in manybody systems including fractional quantum Hall fluids.

  18. Photonic Landau levels on cones

    NASA Astrophysics Data System (ADS)

    Schine, Nathan; Ryou, Albert; Gromov, Andrey; Sommer, Ariel; Simon, Jonathan

    2016-05-01

    Creating photonic materials with nontrivial topological characteristics has seen burgeoning interest in recent years; however, a major route to topology, a magnetic field for continuum photons, has remained elusive. We present the first experimental realization of a bulk magnetic field for optical photons. By using a non-planar ring resonator, we induce an image rotation on each round trip through the resonator. This results in a Coriolis/Lorentz force and a centrifugal anticonfining force, the latter of which is cancelled by mirror curvature. Spatial- and energy- resolved spectroscopy tracks photonic eigenstates as residual trapping is reduced, and we observe photonic Landau levels as the eigenstates become degenerate. We will discuss the conical geometry of the resulting manifold for photon dynamics and present a measurement of the local density of states that is consistent with Landau levels on a cone. While our work already demonstrates an integer quantum Hall material composed of photons, we have ensured compatibility with strong photon-photon interactions, which will allow quantum optical studies of entanglement and correlation in manybody systems including fractional quantum Hall fluids.

  19. Vaginal cone use in passive and active phases in patients with stress urinary incontinence

    PubMed Central

    Haddad, Jorge Milhem; Ribeiro, Ricardo Muniz; Bernardo, Wanderley Marques; Abrão, Maurício Simões; Baracat, Edmund Chada

    2011-01-01

    OBJECTIVE: To evaluate vaginal cone therapy in two phases, passive and active, in women with stress urinary incontinence. METHODS: A prospective study was conducted at the Department of Obstetrics and Gynecology, São Paulo University, Brazil. Twenty-four women with a clinical and urodynamic diagnosis of stress urinary incontinence were treated with vaginal cones in a passive phase (without voluntary contractions of the pelvic floor) and an active phase (with voluntary contractions), each of which lasted three months. Clinical complaints, a functional evaluation of the pelvic floor, a pad test, and bladder neck mobility were analyzed before and after each phase. RESULTS: Twenty-one patients completed the treatment. The reduction in absolute risk with the pad test was 0.38 (p<0.034) at the end of the passive phase and 0.67 (p<0.0001) at the end of the active phase. The reduction in absolute risk with the pelvic floor evaluation was 0.62 (p<0.0001) at the end of the passive phase and 0.77 (p<0.0001) at the end of the active phase. The reduction in absolute risk of bladder neck mobility was 0.38 (p<0.0089) at the end of the passive phase and 0.52 (p<0.0005) at the end of the active phase. Complete reversal of symptomatology was observed in 12 (57.1%) patients, and satisfaction was expressed by 19 (90.4%). CONCLUSION: Using vaginal cones in the passive phase, as other researchers did, was effective. Inclusion of the active phase led to additional improvement in all of the study parameters evaluated in women with stress urinary incontinence. Randomized studies are needed, however, to confirm these results. PMID:21789381

  20. Necking evolution in dynamically stretched bars: New experimental and computational insights

    NASA Astrophysics Data System (ADS)

    Vaz-Romero, A.; Rotbaum, Y.; Rodríguez-Martínez, J. A.; Rittel, D.

    2016-06-01

    This paper presents new results on dynamic neck evolution in steel bars of varying diameters. Dynamic tensile tests were carried out in a Kolsky apparatus using cylindrical steel specimens with various cross-section diameters ranging from 1.5 mm to 4 mm. A high speed digital camera was used to record the deformation of the specimen during the loading process. Video recording of the tests enabled accurate experimental measurements of the necking evolution, specifically its growth rate as a function of the diameter. The experiments show that increasing the specimen cross-section slows down the neck development. This behavior has been further investigated using two different kinds of numerical calculations: (1) axisymmetric finite element simulations and (2) one-dimensional finite difference computations. While the finite difference model only considers the normal stress along the longitudinal direction of the bar, the finite element model does not entail any simplification on the stress state of the specimen during the loading process. In agreement with the experiments, the finite element calculations show a decrease of the necking growth rate with the increase in the cross-section of the sample. On the contrary, the damping effect of the specimen cross-section on the necking evolution is not captured by the finite difference computations. We postulate that this result comes from the one-dimensional nature of the finite difference model. This work uncovers, by means of combined experiments and modelling, the key role played by stress multiaxiality in the growth rate of dynamic necks.

  1. Evaluation of lens absorbed dose with Cone Beam IGRT procedures.

    PubMed

    Palomo, R; Pujades, M C; Gimeno-Olmos, J; Carmona, V; Lliso, F; Candela-Juan, C; Vijande, J; Ballester, F; Perez-Calatayud, J

    2015-12-01

    The purpose of this work is to evaluate the absorbed dose to the eye lenses due to the cone beam computed tomography (CBCT) system used to accurately position the patient during head-and-neck image guided procedures. The on-board imaging (OBI) systems (v.1.5) of Clinac iX and TrueBeam (Varian) accelerators were used to evaluate the imparted dose to the eye lenses and some additional points of the head. All CBCT scans were acquired with the Standard-Dose Head protocol from Varian. Doses were measured using thermoluminescence dosimeters (TLDs) placed in an anthropomorphic phantom. TLDs were calibrated at the beam quality used to reduce their energy dependence. Average dose to the lens due to the OBI systems of the Clinac iX and the TrueBeam were 0.71  ±  0.07 mGy/CBCT and 0.70  ±  0.08 mGy/CBCT, respectively. The extra absorbed dose received by the eye lenses due to one CBCT acquisition with the studied protocol is far below the 500 mGy threshold established by ICRP for cataract formation (ICRP 2011 Statement on Tissue Reactions). However, the incremental effect of several CBCT acquisitions during the whole treatment should be taken into account. PMID:26457404

  2. Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-10-18

    Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck

  3. Growth

    NASA Astrophysics Data System (ADS)

    Waag, Andreas

    This chapter is devoted to the growth of ZnO. It starts with various techniques to grow bulk samples and presents in some detail the growth of epitaxial layers by metal organic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), and pulsed laser deposition (PLD). The last section is devoted to the growth of nanorods. Some properties of the resulting samples are also presented. If a comparison between GaN and ZnO is made, very often the huge variety of different growth techniques available to fabricate ZnO is said to be an advantage of this material system. Indeed, growth techniques range from low cost wet chemical growth at almost room temperature to high quality MOCVD growth at temperatures above 1, 000∘C. In most cases, there is a very strong tendency of c-axis oriented growth, with a much higher growth rate in c-direction as compared to other crystal directions. This often leads to columnar structures, even at relatively low temperatures. However, it is, in general, not straight forward to fabricate smooth ZnO thin films with flat surfaces. Another advantage of a potential ZnO technology is said to be the possibility to grow thin films homoepitaxially on ZnO substrates. ZnO substrates are mostly fabricated by vapor phase transport (VPT) or hydrothermal growth. These techniques are enabling high volume manufacturing at reasonable cost, at least in principle. The availability of homoepitaxial substrates should be beneficial to the development of ZnO technology and devices and is in contrast to the situation of GaN. However, even though a number of companies are developing ZnO substrates, only recently good quality substrates have been demonstrated. However, these substrates are not yet widely available. Still, the situation concerning ZnO substrates seems to be far from low-cost, high-volume production. The fabrication of dense, single crystal thin films is, in general, surprisingly difficult, even when ZnO is grown on a ZnO substrate. However

  4. 3D modelling of the Tejeda Caldera cone-sheet swarm, Gran Canaria, Canary Islands, Spain

    NASA Astrophysics Data System (ADS)

    Samrock, Lisa K.; Jensen, Max J.; Burchardt, Steffi; Troll, Valentin R.; Mattsson, Tobias; Geiger, Harri

    2015-04-01

    . 2011, and references therein), and we discuss the implications of this architecture for the feeding system of the Tejeda volcano and the associated temporal variations of cone-sheet emplacement. References: Burchardt, S., Tanner, D.C., Troll, V.R., Krumbholz, M., Gustafsson, L.E. (2011) Three-dimensional geometry of concentric intrusive sheet swarms in the Geitafell and the Dyrfjöll volcanoes, eastern Iceland. Geochemistry, Geophysics, Geosystems 12(7): Q0AB09. Burchardt, S., Troll, V.R., Mathieu, L., Emeleus, H.C., Donaldson, C.H. (2013) Ardnamruchan 3D cone-sheet architecture explained by a single elongate magma chamber. Scientific Reports 3:2891. Schirnick, C. (1996) Formation of an intracaldera cone sheet dike swarm (Tejeda Caldera, Gran Canaria) (Dissertation). Christian-Albrechts-Universität, Kiel, Germany. Schirnick, C., van den Bogaard, P., Schmincke, H.-U. (1999) Cone-sheet formation and intrusive growth of an oceanic island - The Miocene Tejeda complex on Gran Canaria (Canary Islands). Geology, 27: 207-210.

  5. Submicrometer Hollow Bioglass Cones Deposited by Radio Frequency Magnetron Sputtering: Formation Mechanism, Properties, and Prospective Biomedical Applications.

    PubMed

    Popa, A C; Stan, G E; Besleaga, C; Ion, L; Maraloiu, V A; Tulyaganov, D U; Ferreira, J M F

    2016-02-01

    This work reports on the unprecedented magnetron sputtering deposition of submicrometric hollow cones of bioactive glass at low temperature in the absence of any template or catalyst. The influence of sputtering conditions on the formation and development of bioglass cones was studied. It was shown that larger populations of well-developed cones could be achieved by increasing the argon sputtering pressure. A mechanism describing the growth of bioglass hollow cones is presented, offering the links for process control and reproducibility of the cone features. The composition, structure, and morphology of the as-synthesized hollow cones were investigated by energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), grazing incidence geometry X-ray diffraction (GIXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM)-selected area electron diffraction (SAED). The in vitro biological performance, assessed by degradation tests (ISO 10993-14) and cytocompatibility assays (ISO 10993-5) in endothelial cell cultures, was excellent. This allied with resorbability and the unique morphological features make the submicrometer hollow cones interesting candidate material devices for focal transitory permeabilization of the blood-brain barrier in the treatment of carcinoma and neurodegenerative disorders.

  6. Shape of scoria cones on Mars: Insights from numerical modeling of ballistic pathways

    NASA Astrophysics Data System (ADS)

    Brož, Petr; Čadek, Ondřej; Hauber, Ernst; Rossi, Angelo Pio

    2014-11-01

    Morphological observations of scoria cones on Mars show that their cross-sectional shapes are different from those on Earth. Due to lower gravity and atmospheric pressure on Mars, particles are spread over a larger area than on Earth. Hence, erupted volumes are typically not large enough for the flank slopes to attain the angle of repose, in contrast to Earth where this is common. The distribution of ejected material forming scoria cones on Mars, therefore, is ruled mainly by ballistic distribution and not by redistribution of flank material by avalanching after the static angle of repose is reached. As a consequence, the flank slopes of the Martian scoria cones do not reach the critical angle of repose in spite of a large volume of ejected material. Therefore, the topography of scoria cones on Mars is governed mainly by ballistic distribution of ejected particles and is not influenced by redistribution of flank material by avalanching. The growth of a scoria cone can be studied numerically by tracking the ballistic trajectories and tracing the cumulative deposition of repeatedly ejected particles. We apply this approach to a specific volcanic field, Ulysses Colles on Mars, and compare our numerical results with observations. The scoria cones in this region are not significantly affected by erosion and their morphological shape still preserves a record of physical conditions at the time of eruption. We demonstrate that the topography of these scoria cones can be rather well (with accuracy of ∼10 m) reproduced provided that the ejection velocities are a factor of ∼2 larger and the ejected particles are about ten times finer than typical on Earth, corresponding to a mean particle velocity of ∼92 m/s and a real particle size of about 4 mm. This finding is in agreement with previous theoretical works that argued for larger magma fragmentation and higher ejection velocities on Mars than on Earth due to lower gravity and different environmental conditions.

  7. Alternative treatments for neck sprain.

    PubMed

    Hogg, Kerstin; Morton, Rosemary

    2003-01-01

    A short cut review was carried out to establish whether osteopathy or chiropractic treatments improve outcome in patients with neck sprain. Altogether 206 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated

  8. Light responses of primate and other mammalian cones

    PubMed Central

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-01-01

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  9. Origin and Impact of Phototransduction Noise in Primate Cone Photoreceptors

    PubMed Central

    Angueyra, Juan Manuel; Rieke, Fred

    2013-01-01

    Noise in the responses of cone photoreceptors sets a fundamental limit to visual sensitivity, yet the origin of noise in mammalian cones and its relation to behavioral sensitivity are poorly understood. Our work here on primate cones improves understanding of these issues in three ways. First, we find that cone noise is not dominated by spontaneous photopigment activation or by quantal fluctuations in photon absorption but instead by other sources, namely channel noise and fluctuations in cGMP. Second, we find that adaptation in cones, unlike that in rods, affects signals and noise differently. This difference helps explain why thresholds for rod- and cone-mediated signals have different dependencies on background light level. Third, past estimates of noise in mammalian cones are too high to explain behavioral sensitivity. Our measurements indicate a lower level of cone noise, and thus help reconcile physiological and behavioral estimates of cone noise and sensitivity. PMID:24097042

  10. Light responses of primate and other mammalian cones.

    PubMed

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-02-18

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  11. Ecophysiological variables influencing Aleppo pine seed and cone production: a review.

    PubMed

    Ayari, Abdelaziz; Khouja, Mohamed Larbi

    2014-04-01

    The most interesting factors associated with seed and cone production of Aleppo pine were largely reviewed to identify broad patterns and potential effectiveness of reforestation efforts and planning. Aleppo pine cone production and seed yields are relatively variable, with differences between spatial and temporal influences. These differences are considered, mainly between (i) year, (ii) stand characteristics and (iii) individual tree measurements. Annual variability among populations was recorded for cone production per tree, based on influencing factors such as genetic characteristics, wetness, nutrient availability, insect pests and disease. In addition, some factors may affect Aleppo pine tree growth directly but may be affecting seed and cone production indirectly. Therefore, reduced stand density results in less competition among Aleppo pine trees and accompanying understory flora, which subsequently increases the stem diameter and other tree dimensions, including seed production. This review suggests that reforestation planning, particularly thinning, will result in improved tree morphology that will increase Aleppo pine seed and cone crops. Wildfire intensity and stand conditions such as light and soil nutrient status are also examined.

  12. Multiple dendrochronological responses to the eruption of Cinder Cone, Lassen Volcanic National Park, California

    USGS Publications Warehouse

    Sheppard, P.R.; Ort, M.H.; Anderson, K.C.; Clynne, M.A.; May, E.M.

    2009-01-01

    Two dendrochronological properties – ring width and ring chemistry – were investigated in trees near Cinder Cone in Lassen Volcanic National Park, northeastern California, for the purpose of re-evaluating the date of its eruption. Cinder Cone is thought to have erupted in AD 1666 based on ring-width evidence, but interpreting ring-width changes alone is not straightforward because many forest disturbances can cause changes in ring width. Old Jeffrey pines growing in Cinder Cone tephra and elsewhere for control comparison were sampled. Trees growing in tephra show synchronous ring-width changes at AD 1666, but this ring-width signal could be considered ambiguous for dating the eruption because changes in ring width can be caused by other events. Trees growing in tephra also show changes in ring phosphorus, sulfur, and sodium during the late 1660s, but inter-tree variability in dendrochemical signals makes dating the eruption from ring chemistry alone difficult. The combination of dendrochemistry and ring-width signals improves confidence in dating the eruption of Cinder Cone over the analysis of just one ring-growth property. These results are similar to another case study using dendrochronology of ring width and ring chemistry at Parícutin, Michoacán, Mexico, a cinder cone that erupted beginning in 1943. In both cases, combining analysis with ring width and ring chemistry improved confidence in the dendro-dating of the eruptions.

  13. Neck pain: manipulating the upper back helps lessen pain and improve neck motion.

    PubMed

    2011-09-01

    Neck pain is very common. In the United States, between 30% and 50% of people suffer from an aching neck each year. Although neck pain can be caused by injury, most of this pain results from more gradual stresses, such as particular sitting, standing, or work postures, lifting patterns, or sleeping positions. Typical neck pain can also cause headaches, pain between your shoulders, or a feeling of knots in your neck and upper back muscles. Although manual therapy, sometimes called "manipulation," is a common treatment for many types of spine pain, some people are uncomfortable having their necks manipulated. Recently, though, researchers have tested the benefits of a thrust manipulation of the upper back to treat neck pain. A study published in the September 2011 issue of JOSPT provides new insight and an evidence-based summary of the benefits of manipulating the upper back to ease and eliminate neck pain.

  14. Paragangliomas of the Head and Neck.

    PubMed

    Woolen, Sean; Gemmete, Joseph J

    2016-05-01

    Paragangliomas of the head and neck are rare vascular skull-base tumors derived from the paraganglionic system with an estimated incidence of 1:30,000 accounting for 3% of all paragangliomas. The most common paraganglioma locations of the head and neck in descending order are the carotid body, jugular, tympanic, and vagal paragangliomas. This article discusses the clinical characterics, normal anatamy, imaging findings and protocols, pathology, staging, and differential diagnosis for paragangliomas of the head and neck. PMID:27154608

  15. On the transient dynamics of the wake and trajectory of free falling cones with various apex angles

    NASA Astrophysics Data System (ADS)

    Hamed, Ali M.; Jin, Yaqing; Chamorro, Leonardo P.

    2015-11-01

    The early free fall stages of cones with a density ratio 1.18 and apex angles of 30°, 45°, 60°, and 90° were studied using a wireless 3-axis gyroscope and accelerometer to describe the cone 3D motions, while particle image velocimetry was used to capture the induced flow in the near wake. The Reynolds number based on the cones diameter and the velocity at which the cone reaches the first local velocity maximum is found to consistently set the limit between two distinctive states. Relatively rapid growth in the cone nutation and departure from the vertical axis is observed after this Re is reached. Sequences of vertical velocity, swirling strength, LES-decomposed velocity, and pressure fields show the formation and growth of a large and initially symmetric recirculation bubble at the cone base. Those also highlight the presence of a symmetric 3D vortex rollup dominating the near wake in the early stages of the fall. A shear layer develops at the edge of the wake and manifests in the periodic shedding of Kelvin-Helmholtz vortices that, due to the nature of the recirculation bubble, reorganize to constitute a part of the rollup. Later in the fall, the wake loses symmetry and shows high population of vortical structures leading to turbulence. The asymmetric wake leads to strong interactions between the flow field and the cone evidenced by the shedding of a part of the 3D large-scale vortex rollup. This shedding process along with the cone rotation around its own axis provides a possible explanation of the helical wake structure observed in other studies.

  16. Hurricane track forecast cones from fluctuations

    NASA Astrophysics Data System (ADS)

    Meuel, T.; Prado, G.; Seychelles, F.; Bessafi, M.; Kellay, H.

    2012-06-01

    Trajectories of tropical cyclones may show large deviations from predicted tracks leading to uncertainty as to their landfall location for example. Prediction schemes usually render this uncertainty by showing track forecast cones representing the most probable region for the location of a cyclone during a period of time. By using the statistical properties of these deviations, we propose a simple method to predict possible corridors for the future trajectory of a cyclone. Examples of this scheme are implemented for hurricane Ike and hurricane Jimena. The corridors include the future trajectory up to at least 50 h before landfall. The cones proposed here shed new light on known track forecast cones as they link them directly to the statistics of these deviations.

  17. Hurricane track forecast cones from fluctuations.

    PubMed

    Meuel, T; Prado, G; Seychelles, F; Bessafi, M; Kellay, H

    2012-01-01

    Trajectories of tropical cyclones may show large deviations from predicted tracks leading to uncertainty as to their landfall location for example. Prediction schemes usually render this uncertainty by showing track forecast cones representing the most probable region for the location of a cyclone during a period of time. By using the statistical properties of these deviations, we propose a simple method to predict possible corridors for the future trajectory of a cyclone. Examples of this scheme are implemented for hurricane Ike and hurricane Jimena. The corridors include the future trajectory up to at least 50 h before landfall. The cones proposed here shed new light on known track forecast cones as they link them directly to the statistics of these deviations.

  18. Hurricane track forecast cones from fluctuations

    PubMed Central

    Meuel, T.; Prado, G.; Seychelles, F.; Bessafi, M.; Kellay, H.

    2012-01-01

    Trajectories of tropical cyclones may show large deviations from predicted tracks leading to uncertainty as to their landfall location for example. Prediction schemes usually render this uncertainty by showing track forecast cones representing the most probable region for the location of a cyclone during a period of time. By using the statistical properties of these deviations, we propose a simple method to predict possible corridors for the future trajectory of a cyclone. Examples of this scheme are implemented for hurricane Ike and hurricane Jimena. The corridors include the future trajectory up to at least 50 h before landfall. The cones proposed here shed new light on known track forecast cones as they link them directly to the statistics of these deviations. PMID:22701776

  19. Pure bending of a solid cone

    NASA Astrophysics Data System (ADS)

    Renton, J. D.

    1997-05-01

    The problems of torsion, axial loading and shear of a solid cone were solved around the turn of the century by Michell and Föppl. Surprisingly, no solution to the problem of the elastic response of a cone to the only other possible resultant applied to its apex seems to have been published until now. The method used here is based on certain theoretical considerations related to the author's work on generalizing the engineering theory of beams. This means that the result is derived rather than being the result of a trial-and-error process. A comparison is made with the usual engineering theory as modified for variable bending stiffness. The two analyses give the same results at the limit as the cone angle tends to zero.

  20. Immunology and Immunotherapy of Head and Neck Cancer

    PubMed Central

    Ferris, Robert L.

    2015-01-01

    The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented. PMID:26351330

  1. A NEW DIAGNOSTIC SIGN IN NECK INJURIES.

    PubMed

    CROWE, H

    1964-01-01

    The aggravation of neck pain and headache as a result of the use of diathermy or other forms of energy in the treatment of neck sprain may represent a diagnostic sign by which to distinguish severe injury of the neck from simple sprain. In the case of simple neck sprain, the patient's complaints may be inadvertently continued more or less indefinitely by the use of high frequency energy or even locally applied heat. That recovery sometimes follows settlement of litigation in such cases may be due not to the award of money but to discontinuance of an aggravating medical treatment.

  2. Infections of the deep neck spaces.

    PubMed

    Hedge, Amogh; Mohan, Suyash; Lim, Winston Eng Hoe

    2012-05-01

    Deep neck infections (DNI) have a propensity to spread rapidly along the interconnected deep neck spaces and compromise the airway, cervical vessels and spinal canal. The value of imaging lies in delineating the anatomical extent of the disease process, identifying the source of infection and detecting complications. Its role in the identification and drainage of abscesses is well known. This paper pictorially illustrates infections of important deep neck spaces. The merits and drawbacks of imaging modalities used for assessment of DNI, the relevant anatomy and the possible sources of infection of each deep neck space are discussed. Certain imaging features that alter the management of DNI have been highlighted. PMID:22584969

  3. Lightcone: Light-cone generating script

    NASA Astrophysics Data System (ADS)

    Bernyk, Max

    2014-03-01

    Lightcone works with simulated galaxy data stored in a relational database to rearrange the data in a shape of a light-cone; simulated galaxy data is expected to be in a box volume. The light-cone constructing script works with output from the SAGE semi-analytic model, but will work with any other model that has galaxy positions (and other properties) saved per snapshots of the simulation volume distributed in time. The database configuration file is set up for PostgreSQL RDBMS, but can be modified for use with any other SQL database.

  4. Understanding Cone Photoreceptor Cell Death in Achromatopsia.

    PubMed

    Carvalho, Livia S; Vandenberghe, Luk H

    2016-01-01

    Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research. PMID:26427416

  5. Bipolar Hemarthroplasty Using Cementless Conical Stem for Treatment of Dorr Type B and C Femoral Neck Fracture

    PubMed Central

    Kang, Jeong Hoon; Jung, Sung

    2015-01-01

    Purpose The current study aims to evaluate the clinical and the radiological outcome of bipolar hemiarthroplasty using cementless cone stem to treat osteoporotic femoral neck fracture and compare the results according to the proximal femur geometry. Materials and Methods Seventy-five hips (75 patients) that underwent bipolar hemiarthroplasty with cementless cone stem between September 2006 and December 2011 were analyzed. The minimum follow-up period was 3 years. Thirty-three hips were classified as type B and 41 as type C. The clinical outcome was assessed using Harris hip score and the walking ability score. Radiographic evaluation was performed to evaluate the stability of the prosthesis. Results At the most recent follow up, the mean Harris hip score was 86 (range, 70-92) and 65% recovered to preoperative ambulatory status. In the radiographic exam, stable stem fixation was achieved in all cases. For the complications, eight hips developed deep vein thrombosis while three hips showed heterotopic ossification. Dislocation and delayed deep infection occurred in one hip resepectively. There were no significance differences in Harris hip score and walking ability score when the type B group was compare with the type C. Conclusion Bipolar hemiarthroplasty with cementless cone stem showed an excellent early outcome both clinically and radiographically regardless of the shape of the proximal femur. We believe this prosthesis can provide early stability to the Dorr type B and C femur and is an effective treatment for treating osteoporotic femoral neck fracture. PMID:27536631

  6. Sedimentary Biosignatures of Social Organization in Cone-Forming Filamentous Bacteria

    NASA Astrophysics Data System (ADS)

    Tice, M. M.; Gong, J.; Zeng, Z.; Sneed, J.; Wehner, M.; Sparks, D. W.

    2013-12-01

    Conical mats consisting of centimeter-scale steep-sided cones growing above flat basal films form some of the most distinctive fossil microbial communities in the geologic record. Cones have been hypothesized to form by the initially random motion of filamentous bacteria into small tangled clumps followed by the phototactic motion of the same bacteria up resulting slopes. More recent models of cone development suggest that they form in response to growth in stagnant fluids where diffusion limits exchange of nutrients and wastes with the environment. Determining the biological and environmental factors that promote cone formation will be important for interpreting the geological record of fossil mats and stromatolites, on Earth and potentially on Mars. Here we report the results of new experiments demonstrating complex social organization of cone-forming communities and a novel biosignature of the growth of such communities on sandy sediments, as well as detection of that biosignature in 3.2 Ga fossil mats of the Moodies Group (Barberton greenstone belt, South Africa). In order to investigate the processes involved in cone formation, we grew cultures of a filamentous cyanobacterium originally isolated from tufted cones in Yellowstone National Park, Montana, U.S.A. (Leptolyngbya sp. Y-WT-2000 Cl 1). During early mat development, filaments coat sand grain surfaces and aggregate into ~100-μm-long tufts, or mutually aligned bundles of filaments. Tufts are highly motile, bridging sand grains and merging to form larger tufts. After 10-14 days of growth, tufts aggregate during the early morning into centers composed of many tufts that wave vertically and along the sand surface. Centers move across the sediment surface during the middle of the day and merge along bridging tufts. These bridges transmit force to the underlying sediment and are capable of rolling sand grains. At this stage, mats are composed of small mobile centers that disperse along streams of co

  7. [Neck chylous fistula: conservative treatment].

    PubMed

    López Otero, Maria J; Fernández López, Maria T; Outeiriño Blanco, E; Álvarez Vázquez, P; Pinal Osorio, I; Iglesias Diz, D

    2010-01-01

    Injury to the thoracic duct, leading to chyle leak, occurs in 1-2,5% of patients who undergo neck dissection. Associated complications include malnutrition, immune compromise, fistula formation and carotid blowout. No definitive treatment algorithm can be deduced from the current literature, but on last reviews, there is an agreement on the conservative management. Medical management is based on that decreasing chyle flow will allow for spontaneous closure of the chyle leak. Conservative treatment includes: closed vacuum drainage, bed-rest, nutrition modification and synthetic somatostatin analog. Nutrition modification involves a low-fat diet supplemented with medium-chain triglycerides (MCT), enteral nutrition with high percentage of MCT or parenteral nutrition.

  8. Basaltic Cone Suggests Constructional Origin of Some Guyots.

    PubMed

    Christensen, M N; Gilbert, C M

    1964-01-17

    A basaltic cinder cone was built beneath the waters of Mono Lake in Pleistocene time. This cone is now exposed. Its internal structure, external form, and petrography suggest that it was constructed with a flat top.

  9. Basaltic Cone Suggests Constructional Origin of Some Guyots.

    PubMed

    Christensen, M N; Gilbert, C M

    1964-01-17

    A basaltic cinder cone was built beneath the waters of Mono Lake in Pleistocene time. This cone is now exposed. Its internal structure, external form, and petrography suggest that it was constructed with a flat top. PMID:17753148

  10. A multiscale filter for noise reduction of low-dose cone beam projections.

    PubMed

    Yao, Weiguang; Farr, Jonathan B

    2015-08-21

    The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, exp(-x2/2σ(2)(f)) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of σ(f), which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ(2)(f)) is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

  11. A multiscale filter for noise reduction of low-dose cone beam projections

    NASA Astrophysics Data System (ADS)

    Yao, Weiguang; Farr, Jonathan B.

    2015-08-01

    The Poisson or compound Poisson process governs the randomness of photon fluence in cone beam computed tomography (CBCT) imaging systems. The probability density function depends on the mean (noiseless) of the fluence at a certain detector. This dependence indicates the natural requirement of multiscale filters to smooth noise while preserving structures of the imaged object on the low-dose cone beam projection. In this work, we used a Gaussian filter, \\text{exp}≤ft(-{{x}2}/2σ f2\\right) as the multiscale filter to de-noise the low-dose cone beam projections. We analytically obtained the expression of {σf} , which represents the scale of the filter, by minimizing local noise-to-signal ratio. We analytically derived the variance of residual noise from the Poisson or compound Poisson processes after Gaussian filtering. From the derived analytical form of the variance of residual noise, optimal σ f2 is proved to be proportional to the noiseless fluence and modulated by local structure strength expressed as the linear fitting error of the structure. A strategy was used to obtain the reliable linear fitting error: smoothing the projection along the longitudinal direction to calculate the linear fitting error along the lateral direction and vice versa. The performance of our multiscale filter was examined on low-dose cone beam projections of a Catphan phantom and a head-and-neck patient. After performing the filter on the Catphan phantom projections scanned with pulse time 4 ms, the number of visible line pairs was similar to that scanned with 16 ms, and the contrast-to-noise ratio of the inserts was higher than that scanned with 16 ms about 64% in average. For the simulated head-and-neck patient projections with pulse time 4 ms, the visibility of soft tissue structures in the patient was comparable to that scanned with 20 ms. The image processing took less than 0.5 s per projection with 1024   ×   768 pixels.

  12. Metal artifacts correction in cone-beam CT bone imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Ning, Ruola; Conover, David

    2007-03-01

    Cone-beam CT (CBCT) technique is needed by orthopaedists in their new studies to monitor bone volume growth and blood vessel growth of structural bone grafts used in reconstruction surgery. However, titanium plate and screws, which are commonly used to connect bone grafts to host bones, can cause severe streaking artifacts and shading artifact in the reconstructed images due to their high attenuation of x-rays. These metal artifacts will distort the information of the bone and cause difficulties when measuring bone volume growth and the inside blood vessel growth. To solve this problem and help orthopaedists quantitatively record the growth of bone grafts, we present a three-dimensional metal artifact correction technique to correct the streaking artifacts generated by titanium implants. In this project not only the artifacts need to be corrected but also the correct information of the bone is required in the image for the quantitative measurements. Both phantom studies and animal studies were conducted to test this correction method. Images without metal correction and images with metal correction were compared together, as well as the reference bone images acquired without metal. It's shown the streaking and shading artifacts were greatly reduced after metal correction. The accuracy of bone volume measurements was also greatly increased by 79% for phantom studies and 53% for animal studies.

  13. ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.

    PubMed

    Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru

    2016-03-01

    Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.

  14. ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones

    PubMed Central

    Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru

    2016-01-01

    Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria. PMID:26926452

  15. Effects of scoria-cone eruptions upon nearby human communities

    USGS Publications Warehouse

    Ort, M.H.; Elson, M.D.; Anderson, K.C.; Duffield, W.A.; Hooten, J.A.; Champion, D.E.; Waring, G.

    2008-01-01

    Scoria-cone eruptions are typically low in volume and explosivity compared with eruptions from stratovolcanoes, but they can affect local populations profoundly. Scoria-cone eruption effects vary dramatically due to eruption style, tephra blanket extent, climate, types of land use, the culture and complexity of the affected group, and resulting governmental action. A comparison of a historic eruption (Pari??cutin, Me??xico) with prehistoric eruptions (herein we primarily focus on Sunset Crater in northern Arizona, USA) elucidates the controls on and effects of these variables. Long-term effects of lava flows extend little beyond the flow edges. These flows, however, can be used for defensive purposes, providing refuges from invasion for those who know them well. In arid lands, tephra blankets serve as mulches, decreasing runoff and evaporation, increasing infiltration, and regulating soil temperature. Management and retention of these scoria mulches, which can open new areas for agriculture, become a priority for farming communities. In humid areas, though, the tephra blanket may impede plant growth and increase erosion. Cultural responses to eruptions vary, from cultural collapse, through fragmentation of society, dramatic changes, and development of new technologies, to little apparent change. Eruptions may also be viewed as retribution for poor behavior, and attempts are made to mollify angry gods. ?? 2008 Geological Society of America.

  16. Receptivity of Hypersonic Boundary Layers over Straight and Flared Cones

    NASA Technical Reports Server (NTRS)

    Balakumar, Ponnampalam; Kegerise, Michael A.

    2010-01-01

    The effects of adverse pressure gradients on the receptivity and stability of hypersonic boundary layers were numerically investigated. Simulations were performed for boundary layer flows over a straight cone and two flared cones. The steady and the unsteady flow fields were obtained by solving the two-dimensional Navier-Stokes equations in axi-symmetric coordinates using the 5th order accurate weighted essentially non-oscillatory (WENO) scheme for space discretization and using third-order total-variation-diminishing (TVD) Runge-Kutta scheme for time integration. The mean boundary layer profiles were analyzed using local stability and non-local parabolized stability equations (PSE) methods. After the most amplified disturbances were identified, two-dimensional plane acoustic waves were introduced at the outer boundary of the computational domain and time accurate simulations were performed. The adverse pressure gradient was found to affect the boundary layer stability in two important ways. Firstly, the frequency of the most amplified second-mode disturbance was increased relative to the zero pressure gradient case. Secondly, the amplification of first- and second-mode disturbances was increased. Although an adverse pressure gradient enhances instability wave growth rates, small nose-tip bluntness was found to delay transition due to the low receptivity coefficient and the resulting weak initial amplitude of the instability waves. The computed and measured amplitude-frequency spectrums in all three cases agree very well in terms of frequency and the shape except for the amplitude.

  17. Current philosophy in the surgical management of neck metastases for head and neck squamous cell carcinoma

    PubMed Central

    Coskun, H. Hakan; Medina, Jesus E.; Robbins, K. Thomas; Silver, Carl E.; Strojan, Primož; Teymoortash, Afshin; Pellitteri, Phillip K.; Rodrigo, Juan P.; Stoeckli, Sandro J.; Shaha, Ashok R.; Suçrez, Carlos; Hartl, Dana M.; de Bree, Remco; Takes, Robert P.; Hamoir, Marc; Pitman, Karen T.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence-based approach. PMID:24623715

  18. Funnel cone for focusing intense ion beams on a target

    SciTech Connect

    Bieniosek, F.M.; Henestroza, E.; Ni, P.

    2009-10-05

    We describe a funnel cone for concentrating an ion beam on a target. The cone utilizes the reflection characteristic of ion beams on solid walls to focus the incident beam andincrease beam intensity on target. The cone has been modeled with the TRIM code. A prototype has been tested and installed for use in the 350-keV K+ NDCX target chamber.

  19. Neck pain brought into focus.

    PubMed

    Richter, Hans O

    2014-01-01

    A time honored dictum states that the eyes "lead the body", i.e., that the body typically adjusts its position to compensate for an impoverished retinal image (e.g., as due to optical blur, and/or inappropriately sized visual target). But only moderate or low level of evidence exists in support of this view. Inconclusive evidence does not, however, equal negative evidence. The accommodation/vergence system does exhibit signs of overload in contemporary working life, including eye discomfort, transient myopia, altered pattern of eye-lens oscillations, and associated phoria. Accommodation/vergence overload, caused by non-ergonomic near work, may also emerge as quickly as within one regular workday. Long-term musculoskeletal consequences of high accommodation/vergence demands have nevertheless not yet been studied in any detail. A research agenda which aims to provide multi-scientific evidence for eye-neck/shoulder interactions with public health implications and which also, in addition, study the eye-neck/shoulder mechanisms and elucidates the operating characteristics, should consequently be highly warranted. This new knowledge would be useful for physiotherapists, ergonomists and opticians, who in their profession treat patients experiencing vision- and musculoskeletal disorders. If both visual and the musculoskeletal aspects are given full and equal weight in the design and evaluation of work places, it is predicted to lead to an improved quality of life for the individual worker, and an enhanced productivity for the employer.

  20. Preventing head and neck injury.

    PubMed

    McIntosh, A S; McCrory, P

    2005-06-01

    A wide range of head and neck injury risks are present in sport, including catastrophic injury. The literature since 1980 on prevention of head and neck injury in sport was reviewed, focusing on catastrophic and brain injury and identifying the range of injury prevention methods in use. There have been few formal evaluations of injury prevention methods. Approaches that are considered, or have been proven, to be successful in preventing injury include: modification of the baseball; implementation of helmet standards in ice hockey and American football and increased wearing rates; use of full faceguards in ice hockey; changes in rules associated with body contact; implementation of rules to reduce the impact forces in rugby scrums. Helmets and other devices have been shown to reduce the risk of severe head and facial injury, but current designs appear to make little difference to rates of concussion. Research methods involving epidemiological, medical, and human factors are required in combination with biomechanical and technological approaches to reduce further injury risks in sport.

  1. Vision. Realignment of cones after cataract removal.

    PubMed

    Smallman, H S; MacLeod, D I; Doyle, P

    2001-08-01

    Through unique observations of an adult case of bilateral congenital cataract removal, we have found evidence that retinal photoreceptors will swiftly realign towards the brightest regions in the pupils of the eye. Cones may be phototropic, actively orientating themselves towards light like sunflowers in a field.

  2. Performance analysis of cone detection algorithms.

    PubMed

    Mariotti, Letizia; Devaney, Nicholas

    2015-04-01

    Many algorithms have been proposed to help clinicians evaluate cone density and spacing, as these may be related to the onset of retinal diseases. However, there has been no rigorous comparison of the performance of these algorithms. In addition, the performance of such algorithms is typically determined by comparison with human observers. Here we propose a technique to simulate realistic images of the cone mosaic. We use the simulated images to test the performance of three popular cone detection algorithms, and we introduce an algorithm which is used by astronomers to detect stars in astronomical images. We use Free Response Operating Characteristic (FROC) curves to evaluate and compare the performance of the four algorithms. This allows us to optimize the performance of each algorithm. We observe that performance is significantly enhanced by up-sampling the images. We investigate the effect of noise and image quality on cone mosaic parameters estimated using the different algorithms, finding that the estimated regularity is the most sensitive parameter. PMID:26366758

  3. Final design report for cone penetrometer platform

    SciTech Connect

    Seda, R.Y., Westinghouse Hanford

    1996-08-13

    The final design report documents the completion of the design review meetings for acceptance of the cone penetrometer from the vendor. All design comments have been dispositioned and closed. Open items dealt with completion of the safety assessment,operational procedures, operational testing and readiness review.

  4. 49 CFR 572.113 - Neck assembly.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Using neck brackets 78051-303 and -307, mount the head/neck assembly to the part 572 pendulum test... to the plane of motion of the pendulum's longitudinal centerline (see § 572.33, Figure 20, except... (horizontal surface at the base of the skull) rotation with respect to the pendulum's longitudinal...

  5. 49 CFR 572.113 - Neck assembly.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Using neck brackets 78051-303 and -307, mount the head/neck assembly to the part 572 pendulum test... to the plane of motion of the pendulum's longitudinal centerline (see § 572.33, Figure 20, except... (horizontal surface at the base of the skull) rotation with respect to the pendulum's longitudinal...

  6. 49 CFR 572.113 - Neck assembly.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Using neck brackets 78051-303 and -307, mount the head/neck assembly to the part 572 pendulum test... to the plane of motion of the pendulum's longitudinal centerline (see § 572.33, Figure 20, except... (horizontal surface at the base of the skull) rotation with respect to the pendulum's longitudinal...

  7. 49 CFR 572.113 - Neck assembly.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Using neck brackets 78051-303 and -307, mount the head/neck assembly to the part 572 pendulum test... to the plane of motion of the pendulum's longitudinal centerline (see § 572.33, Figure 20, except... (horizontal surface at the base of the skull) rotation with respect to the pendulum's longitudinal...

  8. Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health

    PubMed Central

    Deming, Janise D.; Pak, Joseph S.; Brown, Bruce M.; Kim, Moon K.; Aung, Moe H.; Eom, Yun Sung; Shin, Jung-a; Lee, Eun-Jin; Pardue, Machelle T.; Craft, Cheryl Mae

    2015-01-01

    Purpose Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. Methods A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4−/−) compared with age-matched control, wild-type mice. Results When 2-month-old Arr4−/− mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4−/− mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4−/− mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Conclusions Our study demonstrates that Arr4−/− mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy. PMID:26284544

  9. Single vesicle imaging indicates distinct modes of rapid membrane retrieval during nerve growth

    PubMed Central

    2012-01-01

    Background During nerve growth, cytoplasmic vesicles add new membrane preferentially to the growth cone located at the distal tip of extending axons. Growth cone membrane is also retrieved locally, and asymmetric retrieval facilitates membrane remodeling during growth cone repulsion by a chemorepellent gradient. Moreover, growth inhibitory factors can stimulate bulk membrane retrieval and induce growth cone collapse. Despite these functional insights, the processes mediating local membrane remodeling during axon extension remain poorly defined. Results To investigate the spatial and temporal dynamics of membrane retrieval in actively extending growth cones, we have used a transient labeling and optical recording method that can resolve single vesicle events. Live-cell confocal imaging revealed rapid membrane retrieval by distinct endocytic modes based on spatial distribution in Xenopus spinal neuron growth cones. These modes include endocytic "hot-spots" triggered at the base of filopodia, at the lateral margins of lamellipodia, and along dorsal ridges of the growth cone. Additionally, waves of endocytosis were induced when individual filopodia detached from the substrate and fused with the growth cone dorsal surface or with other filopodia. Vesicle formation at sites of membrane remodeling by self-contact required F-actin polymerization. Moreover, bulk membrane retrieval by macroendocytosis correlated positively with the substrate-dependent rate of axon extension and required the function of Rho-family GTPases. Conclusions This study provides insight into the dynamic membrane remodeling processes essential for nerve growth by identifying several distinct modes of rapid membrane retrieval in the growth cone during axon extension. We found that endocytic membrane retrieval is intensified at specific subdomains and may drive the dynamic membrane ruffling and re-absorption of filopodia and lamellipodia in actively extending growth cones. The findings offer a platform

  10. Perturbation theory in light-cone quantization

    SciTech Connect

    Langnau, A.

    1992-01-01

    A thorough investigation of light-cone properties which are characteristic for higher dimensions is very important. The easiest way of addressing these issues is by analyzing the perturbative structure of light-cone field theories first. Perturbative studies cannot be substituted for an analysis of problems related to a nonperturbative approach. However, in order to lay down groundwork for upcoming nonperturbative studies, it is indispensable to validate the renormalization methods at the perturbative level, i.e., to gain control over the perturbative treatment first. A clear understanding of divergences in perturbation theory, as well as their numerical treatment, is a necessary first step towards formulating such a program. The first objective of this dissertation is to clarify this issue, at least in second and fourth-order in perturbation theory. The work in this dissertation can provide guidance for the choice of counterterms in Discrete Light-Cone Quantization or the Tamm-Dancoff approach. A second objective of this work is the study of light-cone perturbation theory as a competitive tool for conducting perturbative Feynman diagram calculations. Feynman perturbation theory has become the most practical tool for computing cross sections in high energy physics and other physical properties of field theory. Although this standard covariant method has been applied to a great range of problems, computations beyond one-loop corrections are very difficult. Because of the algebraic complexity of the Feynman calculations in higher-order perturbation theory, it is desirable to automatize Feynman diagram calculations so that algebraic manipulation programs can carry out almost the entire calculation. This thesis presents a step in this direction. The technique we are elaborating on here is known as light-cone perturbation theory.

  11. Cone-Beam Computed Tomography-Guided Percutaneous Radiologic Gastrostomy

    SciTech Connect

    Moehlenbruch, Markus; Nelles, Michael; Thomas, Daniel; Willinek, Winfried; Gerstner, Andreas; Schild, Hans H.; Wilhelm, Kai

    2010-04-15

    The purpose of this study was to investigate the feasibility of a flat-detector C-arm-guided radiographic technique (cone-beam computed tomography [CBCT]) for percutaneous radiologic gastrostomy (PRG) insertion. Eighteen patients (13 men and 5 women; mean age 62 years) in whom percutaneous endoscopic gastrostomy (PEG) had failed underwent CBCT-guided PRG insertion. PEG failure or unsuitability was caused by upper gastrointestinal tract obstruction in all cases. Indications for gastrostomy were esophageal and head and neck malignancies, respectively. Before the PRG procedure, initial C-arm CBCT scans were acquired. Three- and 2-dimensional soft-tissue reconstructions of the epigastrium region were generated on a dedicated workstation. Subsequently, gastropexy was performed with T-fasteners after CBCT-guided puncture of the stomach bubble, followed by insertion of an 14F balloon-retained catheter through a peel-away introducer. Puncture of the stomach bubble and PRG insertion was technically successful in all patients without alteration of the epigastric region. There was no malpositioning of the tube or other major periprocedural complications. In 2 patients, minor complications occurred during the first 30 days of follow-up (PRG malfunction: n = 1; slight infection: n = 1). Late complications, which were mainly tube disturbances, were observed in 2 patients. The mean follow-up time was 212 days. CBCT-guided PRG is a safe, well-tolerated, and successful method of gastrostomy insertion in patients in whom endoscopic gastrostomy is not feasible. CBCT provides detailed imaging of the soft tissue and surrounding structures of the epigastric region in one diagnostic tour and thus significantly improves the planning of PRG procedures.

  12. Pancreaticogastrostomy: a salvage procedure for pancreatic body and neck resection.

    PubMed

    Li, Ang; Prasoon, Pankaj; Hong, Wu; Lu, Hui Min; Zhang, Zhao Da; Zhaoda, Zhang

    2012-11-01

    The purpose of this analysis was to evaluate the technological viability, basic safety and consequence of central pancreatectomy (CP) with pancreaticogastrostomy in properly chosen sufferers with noncancerous central pancreatic pathology. This research is centered on the infirmary charts of West China hospital. We recruited 20 individuals from 2007 to 2009 diagnosed with benign cancerous growth of pancreatic body and neck. They underwent pancreatic body and neck resection adhering to pancreaticogastrostomy. We carried out central pancreatectomy following pancreaticogastrostomy in 20 patients: 8 with serous cyst adenomas, 11 with mucinous cystadenomas, and 1 with neuroendocrine tumor. The position of all tumors was restricted to body and neck of the pancreas, measuring a mean ± standard deviation of 2.6±1.3cm. The mean post-operative hospital stay was 7 days (ranging from 6 to 16 days).There was no intraoperative additional complications. From a technical perspective, CP is a safe and sound, pancreas-preserving pancreatectomy for non-enucleable non-cancerous pancreatic pathology restricted to the pancreatic body. PMID:23396710

  13. Simulated and empiric wind pollination patterns of conifer ovulate cones

    PubMed Central

    Niklas, Karl J.

    1982-01-01

    Wind tunnel analyses of conifer ovulate cones indicate that the total geometry of the cone enhances the probability of pollen entrapment. Aerodynamic characteristics of cone scale-bract complexes are such that suspended pollen is directed toward the micropyles of attached ovules. Within the taxa examined, there appears to be a preferential entrapment by ovulate cones of pollen of the same species. The data are interpreted as evidence for an aerodynamic reciprocity between wind-suspended pollen and the structure of ovulate cones which increases the frequency of pollination and the potential for fertilization. Images PMID:16593147

  14. The inviscid stability of supersonic flow past a sharp cone

    NASA Technical Reports Server (NTRS)

    Duck, Peter W.; Shaw, Stephen J.

    1990-01-01

    The effects of lateral curvature on the development of supersonic laminar inviscid boundary-layer flow on a sharp cone with adiabatic wall conditions are investigated analytically, with a focus on the linear temporal inviscid stability properties. The derivation of the governing equations and of a 'triply generalized' inflexion condition is outlined, and numerical results for freestream Mach number 3.8 are presented in extensive graphs and characterized in detail. A third instability mode related to the viscous mode observed by Duck and Hall (1990) using triple-deck theory is detected and shown to be more unstable and to have larger growth rates than the second mode in some cases. It is found that the 'sonic' neutral mode is affected by the lateral curvature and becomes a supersonic neutral mode.

  15. MATRIX METALLOPROTEASES IN HEAD AND NECK CANCER

    PubMed Central

    Rosenthal, Eben L.; Matrisian, Lynn M.

    2010-01-01

    Matrix metalloproteases (MMPs) are a collection of enzymes capable of cleaving extracellular matrix components, growth factors, and cell-surface receptors. MMPs modulate most aspects of tumorigenesis and are highly expressed in cancer compared with normal tissues. Preclinical studies have demonstrated that head and neck squamous cell carcinomas (HNSCCs) express high levels of MMPs in vivo and that inhibition of these enzymes in vitro and in mouse models decreases invasion and metastasis. However, the clinical trials for MMP inhibitors have failed to demonstrate a significant survival advantage in most cancers. The disparity between preclinical and clinical studies has led to the reevaluation of how MMP functions in cancer and the design of clinical trials for molecularly targeted agents. Mouse model data and analysis of HNSCC tumor specimens suggests that membrane type-1 MMP (MT1-MMP) may be a critical enzyme in tumor cell invasion and survival in vivo. This accumulated data provide evidence for development of selective MT1-MMP inhibitors as therapy in HNSCC. PMID:16470875

  16. Characterizing the Human Cone Photoreceptor Mosaic via Dynamic Photopigment Densitometry

    PubMed Central

    Sabesan, Ramkumar; Hofer, Heidi; Roorda, Austin

    2015-01-01

    Densitometry is a powerful tool for the biophysical assessment of the retina. Until recently, this was restricted to bulk spatial scales in living humans. The application of adaptive optics (AO) to the conventional fundus camera and scanning laser ophthalmoscope (SLO) has begun to translate these studies to cellular scales. Here, we employ an AOSLO to perform dynamic photopigment densitometry in order to characterize the optical properties and spectral types of the human cone photoreceptor mosaic. Cone-resolved estimates of optical density and photosensitivity agree well with bulk estimates, although show smaller variability than previously reported. Photopigment kinetics of individual cones derived from their selective bleaching allowed efficient mapping of cone sub-types in human retina. Estimated uncertainty in identifying a cone as long vs middle wavelength was less than 5%, and the total time taken per subject ranged from 3–9 hours. Short wavelength cones were delineated in every subject with high fidelity. The lack of a third cone-type was confirmed in a protanopic subject. In one color normal subject, cone assignments showed 91% correspondence against a previously reported cone-typing method from more than a decade ago. Combined with cone-targeted stimulation, this brings us closer in studying the visual percept arising from a specific cone type and its implication for color vision circuitry. PMID:26660894

  17. Prospects for retinal cone-targeted gene therapy.

    PubMed

    Alexander, John J; Hauswirth, William W

    2008-06-01

    Gene therapy strategies that target therapeutic genes to retinal cones are a worthy goal both because cone photoreceptor diseases are severely vision limiting and because many retinal diseases that do not affect cones directly eventually lead to cone loss, the reason for eventual blindness. Human achromatopsia is a genetic disease of cones that renders them nonfunctional but otherwise intact. Thus, animal models of achromatopsia were used in conjunction with adeno-associated virus (AAV) vectors whose serotype efficiently transduces cones and with a promoter that limits transgene expression to cones. In the Gnat2(cpfl3) mouse model of one genetic form of human achromatopsia, we were able to demonstrate recovery of normal cone function and visual acuity after a single subretinal treatment of vector that supplied wild-type Gnat2 protein to cones. This validates the overall strategy of targeting cones using recombinant viral vectors and justifies a more complete examination of animal models of cone disease as a prelude to considering a clinical gene therapy trial. PMID:18596991

  18. Micro focusing of fast electrons with opened cone targets

    SciTech Connect

    Liu Feng; Liu Xiaoxuan; Ding Wenjun; Du Fei; Li Yutong; Ma Jinglong; Liu Xiaolong; Chen Liming; Lu Xin; Dong Quanli; Wang Weimin; Wang Zhaohua; Wei Zhiyi; Liu Bicheng; Sheng Zhengming; Zhang Jie

    2012-01-15

    Using opened reentrant cone silicon targets, we have demonstrated the effect of micro focusing of fast electrons generated in intense laser-plasma interactions. When an intense femtosecond laser pulse is focused tightly onto one of the side walls of the cone, fast electron beam emitted along the side wall is observed. When a line focus spot, which is long enough to irradiate both of the side walls of the cone simultaneously, is used, two electron beams emitted along each side wall, respectively, are observed. The two beams should cross each other near the open tip of the cone, resulting in micro focusing. We use a two-dimensional Particle-In-Cell code to simulate the electron emission both in opened and closed cone targets. The simulation results of the opened cone targets are in agreement with the experimental observation while the results of the closed cone targets do not show the micro focusing effect.

  19. Groundmass Crystallinities of Proximal and Distal Lavas from Cinder Cone, Lassen Volcanic Field

    NASA Astrophysics Data System (ADS)

    Szymanski, M. E.; Teasdale, R.

    2015-12-01

    Cinder Cone is located in the northeast corner of Lassen Volcanic Center, approximately 35 km southeast of Old Station, California. The area consists of a cinder cone constructed of loose scoria, lava flows and a 13-16 km diameter ash deposit. According to radiocarbon ages from trees affected by the lava flows and paleomagnetic data, Cinder Cone erupted in about 1650 AD (1). The youngest products of the Cinder Cone eruption are two Fantastic Lava Beds flows which are basaltic andesite and andesite with olivine (1). Samples were collected along the longest flow from Cinder Cone, the Fantastic Lava Beds Flow 2 (4.5 km) at approximately 0.5 km interval. The samples contain olivine, plagioclase and clinopyroxene phenocrysts in fine grained groundmass with varying vesicularity. Quartz xenocrysts also occur. SEM-Back Scatter Electron images are used to map and quantify groundmass crystallinities along the length of the Fantastic Lava Beds flow 2 and of tephra units. The average area of groundmass plagioclase crystals increases along the length of the lava flow from 94.7 to 292.6 μm2. The number of groundmass plagioclase crystals per area (μm2) decreases from 0.0045 to 0.0018 from proximal to distal samples. Crystals also become blockier in distal samples along the lava flow. The larger number of crystals per area in near vent samples establishes a baseline from which we interpret crystal growth and nucleation to have occurred in the flow channel. Increasing crystal size and a decrease in the number of crystals per area indicates growth dominated nucleation during cooling and crystallization in the flow channel. Relative cooling rates along the length of the flow from proximal to distal samples can be inferred based on groundmass crystallinities, distance travelled and estimates of flow and crystallization rates. (1) Muffler and Clynne, 2015.

  20. [Head and neck adaptive radiotherapy].

    PubMed

    Graff, P; Huger, S; Kirby, N; Pouliot, J

    2013-10-01

    Onboard volumetric imaging systems can provide accurate data of the patient's anatomy during a course of head and neck radiotherapy making it possible to assess the actual delivered dose and to evaluate the dosimetric impact of complex daily positioning variations and gradual anatomic changes such as geometric variations of tumors and normal tissues or shrinkage of external contours. Adaptive radiotherapy is defined as the correction of a patient's treatment planning to adapt for individual variations observed during treatment. Strategies are developed to selectively identify patients that require replanning because of an intolerable dosimetric drift. Automated tools are designed to limit time consumption. Deformable image registration algorithms are the cornerstones of these strategies, but a better understanding of their limits of validity is required before adaptive radiotherapy can be safely introduced to daily practice. Moreover, strict evaluation of the clinical benefits is yet to be proven.

  1. X-linked cone dystrophy caused by mutation of the red and green cone opsins.

    PubMed

    Gardner, Jessica C; Webb, Tom R; Kanuga, Naheed; Robson, Anthony G; Holder, Graham E; Stockman, Andrew; Ripamonti, Caterina; Ebenezer, Neil D; Ogun, Olufunmilola; Devery, Sophie; Wright, Genevieve A; Maher, Eamonn R; Cheetham, Michael E; Moore, Anthony T; Michaelides, Michel; Hardcastle, Alison J

    2010-07-01

    X-linked cone and cone-rod dystrophies (XLCOD and XLCORD) are a heterogeneous group of progressive disorders that solely or primarily affect cone photoreceptors. Mutations in exon ORF15 of the RPGR gene are the most common underlying cause. In a previous study, we excluded RPGR exon ORF15 in some families with XLCOD. Here, we report genetic mapping of XLCOD to Xq26.1-qter. A significant LOD score was detected with marker DXS8045 (Z(max) = 2.41 [theta = 0.0]). The disease locus encompasses the cone opsin gene array on Xq28. Analysis of the array revealed a missense mutation (c. 529T>C [p. W177R]) in exon 3 of both the long-wavelength-sensitive (LW, red) and medium-wavelength-sensitive (MW, green) cone opsin genes that segregated with disease. Both exon 3 sequences were identical and were derived from the MW gene as a result of gene conversion. The amino acid W177 is highly conserved in visual and nonvisual opsins across species. We show that W177R in MW opsin and the equivalent W161R mutation in rod opsin result in protein misfolding and retention in the endoplasmic reticulum. We also demonstrate that W177R misfolding, unlike the P23H mutation in rod opsin that causes retinitis pigmentosa, is not rescued by treatment with the pharmacological chaperone 9-cis-retinal. Mutations in the LW/MW cone opsin gene array can, therefore, lead to a spectrum of disease, ranging from color blindness to progressive cone dystrophy (XLCOD5). PMID:20579627

  2. Scatter correction, intermediate view estimation and dose characterization in megavoltage cone-beam CT imaging

    NASA Astrophysics Data System (ADS)

    Sramek, Benjamin Koerner

    neck phantoms. The conclusions of this investigation were: (1) the implementation of intermediate view estimation techniques to megavoltage cone-beam CT produced improvements in image quality, with the largest impact occurring for smaller numbers of initially-acquired projections, (2) the SPECS scatter correction algorithm could be successfully incorporated into projection data acquired using an electronic portal imaging device during megavoltage cone-beam CT image reconstruction, (3) a large range of SPECS parameters were shown to reduce cupping artifacts as well as improve reconstruction accuracy, with application to anthropomorphic phantom geometries improving the percent difference in reconstructed electron density for soft tissue from -13.6% to -2.0%, and for cortical bone from -9.7% to 1.4%, (4) dose measurements in the anthropomorphic phantoms showed consistent agreement between planar measurements using radiochromic film and point measurements using thermoluminescent dosimeters, and (5) a comparison of normalized dose measurements acquired with radiochromic film to those calculated using multiple treatment planning systems, accelerator-detector combinations, patient geometries and accelerator outputs produced a relatively good agreement.

  3. Establishment of a cone photoreceptor transplantation platform based on a novel cone-GFP reporter mouse line

    PubMed Central

    Smiley, Sheila; Nickerson, Philip E.; Comanita, Lacrimioara; Daftarian, Narsis; El-Sehemy, Ahmed; Tsai, En Leh Samuel; Matan-Lithwick, Stuart; Yan, Keqin; Thurig, Sherry; Touahri, Yacine; Dixit, Rajiv; Aavani, Tooka; De Repentingy, Yves; Baker, Adam; Tsilfidis, Catherine; Biernaskie, Jeff; Sauvé, Yves; Schuurmans, Carol; Kothary, Rashmi; Mears, Alan J.; Wallace, Valerie A.

    2016-01-01

    We report successful retinal cone enrichment and transplantation using a novel cone-GFP reporter mouse line. Using the putative cone photoreceptor-enriched transcript Coiled-Coil Domain Containing 136 (Ccdc136) GFP-trapped allele, we monitored developmental reporter expression, facilitated the enrichment of cones, and evaluated transplanted GFP-labeled cones in wildtype and retinal degeneration mutant retinas. GFP reporter and endogenous Ccdc136 transcripts exhibit overlapping temporal and spatial expression patterns, both initiated in cone precursors of the embryonic retina and persisting to the adult stage in S and S/M opsin+ cones as well as rod bipolar cells. The trapped allele does not affect cone function or survival in the adult mutant retina. When comparing the integration of GFP+ embryonic cones and postnatal Nrl−/− ‘cods’ into retinas of adult wildtype and blind mice, both cell types integrated and exhibited a degree of morphological maturation that was dependent on donor age. These results demonstrate the amenability of the adult retina to cone transplantation using a novel transgenic resource that can advance therapeutic cone transplantation in models of age-related macular degeneration. PMID:26965927

  4. The S-cone contribution to luminance depends on the M- and L-cone adaptation levels: silent surrounds?

    PubMed

    Ripamonti, Caterina; Woo, Wen Ling; Crowther, Elizabeth; Stockman, Andrew

    2009-01-01

    Under dim background conditions, the S-cones make little or no contribution to luminance (A. Eisner & D. I. MacLeod, 1980; W. Verdon & A. J. Adams, 1987), yet under conditions of intense long-wavelength adaptation, a small but robust contribution to luminance--as defined by heterochromatic flicker photometry (A. Stockman, D. I. MacLeod, & D. D. DePriest, 1987, 1991) or motion (J. Lee & C. F. Stromeyer, 1989)--can be found. Here, by using selective adaptation and/or tritanopic metamers to isolate the S-cone response, we investigate the dependence of the S-cone luminance input on changes in background wavelength and radiance. Interestingly, the S-cone luminance input disappears completely when no adapting background is present, even though the same S-cone stimulus makes a clear contribution to luminance when a background is present. The dependence of the S-cone luminance input on the wavelength and radiance of the adapting background is surprising. We find that the S-cone signal can be measured on fields of 491 nm and longer wavelengths that exceed a criterion background radiance. These criterion radiances roughly follow an L + M spectral sensitivity, which suggests that the S-cone luminance input is silent unless the L- and M-cones are excited above a certain level. We hypothesize that the L + M cone signals produced by the steady adapting backgrounds somehow "gate" the S-cone luminance signals, perhaps by being modulated by them.

  5. History of imaging in orthodontics from Broadbent to cone-beam computed tomography.

    PubMed

    Hans, Mark G; Palomo, J Martin; Valiathan, Manish

    2015-12-01

    The history of imaging and orthodontics is a story of technology informing biology. Advances in imaging changed our thinking as our understanding of craniofacial growth and the impact of orthodontic treatment deepened. This article traces the history of imaging in orthodontics from the invention of the cephalometer by B. Holly Broadbent in 1930 to the introduction of low-cost, low-radiation-dose cone-beam computed tomography imaging in 2015. PMID:26672697

  6. History of imaging in orthodontics from Broadbent to cone-beam computed tomography.

    PubMed

    Hans, Mark G; Palomo, J Martin; Valiathan, Manish

    2015-12-01

    The history of imaging and orthodontics is a story of technology informing biology. Advances in imaging changed our thinking as our understanding of craniofacial growth and the impact of orthodontic treatment deepened. This article traces the history of imaging in orthodontics from the invention of the cephalometer by B. Holly Broadbent in 1930 to the introduction of low-cost, low-radiation-dose cone-beam computed tomography imaging in 2015.

  7. Gynecomastia presenting as a neck mass.

    PubMed

    Rickard, Kyle A; Vemavarapu, Lakshmi K; Sahoo, Sunati

    2013-04-01

    The differential diagnoses of neck mass may include a wide spectrum of lesions ranging from cysts, inflammatory processes, benign and malignant tumors arising from skin, soft tissue, lymph nodes, endocrine glands, salivary glands to metastatic tumors. In adults, malignant non-thyroid neck masses are often metastatic squamous cell carcinoma. Gynecomastia, presenting as a mass or enlargement in its typical subareolar location is usually a straightforward diagnosis. Enlargement due to gynecomastia in locations other than subareola can pose diagnostic challenge. We describe a unique case of gynecomastia presenting as a neck mass in a patient who was diagnosed and treated for squamous cell carcinoma of the floor of the mouth.

  8. 3D In Vivo Dosimetry Using Megavoltage Cone-Beam CT and EPID Dosimetry

    SciTech Connect

    Elmpt, Wouter van Nijsten, Sebastiaan; Petit, Steven; Mijnheer, Ben; Lambin, Philippe; Dekker, Andre

    2009-04-01

    Purpose: To develop a method that reconstructs, independently of previous (planning) information, the dose delivered to patients by combining in-room imaging with transit dose measurements during treatment. Methods and Materials: A megavoltage cone-beam CT scan of the patient anatomy was acquired with the patient in treatment position. During treatment, delivered fields were measured behind the patient with an electronic portal imaging device. The dose information in these images was back-projected through the cone-beam CT scan and used for Monte Carlo simulation of the dose distribution inside the cone-beam CT scan. Validation was performed using various phantoms for conformal and IMRT plans. Clinical applicability is shown for a head-and-neck cancer patient treated with IMRT. Results: For single IMRT beams and a seven-field IMRT step-and-shoot plan, the dose distribution was reconstructed within 3%/3mm compared with the measured or planned dose. A three-dimensional conformal plan, verified using eight point-dose measurements, resulted in a difference of 1.3 {+-} 3.3% (1 SD) compared with the reconstructed dose. For the patient case, planned and reconstructed dose distribution was within 3%/3mm for about 95% of the points within the 20% isodose line. Reconstructed mean dose values, obtained from dose-volume histograms, were within 3% of prescribed values for target volumes and normal tissues. Conclusions: We present a new method that verifies the dose delivered to a patient by combining in-room imaging with the transit dose measured during treatment. This verification procedure opens possibilities for offline adaptive radiotherapy and dose-guided radiotherapy strategies taking into account the dose distribution delivered during treatment sessions.

  9. k-cones and kirigami metamaterials

    NASA Astrophysics Data System (ADS)

    Seffen, Keith A.

    2016-09-01

    We are inspired by the tensile buckling of a thin sheet with a slit to create a foldable planar metamaterial. The buckled shape comprises two pairs of identical e-cones connected to the slit, which we refer to as a k-cone. We approximate this shape as discrete vertices that can be folded out of plane as the slit is pulled apart. We determine their kinematics and we calculate generic shape properties using a simple elastic model of the folded shape. We then show how the folded sheet may be tessellated as a unit cell within a larger sheet, which may be constructed a priori by cutting and folding the latter in a regular way, in order to form a planar kirigami structure with a single degree of freedom.

  10. Instantons on Calabi-Yau cones

    NASA Astrophysics Data System (ADS)

    Sperling, Marcus

    2015-12-01

    The Hermitian Yang-Mills equations on certain vector bundles over Calabi-Yau cones can be reduced to a set of matrix equations; in fact, these are Nahm-type equations. The latter can be analysed further by generalising arguments of Donaldson and Kronheimer used in the study of the original Nahm equations. Starting from certain equivariant connections, we show that the full set of instanton equations reduce, with a unique gauge transformation, to the holomorphicity condition alone.

  11. Hadronic wavefunctions in light-cone quantization

    SciTech Connect

    Hyer, T.

    1994-05-01

    The analysis of light-cone wavefunctions seems the most promising theoretical approach to a detailed understanding of the structure of relativistic bound states, particularly hadrons. However, there are numerous complications in this approach. Most importantly, the light-cone approach sacrifices manifest rotational invariance in exchange for the elimination of negative-energy states. The requirement of rotational invariance of the full theory places important constraints on proposed light-cone wavefunctions, whether they are modelled or extracted from some numerical procedure. A formulation of the consequences of the hidden rotational symmetry has been sought for some time; it is presented in Chapter 2. In lattice gauge theory or heavy-quark effective theory, much of the focus is on the extraction of numerical values of operators which are related to the hadronic wavefunction. These operators are to some extent interdependent, with relations induced by fundamental constraints on the underlying wavefunction. The consequences of the requirement of unitarity are explored in Chapter 3, and are found to have startling phenomenological relevance. To test model light-cone wavefunctions, experimental predictions must be made. The reliability of perturbative QCD as a tool for making such predictions has been questioned. In Chapter 4, the author presents a computation of the rates for nucleon-antinucleon annihilation, improving the reliability of the perturbative computation by taking into account the Sudakov suppression of exclusive processes at large transverse impact parameter. In Chapter 5, he develops the analysis of semiexclusive production. This work focuses on processes in which a single isolated meson is produced perturbatively and recoils against a wide hadronizing system. At energies above about 10 GeV, semiexclusive processes are shown to be the most sensitive experimental probes of hadronic structure.

  12. Analytic image reconstruction from partial data for a single-scan cone-beam CT with scatter correction

    SciTech Connect

    Min, Jonghwan; Pua, Rizza; Cho, Seungryong; Kim, Insoo; Han, Bumsoo

    2015-11-15

    proposed scanning method and image reconstruction algorithm can effectively estimate the scatter in cone-beam projections and produce tomographic images of nearly scatter-free quality. The authors believe that the proposed method would provide a fast and efficient CBCT scanning option to various applications particularly including head-and-neck scan.

  13. Evaluation of document location during computer use in terms of neck muscle activity and neck movement.

    PubMed

    Goostrey, Sonya; Treleaven, Julia; Johnston, Venerina

    2014-05-01

    This study evaluated the impact on neck movement and muscle activity of placing documents in three commonly used locations: in-line, flat desktop left of the keyboard and laterally placed level with the computer screen. Neck excursion during three standard head movements between the computer monitor and each document location and neck extensor and upper trapezius muscle activity during a 5 min typing task for each of the document locations was measured in 20 healthy participants. Results indicated that muscle activity and neck flexion were least when documents were placed laterally suggesting it may be the optimal location. The desktop option produced both the greatest neck movement and muscle activity in all muscle groups. The in-line document location required significantly more neck flexion but less lateral flexion and rotation than the laterally placed document. Evaluation of other holders is needed to guide decision making for this commonly used office equipment.

  14. Internal Reflection Sensor for the Cone Penetrometer

    SciTech Connect

    Job Bello

    1998-05-29

    The objectives of this project are to design, assemble, test, and demonstrate a prototype Internal Reflection Sensor (IRS) for the cone penetrometer. The sensor will ultimately be deployed during site characterization with the goal of providing real-time, in situ detection of NonAqueous Phase Liquids (NAPLs) in the subsurface. In the first phase of this program, we have designed and assembled an IRS module that interfaces directly to a standard cone penetrometer system. Laboratory tests demonstrated that the sensor responds in real-time to a wide variety of free phase NAPLs without interference from natural materials such as water and soil of various types or dissolved contaminants. In a preliminary field test, the sensor was able to locate NAPLs at thin, discrete depths in a soil test pit when deployed with a cone penetrometer. Ruggedness of the device was tested with a series of penetrometer pushes to the depth of refusal at a clean location. There was no visible damage to the sensor and its performance did not change in the course of these experiments. Based on the successes of the Phase I program, it is recommended that the project proceed to full-scale demonstration in Phase II.

  15. Long polymers near wedges and cones

    NASA Astrophysics Data System (ADS)

    Hammer, Yosi; Kantor, Yacov

    2015-12-01

    We perform a Monte Carlo study of N -step self-avoiding walks, attached to the corner of an impenetrable wedge in two dimensions (d =2 ), or the tip of an impenetrable cone in d =3 , of sizes ranging up to N =106 steps. We find that the critical exponent γα, which determines the dependence of the number of available conformations on N for a cone or wedge with opening angle α , is in good agreement with the theory for d =2 . We study the end-point distribution of the walks in the allowed space and find similarities to the known behavior of random walks (ideal polymers) in the same geometry. For example, the ratio between the mean square end-to-end distances of a polymer near the cone or wedge and a polymer in free space depends linearly on γα, as is known for ideal polymers. We show that the end-point distribution of polymers attached to a wedge does not separate into a product of angular and radial functions, as it does for ideal polymers in the same geometry. The angular dependence of the end position of polymers near the wedge differs from theoretical predictions.

  16. Long polymers near wedges and cones.

    PubMed

    Hammer, Yosi; Kantor, Yacov

    2015-12-01

    We perform a Monte Carlo study of N-step self-avoiding walks, attached to the corner of an impenetrable wedge in two dimensions (d=2), or the tip of an impenetrable cone in d=3, of sizes ranging up to N=10(6) steps. We find that the critical exponent γ(α), which determines the dependence of the number of available conformations on N for a cone or wedge with opening angle α, is in good agreement with the theory for d=2. We study the end-point distribution of the walks in the allowed space and find similarities to the known behavior of random walks (ideal polymers) in the same geometry. For example, the ratio between the mean square end-to-end distances of a polymer near the cone or wedge and a polymer in free space depends linearly on γ(α), as is known for ideal polymers. We show that the end-point distribution of polymers attached to a wedge does not separate into a product of angular and radial functions, as it does for ideal polymers in the same geometry. The angular dependence of the end position of polymers near the wedge differs from theoretical predictions. PMID:26764719

  17. Numerical Simulation of Taylor Cone-Jet

    NASA Astrophysics Data System (ADS)

    Toledo, Ronne

    The Taylor cone-jet is a particular type of electrohydrodynamic phenomenon where electrostatic stresses and surface tension effects shape the interface of the jet in a peculiar conical shape. A thin jet is issued from the cone apex that further breaks up into a fine aerosol. Due to its monodispersive properties, this fine aerosol has found a number of applications, ranging from mass spectrometry, colloidal space propulsion, combustion, nano-fabrication, coating/painting, and many others. In this study, a general non-dimensional analysis is performed to derive the governing equations and boundary conditions. In accordance with the observations of Gamero-Castano (2010), noting that droplet electric potential is insensitive to the flow rate conditions, a particular set of characteristic parameters is proposed, based on the terminal jet diameter. In order to solve the non-dimensional set of governing equations and boundary conditions, a numerical method combining the Boundary Element Method and the Finite Volume Method is developed. Results of electric current have shown good agreement with numerical and experimental data available in the literature. The main feature of the algorithm developed is related to the decoupling of the electrostatic from the hydrodynamic problem, allowing us to accurately prescribe the far field electric potential boundary conditions away from the hydrodynamic computational domain used to solve the hydrodynamics of the transition region near the cone apex.

  18. Cusp formation in drops inside Taylor cones

    NASA Astrophysics Data System (ADS)

    Marin, Alvaro G.; Loscertales, Ignacio G.; Barrero, Antonio

    2005-11-01

    Here, we report the formation of cusp in insulating drops inside compound Taylor cones. The action of the electrical shear stress acting on the outer interface, which is transmitted by viscous forces inside the Taylor cone, tends to deform the drop of insulating liquid placed inside. For appropriate values of the capillary number, the insulating drop develops a steady cusp angle which depends on both the capillary number and the conducting to insulating viscosity ratio. A self-similar analysis has been developed to qualitatively describe the flow inside these compounds Taylor cones. Any perturbation of the cusp gives rise to an intermittent emission of tiny droplets; this effect may recall the tip-streaming observed by G.I. Taylor in his four-roll mill device. This emission can be stabilized by an appropriate control of the injected flow rate of the insulating liquid. When the capillary number increases, the cusped interface turns into a spout which flows coated by the conducting liquid forming the electrified coaxial jet which has been successfully employed for the production of nanocapsules, coaxial nanofibers and nanotubes (Science 295, n. 5560, 1695, 2002; JACS 126, 5376, 2004).

  19. Reconfiguration of broad leaves into cones

    NASA Astrophysics Data System (ADS)

    Miller, Laura

    2013-11-01

    Flexible plants, fungi, and sessile animals are thought to reconfigure in the wind and water to reduce the drag forces that act upon them. Simple mathematical models of a flexible beam immersed in a two-dimensional flow will also exhibit this behavior. What is less understood is how the mechanical properties of a leaf in a three-dimensional flow will passively allow roll up and reduce drag. This presentation will begin by examining how leaves roll up into drag reducing shapes in strong flow. The dynamics of the flow around the leaf of the wild ginger Hexastylis arifolia are described using particle image velocimetry. The flows around the leaves are compared with those of simplified sheets using 3D numerical simulations and physical models. For some reconfiguration shapes, large forces and oscillations due to strong vortex shedding are produced. In the actual leaf, a stable recirculation zone is formed within the wake of the reconfigured cone. In physical and numerical models that reconfigure into cones, a similar recirculation zone is observed with both rigid and flexible tethers. These results suggest that the three-dimensional cone structure in addition to flexibility is significant to both the reduction of vortex-induced vibrations and the forces experienced by the leaf.

  20. Correlation among scapular asymmetry, neck pain, and neck disability index (NDI) in young women with slight neck pain

    PubMed Central

    Kim, Su-Rim; Kang, Mi-Hee; Bahng, Sun-Young; An, Jin-Kyoung; Lee, Ji-Young; Park, Sang-Young; Kim, Seong-Gil

    2016-01-01

    [Purpose] This study aimed to investigate the correlations among scapular asymmetry, neck pain, and neck disability index in women in their 20s with slight neck pain. [Subjects and Methods] A total of 60 female students at U university in Gyeongsangbuk-do, South Korea, participated in this study. The lateral scapular slide test, which measures the distance between the thorax and scapula, was used to analyze the scapular asymmetry. The lateral scapular slide test was performed in three positions. The visual analogue scale and neck disability index were used to measure neck pain. [Results] In the lateral scapular slide test in position 3 (shoulder abduction at 90 degrees), the scapular left-right asymmetry and VAS showed a moderate positive linear relationship, with r=0.344. The VAS and NDI showed a moderate positive linear relationship, with r = 0.632. [Conclusion] Scapular asymmetry indicates imbalance of surrounding muscles of the scapula and is related to neck pain based on the results of measuring the distance from the thorax to the scapula. PMID:27313361

  1. CRALBP supports the mammalian retinal visual cycle and cone vision

    PubMed Central

    Xue, Yunlu; Shen, Susan Q.; Jui, Jonathan; Rupp, Alan C.; Byrne, Leah C.; Hattar, Samer; Flannery, John G.; Corbo, Joseph C.; Kefalov, Vladimir J.

    2015-01-01

    Mutations in the cellular retinaldehyde–binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor–mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient animals. While rearing CRALBP-deficient mice in the dark prevented the deterioration of cone function, it did not rescue cone dark adaptation. Adeno-associated virus–mediated restoration of CRALBP expression specifically in Müller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Müller cell CRALBP as a key component of the retinal visual cycle and demonstrate that this pathway is important for maintaining normal cone–driven vision and accelerating cone dark adaptation. PMID:25607845

  2. Neck muscle function in violinists/violists with and without neck pain.

    PubMed

    Steinmetz, Anke; Claus, Andrew; Hodges, Paul W; Jull, Gwendolen A

    2016-04-01

    Neck pain is associated with changes in neuromuscular control of cervical muscles. Violin and viola playing requires good function of the flexor muscles to stabilize the instrument. This study investigated the flexor muscle behaviour in violin/viola players with and without neck pain using the craniocervical flexion test (CCFT). In total, 12 violin/viola players with neck pain, 21 violin/viola players without neck pain in the preceding 12 weeks and 21 pain-free non-musicians were included. Activity of the sternocleidomastoid muscles (SCM) was measured with surface electromyography (EMG) during the CCFT. Violin/viola players with neck pain displayed greater normalised SCM EMG amplitudes during CCFT than the pain-free musicians and non-musicians (P < 0.05). Playing-related neck pain in violinists/violists is associated with altered behaviour of the superficial neck flexor muscles consistent with neck pain, despite the specific use of the deep and superficial neck flexors during violin playing.

  3. Neck muscle function in violinists/violists with and without neck pain.

    PubMed

    Steinmetz, Anke; Claus, Andrew; Hodges, Paul W; Jull, Gwendolen A

    2016-04-01

    Neck pain is associated with changes in neuromuscular control of cervical muscles. Violin and viola playing requires good function of the flexor muscles to stabilize the instrument. This study investigated the flexor muscle behaviour in violin/viola players with and without neck pain using the craniocervical flexion test (CCFT). In total, 12 violin/viola players with neck pain, 21 violin/viola players without neck pain in the preceding 12 weeks and 21 pain-free non-musicians were included. Activity of the sternocleidomastoid muscles (SCM) was measured with surface electromyography (EMG) during the CCFT. Violin/viola players with neck pain displayed greater normalised SCM EMG amplitudes during CCFT than the pain-free musicians and non-musicians (P < 0.05). Playing-related neck pain in violinists/violists is associated with altered behaviour of the superficial neck flexor muscles consistent with neck pain, despite the specific use of the deep and superficial neck flexors during violin playing. PMID:26175099

  4. SU-E-J-92: On-Line Cone Beam CT Based Planning for Emergency and Palliative Radiation Therapy

    SciTech Connect

    Held, M; Morin, O; Pouliot, J

    2014-06-01

    Purpose: To evaluate and develop the feasibility of on-line cone beam CT based planning for emergency and palliative radiotherapy treatments. Methods: Subsequent to phantom studies, a case library of 28 clinical megavoltage cone beam CT (MVCBCT) was built to assess dose-planning accuracies on MVCBCT for all anatomical sites. A simple emergency treatment plan was created on the MVCBCT and copied to its reference CT. The agreement between the dose distributions of each image pair was evaluated by the mean dose difference of the dose volume and the gamma index of the central 2D axial plane. An array of popular urgent and palliative cases was also evaluated for imaging component clearance and field-of-view. Results: The treatment cases were categorized into four groups (head and neck, thorax/spine, pelvis and extremities). Dose distributions for head and neck treatments were predicted accurately in all cases with a gamma index of >95% for 2% and 2 mm criteria. Thoracic spine treatments had a gamma index as low as 60% indicating a need for better uniformity correction and tissue density calibration. Small anatomy changes between CT and MVCBCT could contribute to local errors. Pelvis and sacral spine treatment cases had a gamma index between 90% and 98% for 3%/3 mm criteria. The limited FOV became an issue for large pelvis patients. Imaging clearance was difficult for cases where the tumor was positioned far off midline. Conclusion: The MVCBCT based dose planning and delivery approach is feasible in many treatment cases. Dose distributions for head and neck patients are unrestrictedly predictable. Some FOV restrictions apply to other treatment sites. Lung tissue is most challenging for accurate dose calculations given the current imaging filters and corrections. Additional clinical cases for extremities need to be included in the study to assess the full range of site-specific planning accuracies. This work is supported by Siemens.

  5. Radiation Dose From Cone Beam Computed Tomography for Image-Guided Radiation Therapy

    SciTech Connect

    Kan, Monica W.K. Leung, Lucullus H.T.; Wong, Wicger; Lam, Nelson

    2008-01-01

    Purpose: To perform a comprehensive study on organ absorbed doses and effective doses from cone beam computed tomography (CBCT) for three different treatment sites. Methods and Materials: An extensive set of dosimetric measurements were performed using a widely used CBCT system, the On-Board Imager (OBI). Measurements were performed using a female anthropomorphic phantom with thermoluminescent dosimeters (TLD). The effective doses to the body and the absorbed doses to 26 organs were reported using two different technical settings, namely, the standard mode and the low-dose mode. The measurements were repeated for three different scan sites: head and neck, chest, and pelvis. Comparisons of patient doses as well as image quality were performed among the standard mode CBCT, low-dose mode CBCT, and fan beam CT. Results: The mean skin doses from standard mode CBCT to head and neck, chest and pelvis were 6.7, 6.4, and 5.4 cGy per scan, respectively. The effective doses to the body from standard mode CBCT for imaging of head and neck, chest, and pelvis were 10.3, 23.7, and 22.7 mSv per scan, respectively. Patient doses from low-dose mode CBCT were approximately one fifth of those from standard mode CBCT. Conclusions: Patient position verification by standard mode CBCT acquired by OBI on a daily basis could increase the secondary cancer risk by up to 2% to 4%. Therefore lower mAs settings for daily CBCT should be considered, especially when bony anatomy is the main interest.

  6. Drugs Approved for Head and Neck Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for head and neck cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  7. Aging small Canada geese by neck plumage

    USGS Publications Warehouse

    Higgins, K.F.; Schoonover, L.J.

    1969-01-01

    The neck plumage method, a new technique for separating immature from adult Canada geese (Branta canadensis) in the hand, was evaluated by comparison with the notched tail feather and cloacal examination methods. Two (1.4 percent) of 141 geese examined were misaged, resulting in a 6 percent error in the immature-adult ratio obtained by the neck plumage method. The neck plumage method is a rapid aging method and reasonable accuracy (94 percent) can be obtained. It can also be used to differentiate immatures from adults on the ground at distances up to 175 yards, but was almost impossible to use when geese were in flight. As yet, the neck plumage method has only been tested on the subspecies (B. c. hutchinsii-parvipes complex) in the Tall-Grass Prairie population of small Canada geese.

  8. Jaw-neck dysfunction in whiplash-associated disorders.

    PubMed

    Eriksson, Per-Olof; Häggman-Henrikson, Birgitta; Zafar, Hamayun

    2007-04-01

    This paper reports data from recent studies on integrative jaw-neck motor control in healthy subjects and disturbed jaw-neck behaviour in whiplash-associated disorders (WAD). The results show that neck function is an integral part of natural jaw behaviour, and that neck injury can impair jaw function and therefore disturb eating behaviour. We also show preliminary results from implementation of a new approach for rehabilitation of jaw-neck dysfunction and pain in WAD.

  9. Improved Jänecke mass formula

    NASA Astrophysics Data System (ADS)

    He, Z.; Bao, M.; Zhao, Y. M.; Arima, A.

    2014-11-01

    In this paper we improve an empirical mass formula constructed by Jänecke and collaborators. This formula is enlightened by the Garvey-Kelson mass relations. The new version of the Jänecke formula reproduces 2275 atomic masses with neutron number N ≥10 and proton number Z ≥6 , at an average accuracy of 128 keV, by employing 576 parameters. The predictive power of our formula is exemplified by comparison with predicted results of other mass models.

  10. Musculocutaneous flaps in head and neck reconstruction.

    PubMed Central

    Leonard, A. G.

    1989-01-01

    The introduction of musculocutaneous flaps to head and neck reconstructive surgery is described. The flaps available are listed, and the most important ones described and illustrated. Both the latissimus dorsi and pectoralis major flaps are felt to have a role in head and neck reconstruction, though they have largely been superseded by microvascular free flaps such as the radial forearm flap. Images fig. 1 fig. 2 fig. 3 fig. 4 fig. 5 fig. 6 fig. 7 fig. 8 PMID:2686511

  11. Intrathecal bupivacaine for head and neck pain.

    PubMed

    Belverud, Shawn A; Mogilner, Alon Y; Schulder, Michael

    2010-01-01

    Direct central nervous system (CNS) analgesic delivery is a useful option when more traditional means of dealing with chronic pain fail. Solutions containing local anesthetic have been effective in certain disease states, particularly in patients suffering from intractable head and neck pain. This review discusses historical aspects of CNS drug delivery and the role of intrathecal bupivacaine-containing solutions in refractory head and neck pain patients. PMID:22915879

  12. 49 CFR 572.33 - Neck.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... sensor of the six axis neck transducer and Fx is the force measured in lbs by the “X” axis force sensor... My is the moment measured in lbs-ft by the “Y” axis moment sensor of the six axis neck transducer and Fx is the force measured in lbs by the “X” axis force sensor (Channel Class 600) of the six axis...

  13. Treatment of head and neck cancers: issues for clinical pharmacists.

    PubMed

    Scarpace, Sarah L; Brodzik, Frank A; Mehdi, Syed; Belgam, Robert

    2009-05-01

    Head and neck cancers are a heterogeneous group of diseases involving the oral cavity, pharyngeal tube, and larynx. Given the drug therapy options available, clinical pharmacists can play an important role in the care of this patient population. They can recommend a regimen based on efficacy, toxicity, and patient-specific factors; ensure that the prescribed regimen has been studied and reported in the literature; verify dosages; and monitor and counsel patients about adverse effects. Chemotherapy plus radiation (chemoradiation) is often the standard treatment for patients with stage III or nonmetastatic stage IV head and neck cancer. Cisplatin-based regimens are preferred, although carboplatin may be appropriate in some circumstances. Induction therapy with a docetaxel-based regimen is recommended for some patients; however, this therapy has been associated with a high frequency of grade 3 and 4 neutropenia and febrile neutropenia. Cetuximab, an epidermal growth factor receptor inhibitor, is the newest agent approved for treatment of head and neck cancer. Although evidence supports cetuximab combined with cisplatin versus cisplatin alone for patients with metastatic disease, the role of combination therapy is less clear in patients undergoing chemoradiation. Patients with head and neck cancer may experience swallowing difficulties or mouth pain, possibly interfering with drug administration and adherence; thus, pharmacists in all practice settings should be knowledgeable about different regimens and alternative routes of administration. Xerostomia and mucositis are common adverse effects of radiation therapy, and it is critical that good oral hygiene practices are maintained. Patients may achieve symptomatic relief from xerostomia with saliva substitutes, and clinical experience suggests that use of pilocarpine is worthwhile. Until more evidence becomes available, prevention of xerostomia and mucositis with amifostine is still controversial. Salt-water rinses

  14. Targeting Head and Neck Cancer Stem Cells: Current Advances and Future Challenges.

    PubMed

    Birkeland, A C; Owen, J H; Prince, M E

    2015-11-01

    Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor cells with demonstrated ability for tumor growth, invasion, metastasis, and resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive yet elusive therapeutic option, with the goal of increasing specificity and effectiveness in tumor eradication, as well as decreasing off-target or systemic toxicity. Research into further characterization and targeted therapy toward head and neck CSCs is an active and rapidly evolving field. This review discusses the current state of research into therapy against head and neck CSCs and future directions for targeted therapy.

  15. Modeling neck mobility in fossil turtles.

    PubMed

    Werneburg, Ingmar; Hinz, Juliane K; Gumpenberger, Michaela; Volpato, Virginie; Natchev, Nikolay; Joyce, Walter G

    2015-05-01

    Turtles have the unparalleled ability to retract their heads and necks within their shell but little is known about the evolution of this trait. Extensive analysis of neck mobility in turtles using radiographs, CT scans, and morphometry reveals that basal turtles possessed less mobility in the neck relative to their extant relatives, although the anatomical prerequisites for modern mobility were already established. Many extant turtles are able to achieve hypermobility by dislocating the central articulations, which raises cautions about reconstructing the mobility of fossil vertebrates. A 3D-model of the Late Triassic turtle Proganochelys quenstedti reveals that this early stem turtle was able to retract its head by tucking it sideways below the shell. The simple ventrolateral bend seen in this stem turtle, however, contrasts with the complex double-bend of extant turtles. The initial evolution of neck retraction therefore occurred in a near-synchrony with the origin of the turtle shell as a place to hide the unprotected neck. In this early, simplified retraction mode, the conical osteoderms on the neck provided further protection.

  16. M-cone opsin gene number does not correlate with variation in L/M-cone sensitivity.

    PubMed

    Knau, H; Kremers, J; Schmidt, H-J; Wolf, S; Wissinger, B; Sharpe, L T

    2002-07-01

    Molecular genetic studies demonstrate that the human cone opsin gene array on the q-arm of the X-chromosome typically consists of one long-wave-sensitive (L) cone opsin gene and from one to several middle-wave-sensitive (M) cone opsin genes. Although the presence of the single L-cone opsin gene and at least one M-cone opsin gene is essential for normal red-green colour discrimination, the function of the additional M-cone opsin genes is still unclear. To investigate whether any variations in phenotype correlate with differences in the number of M-cone opsin genes, we selected 13 normal trichromat males, for whom four independent molecular techniques have exactly determined their number of M-cone opsin genes, ranging from one to four. Their phenotype was characterized by estimating their foveal L- to M-cone ratio from heterochromatic flicker photometric (HFP) thresholds, by measuring the wavelength corresponding to their 'unique yellow', and by determining their L- and M-cone modulation thresholds (CMTs). No correlation was found between these psychophysical measures and the number of M-cone opsin genes. Although, we found a reasonably good correlation between the L/M-cone ratios based on HFP and on CMT, we did not find any correlation between the estimated L/M-cone ratios and the settings of 'unique yellow'. Our results accord with previous molecular genetic studies that suggest that only the first two genes in the X-linked opsin gene array are expressed.

  17. Comparison of cone and cone shell configuration for depth sensitive fluorescence measurements in turbid media

    NASA Astrophysics Data System (ADS)

    Ong, Yi Hong; Liu, Quan

    2014-03-01

    We have developed a novel cone shell illumination and detection configurations using combination of axicon lenses for depth sensitive fluorescence spectroscopy. The probe was demonstrated experimentally to be able to selectively detecting fluorescence from different depths from a two-layered turbid agar phantom. In addition to enhanced contrast of subsurface fluorescence measurement as compared to a conventional cone configuration implemented by a microscope objective lens, the axicon lenses based setup eliminated the need of moving the objective lens up or down to achieve depth sensitive measurements, which effectively improves the consistency of optical coupling thus would be preferred in a clinical setting.

  18. Tantalum cones and bone defects in revision total knee arthroplasty.

    PubMed

    Boureau, F; Putman, S; Arnould, A; Dereudre, G; Migaud, H; Pasquier, G

    2015-04-01

    Management of bone loss is a major challenge in revision total knee arthroplasty (TKA). The development of preformed porous tantalum cones offers new possibilities, because they seem to have biological and mechanical qualities that facilitate osseointegration. Compared to the original procedure, when metaphyseal bone defects are too severe, a single tantalum cone may not be enough and we have developed a technique that could extend the indications for this cone in these cases. We used 2 cones to fill femoral bone defects in 7 patients. There were no complications due to wear of the tantalum cones. Radiological follow-up did show any migration or loosening. The short-term results confirm the interest of porous tantalum cones and suggest that they can be an alternative to allografts or megaprostheses in case of massive bone defects.

  19. Pulsar average waveforms and hollow cone beam models

    NASA Technical Reports Server (NTRS)

    Backer, D. C.

    1975-01-01

    An analysis of pulsar average waveforms at radio frequencies from 40 MHz to 15 GHz is presented. The analysis is based on the hypothesis that the observer sees one cut of a hollow-cone beam pattern and that stationary properties of the emission vary over the cone. The distributions of apparent cone widths for different observed forms of the average pulse profiles (single, double/unresolved, double/resolved, triple and multiple) are in modest agreement with a model of a circular hollow-cone beam with random observer-spin axis orientation, a random cone axis-spin axis alignment, and a small range of physical hollow-cone parameters for all objects.

  20. Heating distribution comparison between asymmetric and symmetric blunt cones

    NASA Technical Reports Server (NTRS)

    Stewart, D. A.; Kolodziej, P.

    1986-01-01

    An experiment was performed to compare the heating distribution between symmetric and asymmetric large-angle blunt cones, with cone angles of 100, 120, and 140 deg. These hot-wall data were obtained from models made from typical thermal protection insulation for proposed aeroassisted orbital transfer vehicles. Experimental data are compared with predictions using a boundary-layer integral matrix procedure with kinetics to determine how well the heating distribution over an asymmetric cone could be approximated using axisymmetric solutions for a cone and spherical segment. In addition, a relationship between the stagnation-point heat-transfer rate and the bow-shock standoff distance for these cones is discussed. The heat-distribution data from the symmetric and asymmetric cones were very similar. Numerical results compared well with the measured wall temperatures at the stagnation point but slightly underpredicted them over the conical portion of the models.

  1. Rod-cone interactions and analysis of retinal disease.

    PubMed Central

    Arden, G B; Hogg, C R

    1985-01-01

    Cone flicker threshold rises as the rods dark adapt, though the cone threshold to continuous light remains constant. The rise is normally about 1 log unit, but in certain patients who complain of night blindness it may be as great as 2.5 log units. In these persons the kinetics of the rod-cone interaction are those of the recovery of rod sensitivity. The rods impose a low-pass filter on the cones. This effect is absent in congenital nyctalopia and X-linked retinoschisis. We suggest that cone flicker is maintained through a feedback system involving horizontal cells, and when the rod dark current returns in dark adaptation this feedback is altered. Rod cone interaction thus tests rod dark current, and cases of abnormal interaction in patients with retinitis pigmentosa occur, which indicate that the transduction mechanism and the membrane dark current may be differentially affected. Images PMID:3873959

  2. Partial cone calix[4]arene-crown-6-ethers

    SciTech Connect

    Das, G.; Sachleben, R.A.; Descazeaud, T.; Bryan, J.C.; Moyer, B.A.

    1997-12-31

    Partial cone calix[4] arene crown ethers represents a new category of lariat ethers. In general, calix arene crown ethers have been previously shown to be efficient extractants for metal cations. Appropriately substituted cone and 1, 3-alt conformers of calix crowns exhibit selectivities for Na{sup +} and Cs{sup +}, respectively. The partial cone conformers have not been as throughly studied. We have developed an efficient method of synthesis of partial cone calix[4]arene-crown ethers and have synthesized a variety of partial cone calix[4]arene crowns. Solution and solid-state structures of representative examples have been determined by {sup 1}H NMR spectroscopy and X-ray crystallography. Relative affinities of these partial cone calix[4]arene crowns for alkali metal ions have been investigated by solvent extraction techniques.

  3. A new model for cone sheet emplacement: data from the Isle of Skye (UK) and numerical modeling

    NASA Astrophysics Data System (ADS)

    Tibaldi, A.; Bistacchi, A.; Pasquare, F.; Rust, D.

    2009-12-01

    The mechanics of intrusive sheet propagation from a shallow magma chamber is of paramount importance in understanding eruptive processes and the internal growth and stability of volcanoes. In order to contribute to these topics, we went back to the classical Cuillins cone sheet complex on the Isle of Skye, where the roots of a Tertiary basaltic volcano are exposed (Anderson, 1936, Proceedings of the Royal Society of Edinburgh, 56, 128-157), and performed a new field and numerical modeling study. Our structural data show that, in the Cuillins complex, inward dipping cone sheets have a constant average dip angle (ca. 45°) and show either pure dilational or hybrid shear kinematics. These might be general features of cone sheet complexes, since they are in agreement with results from Gran Canaria (Schirnick, van den Bogaard, Schmincke, 1999, Geology, 27, 207-210). In order to explain these data, we developed a set of finite element models, which for the first time include an elasto-plastic rheology and consider the total stress field deriving from gravity, tectonics and magma chamber overpressure. Numerical modeling shows that only in the case of a shallow oblate magma chamber may cone sheets be predicted for realistic magma overpressure values (ca. 10-20 MPa). In contrast, cone sheets should not develop, for realistic overpressures (< 40 MPa), with sub-spherical or prolate magma chambers. In any case, cone sheets appear to be confined within a distance from the central axis of about 1-1.2 diameters of the magma chamber and in the volume immediately above it, whilst radial dikes dominate beyond the 1-1.2 diameter limit. When a realistic regional stress field is considered, the radial dikes progressively merge into a regional swarm of parallel dikes, oriented perpendicular to the least compressive stress axis. Of significance for active volcanoes, the following points can be highlighted: (i) the association of cone sheets and radial dikes is likely to be linked to a

  4. Photovoltage of Rods and Cones in the Macaque Retina

    NASA Astrophysics Data System (ADS)

    Schneeweis, David M.; Schnapf, Julie L.

    1995-05-01

    The kinetics, gain, and reliability of light responses of rod and cone photoreceptors are important determinants of overall visual sensitivity. In voltage recordings from photoreceptors in an intact primate retina, rods were found to be functionally isolated from each other, unlike the tightly coupled rods of cold-blooded vertebrates. Cones were observed to receive excitatory input from rods, which indicates that the cone pathway also processes rod signals. This input might be expected to degrade the spatial resolution of mesopic vision.

  5. The Role of p53 and MDM2 in Head and Neck Cancer

    PubMed Central

    Denaro, N.; Lo Nigro, C.; Natoli, G.; Russi, E. G.; Adamo, V.; Merlano, M. C.

    2011-01-01

    Head and neck cancer is a complex disorder that includes mostly squamous cell carcinomas that can develop in the throat, larynx, nose, sinuses, and mouth. Etiopathogenesis is due to tobacco and alcohol consumption and to infection by human papillomavirus (HPV) type 16/18. Tumors often develop within preneoplastic fields of genetically altered cells. Most head and neck cancers result from multistep accumulation of genetic alterationsm resulting in clonal outgrowth of transformed cells. These DNA changes are caused by a variety of mechanisms like endogenous mutations and exogenous mutations. Dysregulated molecular pathway includes alterations of critical inhibitor of cyclin CDK complexes, inactivating mutations of p53 gene, and activation of oncogenes and growth factors. This paper attempts to review the role of p53 and MDM2 genetic aberrations and pathways in head and neck cancer. PMID:23724261

  6. Comparison of electromyographic activity and range of neck motion in violin students with and without neck pain during playing.

    PubMed

    Park, Kyue-nam; Kwon, Oh-yun; Ha, Sung-min; Kim, Su-jung; Choi, Hyun-jung; Weon, Jong-hyuck

    2012-12-01

    Neck pain is common in violin students during a musical performance. The purpose of this study was to compare electromyographic (EMG) activity in superficial neck muscles with neck motion when playing the violin as well as neck range of motion (ROM) at rest, between violin students with and without neck pain. Nine violin students with neck pain and nine age- and gender-matched subjects without neck pain were recruited. Muscle activity of the bilateral upper trapezius, sternocleidomastoid, and superficial cervical extensor muscles was measured using surface EMG. Kinematic data on neck motion while playing and active neck ROM were also measured using a three-dimensional motion analysis system. Independent t-tests were used to compare EMG activity with kinematic data between groups. These analyses revealed that while playing, both the angle of left lateral bending and leftward rotation of the cervical spine were significantly greater in the neck pain group than among those without neck pain. Similarly, EMG activity of the left upper trapezius, both cervical extensors, and both sternocleidomastoid muscles were significantly greater in the neck pain group. The active ROM of left axial rotation was significantly lower in the neck pain group. These results suggest that an asymmetric playing posture and the associated increased muscle activity as well as decreased neck axial rotation may contribute to neck pain in violin students. PMID:23247874

  7. Comparison of electromyographic activity and range of neck motion in violin students with and without neck pain during playing.

    PubMed

    Park, Kyue-nam; Kwon, Oh-yun; Ha, Sung-min; Kim, Su-jung; Choi, Hyun-jung; Weon, Jong-hyuck

    2012-12-01

    Neck pain is common in violin students during a musical performance. The purpose of this study was to compare electromyographic (EMG) activity in superficial neck muscles with neck motion when playing the violin as well as neck range of motion (ROM) at rest, between violin students with and without neck pain. Nine violin students with neck pain and nine age- and gender-matched subjects without neck pain were recruited. Muscle activity of the bilateral upper trapezius, sternocleidomastoid, and superficial cervical extensor muscles was measured using surface EMG. Kinematic data on neck motion while playing and active neck ROM were also measured using a three-dimensional motion analysis system. Independent t-tests were used to compare EMG activity with kinematic data between groups. These analyses revealed that while playing, both the angle of left lateral bending and leftward rotation of the cervical spine were significantly greater in the neck pain group than among those without neck pain. Similarly, EMG activity of the left upper trapezius, both cervical extensors, and both sternocleidomastoid muscles were significantly greater in the neck pain group. The active ROM of left axial rotation was significantly lower in the neck pain group. These results suggest that an asymmetric playing posture and the associated increased muscle activity as well as decreased neck axial rotation may contribute to neck pain in violin students.

  8. Dynamics on the cone: Closed orbits and superintegrability

    SciTech Connect

    Brihaye, Y.; Kosiński, P.

    2014-05-15

    The generalization of Bertrand’s theorem to the case of the motion of point particle on the surface of a cone is presented. The superintegrability of such models is discussed. The additional integrals of motion are analysed for the case of Kepler and harmonic oscillator potentials. -- Highlights: •Bertrand’s theorem is generalized to the case of the motion on a cone. •The superintegrability of the dynamics on a cone is discussed. •The W-algebra of integrals of motion for Kepler and harmonic oscillator problems on a cone is derived.

  9. Associating color appearance with the cone chromaticity space.

    PubMed

    Cao, Dingcai; Pokorny, Joel; Smith, Vivianne C

    2005-07-01

    A cone chromaticity space, a transform of a colorimetric specification system into coordinates that represent cone excitations, does not provide color appearance information. Boynton and Olson (Color Research and Application 12, 94-105, 1987) gathered color naming for the 424 Optical Society of America Uniform Color Scales (OSA-UCS) color samples. Here, a computational algorithm was developed that converts OSA-UCS sample values into L, M, S cone excitations based on the 1964 CIE 10 degrees Standard Observer. This makes it possible to plot the cone chromaticities associated with the eight color names used by Boynton and Olsen's observers to describe the non-dark appearing colors.

  10. Psychophysical definition of S-cone stimuli in the macaque

    PubMed Central

    Hall, Nathan; Colby, Carol

    2013-01-01

    We used the perceptual reports of nonhuman primates to perform psychophysical calibrations of S-cone isolating stimuli. S-cone stimuli were calibrated separately at several spatial locations for each monkey. To do this we exploited the effect of transient tritanopia, which causes a selective decrease of sensitivity in the observer's S-cone channel. At the start of each transient tritanopia trial monkeys were visually adapted to a bright yellow background. This type of adaptation is known to induce transient tritanopia. Calibrated S-cone isolating stimuli were determined by finding a near S-cone stimulus whose detection threshold was maximally elevated during transient tritanopia. At the start of each control trial, monkeys were adapted to a bright white background. In these trials, monkeys' detection thresholds for near S-cone stimuli were unchanged. We found that S-cone isolating stimuli could be determined at most locations tested in each monkey. Calibrated S-cone stimuli were particular to both spatial location and animal. To understand the visual system as a whole in vivo requires physiological methods not possible in human subjects. The present results open the door to novel behavioral and physiological experiments by showing that S-cone isolating stimuli can be calibrated in monkeys. PMID:23412341

  11. Femoral neck shortening after internal fixation of a femoral neck fracture.

    PubMed

    Zielinski, Stephanie M; Keijsers, Noël L; Praet, Stephan F E; Heetveld, Martin J; Bhandari, Mohit; Wilssens, Jean Pierre; Patka, Peter; Van Lieshout, Esther M M

    2013-07-01

    This study assesses femoral neck shortening and its effect on gait pattern and muscle strength in patients with femoral neck fractures treated with internal fixation. Seventy-six patients from a multicenter randomized controlled trial participated. Patient characteristics and Short Form 12 and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected. Femoral neck shortening, gait parameters, and maximum isometric forces of the hip muscles were measured and differences between the fractured and contralateral leg were calculated. Variables of patients with little or no shortening, moderate shortening, and severe shortening were compared using univariate and multivariate analyses. Median femoral neck shortening was 1.1 cm. Subtle changes in gait pattern, reduced gait velocity, and reduced abductor muscle strength were observed. Age, weight, and Pauwels classification were risk factors for femoral neck shortening. Femoral neck shortening decreased gait velocity and seemed to impair gait symmetry and physical functioning. In conclusion, internal fixation of femoral neck fractures results in permanent physical limitations. The relatively young and healthy patients in our study seem capable of compensating. Attention should be paid to femoral neck shortening and proper correction with a heel lift, as inadequate correction may cause physical complaints and influence outcome. PMID:23823040

  12. Light-cone quantization and QCD phenomenology

    SciTech Connect

    Brodsky, S.J.; Robertson, D.G.

    1995-12-31

    In principle, quantum chromodynamics provides a fundamental description of hadronic and nuclear structure and dynamics in terms of their elementary quark and gluon degrees of freedom. In practice, the direct application of QCD to reactions involving the structure of hadrons is extremely complex because of the interplay of nonperturbative effects such as color confinement and multi-quark coherence. A crucial tool in analyzing such phenomena is the use of relativistic light-cone quantum mechanics and Fock state methods to provide tractable and consistent treatments of relativistic many-body systems. In this article we present an overview of this formalism applied to QCD, focusing in particular on applications to the final states in deep inelastic lepton scattering that will be relevant for the proposed European Laboratory for Electrons (ELFE), HERMES, HERA, SLAC, and CEBAF. We begin with a brief introduction to light-cone field theory, stressing how it many allow the derivation of a constituent picture, analogous to the constituent quark model, from QCD. We then discuss several applications of the light-cone Fock state formalism to QCD phenomenology. The Fock state representation includes all quantum fluctuations of the hadron wavefunction, including far off-shell configurations such as intrinsic charm and, in the case of nuclei, hidden color. In some applications, such as exclusive processes at large momentum transfer, one can make first-principle predictions using factorization theorems which separate the hard perturbative dynamics from the nonpertubative physics associated with hadron binding. The Fock state components of the hadron with small transverse size, which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions. Thus QCD predicts minimal absorptive corrections, i.e., color transparency for quasi-elastic exclusive reactions in nuclear targets at large momentum transfer.

  13. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    SciTech Connect

    Yan, Hao E-mail: xun.jia@utsouthwestern.edu; Shi, Feng; Jiang, Steve B.; Jia, Xun E-mail: xun.jia@utsouthwestern.edu; Wang, Xiaoyu; Cervino, Laura; Bai, Ti; Folkerts, Michael

    2014-11-01

    Purpose: Compressed sensing (CS)-based iterative reconstruction (IR) techniques are able to reconstruct cone-beam CT (CBCT) images from undersampled noisy data, allowing for imaging dose reduction. However, there are a few practical concerns preventing the clinical implementation of these techniques. On the image quality side, data truncation along the superior–inferior direction under the cone-beam geometry produces severe cone artifacts in the reconstructed images. Ring artifacts are also seen in the half-fan scan mode. On the reconstruction efficiency side, the long computation time hinders clinical use in image-guided radiation therapy (IGRT). Methods: Image quality improvement methods are proposed to mitigate the cone and ring image artifacts in IR. The basic idea is to use weighting factors in the IR data fidelity term to improve projection data consistency with the reconstructed volume. In order to improve the computational efficiency, a multiple graphics processing units (GPUs)-based CS-IR system was developed. The parallelization scheme, detailed analyses of computation time at each step, their relationship with image resolution, and the acceleration factors were studied. The whole system was evaluated in various phantom and patient cases. Results: Ring artifacts can be mitigated by properly designing a weighting factor as a function of the spatial location on the detector. As for the cone artifact, without applying a correction method, it contaminated 13 out of 80 slices in a head-neck case (full-fan). Contamination was even more severe in a pelvis case under half-fan mode, where 36 out of 80 slices were affected, leading to poorer soft tissue delineation and reduced superior–inferior coverage. The proposed method effectively corrects those contaminated slices with mean intensity differences compared to FDK results decreasing from ∼497 and ∼293 HU to ∼39 and ∼27 HU for the full-fan and half-fan cases, respectively. In terms of efficiency boost

  14. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    PubMed Central

    Yan, Hao; Wang, Xiaoyu; Shi, Feng; Bai, Ti; Folkerts, Michael; Cervino, Laura; Jiang, Steve B.; Jia, Xun

    2014-01-01

    Purpose: Compressed sensing (CS)-based iterative reconstruction (IR) techniques are able to reconstruct cone-beam CT (CBCT) images from undersampled noisy data, allowing for imaging dose reduction. However, there are a few practical concerns preventing the clinical implementation of these techniques. On the image quality side, data truncation along the superior–inferior direction under the cone-beam geometry produces severe cone artifacts in the reconstructed images. Ring artifacts are also seen in the half-fan scan mode. On the reconstruction efficiency side, the long computation time hinders clinical use in image-guided radiation therapy (IGRT). Methods: Image quality improvement methods are proposed to mitigate the cone and ring image artifacts in IR. The basic idea is to use weighting factors in the IR data fidelity term to improve projection data consistency with the reconstructed volume. In order to improve the computational efficiency, a multiple graphics processing units (GPUs)-based CS-IR system was developed. The parallelization scheme, detailed analyses of computation time at each step, their relationship with image resolution, and the acceleration factors were studied. The whole system was evaluated in various phantom and patient cases. Results: Ring artifacts can be mitigated by properly designing a weighting factor as a function of the spatial location on the detector. As for the cone artifact, without applying a correction method, it contaminated 13 out of 80 slices in a head-neck case (full-fan). Contamination was even more severe in a pelvis case under half-fan mode, where 36 out of 80 slices were affected, leading to poorer soft tissue delineation and reduced superior–inferior coverage. The proposed method effectively corrects those contaminated slices with mean intensity differences compared to FDK results decreasing from ∼497 and ∼293 HU to ∼39 and ∼27 HU for the full-fan and half-fan cases, respectively. In terms of efficiency boost

  15. Cone Beam Computed Tomography - Know its Secrets

    PubMed Central

    Kumar, Mohan; Shanavas, Muhammad; Sidappa, Ashwin; Kiran, Madhu

    2015-01-01

    Cone-beam computed tomography (CBCT) is an advanced imaging modality that has high clinical applications in the field of dentistry. CBCT proved to be a successful investigative modality that has been used for dental and maxillofacial imaging. Radiation exposure dose from CBCT is 10 times less than from conventional CT scans during maxillofacial exposure. Furthermore, CBCT is highly accurate and can provide a three-dimensional volumetric data in axial, sagittal and coronal planes. This article describes the basic technique, difference in CBCT from CT and main clinical applications of CBCT. PMID:25859112

  16. Bistatic scattering from a cone frustum

    NASA Technical Reports Server (NTRS)

    Ebihara, W.; Marhefka, R. J.

    1986-01-01

    The bistatic scattering from a perfectly conducting cone frustum is investigated using the Geometrical Theory of Diffraction (GTD). The first-order GTD edge-diffraction solution has been extended by correcting for its failure in the specular region off the curved surface and in the rim-caustic regions of the endcaps. The corrections are accomplished by the use of transition functions which are developed and introduced into the diffraction coefficients. Theoretical results are verified in the principal plane by comparison with the moment method solution and experimental measurements. The resulting solution for the scattered fields is accurate, easy to apply, and fast to compute.

  17. Stability of drift-cyclotron loss-cone waves in H-mode plasmas

    DOE PAGESBeta

    Farmer, W. A.; Morales, G. J.

    2016-05-24

    The drift-cyclotron loss-cone mode was first studied in mirror machines. In such devices, particles with small pitch angles are not confined, creating a hole in the velocity distribution function that is a source of free energy and leads to micro-instabilities in the cyclotron-range of frequencies. In the edge region of tokamak devices operating under H-mode conditions, ion loss also occurs. In this case, gradient drift carries ions moving opposite to the plasma current preferentially into the divertor, creating a one-sided loss cone. A simple analysis shows that for the quiescent H-mode plasmas in DIII-D the critical gradient for instability ismore » exceeded within 2 cm of the separatrix, and the maximum growth rate at the separatrix is 3×107 s-1.« less

  18. Stability of drift-cyclotron loss-cone waves in H-mode plasmas

    NASA Astrophysics Data System (ADS)

    Farmer, W. A.; Morales, G. J.

    2016-06-01

    The drift-cyclotron loss-cone mode was first studied in mirror machines. In such devices, particles with small pitch angles are not confined, creating a hole in the velocity distribution function that is a source of free energy and leads to micro-instabilities in the cyclotron-range of frequencies. In the edge region of tokamak devices operating under H-mode conditions, ion loss also occurs. In this case, gradient drift carries ions moving opposite to the plasma current preferentially into the divertor, creating a one-sided loss cone. A simple analysis shows that for the quiescent H-mode plasmas in DIII-D the critical gradient for instability is exceeded within 2 cm of the separatrix, and the maximum growth rate at the separatrix is 3  ×  107 s‑1.

  19. Repositioning accuracy of two different mask systems-3D revisited: Comparison using true 3D/3D matching with cone-beam CT

    SciTech Connect

    Boda-Heggemann, Judit . E-mail: judit.boda-heggemann@radonk.ma.uni-heidelberg.de; Walter, Cornelia; Rahn, Angelika; Wertz, Hansjoerg; Loeb, Iris; Lohr, Frank; Wenz, Frederik

    2006-12-01

    Purpose: The repositioning accuracy of mask-based fixation systems has been assessed with two-dimensional/two-dimensional or two-dimensional/three-dimensional (3D) matching. We analyzed the accuracy of commercially available head mask systems, using true 3D/3D matching, with X-ray volume imaging and cone-beam CT. Methods and Materials: Twenty-one patients receiving radiotherapy (intracranial/head-and-neck tumors) were evaluated (14 patients with rigid and 7 with thermoplastic masks). X-ray volume imaging was analyzed online and offline separately for the skull and neck regions. Translation/rotation errors of the target isocenter were analyzed. Four patients were treated to neck sites. For these patients, repositioning was aided by additional body tattoos. A separate analysis of the setup error on the basis of the registration of the cervical vertebra was performed. The residual error after correction and intrafractional motility were calculated. Results: The mean length of the displacement vector for rigid masks was 0.312 {+-} 0.152 cm (intracranial) and 0.586 {+-} 0.294 cm (neck). For the thermoplastic masks, the value was 0.472 {+-} 0.174 cm (intracranial) and 0.726 {+-} 0.445 cm (neck). Rigid masks with body tattoos had a displacement vector length in the neck region of 0.35 {+-} 0.197 cm. The intracranial residual error and intrafractional motility after X-ray volume imaging correction for rigid masks was 0.188 {+-} 0.074 cm, and was 0.134 {+-} 0.14 cm for thermoplastic masks. Conclusions: The results of our study have demonstrated that rigid masks have a high intracranial repositioning accuracy per se. Given the small residual error and intrafractional movement, thermoplastic masks may also be used for high-precision treatments when combined with cone-beam CT. The neck region repositioning accuracy was worse than the intracranial accuracy in both cases. However, body tattoos and image guidance improved the accuracy. Finally, the combination of both mask

  20. Increased efficiency of short-pulse laser-generated proton beams from novel flat-top cone targets

    SciTech Connect

    Flippo, K. A.; Gautier, D. C.; Kline, J. L.; Albright, B.; Johnson, R. P.; Letzring, S.; Shimada, T.; Fernandez, J. C.; Hegelich, B. M.; D'Humieres, E.; Rassuchine, J.; Bakeman, M.; Renard-LeGalloudec, N.; Sentoku, Y.; Cowan, T. E.; Gaillard, S. A.; Schollmeier, M.; Nuernberg, F.; Harres, K.; Roth, M.

    2008-05-15

    Ion-driven fast ignition (IFI) may have significant advantages over electron-driven FI due to the potentially large reduction in the amount of energy required for the ignition beam and the laser driver. Recent experiments at the Los Alamos National Laboratory's Trident facility employing novel Au flat-top cone targets have produced a fourfold increase in laser-energy to ion-energy efficiency, a 13-fold increase in the number of ions above 10 MeV, and a few times increase in the maximum ion energy compared to Au flat-foil targets. Compared to recently published scaling laws, these gains are even greater. If the efficiency scales with intensity in accordance to flat-foil scaling, then, with little modification, these targets can be used to generate the pulse of ions needed to ignite thermonuclear fusion in the fast ignitor scheme. A proton energy of at least 30 MeV was measured from the flat-top cone targets, and particle-in-cell (PIC) simulations show that the maximum cutoff energy may be as high as 40-45 MeV at modest intensity of 1x10{sup 19} W/cm{sup 2} with 20 J in 600 fs. Simulations indicate that the observed energy and efficiency increase can be attributed to the cone target's ability to guide laser light into the neck to produce hot electrons and transport these electrons to the flat-top of the cone where they can be heated to much higher temperatures, creating a hotter, denser sheath. The PIC simulations also elucidate the critical parameters for obtaining superior proton acceleration such as the dependence on laser contrast/plasma prefill, as well as longitudinal and transverse laser pointing, and cone geometry. These novel cones have the potential to revolutionize inertial confinement fusion target design and fabrication via their ability to be mass produced. In addition, they could have an impact on the general physics community studying basic electron and radiation transport phenomena or as better sources of particle beams to study equations of state

  1. Microcomputed tomography and shock microdeformation studies on shatter cones

    NASA Astrophysics Data System (ADS)

    Zaag, Patrice Tristan; Reimold, Wolf Uwe; Hipsley, Christy Anna

    2016-08-01

    One of the aspects of impact cratering that are still not fully understood is the formation of shatter cones and related fracturing phenomena. Yet, shatter cones have been applied as an impact-diagnostic criterion for decades without the role of shock waves and target rock defects in their formation having been elucidated ever. We have tested the application of the nondestructive microcomputed tomography (μCT) method to visualize the interior of shatter cones in order to possibly resolve links between fracture patterns and shatter cone surface features (striations and intervening "valleys"). Shatter-coned samples from different impact sites and in different lithologies were investigated for their μCT suitability, with a shatter cone in sandstone from the Serra da Cangalha impact structure (Brazil) remaining as the most promising candidate because of the fracture resolution achieved. To validate the obtained CT data, the scanned specimen was cut into three orthogonal sets of thin sections. Scans with 13 μm resolution were obtained. μCT scans and microscopic analysis unraveled an orientation of subplanar fractures and related fluid inclusion trails, and planar fracture (PF) orientations in the interior of shatter cones. Planar deformation features (PDF) were observed predominantly near the shatter cone surface. Previously undescribed varieties of feather features (FF), in the form of lamellae emanating from curviplanar and curved fractures, as well as an "arrowhead"-like FF development with microlamellae originating from both sides of a PF, were observed. The timing of shatter cone formation was investigated by establishing temporal relations to the generation of various shock microscopic effects. Shatter cones are, thus, generated post- or syn-formation of PF, FF, subplanar fractures, and PDF. The earliest possible time for shatter cone formation is during the late stage of the compressional phase, that is, shock wave passage, of an impact event.

  2. Flexibility along the neck of the ostrich (Struthio camelus) and consequences for the reconstruction of dinosaurs with extreme neck length.

    PubMed

    Dzemski, Gordon; Christian, Andreas

    2007-08-01

    The gross morphology and the flexibility along the neck of the ostrich (Struthio camelus) were examined using fresh tissue as well as neck skeletons. The results of the morphologic studies were compared with results from observations of living ostriches. The investigation was focused on differences in the morphology and the function between different sections of the neck. Additionally, the function of major dorsal neck ligaments was examined, including measurements of force-strain-relations. Comparative studies of giraffes (Giraffa camelopardalis) and camels (Camelus bactrianus) were conducted to find relations between the flexibility along the neck and the general feeding strategy. The examinations revealed that the neck of the ostrich can be divided into four sections with different functions. The first is the atlas-axis-complex which is responsible for torsion. The adjacent cranial section of the neck is flexible in dorsoventral and lateral directions but this part of the neck is usually kept straight at rest and during feeding. Dorsoventral flexibility is highest in the middle section of the neck, whereas the base of the neck is primarily used for lateral excursions of the neck. For giraffes and camels, the posture and utilization of the neck are also reflected in the flexibility of the neck. For all three species, it is possible to reconstruct the pattern of flexibility of the neck by using the neck skeletons alone. Therefore, it appears reasonable to reconstruct the neck utilization and the feeding strategies of dinosaurs with long necks by deriving the flexibility of the neck from preserved vertebrae. For Diplodocus carnegii the neck posture and the feeding strategy were reconstructed. Two neck regions, one around the 9th neck vertebra and the second at the base of the neck, indicate that Diplodocus, like the ostrich, adopted different neck postures. The neck was probably kept very low during feeding. During interruptions of the feeding, e.g., in an alert

  3. Real Gas/Blunt Cone. Phase 2

    NASA Technical Reports Server (NTRS)

    Deiwert, George S.; Eitelberg, Georg

    1998-01-01

    In this chapter recent activity in real-gas database definition and code validation will be summarized. In the Phase I report of the Working Group (WG) 181, aerothermodynamic problems were classified, for purpose of discussion, into seven types: aerodynamic parameters, viscous/shock interaction, boundary-layer transition, forebody-heating/heat-transfer, radiation and ablation, lee and base-region flow, and low-density flow. Several of these problem types were the subject of various chapters of the Phase 1 report describing real-gas effects and ground test facility issues. In this chapter some background and objectives outlined in the real-Gas effects Chapter V of the Phase 1 report will be reviewed. The results of the blunt cone test campaign developed under the auspices of the WG18 activity to study real-gas phenomena will be summarized, including the experimental and computational programs, issues and questions, and recommendations. Further, recent progress in other real-gas areas beyond the blunt cone test campaign will be discussed. Finally, a summary in which the present status of our understanding of real-gas issues will be presented.

  4. Light-cone quantization and hadron structure

    SciTech Connect

    Brodsky, S.J.

    1996-04-01

    Quantum chromodynamics provides a fundamental description of hadronic and nuclear structure and dynamics in terms of elementary quark and gluon degrees of freedom. In practice, the direct application of QCD to reactions involving the structure of hadrons is extremely complex because of the interplay of nonperturbative effects such as color confinement and multi-quark coherence. In this talk, the author will discuss light-cone quantization and the light-cone Fock expansion as a tractable and consistent representation of relativistic many-body systems and bound states in quantum field theory. The Fock state representation in QCD includes all quantum fluctuations of the hadron wavefunction, including fax off-shell configurations such as intrinsic strangeness and charm and, in the case of nuclei, hidden color. The Fock state components of the hadron with small transverse size, which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions. Thus QCD predicts minimal absorptive corrections, i.e., color transparency for quasi-elastic exclusive reactions in nuclear targets at large momentum transfer. In other applications, such as the calculation of the axial, magnetic, and quadrupole moments of light nuclei, the QCD relativistic Fock state description provides new insights which go well beyond the usual assumptions of traditional hadronic and nuclear physics.

  5. Scatter corrections for cone beam optical CT

    NASA Astrophysics Data System (ADS)

    Olding, Tim; Holmes, Oliver; Schreiner, L. John

    2009-05-01

    Cone beam optical computed tomography (OptCT) employing the VISTA scanner (Modus Medical, London, ON) has been shown to have significant promise for fast, three dimensional imaging of polymer gel dosimeters. One distinct challenge with this approach arises from the combination of the cone beam geometry, a diffuse light source, and the scattering polymer gel media, which all contribute scatter signal that perturbs the accuracy of the scanner. Beam stop array (BSA), beam pass array (BPA) and anti-scatter polarizer correction methodologies have been employed to remove scatter signal from OptCT data. These approaches are investigated through the use of well-characterized phantom scattering solutions and irradiated polymer gel dosimeters. BSA corrected scatter solutions show good agreement in attenuation coefficient with the optically absorbing dye solutions, with considerable reduction of scatter-induced cupping artifact at high scattering concentrations. The application of BSA scatter corrections to a polymer gel dosimeter lead to an overall improvement in the number of pixel satisfying the (3%, 3mm) gamma value criteria from 7.8% to 0.15%.

  6. Biomechanical based image registration for head and neck radiation treatment

    NASA Astrophysics Data System (ADS)

    Al-Mayah, Adil; Moseley, Joanne; Hunter, Shannon; Velec, Mike; Chau, Lily; Breen, Stephen; Brock, Kristy

    2010-02-01

    Deformable image registration of four head and neck cancer patients was conducted using biomechanical based model. Patient specific 3D finite element models have been developed using CT and cone beam CT image data of the planning and a radiation treatment session. The model consists of seven vertebrae (C1 to C7), mandible, larynx, left and right parotid glands, tumor and body. Different combinations of boundary conditions are applied in the model in order to find the configuration with a minimum registration error. Each vertebra in the planning session is individually aligned with its correspondence in the treatment session. Rigid alignment is used for each individual vertebra and to the mandible since deformation is not expected in the bones. In addition, the effect of morphological differences in external body between the two image sessions is investigated. The accuracy of the registration is evaluated using the tumor, and left and right parotid glands by comparing the calculated Dice similarity index of these structures following deformation in relation to their true surface defined in the image of the second session. The registration improves when the vertebrae and mandible are aligned in the two sessions with the highest Dice index of 0.86+/-0.08, 0.84+/-0.11, and 0.89+/-0.04 for the tumor, left and right parotid glands, respectively. The accuracy of the center of mass location of tumor and parotid glands is also improved by deformable image registration where the error in the tumor and parotid glands decreases from 4.0+/-1.1, 3.4+/-1.5, and 3.8+/-0.9 mm using rigid registration to 2.3+/-1.0, 2.5+/-0.8 and 2.0+/-0.9 mm in the deformable image registration when alignment of vertebrae and mandible is conducted in addition to the surface projection of the body.

  7. The Double Cone: A Mechanical Paradox or a Geometrical Constraint?

    ERIC Educational Resources Information Center

    Gallitto, Aurelio Agliolo; Fiordilino, Emilio

    2011-01-01

    In the framework of the Italian National Plan "Lauree Scientifiche" (PLS) in collaboration with secondary schools, we have investigated the mechanical paradox of the double cone. We have calculated the geometric condition for obtaining an upward movement. Based on this result, we have built a mechanical model with a double cone made of aluminum…

  8. Galileo Spacecraft Scan Platform Celestial Pointing Cone Control Gain Redesign

    NASA Technical Reports Server (NTRS)

    In, C-H. C.; Hilbert, K. B.

    1994-01-01

    During September and October 1991, pictures of the Gaspra asteroid and neighboring stars were taken by the Galileo Optical Navigation (OPNAV) Team for the purpose of navigation the spacecraft for a successful Gaspra encounter. The star tracks in these pictures showed that the scan platform celestial pointing cone controller performed poorly in compensating for wobble-induced cone offsets.

  9. Implosion of indirectly driven reentrant cone shell target

    SciTech Connect

    R.B. Stephens; S.P. Hatchett; R.E. Turner; K.A. Tanaka; R. Kodama

    2003-10-31

    In an x-ray driven reentrant cone fast ignition target the x-ray spectrum contains a high energy component that casuses preheating of the reentrant cone and mixing of the gold into the collapsing shell. Direct laser drive might avoid this problem.

  10. The dynamics of a steady Taylor cone electrospray

    NASA Astrophysics Data System (ADS)

    Bell, Martin; Rutgers, Maarten A.

    1998-11-01

    A liquid drop at the tip of a needle will become conical if a high voltage is supplied to the needle. This is known as a Zeleny^1-Taylor^2 cone. Due to the finite conductivity of most liquids, a thin liquid jet will emerge from the cone tip. This jet can be thinner than 1 micrometer and move with speeds in excess of 10 m/s! The jet breaks up due to a Rayleigh instability into a stream of monodisperse droplets. The particles themselves carry charge and can cause the droplet stream to break up into a diverging conical spray. De La Mora^3 has calculated the relation between the liquid and spray cone angles, but less in known about the dynamics with which the droplets move from the initial jet into the final electrospray cone. We have observed electrosprayed droplets in a regime where the Taylor cone oscillates axisymmetrically, leading to an interrupted spray. By periodically driving the volume of the Taylor cone, and illuminating the spray stroboscopically at the same frequency, we can essentially `freeze' the evolution of a packet of droplets in the spray cone. We clearly observe the disintegration of the initial jet of droplets into a growing spherical cloud. The expanding clouds can be inscribed in the cone of an uninterrupted electrospray. ^1J. Zeleny, Phys. Rev. 3:69, (1914), ^2G.I. Taylor, J. Fluid Mech. 2:1, (1965) ^3J.F. De La Mora, J. Fluid Mech. 243:561, (1992)

  11. Dosimetry characteristics of metallic cones for intraoperative radiotherapy.

    PubMed

    Nyerick, C E; Ochran, T G; Boyer, A L; Hogstrom, K R

    1991-07-01

    Dosimetry data were obtained on the first dedicated linear accelerator of its type designed for electron intraoperative radiotherapy (IORT) within an operating room. The linear accelerator uses a high dose rate, 9 Gy.min-1, to reduce the treatment time. Its chrome-plated brass treatment cones, designed with straight ends and 22.5 degrees beveled ends, are not mechanically attached to the collimator head, but are aligned using a laser projection system. Dosimetry measurements were made for each combination of energy (6, 9, 12, 15, and 16 MeV), cone size (diameters range from 5 to 12 cm), and cone type (22.5 degrees beveled or straight). From these data, depth-dose curves, cone output, and air-gap correction factors were generated that allow the calculation of the monitor setting for delivering a prescribed dose at any depth for any irradiation condition (energy, cone, air gap). Isodose data were measured for every cone using film in a solid water phantom. Scatter off the inside wall of the cone resulted in peripheral dose horns near the surface that were energy and cone dependent, being as large as 120%.

  12. Dosimetry characteristics of metallic cones for intraoperative radiotherapy

    SciTech Connect

    Nyerick, C.E.; Ochran, T.G.; Boyer, A.L.; Hogstrom, K.R. )

    1991-07-01

    Dosimetry data were obtained on the first dedicated linear accelerator of its type designed for electron intraoperative radiotherapy (IORT) within an operating room. The linear accelerator uses a high dose rate, 9 Gy.min-1, to reduce the treatment time. Its chrome-plated brass treatment cones, designed with straight ends and 22.5 degrees beveled ends, are not mechanically attached to the collimator head, but are aligned using a laser projection system. Dosimetry measurements were made for each combination of energy (6, 9, 12, 15, and 16 MeV), cone size (diameters range from 5 to 12 cm), and cone type (22.5 degrees beveled or straight). From these data, depth-dose curves, cone output, and air-gap correction factors were generated that allow the calculation of the monitor setting for delivering a prescribed dose at any depth for any irradiation condition (energy, cone, air gap). Isodose data were measured for every cone using film in a solid water phantom. Scatter off the inside wall of the cone resulted in peripheral dose horns near the surface that were energy and cone dependent, being as large as 120%.

  13. Scoria Cone Construction Mechanism, Lathrop Wells Volcano, Southern Nevada

    SciTech Connect

    G. Valentine; D. Krier; F. Perry; G. Heiken

    2005-01-18

    Scoria cones are commonly assumed to have been constructed by the accumulation of ballistically-ejected clasts from discrete and relatively coarse-grained Strombolian bursts and subsequent avalanching such that the cone slopes are at or near the angle of repose for loose scoria. The cone at the hawaiitic Lathrop Wells volcano, southern Nevada, contains deposits that are consistent with the above processes during early cone-building phases; these early deposits are composed mainly of coarse lapilli and fluidal bombs and are partially welded, indicating relatively little cooling during flight. However, the bulk of the cone is comprised of relatively fine-grained (ash and lapilli), planar beds with no welding, even within a few tens of meters of the vent. This facies is consistent with deposition by direct fallout from sustained eruption columns of relatively well-fragmented material, primarily mantling cone slopes and with a lesser degree of avalanching than is commonly assumed. A laterally extensive fallout deposit (up to 20 km from the vent) is inferred to have formed contemporaneously with these later cone deposits. This additional mechanism for construction of scoria cones may also be important at other locations, particularly where the magmas are relatively high in volatile content and where conditions promote the formation of abundant microlites in the rising mafic magma.

  14. Optimizing Stability in Femoral Neck Fracture Fixation.

    PubMed

    Ye, Ye; Hao, Jiandong; Mauffrey, Cyril; Hammerberg, E Mark; Stahel, Philip F; Hak, David J

    2015-10-01

    Optimizing stability of femoral neck fracture fixation is important in obtaining a successful outcome. The mechanical problems and strategies for achieving optimal stability differ depending on patients' age and degree of osteoporosis. Femoral neck fractures in younger adults usually result from high-energy trauma and have a vertical fracture pattern. Strategies for optimizing fixation stability in this group include placing additional screws at right angles to the fracture plane and medial buttress plate augmentation. In elderly patients, screw position relative to the intact cortical femoral neck bone is of critical importance. Additional strategies for optimizing fixation stability in this group include the concept of length stable fixation, use of adjunctive calcium phosphate cement, and use of novel fixed angle fixation implants. PMID:26488776

  15. An unusual neck mass: the Warthin tumor.

    PubMed

    Scasso, C A; Papini, M; Eligi, C; Ghelardi, F; Cagno, M C; Bruschini, P

    1998-01-01

    The cystoadenolymphoma or Warthin's tumor is a benign lesion of the salivary glands and principally of the parotid gland. We report a case of a 62 year old white male seen at our Institute for evaluation of an asymptomatic right neck mass located 2 cm below the mandible at the anterior margin of the sternocleidomastoid muscle. The echography showed a lymphoid structure simulating a lymphoproliferative process. Histologic examination of the surgical specimen revealed a Warthin's tumor. We discuss the importance of considering Warthin's tumor in the differential diagnosis of an isolated neck mass, and report our experience over a ten year period in the surgical management of neck masses. Additionally, the literature concerning extraparotid Warthin's tumors is reviewed.

  16. The use of the anatomic 'zones' of the neck in the assessment of penetrating neck injury.

    PubMed

    Low, Garren M I; Inaba, Kenji; Chouliaras, Konstantinos; Branco, Bernardino; Lam, Lydia; Benjamin, Elizabeth; Menaker, Jay; Demetriades, Demetrios

    2014-10-01

    The traditional classification of neck injuries uses an anatomic description of Zones I through III. The objective of this article was to characterize the association between external wounds and the corresponding internal injuries after penetrating neck trauma to identify the clinical use of the anatomic zones of the neck. Patients who sustained penetrating neck trauma from December 2008 to March 2011 were analyzed. All patients underwent structured clinical examination documenting the external zone where the wound(s) were located. All internal injuries were then correlated with the external wounds. An internal injury was defined as "unexpected" if it was located outside the borders of the neck zone corresponding to the external wound. In total, 146 patients sustaining a penetrating neck injury were analyzed; 126 (86%) male. The mechanism of injury was stab wounds in 74 (51%) and gunshot wounds in 69 (47%). Mean age was 31 years (range, nine to 62 years). Thirty-seven (25%) patients sustained had a total of 50 internal injuries. There was a high incidence of noncorrelation between the location of the external injury and the internal structures that were damaged in patients with hard signs of vascular or aerodigestive injury. The use of the anatomic zones and their role in the workup of penetrating neck injury are questionable.

  17. Sarcoidosis of the head and neck.

    PubMed

    Badhey, Arvind K; Kadakia, Sameep; Carrau, Ricardo L; Iacob, Codrin; Khorsandi, Azita

    2015-06-01

    Sarcoidosis is a complex disorder that often times involves the head and neck. Despite the presence of strong clinical evidence, tissue diagnosis and imaging is needed for confirmation of the disease. Although typically managed medically, when found in the sinonasal tract or intracranially, it may necessitate the intervention of a rhinologist-skull base surgeon. This article seeks to provide a comprehensive review of head and neck sarcoidosis, as this fascinating disorder often poses a diagnostic and therapeutic challenge. A brief discussion of surgical treatment for pituitary lesions is also provided. Articles from 1997 to 2013 were selected and reviewed by three researchers utilizing the most recent literature regarding sarcoidosis in the head and neck. PubMed searches were conducted using search terms such as "sarcoidosis", "neurosarcoid", and "extra-pulmonary sarcoid", among many others. A large collection of articles was generated and reviewed by the team of authors, and appropriate information was extracted to compose a thorough and expansive review of the subject. 10-15 % of patients with sarcoidosis have head and neck manifestations. Sinonasal and pituitary sarcoidosis presents a diagnostic challenge owing to its non-specific symptoms. Although systemic steroid therapy is often the first time treatment, endoscopic surgery is commonly used to treat advanced pituitary sarcoidosis refractory to medical management. As tissue diagnosis and imaging is key, a multi-disciplinary team approach is advantageous. Our study collates the available literature on head and neck sarcoidosis to provide a comprehensive review of the subject. This provides helpful information to guide all practitioners involved in the care of these challenging patients, namely pathologists, radiologists, otolaryngologists, and skull base surgeons, in the workup and management of head and neck sarcoidosis.

  18. Salamander Blue-sensitive Cones Lost During Metamorphosis†

    PubMed Central

    Chen, Ying; Znoiko, Sergey; DeGrip, Willem J.; Crouch, Rosalie K.; Ma, Jian-xing

    2009-01-01

    The tiger salamander lives in shallow water with bright light in the aquatic phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic phase, there are five types of photoreceptors—two types of rods and three types of cones. Our previous studies showed that the green rods and blue-sensitive cones contain the same visual pigment and have the same absorbance spectra; however, the green rods have a larger photon-catch area and thus have higher light sensitivity than the blue-sensitive cones. Here we show that after metamorphosis, the terrestrial salamander looses the blue-sensitive cones, while the density of the green rods increases. Moreover, the size of the green rod outer segments is increased in the terrestrial phase, compared to that in the aquatic phase. This switch from the blue-sensitive cones to the green rods may represent an adaptation to the dim light environment of the terrestrial phase. PMID:18331398

  19. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa

    PubMed Central

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A.; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R.; Ross, Jason W.; Kaplan, Henry J.; Dean, Douglas C.

    2016-01-01

    Most Retinitis Pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nightime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE), and thus is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment -rich outer segments (OS), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  20. Unsupervised Learning of Cone Spectral Classes from Natural Images

    PubMed Central

    Benson, Noah C.; Manning, Jeremy R.; Brainard, David H.

    2014-01-01

    The first step in the evolution of primate trichromatic color vision was the expression of a third cone class not present in ancestral mammals. This observation motivates a fundamental question about the evolution of any sensory system: how is it possible to detect and exploit the presence of a novel sensory class? We explore this question in the context of primate color vision. We present an unsupervised learning algorithm capable of both detecting the number of spectral cone classes in a retinal mosaic and learning the class of each cone using the inter-cone correlations obtained in response to natural image input. The algorithm's ability to classify cones is in broad agreement with experimental evidence about functional color vision for a wide range of mosaic parameters, including those characterizing dichromacy, typical trichromacy, anomalous trichromacy, and possible tetrachromacy. PMID:24967877

  1. Unsupervised learning of cone spectral classes from natural images.

    PubMed

    Benson, Noah C; Manning, Jeremy R; Brainard, David H

    2014-06-01

    The first step in the evolution of primate trichromatic color vision was the expression of a third cone class not present in ancestral mammals. This observation motivates a fundamental question about the evolution of any sensory system: how is it possible to detect and exploit the presence of a novel sensory class? We explore this question in the context of primate color vision. We present an unsupervised learning algorithm capable of both detecting the number of spectral cone classes in a retinal mosaic and learning the class of each cone using the inter-cone correlations obtained in response to natural image input. The algorithm's ability to classify cones is in broad agreement with experimental evidence about functional color vision for a wide range of mosaic parameters, including those characterizing dichromacy, typical trichromacy, anomalous trichromacy, and possible tetrachromacy. PMID:24967877

  2. Unsupervised learning of cone spectral classes from natural images.

    PubMed

    Benson, Noah C; Manning, Jeremy R; Brainard, David H

    2014-06-01

    The first step in the evolution of primate trichromatic color vision was the expression of a third cone class not present in ancestral mammals. This observation motivates a fundamental question about the evolution of any sensory system: how is it possible to detect and exploit the presence of a novel sensory class? We explore this question in the context of primate color vision. We present an unsupervised learning algorithm capable of both detecting the number of spectral cone classes in a retinal mosaic and learning the class of each cone using the inter-cone correlations obtained in response to natural image input. The algorithm's ability to classify cones is in broad agreement with experimental evidence about functional color vision for a wide range of mosaic parameters, including those characterizing dichromacy, typical trichromacy, anomalous trichromacy, and possible tetrachromacy.

  3. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa.

    PubMed

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R; Ross, Jason W; Kaplan, Henry J; Dean, Douglas C

    2016-04-12

    Most retinitis pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nighttime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE) and, thus, is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment-rich outer segments (OSs), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  4. Shatter cones formed in large-scale experimental explosion craters

    NASA Technical Reports Server (NTRS)

    Roddy, D. J.; Davis, L. K.

    1977-01-01

    In 1968, a series of 0.5-ton and 100-ton TNT explosion experiments were conducted in granitic rock near Cedar City, Utah, as part of a basic research program on cratering and shock wave propagation. Of special interest was the formation of an important type of shock metamorphic feature, shatter cones. A description is presented of the first reported occurrence of shatter cones in high explosion trials. A background to shatter cone studies is presented and attention is given to the test program, geology and physical properties of the test medium, the observed cratering, and the formational pressures for shatter cones. The high explosion trials conducted demonstrate beyond any doubt, that shatter cones can be formed by shock wave processes during cratering and that average formational pressures in these crystalline rocks are in the 20-60 kb range.

  5. Hypersonic boundary-layer transition measurements at Mach 10 on a large seven-degree cone at angle of attack

    NASA Astrophysics Data System (ADS)

    Moraru, Ciprian G.

    The ability to predict the onset of boundary-layer transition is critical for hypersonic flight vehicles. The development of prediction methods depends on a thorough comprehension of the mechanisms that cause transition. In order to improve the understanding of hypersonic boundary-layer transition, tests were conducted on a large 7° half-angle cone at Mach 10 in the Arnold Engineering Development Complex Wind Tunnel 9. Twenty-four runs were performed at varying unit Reynolds numbers and angles of attack for sharp and blunt nosetip configurations. Heat-transfer measurements were used to determine the start of transition on the cone. Increasing the unit Reynolds number caused a forward movement of transition on the sharp cone at zero angle of attack. Increasing nosetip radius delayed transition up to a radius of 12.7 mm. Larger nose radii caused the start of transition to move forward. At angles of attack up to 10°, transition was leeside forward for nose radii up to 12.7 mm and windside forward for nose radii of 25.4 mm and 50.8 mm. Second-mode instability waves were measured on the sharp cone and cones with small nose radii. At zero angle of attack, waves at a particular streamwise location on the sharp cone were in earlier stages of development as the unit Reynolds number was decreased. The same trend was observed as the nosetip radius was increased. No second-mode waves were apparent for the cones with large nosetip radii. As the angle of attack was increased, waves at a particular streamwise location on the sharp cone moved to earlier stages of growth on the windward ray and later stages of growth on the leeward ray. RMS amplitudes of second-mode waves were computed. Comparison between maximum second-mode amplitudes and edge Mach numbers showed good correlation for various nosetip radii and unit Reynolds numbers. Using the e N method, initial amplitudes were estimated and compared to freestream noise in the second-mode frequency band. Correlations indicate

  6. Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Thariat, Juliette; Ahamad, Anesa; Williams, Michelle D.; Myers, Jeffrey N.; El-Naggar, Adel K.; Ginsberg, Lawrence E.; Rosenthal, David I.; Glisson, Bonnie S.; Weber, Randal S.; Garden, Adam S.

    2012-03-01

    Background: This analysis was undertaken to assess the need for planned neck dissection in patients with a complete response (CR) of involved nodes after irradiation and to determine the benefit of a neck dissection in those with less than CR by tumor site. Methods: Our cohort included 880 patients with T1-4, N1-3M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received treatment between 1994 and 2004. Survival curves were calculated by the Kaplan-Meier Method, comparisons of rates with the log-rank test and prognostic factors by Cox's proportional hazard model. Results: Nodal CR occurred in 377 (43%) patients, of whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with CR was 92%. Two hundred sixty-eight of the remaining patients (53%) underwent neck dissections. The 5-year actuarial regional control rate for patients without a CR was 84%. Those who had a neck dissection fared better with 5-year actuarial regional control rates of 90% and 76% for those operated and those not operated (p < 0.001). Variables associated with poorer regional control rates included higher T and N stage, non-oropharynx cancers, non-CR, both clinical and pathological. Conclusions: With 92% 5-year neck control rate without neck dissection after CR, there is little justification for systematic neck dissection. The addition of a neck dissection resulted in higher neck control after partial response though patients with viable tumor on pathology specimens had poorer outcomes. The identification of that subgroup that benefits from additional treatment remains a challenge.

  7. Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Thariat, Juliette; Ang, K. Kian; Allen, Pamela K.; Ahamad, Anesa; Williams, Michelle D.; Myers, Jeffrey N.; El-Naggar, Adel K.; Ginsberg, Lawrence E.; Rosenthal, David I.; Glisson, Bonnie S.; Morrison, William H.; Weber, Randal S.; Garden, Adam S.

    2014-01-01

    BACKGROUND This analysis was undertaken to assess the need for planned neck dissection in patients with a complete response (CR) of involved nodes after irradiation, and to determine the benefit of a neck dissection in those with less than CR by tumor site. METHODS Our cohort included 880 patients with T1-4, N1-3M0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx who received treatment between 1994 and 2004. Survival curves were calculated by the Kaplan-Meier Method, comparisons of rates with the log-rank test and prognostic factors by Cox analyses. RESULTS Nodal CR occurred in 377 (43%) patients of whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with CR was 92%. Two hundred sixty-eight of the remaining patients (53%) underwent neck dissections. The 5-year actuarial regional control rate for patients without a CR was 84%. Those who had a neck dissection fared better with 5-year actuarial regional control rates of 90% and 76% for those operated and those not operated (p <.001). Variables associated with poorer regional control rates included higher T and N stage, non-oropharynx cancers, non-CR, both clinical and pathological. CONCLUSIONS With 92% 5-year neck control rate without neck dissection after CR, there is little justification for systematic neck dissection. The addition of a neck dissection resulted in higher neck control after partial response though patients with viable tumor on pathology specimens had poorer outcomes. The identification of that subgroup that benefits from additional treatment remains a challenge. PMID:22284033

  8. Penetrating wounds of the head and neck.

    PubMed

    Jahrsdoerfer, R A; Johns, M E; Cantrell, R W

    1979-12-01

    Wounding capability of bullets is primarily releated to velocity. Bullet mass and shape, and specific gravity of body tissues being struck by the missile, are lesser factors. Seventy cases of penetrating wounds of the head and neck were treated during a six-year period. Vascular injuries were more common with neck wounds, while face and head injuries (extracranial) were similar to maxillofacial trauma. It is recognized that hemorrhage at the base of the skull is difficult to treat, and contemporary training in temporal bone and base of skull surgery is mandatory for the critical management of these wounds.

  9. Neck pain from a rheumatologic perspective.

    PubMed

    Oberstein, Elana M; Carpintero, Maria; Hopkins, Aviva

    2011-08-01

    This article provides a comprehensive review of rheumatologic considerations for a clinician when evaluating a patient with neck pain. Clearly, anatomic derangements of the cervical spine should be considered when a patient complains of cervicalgia. However, one must also entertain the possibility of a systemic illness as the cause of the pain. Examples of diseases that may present with a prominent feature of neck pain are discussed, including rheumatoid arthritis, ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, myositis, and fibromyalgia. Evidence of an underlying rheumatic illness may guide the clinician in a different therapeutic direction. PMID:21824589

  10. Approach to intensely enhancing neck nodes

    PubMed Central

    Karandikar, Amit; Gummalla, Krishna Mohan; Loke, Siu Cheng; Goh, Julian; Tan, Tiong Yong

    2016-01-01

    Cervical node evaluation is one of the most common problems encountered by a radiologist. Here, we present a pictorial review of intensely enhancing neck nodes. While enhancement in a cervical node is a common radiologic finding on contrast-enhanced computed tomography scan, only few conditions cause intense enhancement in cervical nodes. We discuss the common causes of intensely enhancing neck nodes along with pertinent radiologic features and key differentiating points that aid radiologists in reaching a diagnosis. In addition, we discuss certain potential non-nodal mimics, which need to be excluded. PMID:26782154

  11. Hyperparathyroidism following head and neck irradiation

    SciTech Connect

    Rao, S.D.; Frame, B.; Miller, M.J.; Kleerskoper, M.; Block, M.A.; Parfitt, A.M.

    1980-02-01

    A history of head and neck irradiation in childhood or adolescence was found in 22 of 130 patients with primary hyperparathyroidism compared with only 12 of 400 control patients. Among 200 patients with a known history of childhood irradiation, biochemical or surgical evidence of hyperparathyroidism was found in ten, a prevalence of 5%. This is at least 30 times the prevalence of hyperparathyroidism in the general population. The data indicate that head and neck irradiation should be regarded as an important risk factor in the subsequent development of hyperparathyroidism.

  12. Malignant lymphoma of the head and neck.

    PubMed

    Zapater, E; Bagán, J V; Carbonell, F; Basterra, J

    2010-03-01

    Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck area. They are classically divided into two subgroups, Hodgkin's lymphomas (HLs) and non-Hodgkin's lymphomas (NHLs). We describe the clinical characteristics of head and neck lymphomas and the methods to establish the diagnosis. The World Health Organization classification of lymphoid tissues describes more than 50 different histological types, and we analyse the most common staging system for lymphomas, the Ann Arbor staging system. Finally, the different therapeutic approaches are discussed. PMID:20374502

  13. Molecular profiling of head and neck squamous cell carcinoma

    PubMed Central

    Gatalica, Zoran; Knezetic, Joseph; Reddy, Sandeep; Nathan, Cherie‐Ann; Javadi, Nader; Teknos, Theodoros

    2015-01-01

    Abstract Background Head and neck squamous cell carcinoma (HNSCC) exhibits high rates of recurrence, and with few approved targeted agents, novel treatments are needed. We analyzed a molecular profiling database for the distribution of biomarkers predictive of chemotherapies and targeted agents. Methods Seven hundred thirty‐five patients with advanced HNSCC (88 with known human papillomavirus [HPV] status), were profiled using multiple platforms (gene sequencing, gene copy number, and protein expression). Results Among the entire patient population studied, epidermal growth factor receptor (EGFR) was the protein most often overexpressed (90%), TP53 gene most often mutated (41%), and phosphatidylinositol 3‐kinase (PIK3CA) most often amplified (40%; n = 5). With the exception of TP53 mutation, other biomarker frequencies were not significantly different among HPV‐positive or HPV‐negative patients. PIK3CA mutations and phosphatase and tensin homolog (PTEN) loss are frequent events, independent of HPV status. The immune response‐modulating programmed cell death 1 (PD1) and programmed cell death ligand 1 (PDL1) axis was active across sites, stages, and HPV status. Conclusion Molecular profiling utilizing multiple platforms provides a range of therapy options beyond standard of care. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1625–E1638, 2016 PMID:26614708

  14. S cones: Evolution, retinal distribution, development, and spectral sensitivity.

    PubMed

    Hunt, David M; Peichl, Leo

    2014-03-01

    S cones expressing the short wavelength-sensitive type 1 (SWS1) class of visual pigment generally form only a minority type of cone photoreceptor within the vertebrate duplex retina. Hence, their primary role is in color vision, not in high acuity vision. In mammals, S cones may be present as a constant fraction of the cones across the retina, may be restricted to certain regions of the retina or may form a gradient across the retina, and in some species, there is coexpression of SWS1 and the long wavelength-sensitive (LWS) class of pigment in many cones. During retinal development, SWS1 opsin expression generally precedes that of LWS opsin, and evidence from genetic studies indicates that the S cone pathway may be the default pathway for cone development. With the notable exception of the cartilaginous fishes, where S cones appear to be absent, they are present in representative species from all other vertebrate classes. S cone loss is not, however, uncommon; they are absent from most aquatic mammals and from some but not all nocturnal terrestrial species. The peak spectral sensitivity of S cones depends on the spectral characteristics of the pigment present. Evidence from the study of agnathans and teleost fishes indicates that the ancestral vertebrate SWS1 pigment was ultraviolet (UV) sensitive with a peak around 360 nm, but this has shifted into the violet region of the spectrum (>380 nm) on many separate occasions during vertebrate evolution. In all cases, the shift was generated by just one or a few replacements in tuning-relevant residues. Only in the avian lineage has tuning moved in the opposite direction, with the reinvention of UV-sensitive pigments. PMID:23895771

  15. S cones: Evolution, retinal distribution, development, and spectral sensitivity.

    PubMed

    Hunt, David M; Peichl, Leo

    2014-03-01

    S cones expressing the short wavelength-sensitive type 1 (SWS1) class of visual pigment generally form only a minority type of cone photoreceptor within the vertebrate duplex retina. Hence, their primary role is in color vision, not in high acuity vision. In mammals, S cones may be present as a constant fraction of the cones across the retina, may be restricted to certain regions of the retina or may form a gradient across the retina, and in some species, there is coexpression of SWS1 and the long wavelength-sensitive (LWS) class of pigment in many cones. During retinal development, SWS1 opsin expression generally precedes that of LWS opsin, and evidence from genetic studies indicates that the S cone pathway may be the default pathway for cone development. With the notable exception of the cartilaginous fishes, where S cones appear to be absent, they are present in representative species from all other vertebrate classes. S cone loss is not, however, uncommon; they are absent from most aquatic mammals and from some but not all nocturnal terrestrial species. The peak spectral sensitivity of S cones depends on the spectral characteristics of the pigment present. Evidence from the study of agnathans and teleost fishes indicates that the ancestral vertebrate SWS1 pigment was ultraviolet (UV) sensitive with a peak around 360 nm, but this has shifted into the violet region of the spectrum (>380 nm) on many separate occasions during vertebrate evolution. In all cases, the shift was generated by just one or a few replacements in tuning-relevant residues. Only in the avian lineage has tuning moved in the opposite direction, with the reinvention of UV-sensitive pigments.

  16. Formation of shatter cones in MEMIN impact experiments

    NASA Astrophysics Data System (ADS)

    Wilk, J.; Kenkmann, T.

    2016-08-01

    Shatter cones are the only macroscopic feature considered as evidence for shock metamorphism. Their presence is diagnostic for the discovery and verification of impact structures. The occurrence of shatter cones is heterogeneous throughout the crater record and their geometry can diverge from the typical cone shape. The precise formation mechanism of shatter cones is still not resolved. In this study, we aim at better constraining the boundary conditions of shatter cone formation in impact experiments and test a novel approach to qualitatively and quantitatively describe shatter cone geometries by white light interferometry. We recovered several ejected fragments from MEMIN cratering experiments that show slightly curved, striated surfaces and conical geometries with apices of 36°-52°. These fragments fulfilling the morphological criteria of shatter cones were found in experiments with 20-80 cm sized target cubes of sandstone, quartzite and limestone, but not in highly porous tuff. Targets were impacted by aluminum, steel, and iron meteorite projectiles at velocities of 4.6-7.8 km s-1. The projectile sizes ranged from 2.5-12 mm in diameter and produced experimental peak pressures of up to 86 GPa. In experiments with lower impact velocities shatter cones could not be found. A thorough morphometric analysis of the experimentally generated shatter cones was made with 3D white light interferometry scans at micrometer accuracy. SEM analysis of the surfaces of recovered fragments showed vesicular melt films alternating with smoothly polished surfaces. We hypothesize that the vesicular melt films predominantly form at strain releasing steps and suggest that shatter cones are probably mixed mode fractures.

  17. Dermatoses of the neck affecting violin and viola players ("fiddler's neck", and contact dermatitis).

    PubMed

    Tennstedt, D; Cromphaut, P; Dooms-Goossens, A; Lachapelle, J M

    1979-01-01

    Skin lesions occurring on the neck of violin or viola players are described, in the light of two personal observations. The lesions can be divided into two types: 1. Lesions described as "fiddler's neck", i.e. an area of erythematous, sometimes pigmented or scaly lichenification on the left side of the neck, just below the angle of the jaw, where the chin rest of the instrument is in contact with the skin. Histopathologic features of the lesions are described. 2. Allergic contact dermatitis to wooden or metallic parts of the violin. The recent literature is reviewed.

  18. Comfort effects of a new car headrest with neck support.

    PubMed

    Franz, M; Durt, A; Zenk, R; Desmet, P M A

    2012-03-01

    This paper describes the design of a neck-/headrest to increase car comfort. Two studies were undertaken to create a new comfortable headrest with neck support. In experiment one, neck- and headrest data were gathered using 35 test subjects. The pressure distribution, stiffness of the foam material and position of the head and neck support were determined. In experiment two a full adjustable final headrest with adjustable neck support was constructed and tested with 12 subjects using a new adjustable headrest under virtual reality driving conditions. Experiment two showed that the headrest with the new/adjustable neck support was favoured by the majority of the subjects. 83% were satisfied with the stiffness of the material. 92% were satisfied with the size of the neck- and headrest. All subjects mentioned that the neck support is a comfort benefit in calm traffic conditions or on the motorway.

  19. PET-CT–Guided Surveillance of Head and Neck Cancers

    Cancer.gov

    Patients with advanced squamous cell carcinoma of the head and neck who underwent PET-CT–guided surveillance had fewer operations but similar overall survival rates to those of patients who underwent planned neck dissection.

  20. Cone-based electrical resistivity tomography

    NASA Astrophysics Data System (ADS)

    Pidlisecky, Adam

    Determining the 3-D spatial distribution of subsurface properties is a critical part of managing the clean-up of contaminated sites. Most standard hydrologic methods sample small regions immediately adjacent to wells or testing devices. This provides data which are not representative of the entire region of interest. Furthermore, at many contaminated sites invasive methods are not acceptable, due to the risks associated with contacting and spreading the contaminants. To address these issues, I have developed a minimally invasive technology that provides information about the 3-D distribution of electrical conductivity. This new technique, cone-based electrical resistivity tomography (C-bert), integrates the existing technologies of resistivity cone penetration testing (RCPT) with electrical resistivity tomography. Development of this tool included the creation of new software and modeling algorithms, the design of field equipment, field testing, and processing and interpretation of the resulting data. I present a 2.5-D forward modeling algorithm that incorporates an effective correction for the errors caused by boundary effects and source singularities. The algorithm includes an optimization technique for acquiring the Fourier coefficients required for the solution. A 3-D inversion algorithm is presented that has two major improvements over existing algorithms. First, it includes a 3-D version of the boundary correction/source singularity correction developed for the 2.5-D problem. Second, the algorithm can handle any type of acquisition geometry; this was a requirement for the development of C-bert. C-bert involves placing several permanent current electrodes in the subsurface and using electrodes mounted on a cone penetrometer and at the surface to measure the resultant potential field. In addition to these measurements, we obtain the standard suite of RCPT data, including high resolution resistivity logs. The RCPT data can be used to generate a realistic

  1. The evolution of surgery in the management of neck metastases

    PubMed Central

    Subramanian, S; Chiesa, F; Lyubaev, V; Aidarbekova, A; Brzhezovskiy, V

    2006-01-01

    Summary In spite of advancement in science, molecular medicine and target therapies, surgical treatment of metastases using different techniques, from selective neck dissection to extended radical neck dissections, form a major part in the management of neck metastases. This is due to the fact that, so far, there is no treatment more effective for resectable neck metastases, than surgery. Since most head and neck cancer patients die due to loco-regional progression of disease, and a very large majority of them do not live long enough to develop distant metastases, the status of neck lymph nodes remains the single most important prognostic factor, in these cases. In the 100 years since George Washington Crile described Radical Neck Dissection, we now have a much better understanding of the biological and clinical behaviour of neck metastases. This has ultimately led to the conservative approaches of selective neck dissections depending on the primary site of the tumour, type of tumour and the characteristic features of the metastases themselves. A search of the literature on neck lymph nodes and neck dissections, on the internet and in old publications, not available in the electronic media, has been carried out. Using this as the basis, we arranged, in sequence, the dates of various landmarks in the treatment of head and neck cancer related to neck dissections to emphasize the overall process of evolution of neck dissection thereby showing how the field of head and neck surgery has travelled a long way from radical neck dissection to its modifications and further to selective neck dissections and sentinel node biopsies. The present understanding of the patterns of neck metastases enables us not only to adequately treat the neck metastases, but also to diagnose metastases from unknown primaries. Therefore, depending on the site of the primary tumour, it is now easy to predict the most probable route of metastatic spread and vice versa. This has enabled us to adopt

  2. Water coning in fractured basement reservoirs

    SciTech Connect

    Saad, S.E.D.M.; Darwich, T.D.; Asaad, Y.

    1995-11-01

    The problem of water coning in fractured basement reservoirs has been addressed in this work. The outcome of experimental and theoretical investigation to determine the critical production rate for single- and multi-fractured system, the capillary pressure effect, and the break-through time is presented. The results of the experimental work verify the presented theoretical relationship for different fluid viscosities, fracture angles, oil-water contacts (OWC), and rates for the case of single fracture system. The results also indicate that the capillary pressure effect may be generally neglected if the distance between the OWC and the fluid entry is sufficiently large compared to the capillary rise. The extension of the critical rate determination for a multi-fractured reservoir is also discussed. Finally, the main factors influencing the break-through time were investigated. The difference in viscosity between the oil and water phases has been fond to be the main factor affecting the breakthrough time.

  3. Nose-cone calorimeter: PHENIX forward upgrade

    NASA Astrophysics Data System (ADS)

    Chvala, Ondrej

    2009-07-01

    PHENIX is a high rate experiment efficient at measuring rare processes, but has limited acceptance in azimuth and pseudorapidity ( η). The Nose Cone Calorimeter (NCC), a W-Si sampling calorimeter in the region of 0.9< η<3, is one of the upgrades which will significantly increase coverage in both azimuth and pseudorapidity. The NCC will expand PHENIX’s precision measurements of electromagnetic probes in η, reconstruct jets, perform a wide scope of correlation measurements, and enhance triggering capabilities. The detector will significantly contribute to measurements of γ-jet correlations, quarkonia production, and low- x nuclear structure functions. This report discusses details of the detector design and its performance concerning a sample of the physics topics which will benefit from the NCC. In view of recent funding difficulties, outlook of the activities is discussed.

  4. Plasmonic corrugated cylinder-cone terahertz probe.

    PubMed

    Yao, Haizi; Zhong, Shuncong

    2014-08-01

    The spoof surface plasmon polariton (SPP) effect on the electromagnetic field distribution near the tip of a periodically corrugated metal cylinder-cone probe working at the terahertz regime was studied. We found that radially polarized terahertz radiation could be coupled effectively through a spoof SPP into a surface wave and propagated along the corrugated surface, resulting in more than 20× electric field enhancement near the tip of probe. Multiple resonances caused by the antenna effect were discussed in detail by finite element computation and theoretical analysis of dispersion relation for spoof SPP modes. Moreover, the key figures of merit such as the resonance frequency of the SPP can be flexibly tuned by modifying the geometry of the probe structure, making it attractive for application in an apertureless background-free terahertz near-field microscope. PMID:25121543

  5. Handling data redundancy in helical cone beam reconstruction with a cone-angle-based window function and its asymptotic approximation

    SciTech Connect

    Tang Xiangyang; Hsieh Jiang

    2007-06-15

    A cone-angle-based window function is defined in this manuscript for image reconstruction using helical cone beam filtered backprojection (CB-FBP) algorithms. Rather than defining the window boundaries in a two-dimensional detector acquiring projection data for computed tomographic imaging, the cone-angle-based window function deals with data redundancy by selecting rays with the smallest cone angle relative to the reconstruction plane. To be computationally efficient, an asymptotic approximation of the cone-angle-based window function is also given and analyzed in this paper. The benefit of using such an asymptotic approximation also includes the avoidance of functional discontinuities that cause artifacts in reconstructed tomographic images. The cone-angle-based window function and its asymptotic approximation provide a way, equivalent to the Tam-Danielsson-window, for helical CB-FBP reconstruction algorithms to deal with data redundancy, regardless of where the helical pitch is constant or dynamically variable during a scan. By taking the cone-parallel geometry as an example, a computer simulation study is conducted to evaluate the proposed window function and its asymptotic approximation for helical CB-FBP reconstruction algorithm to handle data redundancy. The computer simulated Forbild head and thorax phantoms are utilized in the performance evaluation, showing that the proposed cone-angle-based window function and its asymptotic approximation can deal with data redundancy very well in cone beam image reconstruction from projection data acquired along helical source trajectories. Moreover, a numerical study carried out in this paper reveals that the proposed cone-angle-based window function is actually equivalent to the Tam-Danielsson-window, and rigorous mathematical proofs are being investigated.

  6. Effect of neck warming and cooling on thermal comfort

    NASA Technical Reports Server (NTRS)

    Williams, B. A.; Chambers, A. B.

    1972-01-01

    The potential use of local neck cooling in an area superficial to the cerebral arteries was evaluated by circulating cold or hot water through two copper disks held firmly against the neck. Subjective responses indicated that neck cooling improves the thermal comfort in a hot environment.

  7. Rehabilitation of the head and neck cancer patient: Psychosocial aspects

    SciTech Connect

    Blitzer, A.; Baredes, S.; Kutscher, A.; Seeland, I.B.; Barrett, V.W.; Mossman, K.L.

    1985-01-01

    This book contains 42 chapters divided among six sections. Some of the chapter titles are: The Challenge of Cancer; Communicaton Needs of Head and Neck Cancer Patients; Normal Tissue Effects of the Radiotherapy of Head and Neck Cancer; Chemotherapy in the Treatment of Head and Neck Cancer; and Thyroid Cancer.

  8. 49 CFR 572.83 - Head-neck.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Head-neck. 572.83 Section 572.83 Transportation..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 9-Month Old Child § 572.83 Head-neck. The head-neck assembly shown in drawing 1049/A consists of parts specified as items 1 through 16...

  9. 49 CFR 572.83 - Head-neck.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Head-neck. 572.83 Section 572.83 Transportation..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 9-Month Old Child § 572.83 Head-neck. The head-neck assembly shown in drawing 1049/A consists of parts specified as items 1 through 16...

  10. 49 CFR 572.83 - Head-neck.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Head-neck. 572.83 Section 572.83 Transportation..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 9-Month Old Child § 572.83 Head-neck. The head-neck assembly shown in drawing 1049/A consists of parts specified as items 1 through 16...

  11. 49 CFR 572.83 - Head-neck.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Head-neck. 572.83 Section 572.83 Transportation..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 9-Month Old Child § 572.83 Head-neck. The head-neck assembly shown in drawing 1049/A consists of parts specified as items 1 through 16...

  12. 49 CFR 572.83 - Head-neck.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Head-neck. 572.83 Section 572.83 Transportation..., DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 9-Month Old Child § 572.83 Head-neck. The head-neck assembly shown in drawing 1049/A consists of parts specified as items 1 through 16...

  13. JOSPT perspectives for patients. Neck pain: manipulation of your neck and upper back leads to quicker recovery.

    PubMed

    2012-01-01

    Neck pain is very common and fortunately resolves quickly in most individuals. However, in certain cases neck pain can last longer and result in chronic pain, limited neck motion, and disability. In fact, chronic neck pain is the second leading cause of workers' compensation claims in the United States. Treatments that can quickly reduce pain, increase motion, and improve the ability of the muscles to protect the neck may help decrease long-term disability associated with neck pain. A variety of manual therapy treatments are currently used to manage neck pain. These treatments include mobilization, which slowly and repeatedly moves the neck joints and muscles, and manipulation, which delivers a single, small, quick movement to the joints and muscles. A research report published in the January 2012 issue of JOSPT examines the outcomes of these 2 treatment methods and draws conclusions about which one is best.

  14. Nano-cones formation on a surface of Ge, Si crystals and Si1-xGe(x) solid solution by laser radiation.

    PubMed

    Medvid, A; Onufrijevs, P; Lyutovich, K; Oehme, M; Kasper, E

    2011-10-01

    The study of self-assembling nano-cones induced by irradiation of nanosecond Nd:YAG laser pulses on a surface of a Si1-xGe(x) solid solution is reported. It is shown that dynamics of nano-cones formation depends on concentration of Ge atoms (x) in Si lattice and on the intensity of laser radiation. Two different processes of nano-cones formation depending on x are observed. The first one-at higher concentration of Ge atoms x = 0.3-0.4 and the second one-at lower concentration of Ge atoms at x = 0.15 take place. At the first stage, similar processes of nano-cones formation occur. It means, at low intensity of laser radiation 1 < 2.0 MW/cm2 Ge atoms drift to the irradiated surface due to Thermo-gradient effect and Ge-rich phase is formed for both concentration ranges. The second stage is different for low and high Ge content ranges. At the higher concentration of Ge atoms and intensity of laser radiation 1 > 2.0 MW/cm2 nano-cones formation takes place by Stransky-Krastanov mode. On the same time, at lower concentration of Ge atoms cones look like "tree ring" growth due to melting of Ge separated islands on the irradiated surface at intensity of laser radiation 1 = 20 MW/cm2.

  15. Control of cellular vortex shedding over a cone

    NASA Astrophysics Data System (ADS)

    Ramesh, O.; Chopde, Rahul

    2007-11-01

    Vortex shedding over 3D geometries is known to be complex involving the so-called cellular vortex shedding phenomenon, wherein cells of constant frequency are formed. In the present work we consider the passive control methodology of Strykowski and Sreenivasan (of placing a small control cylinder outside the undisturbed wake of the main cylinder) to the cellular shedding problem. It is interesting that this control methodology which was originally meant for 2D flows works well in the present 3D flows also. Similarly, the vortex shedding was quenched by this methodology even for other cellular shedding configurations such as a uniform flow over a stepped cylinder or a shear flow over a uniform cylinder also. The smearing of vorticity due to the control rod (envisaged in the 2D scenario of Strykowski and Sreenivasan hypothesis) may be expected to be non-uniform all over the span in a 3D geometry as the gap between the main cylinder and the control cylinder varies with the span. It is hypothesised that the control rod works on the global instability modes and alters their growth rates all across the span even when the gap between the cone and the control cylinder varies along the span.

  16. 49 CFR 572.193 - Neck assembly.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... environment as specified in 49 CFR 572.200(j); (2) Attach the neck-headform assembly, as shown in Figure V2-A or V2-B in appendix A to this subpart, to the 49 CFR Part 572 pendulum test fixture (Figure 22, 49 CFR 572.33) in either the left or right lateral impact orientations, respectively, so that...

  17. 49 CFR 572.193 - Neck assembly.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... environment as specified in 49 CFR 572.200(j); (2) Attach the neck-headform assembly, as shown in Figure V2-A or V2-B in appendix A to this subpart, to the 49 CFR Part 572 pendulum test fixture (Figure 22, 49 CFR 572.33) in either the left or right lateral impact orientations, respectively, so that...

  18. 49 CFR 572.193 - Neck assembly.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... environment as specified in 49 CFR 572.200(j); (2) Attach the neck-headform assembly, as shown in Figure V2-A or V2-B in appendix A to this subpart, to the 49 CFR Part 572 pendulum test fixture (Figure 22, 49 CFR 572.33) in either the left or right lateral impact orientations, respectively, so that...

  19. 49 CFR 572.193 - Neck assembly.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... environment as specified in 49 CFR 572.200(j); (2) Attach the neck-headform assembly, as shown in Figure V2-A or V2-B in appendix A to this subpart, to the 49 CFR Part 572 pendulum test fixture (Figure 22, 49 CFR 572.33) in either the left or right lateral impact orientations, respectively, so that...

  20. 49 CFR 572.193 - Neck assembly.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... environment as specified in 49 CFR 572.200(j); (2) Attach the neck-headform assembly, as shown in Figure V2-A or V2-B in appendix A to this subpart, to the 49 CFR Part 572 pendulum test fixture (Figure 22, 49 CFR 572.33) in either the left or right lateral impact orientations, respectively, so that...