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Sample records for neck linker ensures

  1. Initial conformation of kinesin's neck linker

    International Nuclear Information System (INIS)

    Geng Yi-Zhao; Yan Shi-Wei; Ji Qing; Liu Shu-Xia

    2014-01-01

    How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanisms. By exploiting a molecular dynamics method, we investigate the initial conformation of kinesin's neck linker in its docking process. We find that, in the initial conformation, the neck linker has interactions with β0 and forms a ‘cover-neck bundle’ structure with β0. From this initial structure, the formation of extra turns and the docking of the cover-neck bundle structure can be achieved. The motor head provides a forward force on the initial cover-neck bundle structure through ATP-induced rotation. This force, together with the hydrophobic interaction of ILE327 with the hydrophobic pocket on the motor head, drives the formation of the extra turn and initiates the neck linker docking process. Based on these findings, a pathway from ATP binding-induced motor head rotation to neck linker docking is proposed. (interdisciplinary physics and related areas of science and technology)

  2. Monte Carlo analysis of neck linker extension in kinesin molecular motors.

    Directory of Open Access Journals (Sweden)

    Matthew L Kutys

    2010-11-01

    Full Text Available Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step--diffusion of the tethered head to the next binding site--is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring, Increasing Stiffness (analogous to a Worm-Like Chain, and Reflecting (negligible stiffness up to a limiting contour length. Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing

  3. Neck Pain: Clinical Practice Guidelines Help Ensure Quality Care.

    Science.gov (United States)

    2017-07-01

    In 2008, physical therapists published the first neck pain clinical practice guidelines. These guidelines have been updated and are now available in the July 2017 issue of JOSPT. To update these guidelines, physical therapists teamed with the International Collaboration on Neck Pain to identify leading practices. These revised guidelines provide direction to clinicians as they screen, evaluate, diagnose, and make treatment-based classifications of neck pain. They also outline the best nonsurgical treatment options based on the published literature. At the end of the day, the best care is a combination of the leading science, the clinical expertise of your health care provider, and your input as the patient. These guidelines help inform the first step in this process. J Orthop Sports Phys Ther 2017;47(7):513. doi:10.2519/jospt.2017.0508.

  4. Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin.

    Science.gov (United States)

    Zhang, Zhechun; Goldtzvik, Yonathan; Thirumalai, D

    2017-11-14

    Kinesin walks processively on microtubules (MTs) in an asymmetric hand-over-hand manner consuming one ATP molecule per 16-nm step. The individual contributions due to docking of the approximately 13-residue neck linker to the leading head (deemed to be the power stroke) and diffusion of the trailing head (TH) that contributes in propelling the motor by 16 nm have not been quantified. We use molecular simulations by creating a coarse-grained model of the MT-kinesin complex, which reproduces the measured stall force as well as the force required to dislodge the motor head from the MT, to show that nearly three-quarters of the step occurs by bidirectional stochastic motion of the TH. However, docking of the neck linker to the leading head constrains the extent of diffusion and minimizes the probability that kinesin takes side steps, implying that both the events are necessary in the motility of kinesin and for the maintenance of processivity. Surprisingly, we find that during a single step, the TH stochastically hops multiple times between the geometrically accessible neighboring sites on the MT before forming a stable interaction with the target binding site with correct orientation between the motor head and the [Formula: see text] tubulin dimer.

  5. Does IGRT ensure target dose coverage of head and neck IMRT patients?

    International Nuclear Information System (INIS)

    Graff, Pierre; Hu Weigang; Yom, Sue S.; Pouliot, Jean

    2012-01-01

    Purpose: To determine if image-guided radiotherapy (IGRT) ensures dose coverage to the target, and to assess the dosimetric impact of anatomic changes using megavoltage cone-beam CT (MVCBCT) for patient positioning during head and neck IMRT. Methods and materials: Forty-eight MVCBCT from 10 head and neck IMRT/IGRT patients were analyzed off-line. Target volumes and organs at risk (OARs) contours delineated on CT were transferred and adjusted on MVCBCT images. Each MVCBCT was processed to allow dose recalculation, resulting in 469 dose–volume histograms (DVHs). The concept of dosimetric latitude was introduced to provide a clinical perspective. Results: MVCBCT target DVHs showed a moderate level of difference in D95 (dose to ⩾95% of volume), generally less than a 5% difference from the planned dose. Delivered-dose increases to the spinal cord and brainstem showed no apparent time trend. The 4 mm margin around OARs was a useful precaution to prevent exceeding critical dose thresholds. The parotid glands showed progressive increases in mean dose related to shrinkage of the external contours. Conclusion: IGRT repositioning ensured target volume coverage, but significant dose variations were observed for OARs. The dosimetric impact of anatomic changes during radiotherapy was of lesser importance than the effects of IGRT repositioning.

  6. Backbone amide linker strategy

    DEFF Research Database (Denmark)

    Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

    2013-01-01

    In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy...

  7. Structure and Functions of Linker Histones.

    Science.gov (United States)

    Lyubitelev, A V; Nikitin, D V; Shaytan, A K; Studitsky, V M; Kirpichnikov, M P

    2016-03-01

    Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions - from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed.

  8. Hydroquinone–pyrrole dyads with varied linkers

    Directory of Open Access Journals (Sweden)

    Hao Huang

    2016-01-01

    Full Text Available A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO–LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices.

  9. Solid colloids with surface-mobile linkers

    International Nuclear Information System (INIS)

    Van der Meulen, Stef A J; Helms, Gesa; Dogterom, Marileen

    2015-01-01

    In this report we review the possibilities of using colloids with surface mobile linkers for the study of colloidal self-assembly processes. A promising route to create systems with mobile linkers is the use of lipid (bi-)layers. These lipid layers can be either used in the form of vesicles or as coatings for hard colloids and emulsion droplets. Inside the lipid bilayers molecules can be inserted via membrane anchors. Due to the fluidity of the lipid bilayer, the anchored molecules remain mobile. The use of different lipid mixtures even allows creating Janus-like particles that exhibit directional bonding if linkers are used which have a preference for a certain lipid phase. In nature mobile linkers can be found e.g. as receptors in cells. Therefore, towards the end of the review, we also briefly address the possibility of using colloids with surface mobile linkers as model systems to mimic cell–cell interactions and cell adhesion processes. (topical review)

  10. Water-soluble heterobifunctional fluorescent linkers

    Czech Academy of Sciences Publication Activity Database

    Bartoň, Jan; Cígler, Petr

    2017-01-01

    Roč. 15, č. 1 (2017), s. 4 ISSN 2336-7202. [Mezioborové setkání mladých biologů, biochemiků a chemiků /17./. 30.05.2017-01.06.2017, Milovy] Institutional support: RVO:61388963 Keywords : fluorescent probes * heterobifunctional linkers Subject RIV: CA - Inorganic Chemistry

  11. Neck Pain

    Science.gov (United States)

    ... too many hours hunched over your computer or smartphone, often triggers muscle strains. Even minor things, such ... your shoulder. The weight can strain your neck. Sleep in a good position. Your head and neck ...

  12. Desmosine-Inspired Cross-Linkers for Hyaluronan Hydrogels

    Science.gov (United States)

    Hagel, Valentin; Mateescu, Markus; Southan, Alexander; Wegner, Seraphine V.; Nuss, Isabell; Haraszti, Tamás; Kleinhans, Claudia; Schuh, Christian; Spatz, Joachim P.; Kluger, Petra J.; Bach, Monika; Tussetschläger, Stefan; Tovar, Günter E. M.; Laschat, Sabine; Boehm, Heike

    2013-06-01

    We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.

  13. Ensuring Software IP Cleanliness

    Directory of Open Access Journals (Sweden)

    Mahshad Koohgoli

    2007-12-01

    Full Text Available At many points in the life of a software enterprise, determination of intellectual property (IP cleanliness becomes critical. The value of an enterprise that develops and sells software may depend on how clean the software is from the IP perspective. This article examines various methods of ensuring software IP cleanliness and discusses some of the benefits and shortcomings of current solutions.

  14. Ensuring Software IP Cleanliness

    OpenAIRE

    Mahshad Koohgoli; Richard Mayer

    2007-01-01

    At many points in the life of a software enterprise, determination of intellectual property (IP) cleanliness becomes critical. The value of an enterprise that develops and sells software may depend on how clean the software is from the IP perspective. This article examines various methods of ensuring software IP cleanliness and discusses some of the benefits and shortcomings of current solutions.

  15. Ensuring effective project management

    International Nuclear Information System (INIS)

    Ward, J.N.

    1980-01-01

    A brief description is given of the organisation methods employed by the Bechtel Power Corporation, in their contract with Mississippi Power and Light Company for the design, construction and procurement activities for the Grand Gulf Nuclear Station. The aim is to ensure effective management, and good communications at all stages of construction, between the project team and the client. (U.K.)

  16. Neck Pain

    Science.gov (United States)

    ... Vomiting Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath ... worse or doesn’t get better. Start OverDiagnosisYour pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

  17. Towards ensuring gender equity.

    Science.gov (United States)

    Basu, A

    1996-01-01

    All people should participate in the development process. Many, however, remain excluded from the benefits of development. For example, women are privy to only a small share of developmental opportunities. The goals of equality, development, and peace were stated during the Fourth World Conference on Women held in Beijing in September 1995. The author considers whether women truly have equitable access to literacy, education, food, nutrition, health, employment, and the political and economic decision making process. She stresses that the goals pronounced at the Fourth World Conference on Women must be backed up with the necessary resources, including institutions established at the local, state, and national levels to ensure that the objectives are implemented and the implementation is monitored. The author further argues that in order for women to achieve equality with men, all girls must have access to primary and secondary schools; basic literacy is inadequate. Moreover, gender stereotyping must be avoided and gender sensitization ensured at all levels.

  18. Photolabile linker for the synthesis of hydroxamic acids

    DEFF Research Database (Denmark)

    2013-01-01

    a hydroxylamine - functionalized photolabile linker, and the so produced hydroxylamine - functionalized photolabile solid support. The invention further provides a method for synthesizing a one-bead-one compound library of hydroxamic acid derivatives on a photolabile linker, as well as a method for screening...

  19. Duality ensures modular covariance

    International Nuclear Information System (INIS)

    Li Miao; Yu Ming

    1989-11-01

    We show that the modular transformations for one point functions on the torus, S(n), satisfy the polynomial equations derived by Moore and Seiberg, provided the duality property of the model is ensured. The formula for S(n) is derived by us previously and should be valid for any conformal field theory. As a consequence, the full consistency conditions for modular invariance at higher genus are completely guaranteed by duality of the theory on the sphere. (orig.)

  20. A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

    2016-01-01

    Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

  1. Neck pain

    Science.gov (United States)

    ... cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such ... of a heart attack , such as shortness of breath, sweating, nausea, vomiting, or arm or jaw pain. ...

  2. Bifunctional bridging linker-assisted synthesis and characterization of TiO{sub 2}/Au nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Žunič, Vojka, E-mail: vojka.zunic@ijs.si, E-mail: vojka13@gmail.com; Kurtjak, Mario; Suvorov, Danilo [Jožef Stefan Institute, Advanced Materials Department (Slovenia)

    2016-11-15

    Using a simple organic bifunctional bridging linker, titanium dioxide (TiO{sub 2}) nanoparticles were coupled with the Au nanoparticles to form TiO{sub 2}/Au nanocomposites with a variety of Au loadings. This organic bifunctional linker, meso-2,3-dimercaptosuccinic acid, contains two types of functional groups: (i) the carboxyl group, which enables binding to the TiO{sub 2}, and (ii) the thiol group, which enables binding to the Au. In addition, the organic bifunctional linker acts as a stabilizing agent to prevent the agglomeration and growth of the Au particles, resulting in the formation of highly dispersed Au nanoparticles. To form the TiO{sub 2}/Au nanocomposites in a simple way, we deliberately applied a synthetic method that simultaneously ensures: (i) the capping of the Au nanoparticles and (ii) the binding of different amounts of Au to the TiO{sub 2}. The TiO{sub 2}/Au nanocomposites formed with this method show enhanced UV and Vis photocatalytic activities when compared to the pure TiO{sub 2} nanopowders.Graphical Abstract.

  3. Structural Mechanisms of Nucleosome Recognition by Linker Histones.

    Science.gov (United States)

    Zhou, Bing-Rui; Jiang, Jiansheng; Feng, Hanqiao; Ghirlando, Rodolfo; Xiao, T Sam; Bai, Yawen

    2015-08-20

    Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Toward Ensuring Health Equity

    DEFF Research Database (Denmark)

    Petkovic, Jennifer; Epstein, Jonathan; Buchbinder, Rachelle

    2015-01-01

    , the Evaluative Linguistic Framework for Questionnaires, developed to assess text quality of questionnaires. We also considered a study assessing cross-cultural adaptation with/without back-translation and/or expert committee. The results of this preconference work were presented to the equity working group......OBJECTIVE: The goal of the Outcome Measures in Rheumatology (OMERACT) 12 (2014) equity working group was to determine whether and how comprehensibility of patient-reported outcome measures (PROM) should be assessed, to ensure suitability for people with low literacy and differing cultures. METHODS......: The English, Dutch, French, and Turkish Health Assessment Questionnaires and English and French Osteoarthritis Knee and Hip Quality of Life questionnaires were evaluated by applying 3 readability formulas: Flesch Reading Ease, Flesch-Kincaid grade level, and Simple Measure of Gobbledygook; and a new tool...

  5. Nanohashtag structures based on carbon nanotubes and molecular linkers

    Science.gov (United States)

    Frye, Connor W.; Rybolt, Thomas R.

    2018-03-01

    Molecular mechanics was used to study the noncovalent interactions between single-walled carbon nanotubes and molecular linkers. Groups of nanotubes have the tendency to form tight, parallel bundles (||||). Molecular linkers were introduced into our models to stabilize nanostructures with carbon nanotubes held in perpendicular orientations. Molecular mechanics makes it possible to estimate the strength of noncovalent interactions holding these structures together and to calculate the overall binding energy of the structures. A set of linkers were designed and built around a 1,3,5,7-cyclooctatetraene tether with two corannulene containing pincers that extend in opposite directions from the central cyclooctatetraene portion. Each pincer consists of a pairs of "arms." These molecular linkers were modified so that the "hand" portions of each pair of "arms" could close together to grab and hold two carbon nanotubes in a perpendicular arrangement. To illustrate the possibility of more complicated and open perpendicular CNTs structures, our primary goal was to create a model of a nanohashtag (#) CNT conformation that is more stable than any parallel CNT arrangements with bound linker molecules forming clumps of CNTs and linkers in non-hashtag arrangements. This goal was achieved using a molecular linker (C280H96) that utilizes van der Waals interactions to two perpendicular oriented CNTs. Hydrogen bonding was then added between linker molecules to augment the stability of the hashtag structure. In the hashtag structure with hydrogen bonding, four (5,5) CNTs of length 4.46 nm (18 rings) and four linkers (C276H92N8O8) stabilized the hashtag so that the average binding energy per pincer was 118 kcal/mol.

  6. Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker

    Directory of Open Access Journals (Sweden)

    Yunlong Si

    2016-12-01

    Full Text Available Galectin-8 (Gal-8 plays a significant role in normal immunological function as well as in cancer. This lectin contains two carbohydrate recognition domains (CRD connected by a peptide linker. The N-terminal CRD determines ligand binding specificity, whereas the linker has been proposed to regulate overall Gal-8 function, including multimerization and biological activity. Here, we crystallized the Gal-8 N-terminal CRD with the peptide linker using a crystallization condition that contains Ni2+. The Ni2+ ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni2+ and Asp25 plays an indirect role in determining the structure of β-strand F0 and in influencing the linker conformation which could not be defined due to its dynamic nature. The linker was also shortened in situ and crystallized under a different condition, leading to a higher resolution structure refined to 1.08 Å. This crystal structure allowed definition of a short portion of the linker interacting with the Gal-8 N-terminal tail via ionic interactions and hydrogen bonds. Observation of two Gal-8 N-terminal CRD structures implies that the N-terminal tail and the linker may influence each other’s conformation. In addition, under specific crystallization conditions, glycerol could replace lactose and was observed at the carbohydrate binding site. However, glycerol did not show inhibition activity in hemagglutination assay.

  7. Ensuring food security

    Directory of Open Access Journals (Sweden)

    Valeriy Valentinovich Patsiorkovskiy

    2011-12-01

    Full Text Available This paper is devoted to the questions of further development of agricultural and food policy in the Russian Federation. The subject of in-depth consideration is the problem related to ensuring food safety. A critical review and analysis of major regulations in the field of food safety is made, including in the implementation of sanitary and epidemiological surveillance. The necessity of the expansion of measures to improve the statistics of food poisoning is grounded. The basic reasons for the spread of management practices of production and sale of food products that pose a threat to human life are revealed. The factors of unhindered penetration of local markets in the cities and the surrounding countrysides with counterfeiting, smuggling and production of global junk food manufacturers and consumer goods are defined. A systematic view is put on the problems of food production in the private farms, ways to limit direct access to the market of food and food raw materials, which production was not controlled and who have not passed state registration, are suggested. One of these problems is creation of independent industrial structures that link production and sales of small-scale sector goods.

  8. Novel mixing method for cross linker introduction into droplet emulsions

    CSIR Research Space (South Africa)

    Land, KJ

    2013-10-01

    Full Text Available the introduction of cross linker after droplet formation, together with the utilisation of topological microfluidic channel structures, allowing for the novel manufacture of particles. Flow over these structures has been simulated in order to choose the most...

  9. Linker-mediated assembly of gold nanoparticles into multimeric motifs

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, Mateusz; Cieplak, Marek [Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32/46, 02-668 Warsaw (Poland); Szymczak, Piotr [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw, ulica Hoza 69, 00-681 Warsaw (Poland); Thompson, Damien, E-mail: mc@ifpan.edu.pl [Tyndall National Institute, Lee Maltings, University College Cork, Cork (Ireland)

    2011-11-04

    We present a theoretical description of linker-mediated self-assembly of gold nanoparticles (Au-NP). Using mesoscale simulations with a coarse-grained model for the Au NPs and dirhenium-based linker molecules, we investigate the conditions under which large clusters can grow and construct a phase diagram that identifies favorable growth conditions in terms of floating and bound linker concentrations. The findings can be considered as generic, as we expect other NP-linker systems to behave in a qualitatively similar way. In particular, we also discuss the case of antibody-functionalised Au NPs connected by the C-reactive proteins (CRPs). We extract some general rules for NP linking that may aid the production of size- and shape-specific NP clusters for technology applications.

  10. Improved sensitivity of a graphene FET biosensor using porphyrin linkers

    Science.gov (United States)

    Kawata, Takuya; Ono, Takao; Kanai, Yasushi; Ohno, Yasuhide; Maehashi, Kenzo; Inoue, Koichi; Matsumoto, Kazuhiko

    2018-06-01

    Graphene FET (G-FET) biosensors have considerable potential due to the superior characteristics of graphene. Realizing this potential requires judicious choice of the linker molecule connecting the target-specific receptor molecule to the graphene surface, yet there are few reports comparing linker molecules for G-FET biosensors. In this study, tetrakis(4-carboxyphenyl)porphyrin (TCPP) was used as a linker for surface modification of a G-FET and the properties of the device were compared to those of a G-FET device modified with the conventional linker 1-pyrenebutanoic acid succinimidyl ester (PBASE). TCPP modification resulted in a higher density of receptor immunoglobulin E (IgE) aptamer molecules on the G-FET. The detection limit of the target IgE was enhanced from 13 nM for the PBASE-modified G-FET to 2.2 nM for the TCPP-modified G-FET, suggesting that the TCPP linker is a powerful candidate for G-FET modification.

  11. A streptavidin linker layer that functions after drying.

    Science.gov (United States)

    Xia, Nan; Shumaker-Parry, Jennifer S; Zareie, M Hadi; Campbell, Charles T; Castner, David G

    2004-04-27

    The ability of streptavidin (SA) to simultaneously bind four biotins is often used in linker layers, where a biotinylated molecule is linked to a biotin-functionalized surface via SA. For biosensor and array applications, it is desirable that the SA linker layer be stable to drying and rehydration. In this study it was observed that a significant decrease in binding capacity of a SA layer occurred when that layer was dried. For this study a SA linker layer was constructed by binding SA to a biotin-containing alkylthiolate monolayer (BAT/OEG) self-assembled onto gold. Its stability after drying was investigated using surface plasmon resonance (SPR). Approximately a quarter of the SA layer was removed from the BAT/OEG surface upon drying and rehydration, suggesting disruption of SA-biotin binding when dry. This resulted in the dried SA layer losing approximately 40% of its biotinylated ferritin (BF) binding capacity. Coating the layer with trehalose before drying was found to inhibit the loss of SA from the BAT/OEG surface. SPR showed that the trehalose-protected SA linker layer retained approximately 91% of its original BF binding capacity after drying and rehydration. Atomic force microscopy, which was used to image individual surface-bound SA and BF molecules, qualitatively confirmed these observations.

  12. Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks

    KAUST Repository

    Feng, Liang; Yuan, Shuai; Zhang, Liang-Liang; Tan, Kui; Li, Jia-Luo; Kirchon, Angelo; Liu, Ling-Mei; Zhang, Peng; Han, Yu; Chabal, Yves J.; Zhou, Hong-Cai

    2018-01-01

    strate-gy, linker thermolysis, to construct ultra-stable hierarchically porous metal−organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores

  13. Open and Closed: The Roles of Linker Histones in Plants and Animals

    OpenAIRE

    Over, Ryan S.; Michaels, Scott D.

    2014-01-01

    Linker histones play key roles alongside core histones in the regulation and maintenance of chromatin. Here, we illustrate our current understanding of the contributions of linker histones to the cell cycle, development, and chromatin structure in plants and animals.

  14. Neck curve polynomials in neck rupture model

    International Nuclear Information System (INIS)

    Kurniadi, Rizal; Perkasa, Yudha S.; Waris, Abdul

    2012-01-01

    The Neck Rupture Model is a model that explains the scission process which has smallest radius in liquid drop at certain position. Old fashion of rupture position is determined randomly so that has been called as Random Neck Rupture Model (RNRM). The neck curve polynomials have been employed in the Neck Rupture Model for calculation the fission yield of neutron induced fission reaction of 280 X 90 with changing of order of polynomials as well as temperature. The neck curve polynomials approximation shows the important effects in shaping of fission yield curve.

  15. Head and neck cancer

    International Nuclear Information System (INIS)

    Vogl, S.E.

    1988-01-01

    This book contains 10 chapters. Some of the titles are: Combined Surgical Resection and Irradiation for Head and Neck Cancers; Analysis of Radiation Therapy Oncology Group Head and Neck Database: Identification of Prognostic Factors and the Re-evaluation of American Joint Committee Stages; Combined Modality Approach to Head and Neck Cancer; Induction Combination Chemotherapy of Regionally Advanced Head and Neck Cancer; and Outcome after Complete Remission to Induction Chemotherapy in Head and Neck Cancer

  16. Dipolar cross-linkers for PDMS networks with enhanced dielectric permittivity and low dielectric loss

    DEFF Research Database (Denmark)

    Bahrt, Frederikke; Daugaard, Anders Egede; Hvilsted, Søren

    2013-01-01

    -(4-((4-nitrophenyl)diazenyl)phenoxy)-prop-1-yn-1-ylium, with a synthesized silicone compatible azide-functional cross-linker by click chemistry. The thermal, mechanical and electromechanical properties were investigated for PDMS films with 0 to 3.6 wt% of dipole-cross-linker. The relative dielectric permittivity......Dipole grafted cross-linkers were utilized to prepare polydimethylsiloxane (PDMS) elastomers with various chain lengths and with various concentrations of functional cross-linker. The grafted cross-linkers were prepared by reaction of two alkyne-functional dipoles, 1-ethynyl-4-nitrobenzene and 3...

  17. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  18. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with ... and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with ...

  19. Ensuring a Safe Technological Revolution

    Science.gov (United States)

    2016-12-01

    much lower, and the performance gained can dramatically reduce life -cycle costs. Validated cost data are scarce, and accurate AM cost models need to be...reduce costs, minimize obsolescence issues and improve both capability and readi- ness across the entire life cycle of naval systems—including both the...of naval weapon systems. The Navy is actively engaging its various communi- ties to align needs and ensure that AM can be safely acceler- ated and

  20. Neck x-ray

    Science.gov (United States)

    X-ray - neck; Cervical spine x-ray; Lateral neck x-ray ... There is low radiation exposure. X-rays are monitored so that the lowest amount of radiation is used to produce the image. Pregnant women and ...

  1. The flexibility of modified-linker MIL-53 materials.

    Science.gov (United States)

    Munn, Alexis S; Pillai, Renjith S; Biswas, Shyam; Stock, Norbert; Maurin, Guillaume; Walton, Richard I

    2016-03-14

    The flexibility of eight aluminium hydroxo terephthalates [Al(OH)(BDC-X)]·n(guest) (BDC = 1,4-benzene-dicarboxylate; X = -H, -CH3, -Cl, -Br, -NH2, -NO2, -(OH)2, -CO2H) crystallising in the MIL-53-type structure was investigated upon thermal dehydration of as-made samples, superhydration and methanol adsorption/desorption using in situ powder X-ray diffraction (PXRD). Profile fitting was used to determine lattice parameters as a function of time and/or temperature to describe their structural evolution. It has thus been shown that while methanol vapour adsorption induces an opening of all the modified frameworks, except the -NH2 material, superhydration only leads to open structures for Al-MIL-53-NO2, -Br and -(OH)2. All the MIL-53 solids, except Al-MIL-53-(OH)2 are present in the open structures upon thermal dehydration. In addition to the exploration of the breathing behavior of this MIL-53 series, the issue of disorder in the distribution of the functional groups between the organic linkers was explored. As a typical illustration, density functional theory calculations were carried out on different structures of Al-MIL-53-Cl, in which the distribution of -Cl within two adjacent BDC linkers is varied. The results show that the most energetically stable configuration leads to the best agreement with the experimental PXRD pattern. This observation supports that the distribution of the selected linker substituent in the functionalised solid is governed by energetics and that there is a preference for an ordering of this arrangement.

  2. Investigation of the Linker Swing Motion in the Zeolitic Imidazolate Framework ZIF-90

    KAUST Repository

    Zheng, Bin

    2018-03-13

    The linker swing motion in the zeolitic imidazolate framework ZIF-90 is investigated by density functional theory (DFT) calculation, molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations. The relation between the terminal aldehyde group rotation and the linker swing motion is revealed. The extremely high activation energy of the linker swing motion in ZIF-90 can be attributed to the asymmetric geometry and electron distribution of aldehyde groups. The change in the gate structure resulting from the linker rotation is used to understand the guest adsorption in ZIF-90. This study shows that it is possible to tune the linker swing motion and then the properties of ZIF-90 by manipulating the terminal group rotation. The results highlight the importance of considering the internal freedom effects to correctly describe the linker swing motion and the flexibility of metal-organic frameworks (MOFs).

  3. Open and closed: the roles of linker histones in plants and animals.

    Science.gov (United States)

    Over, Ryan S; Michaels, Scott D

    2014-03-01

    Histones package DNA in all eukaryotes and play key roles in regulating gene expression. Approximately 150 base pairs of DNA wraps around an octamer of core histones to form the nucleosome, the basic unit of chromatin. Linker histones compact chromatin further by binding to and neutralizing the charge of the DNA between nucleosomes. It is well established that chromatin packing is regulated by a complex pattern of posttranslational modifications (PTMs) to core histones, but linker histone function is less well understood. In this review, we describe the current understanding of the many roles that linker histones play in cellular processes, including gene regulation, cell division, and development, while putting the linker histone in the context of other nuclear proteins. Although intriguing roles for plant linker histones are beginning to emerge, much of our current understanding comes from work in animal systems. Many unanswered questions remain and additional work is required to fully elucidate the complex processes mediated by linker histones in plants.

  4. Specific distribution of the Saccharomyces cerevisiae linker histone homolog HHO1p in the chromatin

    OpenAIRE

    Freidkin, Ilya; Katcoff, Don J.

    2001-01-01

    In virtually all eukaryotic organisms, linker DNA between nucleosomes is associated with a histone termed linker histone or histone H1. In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The encoded protein is expressed in the nucleus, but has not been shown to affect global chromatin structure, nor has its deletion shown any detectable phenotype. In vitro chromatin assembly experiments with recombinant HHO1p have shown that it is...

  5. Tunable CO 2 Adsorbents by Mixed-Linker Synthesis and Postsynthetic Modification of Zeolitic Imidazolate Frameworks

    KAUST Repository

    Thompson, Joshua A.

    2013-04-25

    The incorporation of accessible amine functionality in zeolitic imidazolate frameworks (ZIFs) is used to improve the adsorption selectivity for CO 2/CH4 gas separation applications. Two synthetic approaches are described in this work to introduce functionality into the ZIF: (i) mixed-linker ZIF synthesis with 2-aminobenzimidazole as a substitution linker and (ii) postsynthetic modification of a mixed-linker ZIF with ethylenediamine. Using 2-aminobenzimidazole, a linker with a primary amine functional group, substitution of the ZIF-8 linker during synthesis allows for control over the adsorption properties while maintaining the ZIF-8 structure with up to nearly 50% substitution in the mixed-linker ZIF framework, producing a material with tunable pore size and amine functionality. Alternatively, postsynthetic modification of a mixed-linker ZIF containing an aldehyde functional group produces a ZIF material with a primary amine without detrimental loss of micropore volume by controlling the amount of functional group sites for modification. Both approaches using mixed-linker ZIFs yield new materials that show improvement in adsorption selectivity for the CO 2/CH4 gas pair over ZIF-8 and commercially available adsorbents as well as an increase in the heat of adsorption for CO2 without significant changes to the crystal structure. These results indicate that tuning the surface properties of ZIFs by either mixed-linker synthesis and/or postsynthetic modification may generate new materials with improved gas separation properties, thereby providing a new method for tailoring metal-organic frameworks. © 2013 American Chemical Society.

  6. Tunable CO 2 Adsorbents by Mixed-Linker Synthesis and Postsynthetic Modification of Zeolitic Imidazolate Frameworks

    KAUST Repository

    Thompson, Joshua A.; Brunelli, Nicholas A.; Lively, Ryan P.; Johnson, J. R.; Jones, Christopher W.; Nair, Sankar

    2013-01-01

    The incorporation of accessible amine functionality in zeolitic imidazolate frameworks (ZIFs) is used to improve the adsorption selectivity for CO 2/CH4 gas separation applications. Two synthetic approaches are described in this work to introduce functionality into the ZIF: (i) mixed-linker ZIF synthesis with 2-aminobenzimidazole as a substitution linker and (ii) postsynthetic modification of a mixed-linker ZIF with ethylenediamine. Using 2-aminobenzimidazole, a linker with a primary amine functional group, substitution of the ZIF-8 linker during synthesis allows for control over the adsorption properties while maintaining the ZIF-8 structure with up to nearly 50% substitution in the mixed-linker ZIF framework, producing a material with tunable pore size and amine functionality. Alternatively, postsynthetic modification of a mixed-linker ZIF containing an aldehyde functional group produces a ZIF material with a primary amine without detrimental loss of micropore volume by controlling the amount of functional group sites for modification. Both approaches using mixed-linker ZIFs yield new materials that show improvement in adsorption selectivity for the CO 2/CH4 gas pair over ZIF-8 and commercially available adsorbents as well as an increase in the heat of adsorption for CO2 without significant changes to the crystal structure. These results indicate that tuning the surface properties of ZIFs by either mixed-linker synthesis and/or postsynthetic modification may generate new materials with improved gas separation properties, thereby providing a new method for tailoring metal-organic frameworks. © 2013 American Chemical Society.

  7. Germline-specific H1 variants: the "sexy" linker histones.

    Science.gov (United States)

    Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

    2016-03-01

    The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

  8. Communication equipment radiation resistance ensurance

    International Nuclear Information System (INIS)

    Myrova, L.O.; Chelizhenko, A.Z.

    1983-01-01

    A review of works on radiation resistance of electronic equipment (epsilon epsilon) for 15 years is presented. The effect of ionizing radiation appearing as a result of nuclear explosions in nuclear facilities and in outerspace on epsilon epsilon has been considered. Types of radiation effects in epsilon epsilon, radiation effect on semiconductor devices and integrated circUits, types of epsilon epsilon failures, as well as the procass of radiation-resistant epsilon epsilon designing and selection of its main parameters have been described. The methods of epsilon epsilon flowsheet optimization, application of mathematical simulation and peculiarities of ensurance of epsilon epsilon radiation resistance of communication systems are considered. Peculiarities of designing of radiation-resistant quartz generators, secondary power supply sources and amplifiers are discussed

  9. Cellulase linkers are optimized based on domain type and function: insights from sequence analysis, biophysical measurements, and molecular simulation.

    Directory of Open Access Journals (Sweden)

    Deanne W Sammond

    Full Text Available Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs to carbohydrate-binding modules (CBMs. Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests

  10. Engineering of a novel Ca2+-regulated kinesin molecular motor using a calmodulin dimer linker

    International Nuclear Information System (INIS)

    Shishido, Hideki; Maruta, Shinsaku

    2012-01-01

    Highlights: ► Engineered kinesin–M13 and calmodulin involving single cysteine were prepared. ► CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. ► Kinesin–M13 was dimerized via CaM dimer in the presence of calcium. ► Function of the engineered kinesin was regulated by a Ca 2+ -calmodulin dimer linker. -- Abstract: The kinesin–microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have “on–off” control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355–M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355–M13 dimerization with CaM dimers, we measured K355–M13 motility and found that it can be reversibly regulated in a Ca 2+ -dependent manner. We also found that velocities of K355–M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca 2+ -dependent dimerization of K355–M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  11. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

    Science.gov (United States)

    Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

    2017-11-15

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Description of a cellulose-binding domain and a linker sequence from Aspergillus fungi

    NARCIS (Netherlands)

    Quentin, M; Ebbelaar, M; Derksen, J; Mariani, C; van der Valk, H

    A family I cellulose-binding domain (CBD) and a serine- and threonine-rich linker peptide were cloned from the fungi Aspergillus japonicus and Aspergillus aculeatus. A glutathione S-transferase (GST) fusion protein comprising GST and a peptide linker with the CBD fused to its C-terminus, was

  13. Novel silicone compatible cross-linkers for controlled functionalization of PDMS networks

    DEFF Research Database (Denmark)

    Madsen, Frederikke Bahrt; Daugaard, Anders Egede; Hvilsted, Søren

    2013-01-01

    . In order to improve the dielectric properties of PDMS a novel system is developed where push-pull dipoles are grafted to a new silicone compatible cross-linker. The grafted cross-linkers are prepared by reaction of two different push-pull dipole alkynes as well as a fluorescent alkyne with the new azide...

  14. P-Link: A method for generating multicomponent cytochrome P450 fusions with variable linker length

    DEFF Research Database (Denmark)

    Belsare, Ketaki D.; Ruff, Anna Joelle; Martinez, Ronny

    2014-01-01

    Fusion protein construction is a widely employed biochemical technique, especially when it comes to multi-component enzymes such as cytochrome P450s. Here we describe a novel method for generating fusion proteins with variable linker lengths, protein fusion with variable linker insertion (P...

  15. Library of biphenyl privileged substructures using a safety-catch linker approach

    DEFF Research Database (Denmark)

    Severinsen, Rune; Bourne, Gregory T; Tran, Tran T

    2008-01-01

    A biphenyl privileged structure library containing three attachment points were synthesized using a catechol-based safety-catch linker strategy. The method requires the attachment of a bromo-acid to the linker, followed by a Pd-catalyzed Suzuki cross-coupling reaction. Further derivatization...

  16. The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

    Science.gov (United States)

    Chen, Shugui; Brier, Sébastien; Smithgall, Thomas E; Engen, John R

    2007-04-01

    The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain.

  17. Linkers, resins, and general procedures for solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

    2013-01-01

    and linkers for solid-phase synthesis is a key parameter for successful peptide synthesis. This chapter provides an overview of the most common and useful resins and linkers for the synthesis of peptides with C-terminal amides, carboxylic acids, and more. The chapter finishes with robust protocols for general...

  18. Construction of hierarchically porous metal-organic frameworks through linker labilization

    Science.gov (United States)

    Yuan, Shuai; Zou, Lanfang; Qin, Jun-Sheng; Li, Jialuo; Huang, Lan; Feng, Liang; Wang, Xuan; Bosch, Mathieu; Alsalme, Ali; Cagin, Tahir; Zhou, Hong-Cai

    2017-05-01

    A major goal of metal-organic framework (MOF) research is the expansion of pore size and volume. Although many approaches have been attempted to increase the pore size of MOF materials, it is still a challenge to construct MOFs with precisely customized pore apertures for specific applications. Herein, we present a new method, namely linker labilization, to increase the MOF porosity and pore size, giving rise to hierarchical-pore architectures. Microporous MOFs with robust metal nodes and pro-labile linkers were initially synthesized. The mesopores were subsequently created as crystal defects through the splitting of a pro-labile-linker and the removal of the linker fragments by acid treatment. We demonstrate that linker labilization method can create controllable hierarchical porous structures in stable MOFs, which facilitates the diffusion and adsorption process of guest molecules to improve the performances of MOFs in adsorption and catalysis.

  19. Head and Neck Cancer Treatment

    Science.gov (United States)

    ... Professions Site Index A-Z Head and Neck Cancer Treatment Head and neck cancer overview What are my ... and neck cancer. For updated information on new cancer treatments that are available, you should discuss these issues ...

  20. Congenital neck masses.

    Science.gov (United States)

    Rosa, Peter A; Hirsch, David L; Dierks, Eric J

    2008-08-01

    Congenital neck lesions reflect abnormal embryogenesis in head and neck development. A thorough knowledge of embryology and anatomy is critical in the diagnosis and treatment of these lesions. The appropriate diagnosis of these lesions is necessary to provide appropriate treatment and long-term follow up, because some of these lesions may undergo malignant transformation or be harbingers of malignant disease.

  1. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Ichida, Yu, E-mail: ichida-y@ncchd.go.jp; Utsunomiya, Yuko; Onodera, Masafumi

    2016-03-18

    Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are required for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.

  2. Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

    Directory of Open Access Journals (Sweden)

    Maike Martini

    2016-09-01

    Full Text Available Polyelectrolyte hydrogels play an important role in tissue engineering and can be produced from natural polymers, such as the glycosaminoglycan hyaluronan. In order to control charge density and mechanical properties of hyaluronan-based hydrogels, we developed cross-linkers with a neutral or positively charged triazole core with different lengths of spacer arms and two terminal maleimide groups. These cross-linkers react with thiolated hyaluronan in a fast, stoichiometric thio-Michael addition. Introducing a positive charge on the core of the cross-linker enabled us to compare hydrogels with the same interconnectivity, but a different charge density. Positively charged cross-linkers form stiffer hydrogels relatively independent of the size of the cross-linker, whereas neutral cross-linkers only form stable hydrogels at small spacer lengths. These novel cross-linkers provide a platform to tune the hydrogel network charge and thus the mechanical properties of the network. In addition, they might offer a wide range of applications especially in bioprinting for precise design of hydrogels.

  3. Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks.

    Science.gov (United States)

    Feng, Liang; Yuan, Shuai; Zhang, Liang-Liang; Tan, Kui; Li, Jia-Luo; Kirchon, Angelo; Liu, Ling-Mei; Zhang, Peng; Han, Yu; Chabal, Yves J; Zhou, Hong-Cai

    2018-02-14

    Sufficient pore size, appropriate stability, and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization, and catalysis involving large molecules. Herein, we report a powerful and general strategy, linker thermolysis, to construct ultrastable hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal-organic frameworks (MTV-MOFs) through a decarboxylation process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultrasmall metal oxide nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid-catalyzed reactions. Most importantly, this work provides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on probing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.

  4. Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks

    KAUST Repository

    Feng, Liang

    2018-01-18

    Sufficient pore size, appropriate stability and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization and catalysis involving large molecules. Herein, we report a powerful and general strate-gy, linker thermolysis, to construct ultra-stable hierarchically porous metal−organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal-organic frameworks (MTV-MOFs) through a decarboxyla-tion process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultra-small metal oxide (MO) nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid catalyzed reactions. Most importantly, this work pro-vides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on prob-ing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.

  5. Morbidity of the neck after head and neck cancer therapy

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    Background. Studies on morbidity of the neck after head and neck cancer therapy are scarcely described. Methods. Patients who underwent surgery, including neck dissection, with and without radiation therapy at least 1 year before the study were asked to participate. We assessed neck pain, loss of

  6. A Traceless Aryl-Triazene Linker for DNA-Directed Chemistry

    DEFF Research Database (Denmark)

    Hejesen, Christian; Pedersen, Lars Kolster; Gothelf, Kurt Vesterager

    2013-01-01

    DNA-directed synthesis of encoded combinatorial libraries of small organic compounds most often involves transfer of organic building blocks from one DNA strand to another. This requires cleavable linkers to enable cleavage of the link to the original DNA strand from which the building block...... is transferred. Relatively few cleavable linkers are available for DNA-directed synthesis and most often they leave an amino group at the organic molecule. Here we have extended the application of 10 aryltriazenes as traceless linkers for DNA-directed synthesis. After reaction of one building block...

  7. Pitfalls in neck imaging

    International Nuclear Information System (INIS)

    Gay, S.B.; Phillips, C.D.; Cornett, J.B.

    1991-01-01

    CT and MR imaging have become effective imaging modalities in the evaluation of primary head and neck neoplasms. As radiologists have gained experience in head and neck imaging, certain pitfalls have become evident. Identification of pathologic lymph nodes is the critical element in staging neoplasms of the head and neck. The diagnosis of cervical lymphadenopathy may be complicated by confusion with normal structures, inadequate contrast opacification of vascular structures, and poor scanning technique. This paper illustrates these potential problem areas on both CT and MR images and offers the authors' approach to further evaluation in problem cases

  8. Multidisciplinary treatment of the neck

    NARCIS (Netherlands)

    de Bree, Remco; Langendijk, Johannes A.; Leemans, C. R.

    2016-01-01

    Since lymph node metastases are one of the most important prognostic factors, treatment of the neck is challenging. In clinically N0 neck, (super)selective neck dissection is indicated, whereas a more extensive neck dissection with preservation of important structures is performed in N2-N3 disease.

  9. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  10. Head, Neck, and Oral Cancer

    Science.gov (United States)

    ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  11. Tethering metal ions to photocatalyst particulate surfaces by bifunctional molecular linkers for efficient hydrogen evolution

    KAUST Repository

    Yu, Weili

    2014-08-19

    A simple and versatile method for the preparation of photocatalyst particulates modified with effective cocatalysts is presented; the method involves the sequential soaking of photocatalyst particulates in solutions containing bifunctional organic linkers and metal ions. The modification of the particulate surfaces is a universal and reproducible method because the molecular linkers utilize strong covalent bonds, which in turn result in modified monolayer with a small but controlled quantity of metals. The photocatalysis results indicated that the CdS with likely photochemically reduced Pd and Ni, which were initially immobilized via ethanedithiol (EDT) as a linker, were highly efficient for photocatalytic hydrogen evolution from Na2S-Na2SO3-containing aqueous solutions. The method developed in this study opens a new synthesis route for the preparation of effective photocatalysts with various combinations of bifunctional linkers, metals, and photocatalyst particulate materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Tethering metal ions to photocatalyst particulate surfaces by bifunctional molecular linkers for efficient hydrogen evolution

    KAUST Repository

    Yu, Weili; Isimjan, Tayirjan T.; Del Gobbo, Silvano; Anjum, Dalaver Hussain; Abdel-Azeim, Safwat; Cavallo, Luigi; Garcia Esparza, Angel T.; Domen, Kazunari; Xu, Wei; Takanabe, Kazuhiro

    2014-01-01

    A simple and versatile method for the preparation of photocatalyst particulates modified with effective cocatalysts is presented; the method involves the sequential soaking of photocatalyst particulates in solutions containing bifunctional organic linkers and metal ions. The modification of the particulate surfaces is a universal and reproducible method because the molecular linkers utilize strong covalent bonds, which in turn result in modified monolayer with a small but controlled quantity of metals. The photocatalysis results indicated that the CdS with likely photochemically reduced Pd and Ni, which were initially immobilized via ethanedithiol (EDT) as a linker, were highly efficient for photocatalytic hydrogen evolution from Na2S-Na2SO3-containing aqueous solutions. The method developed in this study opens a new synthesis route for the preparation of effective photocatalysts with various combinations of bifunctional linkers, metals, and photocatalyst particulate materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. High-Flux Zeolitic Imidazolate Framework Membranes for Propylene/Propane Separation by Postsynthetic Linker Exchange.

    Science.gov (United States)

    Lee, Moon Joo; Kwon, Hyuk Taek; Jeong, Hae-Kwon

    2018-01-02

    While zeolitic imidazolate framework, ZIF-8, membranes show impressive propylene/propane separation, their throughput needs to be greatly improved for practical applications. A method is described that drastically reduces the effective thickness of ZIF-8 membranes, thereby substantially improving their propylene permeance (that is, flux). The new strategy is based on a controlled single-crystal to single-crystal linker exchange of 2-methylimidazole in ZIF-8 membrane grains with 2-imidazolecarboxaldehyde (ZIF-90 linker), thereby enlarging the effective aperture size of ZIF-8. The linker-exchanged ZIF-8 membranes showed a drastic increase in propylene permeance by about four times, with a negligible loss in propylene/propane separation factor when compared to as-prepared membranes. The linker-exchange effect depends on the membrane synthesis method. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Investigation of the Linker Swing Motion in the Zeolitic Imidazolate Framework ZIF-90

    KAUST Repository

    Zheng, Bin; Fu, Fang; Wang, Lian Li; Yang, Limin; Zhu, Yihan; Du, Huiling

    2018-01-01

    The linker swing motion in the zeolitic imidazolate framework ZIF-90 is investigated by density functional theory (DFT) calculation, molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations. The relation between the terminal

  15. Composite materials with metal oxide attached to lead chalcogenide nanocrystal quantum dots with linkers

    Science.gov (United States)

    Fuke, Nobuhiro; Koposov, Alexey Y; Sykora, Milan; Hoch, Laura

    2014-12-16

    Composite materials useful for devices such as photoelectrochemical solar cells include a substrate, a metal oxide film on the substrate, nanocrystalline quantum dots (NQDs) of lead sulfide, lead selenide, and lead telluride, and linkers that attach the NQDs to the metal oxide film. Suitable linkers preserve the 1s absorption peak of the NQDs. A suitable linker has a general structure A-B-C where A is a chemical group adapted for binding to a MO.sub.x and C is a chemical group adapted for binding to a NQD and B is a divalent, rigid, or semi-rigid organic spacer moiety. Other linkers that preserve the 1s absorption peak may also be used.

  16. LRRC45 Is a Centrosome Linker Component Required for Centrosome Cohesion

    Directory of Open Access Journals (Sweden)

    Runsheng He

    2013-09-01

    Full Text Available During interphase, centrosomes are connected by a proteinaceous linker between the proximal ends of the centrioles, which is important for the centrosomes to function as a single microtubule-organizing center. However, the composition and regulation of centrosomal linker remain largely unknown. Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation. Thus, LRRC45 is a critical component of the proteinaceous linker between two centrioles and is required for centrosome cohesion.

  17. Identification of novel post-translational modifications in linker histones from chicken erythrocytes.

    Science.gov (United States)

    Sarg, Bettina; Lopez, Rita; Lindner, Herbert; Ponte, Inma; Suau, Pedro; Roque, Alicia

    2015-01-15

    Chicken erythrocyte nuclei were digested with micrococcal nuclease and fractionated by centrifugation in low-salt buffer into soluble and insoluble fractions. Post-translational modifications of the purified linker histones of both fractions were analyzed by LC-ESI-MS/MS. All six histone H1 subtypes (H1.01, H1.02, H1.03, H1.10, H1.1L and H1.1R) and histone H5 were identified. Mass spectrometry analysis enabled the identification of a wide range of PTMs, including N(α)-terminal acetylation, acetylation, formylation, phosphorylation and oxidation. A total of nine new modifications in chicken linker histones were mapped, most of them located in the N-terminal and globular domains. Relative quantification of the modified peptides showed that linker histone PTMs were differentially distributed among both chromatin fractions, suggesting their relevance in the regulation of chromatin structure. The analysis of our results combined with previously reported data for chicken and some mammalian species showed that most of the modified positions were conserved throughout evolution, highlighting their importance in specific linker histone functions and epigenetics. Post-translational modifications of linker histones could have a role in the regulation of gene expression through the modulation of chromatin higher-order structure and chromatin remodeling. Finding new PTMs in linker histones is the first step to elucidate their role in the histone code. In this manuscript we report nine new post-translational modifications of the linker histones from chicken erythrocytes, one in H5 and eight in the H1 subtypes. Chromatin fractionated by centrifugation in low-salt buffer resulted in two fractions with different contents and compositions of linker histones and enriched in specific core histone PTMs. Of particular interest is the fact that linker histone PTMs were differentially distributed in both chromatin fractions, suggesting specific functions. Future studies are needed to

  18. Head and Neck Cancers

    Science.gov (United States)

    ... and neck include the following: Paan (betel quid) . Immigrants from Southeast Asia who use paan (betel quid) ... use this content on your website or other digital platform? Our syndication services page shows you how. ...

  19. TCGA head Neck

    Science.gov (United States)

    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).

  20. Neck dissection - discharge

    Science.gov (United States)

    ... drain in your neck when you leave the hospital. The provider will tell you how to care for it. Healing time will depend on how much tissue was removed. Diet and Nutrition You can eat your regular foods ...

  1. Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

    OpenAIRE

    Chang, Keejong; Qian, Jin; Jiang, MeiSheng; Liu, Yi-Hsin; Wu, Ming-Che; Chen, Chi-Dar; Lai, Chao-Kuen; Lo, Hsin-Lung; Hsiao, Chin-Ton; Brown, Lucy; Bolen, James; Huang, Hsiao-I; Ho, Pei-Yu; Shih, Ping Yao; Yao, Chen-Wen

    2002-01-01

    Abstract Background Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. Results The linker protein, a monoclonal ...

  2. Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

    Science.gov (United States)

    Chu, Jacquelene; Cheng, Yu-Ling; Rao, A Venketeshwer; Nouraei, Mehdi; Zarate-Muñoz, Silvia; Acosta, Edgar J

    2014-08-25

    Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for β-carotene and β-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of β-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.

    Science.gov (United States)

    Sauer, J; Christensen, T; Frandsen, T P; Mirgorodskaya, E; McGuire, K A; Driguez, H; Roepstorff, P; Sigurskjold, B W; Svensson, B

    2001-08-07

    Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.

  4. Rational design of molecularly imprinted polymer: the choice of cross-linker.

    Science.gov (United States)

    Muhammad, Turghun; Nur, Zohre; Piletska, Elena V; Yimit, Osmanjan; Piletsky, Sergey A

    2012-06-07

    The paper describes a rational approach for the selection of cross-linkers during the development of molecularly imprinted polymers (MIPs). As a model system for this research MIPs specific for the drug zidovudine (AZT) were designed and tested. Three cross-linkers trimethylolpropane trimethacrylate (TRIM), ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB) were studied. The analogue of zidovudine (AZT) ester (AZT-ES) was used as a dummy template. The imprinting factors for all of the polymers in the static adsorption experiments were calculated. The data on the AZT adsorption by control polymers (CP), which were prepared with different cross-linkers without a functional monomer, was also analyzed. DVB was found to be more inert towards zidovudine than EGDMA and TRIM, which was confirmed by both molecular modelling and adsorption experiments. It was demonstrated that DVB-based polymers had a higher imprinting factor (I = 1.85) compared with other tested cross-linked polymers. It was suggested that the selection of the cross-linker should be based on the strength of the interaction with the template: the cross-linker which displays lower binding of the template should be preferential because it generates MIPs with lower non-specific binding and a higher imprinting factor, and therefore specificity. Which cross-linker to use for the preparation of any particular MIP can be determined by analysis of the interactions between the cross-linker and template. This could be done either virtually using computational modelling or by template adsorption using a small library of polymers prepared using different cross-linkers.

  5. Novel Concepts of MS-Cleavable Cross-linkers for Improved Peptide Structure Analysis

    Science.gov (United States)

    Hage, Christoph; Falvo, Francesco; Schäfer, Mathias; Sinz, Andrea

    2017-10-01

    The chemical cross-linking/mass spectrometry (MS) approach is gaining increasing importance as an alternative method for studying protein conformation and for deciphering protein interaction networks. This study is part of our ongoing efforts to develop innovative cross-linking principles for a facile and efficient assignment of cross-linked products. We evaluate two homobifunctional, amine-reactive, and MS-cleavable cross-linkers regarding their potential for automated analysis of cross-linked products. We introduce the bromine phenylurea (BrPU) linker that possesses a unique structure yielding a distinctive fragmentation pattern on collisional activation. Moreover, BrPU delivers the characteristic bromine isotope pattern and mass defect for all cross-linker-decorated fragments. We compare the fragmentation behavior of the BrPU linker with that of our previously described MS-cleavable TEMPO-Bz linker (which consists of a 2,2,6,6-tetramethylpiperidine-1-oxy moiety connected to a benzyl group) that was developed to perform free-radical-initiated peptide sequencing. Comparative collisional activation experiments (collision-induced dissociation and higher-energy collision-induced dissociation) with both cross-linkers were conducted in negative electrospray ionization mode with an Orbitrap Fusion mass spectrometer using five model peptides. As hypothesized in a previous study, the presence of a cross-linked N-terminal aspartic acid residue seems to be the prerequisite for the loss of an intact peptide from the cross-linked products. As the BrPU linker combines a characteristic mass shift with an isotope signature, it presents a more favorable combination for automated assignment of cross-linked products compared with the TEMPO-Bz linker. [Figure not available: see fulltext.

  6. Structural properties of the linkers connecting the N- and C- terminal domains in the MocR bacterial transcriptional regulators

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-12-01

    Full Text Available Peptide inter-domain linkers are peptide segments covalently linking two adjacent domains within a protein. Linkers play a variety of structural and functional roles in naturally occurring proteins. In this work we analyze the sequence properties of the predicted linker regions of the bacterial transcriptional regulators belonging to the recently discovered MocR subfamily of the GntR regulators. Analyses were carried out on the MocR sequences taken from the phyla Actinobacteria, Firmicutes, Alpha-, Beta- and Gammaproteobacteria. The results suggest that MocR linkers display phylum-specific characteristics and unique features different from those already described for other classes of inter-domain linkers. They show an average length significantly higher: 31.8 ± 14.3 residues reaching a maximum of about 150 residues. Compositional propensities displayed general and phylum-specific trends. Pro is dominating in all linkers. Dyad propensity analysis indicate Pro–Pro as the most frequent amino acid pair in all linkers. Physicochemical properties of the linker regions were assessed using amino acid indices relative to different features: in general, MocR linkers are flexible, hydrophilic and display propensity for β-turn or coil conformations. Linker sequences are hypervariable: only similarities between MocR linkers from organisms related at the level of species or genus could be found with sequence searches. The results shed light on the properties of the linker regions of the new MocR subfamily of bacterial regulators and may provide knowledge-based rules for designing artificial linkers with desired properties.

  7. Internal factors influencing the knowledge continuity ensuring

    Directory of Open Access Journals (Sweden)

    Hana Urbancová

    2012-01-01

    Full Text Available The aim of the systematic ensuring of knowledge continuity is the continuity of an organisation’s development, the quality of managerial positions and the continuity of decision-making. By ensuring knowledge continuity, organisations may gain a performance-enhancing factor. The objective of the article is to identify the level of impact of decisive internal factors determining knowledge continuity ensuring and contributing to the efficiency of the organisations. Knowledge continuity ensuring as an internal force, however, can together with the right employees, help adapt more quickly to external conditions that organisations can hardly control. Monitoring and ensuring knowledge continuity can contribute to a higher quality of processes in general, in particular processes exploiting knowledge, and thus help improve the level of management. The first part of the article presents theoretical views on the aspects of knowledge continuity ensuring in organisations while the second part analyses the findings of the surveys carried out among managers in organisations in the Czech Republic. Based on the summary of the outcomes obtained it is possible to say that internal factors influence knowledge continuity ensuring in organisations, however, the level of impact of individual factors is determined by their size. The findings regarding the impact of each of the factors show that the most significant barriers to knowledge continuity ensuring are those associated with the human factor.

  8. Chemical and enzymatic stability of amino acid prodrugs containing methoxy, ethoxy and propylene glycol linkers.

    Science.gov (United States)

    Gupta, Deepak; Gupta, Sheeba Varghese; Lee, Kyung-Dall; Amidon, Gordon L

    2009-01-01

    We evaluated the chemical and enzymatic stabilities of prodrugs containing methoxy, ethoxy and propylene glycol linkers in order to find a suitable linker for prodrugs of carboxylic acids with amino acids. l-Valine and l-phenylalanine prodrugs of model compounds (benzoic acid and phenyl acetic acid) containing methoxy, ethoxy and propylene glycol linkers were synthesized. The hydrolysis rate profile of each compound was studied at physiologically relevant pHs (1.2, 4, 6 and 7.4). Enzymatic hydrolysis of propylene glycol containing compounds was studied using Caco-2 homogenate as well as purified enzyme valacyclovirase. It was observed that the stability of the prodrugs increases with the linker length (propyl > ethyl > methyl). The model prodrugs were stable at acidic pH as compared to basic pH. It was observed that the prodrug with the aliphatic amino acid promoiety was more stable compared to its aromatic counterpart. The comparison between benzyl and the phenyl model compounds revealed that the amino acid side chain is significant in determining the stability of the prodrug whereas the benzyl or phenyl carboxylic acid had little or no effect on the stability. The enzymatic activation studies of propylene glycol linker prodrug in the presence of valacyclovirase and cell homogenate showed faster generation of the parent drug at pH 7.4. The half-life of prodrugs at pH 7.4 was more than 12 h, whereas in the presence of cell homogenate the half-lives were less than 1 h. Hydrolysis by Caco-2 homogenate generated the parent compound in two steps, where the prodrug was first converted to the intermediate, propylene glycol benzoate, which was then converted to the parent compound (benzoic acid). Enzymatic hydrolysis of propylene glycol containing prodrugs by valacyclovirase showed hydrolysis of the amino acid ester part to generate the propylene glycol ester of model compound (propylene glycol benzoate) as the major product. The amino acid prodrugs containing methoxy

  9. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or pharyngeal cancer this ... and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or pharyngeal cancer this ...

  10. Exercises for mechanical neck disorders

    NARCIS (Netherlands)

    Kay, Theresa M.; Gross, Anita; Goldsmith, Charles H.; Rutherford, Sherrill; Voth, Sandra; Hoving, Jan L.; Brønfort, Gert; Santaguida, Pasqualina L.

    2012-01-01

    Background Neck disorders are common, disabling and costly. The effectiveness of exercise as a physiotherapy intervention remains unclear. Objectives To improve pain, disability, function, patient satisfaction, quality of life and global perceived effect in adults with neck pain. Search methods

  11. Heritability of neck pain

    DEFF Research Database (Denmark)

    Fejer, R; Hartvigsen, J; Kyvik, K O

    2006-01-01

    73%) answered the questions regarding neck pain. Probandwise concordance rates, zygosity-specific odds ratios and tetrachoric correlations showed a significant genetic effect on neck pain. An overall additive genetic component of 44% was found. The genetic effect decreased with age, accounting...... for only 10% in the oldest male group and 0% in the oldest female group. There was a statistically significant difference in heritability between males and females (34 vs 52%, P... gradually less important with increasing age, and environmental factors dominate almost completely in the older age groups....

  12. The measles virus phosphoprotein interacts with the linker domain of STAT1

    International Nuclear Information System (INIS)

    Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

    2013-01-01

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway

  13. The measles virus phosphoprotein interacts with the linker domain of STAT1

    Energy Technology Data Exchange (ETDEWEB)

    Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; Priniski, Lauren; Cattaneo, Roberto

    2013-09-15

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

  14. A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death Inhibitors.

    Directory of Open Access Journals (Sweden)

    Andrew R Schwendeman

    Full Text Available Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila. To develop reagents to manipulate LCD, we established a simple high-throughput screening protocol for interrogating the effects of small molecules on C. elegans linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block linker cell death onset. Of these, five induce animal lethality, and six promote a reversible developmental delay. These results provide proof-of principle validation of our screening protocol, demonstrate that developmental progression is required for linker cell death, and suggest that larger scale screens may identify LCD-specific small-molecule regulators that target the LCD execution machinery.

  15. Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

    Science.gov (United States)

    Meiselbach, Heike; Sticht, Heinrich

    2011-08-01

    The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

  16. Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.

    Science.gov (United States)

    Findeisen, Felix; Minor, Daniel L

    2009-03-01

    Two processes dominate voltage-gated calcium channel (Ca(V)) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The Ca(V)beta/Ca(V)alpha(1)-I-II loop and Ca(2+)/calmodulin (CaM)/Ca(V)alpha(1)-C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6-alpha-interaction domain (AID) linker provides a rigid connection between the pore and Ca(V)beta/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate Ca(V)1.2 (L-type) and Ca(V)2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt Ca(V)beta/I-II association sharply decelerate CDI and reduce a second Ca(2+)/CaM/Ca(V)alpha(1)-C-terminal-mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, Ca(V)beta and the IS6-AID linker, are essential for calcium-dependent modulation, and that both Ca(V)beta-dependent and CaM-dependent components couple to the pore by a common mechanism requiring Ca(V)beta and an intact IS6-AID linker.

  17. (indigenous) education ensure effective gender mainstreaming in ...

    African Journals Online (AJOL)

    Leaving no one behind: can (indigenous) education ensure effective gender ... in the distribution of socio-economic and political benefits, depict that additional ... of gender equality and equity and explores in different ways the relationships ...

  18. Writing otorhinolaryngology head & neck surgery operative reports.

    Science.gov (United States)

    Laccourreye, O; Rubin, F; Villeneuve, A; Bonfils, P

    2017-09-01

    Only about ten articles devoted to operative reports have been published in the medical literature, but this document is essential, both medically and legally, to ensure optimal management of operated patients. In this technical note, based on published studies on this subject, the authors describe the key features of operating reports after otorhinolaryngology head & neck surgery and emphasize the need to write this document during the minutes after the end of the operation, the importance of standardization and its teaching role during surgical training. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Linker Histone Phosphorylation Regulates Global Timing of Replication Origin Firing*S⃞

    Science.gov (United States)

    Thiriet, Christophe; Hayes, Jeffrey J.

    2009-01-01

    Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing. PMID:19015270

  20. TC pathological Neck

    International Nuclear Information System (INIS)

    Garcia Fontes, M.

    2012-01-01

    This presentation is about different imaging techniques such as ultrasound, CT, RNM, PET-CT. These techniques permit to detect head and neck tumors, breast and digestive pathologies as well as congenital diseases and glandular tumor in the thyroid, parathyroid, muscles, lymphatic, nerves and vessels

  1. The centrosomal linker and microtubules provide dual levels of spatial coordination of centrosomes.

    Directory of Open Access Journals (Sweden)

    Marko Panic

    2015-05-01

    Full Text Available The centrosome is the principal microtubule organizing center in most animal cells. It consists of a pair of centrioles surrounded by pericentriolar material. The centrosome, like DNA, duplicates exactly once per cell cycle. During interphase duplicated centrosomes remain closely linked by a proteinaceous linker. This centrosomal linker is composed of rootletin filaments that are anchored to the centrioles via the protein C-Nap1. At the onset of mitosis the linker is dissolved by Nek2A kinase to support the formation of the bipolar mitotic spindle. The importance of the centrosomal linker for cell function during interphase awaits characterization. Here we assessed the phenotype of human RPE1 C-Nap1 knockout (KO cells. The absence of the linker led to a modest increase in the average centrosome separation from 1 to 2.5 μm. This small impact on the degree of separation is indicative of a second level of spatial organization of centrosomes. Microtubule depolymerisation or stabilization in C-Nap1 KO cells dramatically increased the inter-centrosomal separation (> 8 μm. Thus, microtubules position centrosomes relatively close to one another in the absence of linker function. C-Nap1 KO cells had a Golgi organization defect with a two-fold expansion of the area occupied by the Golgi. When the centrosomes of C-Nap1 KO cells showed considerable separation, two spatially distinct Golgi stacks could be observed. Furthermore, migration of C-Nap1 KO cells was slower than their wild type RPE1 counterparts. These data show that the spatial organization of centrosomes is modulated by a combination of centrosomal cohesion and microtubule forces. Furthermore a modest increase in centrosome separation has major impact on Golgi organization and cell migration.

  2. A New Achiral Linker Reagent for the Incorporation of Multiple Amino Groups Into Oligonucleotides

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a new functionalized achiral linker reagent for incorporating multiple primary amino groups or reporter groups into oligonucleotides following the phosphoramidite methodology. It is possible to substitute any ribodeoxynucleotide, deoxynucleotide, or nucleotide......-oxyl-2,2,5,5-tetramethylpyrrolidine), TEMPO (N-oxyl-2,2,6,6-tetramethylpiperidine), dinitrophenyl, texas red, tetramethyl rhodamine, 7-nitrobenzo-2-oxa-1-diazole (NBD), or pyrene. The present invention also relates to a solid phase support, e.g. a Controlled Pore Glass (CPG), immobilized linker reagent...

  3. A Photolabile Linker for the Solid-Phase Synthesis of Peptide Hydrazides and Heterocycles

    DEFF Research Database (Denmark)

    Qvortrup, Katrine; Komnatnyy, Vitaly V.; Nielsen, Thomas Eiland

    2014-01-01

    A photolabile hydrazine linker for the solid-phase synthesis of peptide hydrazides and hydrazine-derived heterocycles is presented. The developed protocols enable the efficient synthesis of structurally diverse peptide hydrazides derived from the standard amino adds, including those with side......-chain protected residues at the C-terminal of the resulting peptide hydrazide, and are useful for the synthesis of dihydropyrano[2,3-c]pyrazoles. The linker is compatible with most commonly used coupling reagents and protecting groups for solid-phase peptide synthesis....

  4. Linker-dependent Junction Formation Probability in Single-Molecule Junctions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

    2015-01-15

    We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

  5. Stereotactic Body Radiotherapy for Head and Neck Tumors

    Science.gov (United States)

    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

  6. A photolabile linker for the solid-phase synthesis of 4-substituted NH-1,2,3-triazoles

    DEFF Research Database (Denmark)

    Qvortrup, Katrine; Nielsen, Thomas Eiland

    2011-01-01

    A novel photolabile linker for solid-phase synthesis is presented. The linker displays an azido handle for copper-catalyzed azide–alkyne cycloaddition reactions with a variety of alkynes, remains intact under typical solid-phase reaction conditions, and enables a mild photolytic release of 4...

  7. Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.

    Science.gov (United States)

    Okuwaki, Mitsuru; Abe, Mayumi; Hisaoka, Miharu; Nagata, Kyosuke

    2016-11-01

    Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Onset of grain filling is associated with a change in properties of linker histone variants in maize kernels

    DEFF Research Database (Denmark)

    Kalamajka, R.; Finnie, Christine; Grasser, K.D.

    2010-01-01

    ) initiation of storage synthesis. Six linker histone gene products were identified by MALDI-TOF mass spectrometry. A marked shift of around 4 pH units was observed for the linker histone spot pattern after 2D-gel electrophoresis when comparing the proteins of 11 and 16 dap kernels. The shift from acidic...

  9. A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study

    DEFF Research Database (Denmark)

    Sadaf, Aiman; Mortensen, Jonas S; Capaldi, Stefano

    2016-01-01

    with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively...

  10. Solid-phase synthesis of polyfunctional polylysine dendrons using aldehyde linkers

    DEFF Research Database (Denmark)

    Svenssen, Daniel K.; Mirsharghi, Sahar; Boas, Ulrik

    2014-01-01

    A straightforward method for the solid-phase synthesis of C-terminally modified polylysine dendrons has been developed by applying bisalkoxybenzaldehyde and trisalkoxybenzaldehyde linkers. The method has been used for the synthesis of polylysine dendrons with a variety of C-terminal ‘tail groups’...

  11. Identification of a minimal functional linker in human topoisomerase I by domain swapping with Cre recombinase

    DEFF Research Database (Denmark)

    Hougaard, Rikke Frøhlich; Juul, Sissel; Vinther, Maria

    2008-01-01

    . In this study we replace 86 amino acids including the linker domain of the cellular type IB topoisomerase, human topoisomerase I, with four, six, or eight amino acids from the corresponding short loop region in Cre recombinase. In vitro characterization of the resulting chimeras, denoted Cropos, reveals...

  12. SEVA Linkers: A Versatile and Automatable DNA Backbone Exchange Standard for Synthetic Biology

    DEFF Research Database (Denmark)

    Kim, Se Hyeuk; Cavaleiro, Mafalda; Rennig, Maja

    2016-01-01

    flexibility, and different researchers prefer and master different molecular technologies. Here, we describe a new, highly versatile and automatable standard “SEVA linkers” for vector exchange. SEVA linkers enable backbone swapping with 20 combinations of classical enzymatic restriction/ligation, Gibson...

  13. Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

    Science.gov (United States)

    Mo, Xuejun; Li, Qiushi; Yi Lui, Lena Wai; Zheng, Baixue; Kang, Chiang Huen; Nugraha, Bramasta; Yue, Zhilian; Jia, Rui Rui; Fu, Hong Xia; Choudhury, Deepak; Arooz, Talha; Yan, Jie; Lim, Chwee Teck; Shen, Shali; Hong Tan, Choon; Yu, Hanry

    2010-10-01

    Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications. 2010 Elsevier Ltd. All rights reserved.

  14. Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki

    2014-01-01

    , which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide Gal...

  15. Ensuring Academic Standards in US Higher Education

    Science.gov (United States)

    Dill, David D.

    2014-01-01

    The most recent research on college-student learning in the US by respected scholars such as Richard Arum, Josipa Roksa, and Ernest Pascarella suggests that the nation's means of ensuring academic standards in US colleges and universities are not working effectively. Like US K-12 education and health care, the US higher education system is…

  16. Ensuring Peace and Reconciliation while Holding Leaders ...

    African Journals Online (AJOL)

    need to be adopted to ensure that both organizations fulfil their mandate to address impunity on the ... international law; international relations and political studies. ...... 'not any other consideration', which was an attempt to assuage any fears that she ... system, which should play into the hands of the AU – in theory. Yet this.

  17. Release of 3-methyladenine from linker and core DNA of chromatin by a purified DNA glycosylase

    International Nuclear Information System (INIS)

    Heller, E.P.; Goldthwait, D.A.

    1983-01-01

    Oligonucleosomes were isolated from [ 14 C]thymidine-labeled HeLa cells by digestion of the nuclei with micrococcal nuclease and were then alkylated with [ 3 H]methylnitrosourea. Nucleosome core particles were also prepared by further digestion of the oligonucleosomes. The distribution of 3 H-labeled methyl groups in the linker versus the core DNA was established by a determination of 3 H: 14 C ratios in oligonucleosome and core DNA. The ratios in the core DNA of 145 and 165 base pair DNA fragments were 5.2 and 5.4, respectively, while the ratio in the oligonucleosomal DNA was 8.2. Assuming an equal mixture (as determined) of 145 and 165 base pair fragments of DNA in the 185 base pair repeat, the relative concentration of 3 H methyl groups in the linker versus the core DNA was 4.2. Thus, 45% of the 3 H methyl groups were in the linker DNA, and 55% were in the core DNA. Some shielding of the DNA was evident during alkylation. The concentrations of alkyl groups on the linker and core DNA were 67 and 12% of that found on free DNA alkylated under comparable conditions. No evidence for preferential shielding of the major or minor groove was observed. The purified 3-methyladenine DNA glycosylase I of Escherichia coli released approximately 37% of the 3-methyladenine from the linker DNA and 13% from the core DNA. The limited enzymatic removal of 3-methyladenine in vitro compared to the efficient removal in vivo suggests that conformational changes of the oligonucleosome and core structure must occur for total repair

  18. SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.

    Science.gov (United States)

    Register, A C; Leonard, Stephen E; Maly, Dustin J

    2014-11-11

    Src-family kinases (SFKs) make up a family of nine homologous multidomain tyrosine kinases whose misregulation is responsible for human disease (cancer, diabetes, inflammation, etc.). Despite overall sequence homology and identical domain architecture, differences in SH3 and SH2 regulatory domain accessibility and ability to allosterically autoinhibit the ATP-binding site have been observed for the prototypical SFKs Src and Hck. Biochemical and structural studies indicate that the SH2-catalytic domain (SH2-CD) linker, the intramolecular binding epitope for SFK SH3 domains, is responsible for allosterically coupling SH3 domain engagement to autoinhibition of the ATP-binding site through the conformation of the αC helix. As a relatively unconserved region between SFK family members, SH2-CD linker sequence variability across the SFK family is likely a source of nonredundant cellular functions between individual SFKs via its effect on the availability of SH3 and SH2 domains for intermolecular interactions and post-translational modification. Using a combination of SFKs engineered with enhanced or weakened regulatory domain intramolecular interactions and conformation-selective inhibitors that report αC helix conformation, this study explores how SH2-CD sequence heterogeneity affects allosteric coupling across the SFK family by examining Lyn, Fyn1, and Fyn2. Analyses of Fyn1 and Fyn2, isoforms that are identical but for a 50-residue sequence spanning the SH2-CD linker, demonstrate that SH2-CD linker sequence differences can have profound effects on allosteric coupling between otherwise identical kinases. Most notably, a dampened allosteric connection between the SH3 domain and αC helix leads to greater autoinhibitory phosphorylation by Csk, illustrating the complex effects of SH2-CD linker sequence on cellular function.

  19. The neck-tongue syndrome.

    Science.gov (United States)

    Orrell, R W; Marsden, C D

    1994-01-01

    The neck-tongue syndrome, consisting of pain in the neck and altered sensation in the ipsilateral half of the tongue aggravated by neck movement, has been attributed to damage to lingual afferent fibres travelling in the hypoglossal nerve to the C2 spinal roots. The lingual afferents in the hypoglossal nerve are thought to be proprioceptive. Two further cases of the neck-tongue syndrome are described, the spectrum of its clinical manifestations is explored, and the phenomenon of lingual pseudoathetosis is illustrated as a result of the presumed lingual deafferentation. Images PMID:8158185

  20. Planned neck dissection after weekly docetaxel and concurrent radiotherapy for advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    Tomita, Toshiki; Ozawa, Hiroyuki; Sakamoto, Koji; Fujii, Ryoichi; Ogawa, Kaoru; Fujii, Masato; Yamashita, Taku; Shinden, Seiichi

    2007-01-01

    Small oropharyngeal carcinomas with advanced neck metastases (stage N2 or greater) are common. Patients with small T with large N oropharyngeal carcinoma have high rates of local control but lower rates of regional control when treated with chemoradiotherapy. Clinical assessment after chemoradiotherapy cannot ensure the absence of neck disease. In the last 5 years, we have treated patients with T1-2 with N2-3 oropharyngeal carcinoma with weekly docetaxel radiotherapy followed by planned neck dissection (PND). Our objectives were to clarify the pathologically complete response (CR) rate of neck metastasis after weekly docetaxel radiotherapy, to identify the clinical predictor of residual neck disease, and to determine the mobidity of planned neck dissection. After chemoradiotherapy, all 12 patients had a complete response at the primary site. We conducted 15 neck dissections. Of these, 6 (40%) had positive nodes. The pathological CR rate of neck metastasis was 58.3%, whereas overall 2-year neck control rate was 91.7%. These findings lend support to the role of PND after chemoradiotherapy in N2-3 neck disease. After chemoradiotherapy, clinical parameters including TN status, feasibility of chemoradiotherapy, largest lymph node size or size reduction in MRI, did not identify patients with residual neck disease. We conducted selective neck dissection (SND) in 80% of patients. SND as PND appears to be appropriate in this group of patients because of the low incidence of complications. A further cohort study including the comparison of PND nonenforcement group is necessary to clarify the validity of the addition of PND in weekly docetaxel radiotherapy. (author)

  1. Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

    Science.gov (United States)

    Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

    2007-11-03

    PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

  2. Neck pain or spasms - self care

    Science.gov (United States)

    Pain - neck - self-care; Neck stiffness - self-care; Cervicalgia - self-care; Whiplash - self-care ... some pharmacies or retail stores. Ask your health care provider about using a soft neck collar to ...

  3. Clinical Practice Guideline: Evaluation of the Neck Mass in Adults.

    Science.gov (United States)

    Pynnonen, Melissa A; Gillespie, M Boyd; Roman, Benjamin; Rosenfeld, Richard M; Tunkel, David E; Bontempo, Laura; Brook, Itzhak; Chick, Davoren Ann; Colandrea, Maria; Finestone, Sandra A; Fowler, Jason C; Griffith, Christopher C; Henson, Zeb; Levine, Corinna; Mehta, Vikas; Salama, Andrew; Scharpf, Joseph; Shatzkes, Deborah R; Stern, Wendy B; Youngerman, Jay S; Corrigan, Maureen D

    2017-09-01

    Objective Neck masses are common in adults, but often the underlying etiology is not easily identifiable. While infections cause most of the neck masses in children, most persistent neck masses in adults are neoplasms. Malignant neoplasms far exceed any other etiology of adult neck mass. Importantly, an asymptomatic neck mass may be the initial or only clinically apparent manifestation of head and neck cancer, such as squamous cell carcinoma (HNSCC), lymphoma, thyroid, or salivary gland cancer. Evidence suggests that a neck mass in the adult patient should be considered malignant until proven otherwise. Timely diagnosis of a neck mass due to metastatic HNSCC is paramount because delayed diagnosis directly affects tumor stage and worsens prognosis. Unfortunately, despite substantial advances in testing modalities over the last few decades, diagnostic delays are common. Currently, there is only 1 evidence-based clinical practice guideline to assist clinicians in evaluating an adult with a neck mass. Additionally, much of the available information is fragmented, disorganized, or focused on specific etiologies. In addition, although there is literature related to the diagnostic accuracy of individual tests, there is little guidance about rational sequencing of tests in the course of clinical care. This guideline strives to bring a coherent, evidence-based, multidisciplinary perspective to the evaluation of the neck mass with the intention to facilitate prompt diagnosis and enhance patient outcomes. Purpose The primary purpose of this guideline is to promote the efficient, effective, and accurate diagnostic workup of neck masses to ensure that adults with potentially malignant disease receive prompt diagnosis and intervention to optimize outcomes. Specific goals include reducing delays in diagnosis of HNSCC; promoting appropriate testing, including imaging, pathologic evaluation, and empiric medical therapies; reducing inappropriate testing; and promoting appropriate

  4. Development of Bioorthogonally Degradable Linkers and Polymers Using alpha-Azidoethers

    Science.gov (United States)

    Rajagopalan, Chandrasekhar Ramasubramanian

    Degradable polymers have gained a lot of attention in recent years for applications in biotechnology and medicine. External control over polymer degradation can be obtained by incorporating functional groups that cleave in the presence of triggers that would normally be absent in biological environments, i.e. are bioorthogonal. This thesis explores the use of chemically cleavable alpha-azidoethers as a new method to obtain external control over the degradation behavior of polymers. My first goal is to illustrate the potential of alpha-azidoethers toward developing cleavable linkers. We have studied the relationship between alpha-azidoether structure and hydrolytic stability, to prepare linkers that withstand background hydrolytic cleavage until they are exposed to the cleaving trigger. The cleavage kinetics of the alpha-azidoether functional group was quantified. In addition to the conventionally used tris(2-carboxyethyl)phosphine (TCEP), dihydrolipoic acid (DHLA), a previously unexplored, biocompatible reducing agent, was also evaluated as a cleaving trigger. Based on these results, we have proposed design rules for utilizing alpha-azidoethers as cleavable linkers in applications that require bioorthogonal control over linker cleavage. Secondly, the alpha-azidoether cleavable linker chemistry was implemented into the development of polymeric materials. Two different types of polymers were developed. Polyamides incorporating alpha-azidoethers along the backbone were synthesized, and their physical properties and chemically triggered degradation behavior were characterized. The degradation timescale of these polymers can be tuned simply by manipulating the concentration of the externally applied chemical trigger. The alpha-azidoether functional group was then utilized to develop a unique triggered-release polymeric adhesive for potential applications in dental adhesive formulations. A methacrylamide-phosphonate adhesive monomer incorporating an alpha

  5. Effectiveness of a tailored neck training program on neck strength, movement, and fatigue in under-19 male rugby players: a randomized controlled pilot study

    Directory of Open Access Journals (Sweden)

    Barrett MD

    2015-05-01

    Full Text Available Matthew D Barrett,1 Terence F McLoughlin,2 Kieran R Gallagher,1 Don Gatherer,3 Michael TR Parratt,1 Jonathan R Perera,1 Tim WR Briggs1 1Royal National Orthopaedic Hospital, Stanmore, Middlesex, United Kingdom; 2Royal Liverpool University Hospital, Liverpool, Mersey Deanery, United Kingdom; 3The Gatherer Partnership, Aylesbury, United Kingdom Purpose: To investigate the effect of a tailored neck muscle conditioning program on neck muscle strength, neck muscle fatigue, and range of neck movement in 16–18-year-old male rugby players. Materials and methods: Thirty-four male rugby players were divided into forward and back playing positions and randomized within these groups. Seventeen players were randomly assigned to each group. The test group was given a tailored 6-week exercise regime based on their baseline measurements to be performed three times a week in addition to their normal training and playing. The control group trained and played as normal. The outcome measures used were cervical spine range of movement, neck strength, and neck muscle fatigability. Results: There were no clinically relevant statistically significant differences between the two groups. Trends identified between the two groups suggest that a tailored neck exercise program increases neck strength, particularly neck extension, and increases resistance to fatigue, as well as influencing right- and left-sided neck muscle balance. A reduction in range of movement was also demonstrated in the test group. There was a great deal of variability in range of movement and strength within this age group. No previously undiagnosed neck conditions were detected, and there were no adverse events reported. Conclusion: This study has shown that neck strength, range of movement, and susceptibility of the neck muscles to fatigue can be influenced using a focused neck training regime. It forms an important basis for a larger, multicenter study to ensure the neck is given due attention in

  6. cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage.

    Science.gov (United States)

    Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric

    2011-02-04

    A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

  7. Biogeometry of femoral neck for implant placement

    Directory of Open Access Journals (Sweden)

    Patwa J

    2006-01-01

    Full Text Available Background : Treatment of fracture neck femur with three cannulated cancellous screws in an apex proximal configuration is practised in many parts of the world. Methods : Dimensions of femoral neck at the middle of transcervical neck using CT scan (live neck and vernier caliper (dry cadeveric neck in 20 subjects respectively were measured. Results : Inferior half of the neck is narrower than superior half. Conclusion : Biogeometry of the neck of femur does not accomodate two inferior screws and thus fixation of fracture neck femur with three canulated cancellous screws in an apex distal configuration is recommended.

  8. The Danish Neck Disability Index

    DEFF Research Database (Denmark)

    Lauridsen, Henrik Hein; O'Neill, Lotte; Kongsted, Alice

    2017-01-01

    Objective: To (1) translate and culturally adapt and (2) determine the clinimetric properties of the Danish 8-item Neck Disability Index (NDI-8) in primary sector patients (PSPs) and secondary sector patients (SSPs). Methods: Analyses included 326 patients with neck pain. Validity and reliability...

  9. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    Science.gov (United States)

    Hergeth, Sonja P; Schneider, Robert

    2015-11-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

  10. Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

    Science.gov (United States)

    Cascone, Annunziata; Bruelle, Celine; Lindholm, Dan; Bernardi, Paolo; Eriksson, Ove

    2012-01-01

    Background Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria. Methodology/Principal Findings We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation. Conclusions We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage. PMID:22523586

  11. Linker histones: novel insights into structure-specific recognition of the nucleosome.

    Science.gov (United States)

    Cutter, Amber R; Hayes, Jeffrey J

    2017-04-01

    Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing the wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures, influencing nucleosome spacing on DNA, and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, with a focus on recent advances that suggest multiple modes of H1 interaction in chromatin, while highlighting the remaining questions.

  12. Communication skills to ensure patient satisfaction.

    Science.gov (United States)

    Shendurnikar, Niranjan; Thakkar, Pareshkumar A

    2013-11-01

    Every pediatrician would want to satisfy their patients and their parents to sustain good practice, earn name and fame and simultaneously to avoid litigation in this era of consumer protection act. This can be achieved only by use of good communication skills. Today the patients demand time, information and want their questions to be answered. They expect politeness, empathy and human touch from doctors. Time constraints, arrogance, telephone calls, language barriers and cultural insensitivity are the important barriers to good communication. Research has shown that doctor, who undergoes training to acquire good communication skills, can better satisfy his patients. Good communication skill is an art which can be acquired or improved by putting conscious efforts in day to day practice. Such skills should also be incorporated as part of medical teaching curriculum. Asking open ended questions, effective listening, appropriate praise, providing enough information as part of advice and finally checking their understanding, are the key areas of communication during medical interview. During this process pediatrician should ensure to address the parental concerns, should empathize with parents and involve parents in decision making. This will not only ensure satisfaction of parents but also their adherence to the therapy and to the pediatrician.

  13. Construction of Multivalent Homo- and Heterofunctional ABO Blood Group Glycoconjugates Using a Trifunctional Linker Strategy.

    Science.gov (United States)

    Daskhan, Gour Chand; Tran, Hanh-Thuc Ton; Meloncelli, Peter J; Lowary, Todd L; West, Lori J; Cairo, Christopher W

    2018-02-21

    The design and synthesis of multivalent ligands displaying complex oligosaccharides is necessary for the development of therapeutics, diagnostics, and research tools. Here, we report an efficient conjugation strategy to prepare complex glycoconjugates with 4 copies of 1 or 2 separate glycan epitopes, providing 4-8 carbohydrate residues on a tetravalent poly(ethylene glycol) scaffold. This strategy provides complex glycoconjugates that approach the size of glycoproteins (15-18 kDa) while remaining well-defined. The synthetic strategy makes use of three orthogonal functional groups, including a reactive N-hydroxysuccinimide (NHS)-ester moiety on the linker to install the first carbohydrate epitope via reaction with an amine. A masked amine functionality on the linker is revealed after the removal of a fluorenylmethyloxycarbonyl (Fmoc)-protecting group, allowing the attachment to the NHS-activated poly(ethylene glycol) (PEG) scaffold. An azide group in the linker was then used to incorporate the second carbohydrate epitope via catalyzed alkyne-azide cycloaddition. Using a known tetravalent PEG scaffold (PDI, 1.025), we prepared homofunctional glycoconjugates that display four copies of lactose and the A-type II or the B-type II human blood group antigens. Using our trifunctional linker, we expanded this strategy to produce heterofunctional conjugates with four copies of two separate glycan epitopes. These heterofunctional conjugates included Neu5Ac, 3'-sialyllactose, or 6'-sialyllactose as a second antigen. Using an alternative strategy, we generated heterofunctional conjugates with three copies of the glycan epitope and one fluorescent group (on average) using a sequential dual-amine coupling strategy. These conjugation strategies should be easily generalized for conjugation of other complex glycans. We demonstrate that the glycan epitopes of heterofunctional conjugates engage and cluster target B-cell receptors and CD22 receptors on B cells, supporting the

  14. Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

    Science.gov (United States)

    Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

    2017-06-27

    Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

  15. Computational engineering of cellulase Cel9A-68 functional motions through mutations in its linker region.

    Science.gov (United States)

    Costa, M G S; Silva, Y F; Batista, P R

    2018-03-14

    Microbial cellulosic degradation by cellulases has become a complementary approach for biofuel production. However, its efficiency is hindered by the recalcitrance of cellulose fibres. In this context, computational protein design methods may offer an efficient way to obtain variants with improved enzymatic activity. Cel9A-68 is a cellulase from Thermobifida fusca that is still active at high temperatures. In a previous work, we described a collective bending motion, which governs the overall cellulase dynamics. This movement promotes the approximation of its CBM and CD structural domains (that are connected by a flexible linker). We have identified two residues (G460 and P461) located at the linker that act as a hinge point. Herein, we applied a new level of protein design, focusing on the modulation of this collective motion to obtain cellulase variants with enhanced functional dynamics. We probed whether specific linker mutations would affect Cel9A-68 dynamics through computational simulations. We assumed that P461G and G460+ (with an extra glycine) constructs would present enhanced interdomain motions, while the G460P mutant would be rigid. From our results, the P461G mutation resulted in a broader exploration of the conformational space, as confirmed by clustering and free energy analyses. The WT enzyme was the most rigid system. However, G460P and P460+ explored distinct conformational states described by opposite directions of low-frequency normal modes; they sampled preferentially closed and open conformations, respectively. Overall, we highlight two significant findings: (i) all mutants explored larger conformational spaces than the WT; (ii) the selection of distinct conformational populations was intimately associated with the mutation considered. Thus, the engineering of Cel9A-68 motions through linker mutations may constitute an efficient way to improve cellulase activity, facilitating the disruption of cellulose fibres.

  16. Efficient Naphthalenediimide-Based Hole Semiconducting Polymer with Vinylene Linkers between Donor and Acceptor Units

    KAUST Repository

    Zhang, Lei

    2016-11-04

    We demonstrate a new method to reverse the polarity and charge transport behavior of naphthalenediimide (NDI)-based copolymers by inserting a vinylene linker between the donor and acceptor units. The vinylene linkers minimize the intrinsic steric congestion between the NDI and thiophene moieties to prompt backbone planarity. The polymers with vinylene linkers exhibit electron n-channel transport characteristics under vacuum, similar to the benchmark polymer, P(NDI2OD-T2). To our surprise, when the polymers are measured in air, the dominant carrier type switches from n- to p-type and yield hole mobilities up to 0.45 cm(2) s(-1) with hole to electron mobility ratio of three (mu(h)/mu(e), similar to 3), which indicates that the hole density in the active layer can be significantly increased by exposure to air. This increase is consistent with the intrinsic more delocalized nature of the highest occupied molecular orbital of the charged vinylene polymer, as estimated by density functional theory (DFT) calculations, which facilitates hole transport within the polymer chains. This is the first demonstration of an efficient NDI-based hole semiconducting polymer, which will enable new developments in all-polymer solar cells, complementary circuits, and dopable polymers for use in thermoelectrics.

  17. Efficient Naphthalenediimide-Based Hole Semiconducting Polymer with Vinylene Linkers between Donor and Acceptor Units

    KAUST Repository

    Zhang, Lei; Rose, Bradley Daniel; Liu, Yao; Nahid, Masrur M.; Gann, Eliot; Ly, Jack; Zhao, Wei; Rosa, Stephen J.; Russell, Thomas P.; Facchetti, Antonio; McNei, Christopher R.; Bredas, Jean-Luc; Briseno, Alejandro L.

    2016-01-01

    We demonstrate a new method to reverse the polarity and charge transport behavior of naphthalenediimide (NDI)-based copolymers by inserting a vinylene linker between the donor and acceptor units. The vinylene linkers minimize the intrinsic steric congestion between the NDI and thiophene moieties to prompt backbone planarity. The polymers with vinylene linkers exhibit electron n-channel transport characteristics under vacuum, similar to the benchmark polymer, P(NDI2OD-T2). To our surprise, when the polymers are measured in air, the dominant carrier type switches from n- to p-type and yield hole mobilities up to 0.45 cm(2) s(-1) with hole to electron mobility ratio of three (mu(h)/mu(e), similar to 3), which indicates that the hole density in the active layer can be significantly increased by exposure to air. This increase is consistent with the intrinsic more delocalized nature of the highest occupied molecular orbital of the charged vinylene polymer, as estimated by density functional theory (DFT) calculations, which facilitates hole transport within the polymer chains. This is the first demonstration of an efficient NDI-based hole semiconducting polymer, which will enable new developments in all-polymer solar cells, complementary circuits, and dopable polymers for use in thermoelectrics.

  18. 5-fold increase of hydrogen uptake in MOF74 through linker decorations

    Science.gov (United States)

    Thonhauser, T.; Zuluaga, S.; Harrison, D.; Welchman, E.; Arter, C.

    We present ab initio results for linker decorations in Mg-MOF74-i.e. attaching various metals  = Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker-creating new strong adsorption sites and thus maximizing small molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening we chose metals that bind favorably to the linker and further investigate adsorption of H2, CO2, and H2O for  = Li, Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the MOF unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a 5-fold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular-where the gravimetric hydrogen density increases from 1 . 63 mass% to 7 . 28 mass% and the volumetric density from 15.10 g H2 L-1 to 75.50 g H2 L-1. This work was supported by NSF Grant No. DMR-1145968.

  19. Fivefold increase of hydrogen uptake in MOF74 through linker decorations

    Science.gov (United States)

    Arter, C. A.; Zuluaga, S.; Harrison, D.; Welchman, E.; Thonhauser, T.

    2016-10-01

    We present ab initio results for linker decorations in Mg-MOF74, i.e., attaching various metals M =Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker, creating new strong adsorption sites and thus maximizing small-molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening, we chose metals that bind favorably to the linker and further investigated adsorption of H2,CO2, and H2O for M =Li , Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the metal-organic framework (MOF) unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a fivefold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular, where the gravimetric hydrogen density increases from 1.63 to 7.28 mass % and the volumetric density increases from 15.10 to 75.50 g H2L-1 .

  20. Saccharomyces cerevisiae Linker Histone—Hho1p Maintains Chromatin Loop Organization during Ageing

    Directory of Open Access Journals (Sweden)

    Katya Uzunova

    2013-01-01

    Full Text Available Intricate, dynamic, and absolutely unavoidable ageing affects cells and organisms through their entire lifetime. Driven by diverse mechanisms all leading to compromised cellular functions and finally to death, this process is a challenge for researchers. The molecular mechanisms, the general rules that it follows, and the complex interplay at a molecular and cellular level are yet little understood. Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. By deleting the gene for the linker histone in Saccharomyces cerevisiae we have created a model for studying the role of chromatin structures mainly at its most elusive and so far barely understood higher-order levels of compaction in the processes of yeast chronological lifespan. The mutant cells demonstrated controversial features showing slower growth than the wild type combined with better survival during the whole process. The analysis of the global chromatin organization during different time points demonstrated certain loss of the upper levels of chromatin compaction in the cells without linker histone. The results underlay the importance of this histone for the maintenance of the chromatin loop structures during ageing.

  1. Prevalance of neck pain in computer users

    International Nuclear Information System (INIS)

    Sabeen, F.; Bashir, M.S.; Hussain, S.I.

    2013-01-01

    Prolonged use of computers during daily work activities and recreation is often cited as a cause of neck pain. Neck pain and computer users are clearly connected due to extended periods of sitting in a certain position with no breaks to stretch the neck muscles. Pro-longed computer use with neck bent forward, will cause the anterior neck muscles to gradually get shorter and tighter, while the muscles in the back of neck will grow longer and weaker. These changes will lead to development of neck pain. Objectives: To find incidence of neck pain in computer users, association between neck pain and prolong sitting in wrong posture, association between effects of break during prolong work, association between types of chair in use in prolong sitting and occurrence of neck pain. Methodology: For this observational study data was collected through Questionnaires from office workers (computer users), and students. Results: Out of 50 persons 72% of computer users had neck pain. Strong association was found between neck pain and prolonged computer use (p = 0.001). Those who took break during their work had less neck pain. No significant association was found between type of chair in use and neck pain. Neck pain and type of system in use also had no significant association. Conclusion: So duration of computer use and frequency of breaks are associated with neck pain at work. Severe Neck pain was found in people who use computer for more than 5 hours a day. (author)

  2. Mixed-linker zeolitic imidazolate framework mixed-matrix membranes for aggressive CO2 separation from natural gas

    KAUST Repository

    Thompson, Joshua A.; Vaughn, Justin T.; Brunelli, Nicholas A.; Koros, William J.; Jones, Christopher W.; Nair, Sankar

    2014-01-01

    Zeolitic imidazolate framework (ZIF) materials are a promising subclass of metal-organic frameworks (MOF) for gas separations. However, due to the deleterious effects of gate-opening phenomena associated with organic linker rotation near

  3. Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

    Science.gov (United States)

    Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

    2017-11-21

    Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

  4. How to remain nonfolded and pliable: the linkers in modular α-amylases as a case study.

    Science.gov (United States)

    Feller, Georges; Dehareng, Dominique; Lage, Jean-Luc Da

    2011-07-01

    The primary structure of linkers in a new class of modular α-amylases constitutes a paradigm of the structural basis that allows a polypeptide to remain nonfolded, extended and pliable. Unfolding is mediated through a depletion of hydrophobic residues and an enrichment of hydrophilic residues, amongst which Ser and Thr are over-represented. An extended and flexible conformation is promoted by the sequential arrangement of Pro and Gly, which are the most abundant residues in these linkers. This is complemented by charge repulsion, charge clustering and disulfide-bridged loops. Molecular dynamics simulations suggest the existence of conformational transitions resulting from a transient and localized hydrophobic collapse, arising from the peculiar composition of the linkers. Accordingly, these linkers should not be regarded as fully disordered, but rather as possessing various discrete structural patterns allowing them to fulfill their biological function as a free energy reservoir for concerted motions between structured domains. © 2011 The Authors Journal compilation © 2011 FEBS.

  5. Ensuring the validity of calculated subcritical limits

    International Nuclear Information System (INIS)

    Clark, H.K.

    1977-01-01

    The care taken at the Savannah River Laboratory and Plant to ensure the validity of calculated subcritical limits is described. Close attention is given to ANSI N16.1-1975, ''Validation of Calculational Methods for Nuclear Criticality Safety.'' The computer codes used for criticality safety computations, which are listed and are briefly described, have been placed in the SRL JOSHUA system to facilitate calculation and to reduce input errors. A driver module, KOKO, simplifies and standardizes input and links the codes together in various ways. For any criticality safety evaluation, correlations of the calculational methods are made with experiment to establish bias. Occasionally subcritical experiments are performed expressly to provide benchmarks. Calculated subcritical limits contain an adequate but not excessive margin to allow for uncertainty in the bias. The final step in any criticality safety evaluation is the writing of a report describing the calculations and justifying the margin

  6. Ensuring Economic Security in Lending Sphere

    Directory of Open Access Journals (Sweden)

    Ivan Vadimovich Kochikin

    2016-06-01

    Full Text Available Relevance of the topic is determined by the need for sustainable development of the country’s banking system, capable of ensuring the process of raising funds to producers and the public for their projects. One of the implementation of this objective is to discourage unfair behavior in financial markets. Trust is a key factor in the development of financial markets, therefore it is necessary to suppress the appearance of unfair practices and participants – black creditors, falsification of financial statements, trading on insider information and market manipulation. It requires a whole range of activities, and above all ensuring the inevitability and proportionality of punishment for unscrupulous players, the introduction of requirements for the business reputation of the management of financial institutions.The article is devoted to structuring legal violations in the lending sphere. The analysis of indicators of credit organizations in Russia was conducted to fulfill this aim. This analysis revealed the causes of sustainable growth of overdue accounts payable – job cuts in enterprises, violations in the financial sector, various errors in the credit granting / raising. The authors carry out the systematization and classification of offenses in the area of lending, provide examples, as well as factual material illustrating the violations in the lending process having the characteristics of a fraud. The article substantiates the obligations of employees of the credit institution, in the result of which risks of granting credit to fraudsters can be reduced. The methods of fraud prevention should include the identified methods of protection against fraud in the area under consideration – exchange of information by banks associated with the criminal intentions of customers; technology development and technical support, training, and personnel responsibilities.

  7. Five-step neck lift: integrating anatomy with clinical practice to optimize results.

    Science.gov (United States)

    Narasimhan, Kailash; Stuzin, James M; Rohrich, Rod J

    2013-08-01

    A harmonious and youthful appearing neckline is arguably the most vital aspect of a successful facial rejuveation. Without sound principles, the neck appears skeletonized, tethered, and hollow. The anatomical studies that the authors have performed regarding the neck, jowl, and subplatysmal elements have influenced the techniques that they now use. The authors' approach modifies the classic techniques of the past, and seeks a nuanced approach to each patient by resuspension and reshaping of deeper neck elements. In this article, the authors apply their anatomical research and cadaveric studies to demonstrate and support their neck-lift techniques. The authors integrate their knowledge to describe how the technique of one of the senior authors (R.J.R.) has evolved over time. The main tenets of the authors' approach have evolved into a sequence that involves skin undermining over the neck and cheek, submental access to the neck, with possible excision of fat and midline plication of the platysma with release of the muscle inferiorly, platysmal window suspension laterally, precise release of the mandibular septum and ligament if needed, and finally redraping of the superficial musculoaponeurotic system (SMAS) by plication or SMASecomy. These five steps ensure correction of jowling, a smooth jawline, and a well-shaped neck. The five-step neck lift helps to optimize results in creating the ideal neck contour. The authors provide four points that should be considered in any neck-lift procedure. The end result is a well-defined, well-contoured neck, with an approach grounded in sound anatomical principles.

  8. The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

    Science.gov (United States)

    Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

    2012-01-01

    DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

  9. Mixed-linker zeolitic imidazolate framework mixed-matrix membranes for aggressive CO2 separation from natural gas

    KAUST Repository

    Thompson, Joshua A.

    2014-07-01

    Zeolitic imidazolate framework (ZIF) materials are a promising subclass of metal-organic frameworks (MOF) for gas separations. However, due to the deleterious effects of gate-opening phenomena associated with organic linker rotation near the limiting pore apertures of ZIFs, there have been few demonstrations of improved gas separation properties over pure polymer membranes when utilizing ZIF materials in composite membranes for CO2-based gas separations. Here, we report a study of composite ZIF/polymer membranes, containing mixed-linker ZIF materials with ZIF-8 crystal topologies but composed of different organic linker compositions. Characterization of the mixed-linker ZIFs shows that the mixed linker approach offers control over the porosity and pore size distribution of the materials, as determined from nitrogen physisorption and Horváth-Kawazoe analysis. Single gas permeation measurements on mixed-matrix membranes reveal that inclusion of mixed-linker ZIFs yields membranes with better ideal CO2/CH4 selectivity than membranes containing ZIF-8. This improvement is shown to likely occur from enhancement in the diffusion selectivity of the membranes associated with controlling the pore size distribution of the ZIF filler. Mixed-gas permeation experiments show that membranes with mixed-linker ZIFs display an effective plasticization resistance that is not typical of the pure polymeric matrix. Overall, we demonstrate that mixed-linker ZIFs can improve the gas separation properties in composite membranes and may be applicable to aggressive CO2 concentrations in natural gas feeds. © 2013 Elsevier Inc. All rights reserved.

  10. Head and Neck Cancer

    International Nuclear Information System (INIS)

    Tomita, Toshiki; Imanishi, Yorihisa

    2008-01-01

    The limitation of concurrent chemo-radiotherapy (CCRT) in head and neck cancer (HNC) as the primary treatment is described based on recent findings. Limits in the application/indication involve factors of age, performance status (PS) and renal function. The first is that, as deaths in >71 years old patients are derived from other causes (41%) than HNC, CCRT is only useful for younger population; the second, patients with PS 0-1 or Karnofsky performance score >60-70 can be indicated; and third, contraindicated are those with creatinine clearance (CCr) <60 mL/min as the key drug cisplatin in CCRT has a high renal toxicity. It should be recognized that completion rates of chemotherapy and RT are as low as 66-85% and 84-92%, respectively, in CCRT. CCRT has such limiting adverse events as mucitis, dry mouth, dysohagia, weight loss, neutropenia, sepsis, etc., which are most important in CCRT application. CCRT is recommended for the primary cancers of larynx and hypopharynx because they are significantly better conserved than middle pharyngeal, oral and upper jaw cancers. Evidence of CCRT is poor for cancers in paranasal sinuses. Planned neck dissection (PND) is for the cervical metastatic lymph nodes and conducted 6-12 weeks after CCRT regardless to its outcome. In fluorodeoxyglucose-positron emission tomography (FDG-PET) negative cases, PND can be omitted. Necessity of PND is possibly inversely proportional to CCRT intensity performed. For control of remote metastasis, CCRT has obvious limits and inductive chemotherapy before it is currently considered. Salvage surgery post CCRT does not always yield a relief because of complication. Patients with advanced laryngeal cancer can be selected either to surgery or CCRT depending on results of the inductive chemotherapy. To predict the sensitivity to CCRT, some biomarkers like HPV, EGFR and VEGF have been suggested to be useful by retrospective studies. Understanding the limitation is as important as knowing the usefulness in

  11. Rapid One-Pot Microwave Synthesis of Mixed-Linker Hybrid Zeolitic-Imidazolate Framework Membranes for Tunable Gas Separations.

    Science.gov (United States)

    Hillman, Febrian; Brito, Jordan; Jeong, Hae-Kwon

    2018-02-14

    The relatively slow and complex fabrication processes of polycrystalline metal-organic framework (MOF) membranes often times restrict their way to commercialization, despite their potential for molecular separation applications. Herein, we report a rapid one-pot microwave synthesis of mixed-linker hybrid zeolitic-imidazolate framework (ZIF) membranes consisting of 2-methylimidazolate (ZIF-8 linker) and benzimidazolate (ZIF-7 linker) linkers, termed ZIF-7-8 membranes. The fast-volumetric microwave heating in conjunction with a unique counter diffusion of metal and linker solutions enabled unprecedented rapid synthesis of well-intergrown ZIF-7-8 membranes in ∼90 s, the fastest MOF membrane preparation up to date. Furthermore, we were able to tune the molecular sieving properties of the ZIF-7-8 membranes by varying the benzimidazole-to-2-methylimidazole (bIm-to-mIm) linker ratio in the hybrid frameworks. The tuning of their molecular sieving properties led to the systematic change in the permeance and selectivity of various small gases. The unprecedented rapid synthesis of well-intergrown ZIF-7-8 membranes with tunable molecular sieving properties is an important step forward for the commercial gas separation applications of ZIF membranes.

  12. Effect of linkers on the αvβ3 integrin targeting efficiency of cyclic RGD-conjugates

    Science.gov (United States)

    Karmakar, Partha; Grabowska, Dorota; Sudlow, Gail; Ziabrev, Kostiantyn; Sanyal, Nibedita; Achilefu, Samuel

    2018-02-01

    Cyclic arginine-glycine-aspartic acid (cRGD) peptides are well known to target ανβ3 integrin expressed on cancer cells and neovasculature. Conjugation of these peptides with dyes, drugs, antibodies and other biomolecules through covalent linkers provides a facile way to deliver these products to tumor cells for targeted cancer therapy and diagnosis. Click chemistry and acid-amine couplings are widely used conjugation strategies. However, the effects of different linkers and the distance between the cRGD and the conjugates on the binding of cRGD ligand with ανβ3 has been underexplored. In this present study, we prepared cRGD-conjugates using different linkers and determined how they altered the tumor targeting efficiency in vitro and in vivo. The results demonstrate that different linkers significantly altered the pharmacokinetics of the cRGD conjugates and the tumor uptake kinetics. Unlike large antibodies, this preliminary finding shows that linkers used to attach drugs and fluorescent molecular probes to small peptides play a major role in the accuracy of tumor targeting and treatment outcomes. As a result, considerable attention should be paid to the nature of linkers used in the design of molecular probes and targeted therapeutics.

  13. ATPase Domain and Interdomain Linker Play a Key Role in Aggregation of Mitochondrial Hsp70 Chaperone Ssc1*

    Science.gov (United States)

    Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

    2010-01-01

    The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Δhep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer. PMID:20007714

  14. ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1.

    Science.gov (United States)

    Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

    2010-02-12

    The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Delta hep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer.

  15. A pain in the neck-Imaging in neck sepsis

    International Nuclear Information System (INIS)

    Lyle, N.J.; Rutherford, E.E.; Batty, V.B.

    2011-01-01

    Deep neck infection has a high morbidity and mortality and the extent of infection is often difficult to estimate clinically. The complex anatomy and the communication between neck spaces means that infection can spread along fascial planes leading to life-threatening complications such as airway compromise, vascular erosion/thrombosis, neural dysfunction, and ultimately descending necrotizing mediastinitis. Imaging has an important role to play in identifying the extent of infection and the presence of complications.

  16. A pain in the neck-Imaging in neck sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Lyle, N.J., E-mail: nickylyle@doctors.org.uk [Department of Diagnostic Imaging, Southampton General Hospital, Southampton (United Kingdom); Rutherford, E.E.; Batty, V.B. [Department of Diagnostic Imaging, Southampton General Hospital, Southampton (United Kingdom)

    2011-09-15

    Deep neck infection has a high morbidity and mortality and the extent of infection is often difficult to estimate clinically. The complex anatomy and the communication between neck spaces means that infection can spread along fascial planes leading to life-threatening complications such as airway compromise, vascular erosion/thrombosis, neural dysfunction, and ultimately descending necrotizing mediastinitis. Imaging has an important role to play in identifying the extent of infection and the presence of complications.

  17. Surgical treatment for obesity: ensuring success.

    Science.gov (United States)

    Andris, Deborah A

    2005-01-01

    In the United States, obesity has reached epidemic proportions. Serious medical complications, impaired quality of life, and premature mortality are all associated with obesity. Medical conditions such as type 2 diabetes mellitus, hypertension, hyperlipidemia, or sleep apnea can improve or be cured with weight loss. Medical treatment programs focused on diet, behavior modification, and/or pharmacologic intervention have met with limited long-term success. Although surgical treatments for obesity have become popular in recent years, they should only be used as a last resort for weight loss. Not all patients can be considered appropriate candidates for surgery; therefore, guidelines based on criteria from the National Institutes of Health should be used preoperatively to help identify suitable persons. Most individuals who opt for weight-loss surgery have usually struggled for many years with losing weight and keeping it off, but surgery alone will not ensure successful weight loss. Patient education is imperative for long-term success. Moreover, any such educational regimen should include information on diet, vitamin and mineral supplementation, and lifestyle changes, as well as expected weight-loss results and improvements in comorbid conditions. Patients must be willing to commit to a long-term follow-up program intended to promote successful weight loss and weight maintenance and to prevent metabolic and nutritional complications.

  18. Reproducing Epidemiologic Research and Ensuring Transparency.

    Science.gov (United States)

    Coughlin, Steven S

    2017-08-15

    Measures for ensuring that epidemiologic studies are reproducible include making data sets and software available to other researchers so they can verify published findings, conduct alternative analyses of the data, and check for statistical errors or programming errors. Recent developments related to the reproducibility and transparency of epidemiologic studies include the creation of a global platform for sharing data from clinical trials and the anticipated future extension of the global platform to non-clinical trial data. Government agencies and departments such as the US Department of Veterans Affairs Cooperative Studies Program have also enhanced their data repositories and data sharing resources. The Institute of Medicine and the International Committee of Medical Journal Editors released guidance on sharing clinical trial data. The US National Institutes of Health has updated their data-sharing policies. In this issue of the Journal, Shepherd et al. (Am J Epidemiol. 2017;186:387-392) outline a pragmatic approach for reproducible research with sensitive data for studies for which data cannot be shared because of legal or ethical restrictions. Their proposed quasi-reproducible approach facilitates the dissemination of statistical methods and codes to independent researchers. Both reproducibility and quasi-reproducibility can increase transparency for critical evaluation, further dissemination of study methods, and expedite the exchange of ideas among researchers. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral Surgeries Facial Cosmetic Surgery Facial Injury / Trauma Surgery Obstructive Sleep Apnea (OSA) Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are ...

  20. American Head and Neck Society

    Science.gov (United States)

    ... research and insights. Comments This field is for validation purposes and should be left unchanged. This iframe ... and Announcements Copyright ©2016 · American Head and Neck Society · Privacy and Return Policy Managed by BSC Management, ...

  1. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Neck Pathology Download Download the ebook for further information Your oral and maxillofacial surgeon (OMS) is the ... well be the key to complete recovery. The information provided here is not intended as a substitute ...

  2. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... teeth or become infected. It can also invite bacteria that lead to gum disease. Click here to find out ... and surgically treating cancer of the head, neck and mouth. The Oral Cancer Foundation estimates that close to ...

  3. Neck pain in different cephalalgias

    Directory of Open Access Journals (Sweden)

    E. A. Chechet

    2014-01-01

    Full Text Available The paper reviews the literature related to the investigations of neck pain (cervicalgia in patients with headache (cephalalgia. Neck pain is second to lower back pain as a reason for considerable socioeconomic damage to society. The prevalence of cervicalgia in the population ranges from 5.9 to 38%; the annual incidence is 10.4–21.3%; 14.2 to 71% of people report to have neck pain at some time in their lifetime. Neck pain is concurrent with cephalalgia in 70% of cases. In patients with cervicalgia, the prevalence of headache is 20–40% higher than in those with musculoskeletal pain at another site. Neck pain is as a major risk factor for migraine and tension headache (TH. Neck pain in TH progresses with the increased intensity, frequency, and strength of headache. There is a direct relationship of the quality of life worsening associated withcervicalgia to the frequency of migraine attacks and the risk of its chronization. Neck pain is noted in cervicogenic headache belonging to secondary headaches. The identification of mixed headache in a patient with cervicalgia allows the prescription of a treatment option that may be effective in relieving both headache and neck pain. The paper discusses the causes and pathogenesis of cervicalgia in patients with headache, examination methods, and main approaches to drug and nondrug therapies in relation to the leading pathophysiological mechanism, as well as new possibilities for the effective and safe relief of pain syndrome in this category of patients. Nonsteroidal anti-inflammatory drugs, myorelaxants,and their combination are observed to be effective in treating patients with cervicalgia and cephalalgia.

  4. [Quality assurance in head and neck medical oncology].

    Science.gov (United States)

    Digue, Laurence; Pedeboscq, Stéphane

    2014-05-01

    In medical oncology, how can we be sure that the right drug is being administered to the right patient at the right time? The implementation of quality assurance criteria is important in medical oncology, in order to ensure that the patient receives the best treatment safely. There is very little literature about quality assurance in medical oncology, as opposed to radiotherapy or cancer surgery. Quality assurance must cover the entire patient care process, from the diagnosis, to the therapeutic decision and drug distribution, including its selection, its preparation and its delivery to the patient (administration and dosage), and finally the potential side effects and their management. The dose-intensity respect is crucial, and its reduction can negatively affect overall survival rates, as shown in breast and testis cancers for example. In head and neck medical oncology, it is essential to respect the few well-standardized recommendations and the dose-intensity, in a population with numerous comorbidities. We will first review quality assurance criteria for the general medical oncology organization and then focus on head and neck medical oncology. We will then describe administration specificities of head and neck treatments (chemoradiation, radiation plus cetuximab, postoperative chemoradiation, induction and palliative chemotherapy) as well as their follow-up. Lastly, we will offer some recommendations to improve quality assurance in head and neck medical oncology.

  5. [Construction of cTnC-linker-TnI (P) Genes, Expression of Fusion Protein and Preparation of Lyophilized Protein].

    Science.gov (United States)

    Song, Xiaoli; Liu, Xiaoyun; Cai, Lei; Wu, Jianwei; Wang, Jihua

    2015-12-01

    In order to construct and express human cardiac troponin C-linker-troponin I(P) [ cTnC-linker-TnI(P)] fusion protein, detect its activity and prepare lyophilized protein, we searched the CDs of human cTnC and cTnI from GenBank, synthesized cTnC and cTnI(30-110aa) into cloning vector by a short DNA sequence coding for 15 neutral amino acid residues. pCold I-cTnC-linker-TnI(P) was constructed and transformed into E. coli BL21(DE3). Then, cTnC-linker-TnI(P) fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG). Soluable expression of cTnC-linker-TnI(P) in prokaryotic system was successfully obtained. The fusion protein was purified by Ni²⁺ Sepharose 6 Fast Flow affinity chromatography with over 95% purity and prepared into lyophilized protein. The activity of purified cTnC-linker-TnI(P) and its lyophilized protein were detected by Wondfo Finecare™ cTnI Test. Lyophilized protein of cTnC-linker-TnI(P) was stable for 10 or more days at 37 °C and 4 or more months at 25 °C and 4 °C. The expression system established in this research is feasible and efficient. Lyophilized protein is stable enough to be provided as biological raw materials for further research.

  6. Dynamics of Linker Residues Modulate the Nucleic Acid Binding Properties of the HIV-1 Nucleocapsid Protein Zinc Fingers

    Science.gov (United States)

    Zargarian, Loussiné; Tisné, Carine; Barraud, Pierre; Xu, Xiaoqian; Morellet, Nelly; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

    2014-01-01

    The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity. PMID:25029439

  7. A Novel MS-Cleavable Azo Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS)

    Science.gov (United States)

    Iacobucci, Claudio; Hage, Christoph; Schäfer, Mathias; Sinz, Andrea

    2017-10-01

    The chemical cross-linking/mass spectrometry (MS) approach is a growing research field in structural proteomics that allows gaining insights into protein conformations. It relies on creating distance constraints between cross-linked amino acid side chains that can further be used to derive protein structures. Currently, the most urgent task for designing novel cross-linking principles is an unambiguous and automated assignment of the created cross-linked products. Here, we introduce the homobifunctional, amine-reactive, and water soluble cross-linker azobisimidoester (ABI) as a prototype of a novel class of cross-linkers. The ABI-linker possesses an innovative modular scaffold combining the benefits of collisional activation lability with open shell chemistry. This MS-cleavable cross-linker can be efficiently operated via free radical initiated peptide sequencing (FRIPS) in positive ionization mode. Our proof-of-principle study challenges the gas phase behavior of the ABI-linker for the three amino acids, lysine, leucine, and isoleucine, as well as the model peptide thymopentin. The isomeric amino acids leucine and isoleucine could be discriminated by their characteristic side chain fragments. Collisional activation experiments were conducted via positive electrospray ionization (ESI) on two Orbitrap mass spectrometers. The ABI-mediated formation of odd electron product ions in MS/MS and MS3 experiments was evaluated and compared with a previously described azo-based cross-linker. All cross-linked products were amenable to automated analysis by the MeroX software, underlining the future potential of the ABI-linker for structural proteomics studies. [Figure not available: see fulltext.

  8. Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac

    International Nuclear Information System (INIS)

    Yordanov, A.T.; Garmestani, K.; Zhang, M.; Zhang, Z.; Yao, Z.; Phillips, K.E.; Herring, B.; Horak, E.; Beitzel, M.P.; Schwarz, U.P.; Gansow, O.A.; Plascjak, P.S.; Eckelman, W.C.; Waldmann, T.A.; Brechbiel, M.W.

    2001-01-01

    The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211 At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the α-chain of the IL-2 receptor (IL-2Rα) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211 At of two new linkers, N-succinimidyl 4-[ 211 At]astato-3-methylbenzoate and N-succinimidyl N-(4-[ 211 At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[ 211 At]astatobenzoate and N-succinimidyl 3-[ 211 At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated ( 125 I) Hu-anti-Tac. The N-succinimidyl N-(4-[ 211 At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211 At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[ 125 I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated ( 125 I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer

  9. Managing patients with acute and chronic non-specific neck pain

    DEFF Research Database (Denmark)

    Brockhusen, Simon Sidenius; Bussières, André; French, Simon David

    2017-01-01

    was mainly reserved for chronic patients. Danish chiropractors' compliance with guidelines for neck-pain patients was low, but is neither worse nor better than what is seen for other complaints or health disciplines. Our findings suggest a need for active knowledge translation strategies and robust......Background: Non-specific neck pain represents a quarter of all chiropractic patient visits in Denmark. Evidence informed practice can help ensure providers use best available treatment, speed up patient recovery rate and reduce healthcare utilization. It is generally believed that Danish...... chiropractors treat according to best practice, but we do not know if this is true for management of neck-pain. The objective of this study was to investigate how Danish chiropractors treat patients with acute and chronic non-specific neck pain and determine if management is compliant with recent Canadian...

  10. Accurate distance determination of nucleic acids via Förster resonance energy transfer: implications of dye linker length and rigidity.

    Science.gov (United States)

    Sindbert, Simon; Kalinin, Stanislav; Nguyen, Hien; Kienzler, Andrea; Clima, Lilia; Bannwarth, Willi; Appel, Bettina; Müller, Sabine; Seidel, Claus A M

    2011-03-02

    In Förster resonance energy transfer (FRET) experiments, the donor (D) and acceptor (A) fluorophores are usually attached to the macromolecule of interest via long flexible linkers of up to 15 Å in length. This causes significant uncertainties in quantitative distance measurements and prevents experiments with short distances between the attachment points of the dyes due to possible dye-dye interactions. We present two approaches to overcome the above problems as demonstrated by FRET measurements for a series of dsDNA and dsRNA internally labeled with Alexa488 and Cy5 as D and A dye, respectively. First, we characterize the influence of linker length and flexibility on FRET for different dye linker types (long, intermediate, short) by analyzing fluorescence lifetime and anisotropy decays. For long linkers, we describe a straightforward procedure that allows for very high accuracy of FRET-based structure determination through proper consideration of the position distribution of the dye and of linker dynamics. The position distribution can be quickly calculated with geometric accessible volume (AV) simulations, provided that the local structure of RNA or DNA in the proximity of the dye is known and that the dye diffuses freely in the sterically allowed space. The AV approach provides results similar to molecular dynamics simulations (MD) and is fully consistent with experimental FRET data. In a benchmark study for ds A-RNA, an rmsd value of 1.3 Å is achieved. Considering the case of undefined dye environments or very short DA distances, we introduce short linkers with a propargyl or alkenyl unit for internal labeling of nucleic acids to minimize position uncertainties. Studies by ensemble time correlated single photon counting and single-molecule detection show that the nature of the linker strongly affects the radius of the dye's accessible volume (6-16 Å). For short propargyl linkers, heterogeneous dye environments are observed on the millisecond time scale. A

  11. Ensuring US National Aeronautics Test Capabilities

    Science.gov (United States)

    Marshall, Timothy J.

    2010-01-01

    process; and the reductions in wind tunnel testing requirements within the largest consumer of ATP wind tunnel test time, the Aeronautics Research Mission Directorate (ARMD). Retirement of the Space Shuttle Program and recent perturbations of NASA's Constellation Program will exacerbate this downward trend. Therefore it is crucial that ATP periodically revisit and determine which of its test capabilities are strategically important, which qualify as low-risk redundancies that could be put in an inactive status or closed, and address the challenges associated with both sustainment and improvements to the test capabilities that must remain active. This presentation will provide an overview of the ATP vision, mission, and goals as well as the challenges and opportunities the program is facing both today and in the future. We will discuss the strategy ATP is taking over the next five years to address the National aeronautics test capability challenges and what the program will do to capitalize on its opportunities to ensure a ready, robust and relevant portfolio of National aeronautics test capabilities.

  12. Bioinformatic Analysis Reveals Conservation of Intrinsic Disorder in the Linker Sequences of Prokaryotic Dual-family Immunophilin Chaperones.

    Science.gov (United States)

    Barik, Sailen

    2018-01-01

    The two classical immunophilin families, found essentially in all living cells, are: cyclophilin (CYN) and FK506-binding protein (FKBP). We previously reported a novel class of immunophilins that are natural chimera of these two, which we named dual-family immunophilin (DFI). The DFIs were found in either of two conformations: CYN-linker-FKBP (CFBP) or FKBP-3TPR-CYN (FCBP). While the 3TPR domain can serve as a flexible linker between the FKBP and CYN modules in the FCBP-type DFI, the linker sequences in the CFBP-type DFIs are relatively short, diverse in sequence, and contain no discernible motif or signature. Here, I present several lines of computational evidence that, regardless of their primary structure, these CFBP linkers are intrinsically disordered. This report provides the first molecular foundation for the model that the CFBP linker acts as an unstructured, flexible loop, allowing the two flanking chaperone modules function independently while linked in cis , likely to assist in the folding of multisubunit client complexes.

  13. Hybrid Zeolitic Imidazolate Frameworks: Controlling Framework Porosity and Functionality by Mixed-Linker Synthesis

    KAUST Repository

    Thompson, Joshua A.

    2012-05-22

    Zeolitic imidazolate frameworks (ZIFs) are a subclass of nanoporous metal-organic frameworks (MOFs) that exhibit zeolite-like structural topologies and have interesting molecular recognition properties, such as molecular sieving and gate-opening effects associated with their pore apertures. The synthesis and characterization of hybrid ZIFs with mixed linkers in the framework are described in this work, producing materials with properties distinctly different from the parent frameworks (ZIF-8, ZIF-90, and ZIF-7). NMR spectroscopy is used to assess the relative amounts of the different linkers included in the frameworks, whereas nitrogen physisorption shows the evolution of the effective pore size distribution in materials resulting from the framework hybridization. X-ray diffraction shows these hybrid materials to be crystalline. In the case of ZIF-8-90 hybrids, the cubic space group of the parent frameworks is continuously maintained, whereas in the case of the ZIF-7-8 hybrids there is a transition from a cubic to a rhombohedral space group. Nitrogen physisorption data reveal that the hybrid materials exhibit substantial changes in gate-opening phenomena, either occurring at continuously tunable partial pressures of nitrogen (ZIF-8-90 hybrids) or loss of gate-opening effects to yield more rigid frameworks (ZIF-7-8 hybrids). With this synthetic approach, significant alterations in MOF properties may be realized to suit a desired separation or catalytic process. © 2012 American Chemical Society.

  14. Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

    Directory of Open Access Journals (Sweden)

    Shih Ping Yao

    2002-04-01

    Full Text Available Abstract Background Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT that greatly improves the production efficiency of large transgenic animals. Results The linker protein, a monoclonal antibody (mAb C, is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57 of transgenic pigs (F0 generation. Conclusions Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species.

  15. Ab initio study of hydrogen adsorption on benzenoid linkers in metal-organic framework materials

    International Nuclear Information System (INIS)

    Gao Yi; Zeng, X C

    2007-01-01

    We have computed the energies of adsorption of molecular hydrogen on a number of molecular linkers in metal-organic framework solid materials using density functional theory (DFT) and ab initio molecular orbital methods. We find that the hybrid B3LYP (Becke three-parameter Lee-Yang-Parr) DFT method gives a qualitatively incorrect prediction of the hydrogen binding with benzenoid molecular linkers. Both local-density approximation (LDA) and generalized gradient approximation (GGA) DFT methods are inaccurate in predicting the values of hydrogen binding energies, but can give a qualitatively correct prediction of the hydrogen binding. When compared to the more accurate binding-energy results based on the ab initio Moeller-Plesset second-order perturbation (MP2) method, the LDA results may be viewed as an upper limit while the GGA results may be viewed as a lower limit. Since the MP2 calculation is impractical for realistic metal-organic framework systems, the combined LDA and GGA calculations provide a cost-effective way to assess the hydrogen binding capability of these systems

  16. G-CSF receptor-binding cyclic peptides designed with artificial amino-acid linkers

    International Nuclear Information System (INIS)

    Shibata, Kenji; Maruyama-Takahashi, Kumiko; Yamasaki, Motoo; Hirayama, Noriaki

    2006-01-01

    Designing small molecules that mimic the receptor-binding local surface structure of large proteins such as cytokines or growth factors is fascinating and challenging. In this study, we designed cyclic peptides that reproduce the receptor-binding loop structures of G-CSF. We found it is important to select a suitable linker to join two or more discontinuous sequences and both termini of the peptide corresponding to the receptor-binding loop. Structural simulations based on the crystallographic structure of KW-2228, a stable and potent analog of human G-CSF, led us to choose 4-aminobenzoic acid (Abz) as a part of the linker. A combination of 4-Abz with β-alanine or glycine, and disulfide bridges between cysteins or homocysteins, gave a structure suitable for receptor binding. In this structure, the side-chains of several amino acids important for the interactions with the receptor are protruding from one side of the peptide ring. This artificial peptide showed G-CSF antagonistic activity in a cell proliferation assay

  17. A Switchable Linker-Based Immunoassay for Ultrasensitive Visible Detection of Salmonella in Tomatoes.

    Science.gov (United States)

    Hahn, Jungwoo; Kim, Eunghee; You, Young Sang; Gunasekaran, Sundaram; Lim, Seokwon; Choi, Young Jin

    2017-10-01

    On-site detection for sensitive identification of foodborne pathogens on fresh produce with minimal use of specialized instrumentation is crucial to the food industry. A switchable linker (SL)-based immunoassay was designed for ultrasensitive on-site detection of Salmonella in tomato samples. The assay is based on large-scale aggregation of gold nanoparticles (GNPs), induced by a quantitative relationship among the biotinylated Salmonella polyclonal antibody (b-Ab) used as the SL, the functionalized GNPs, and Salmonella. Important factors such as the concentration of SLs, time required for large-scale aggregation, and selectivity of b-Ab were optimized to minimize the detection time (within 45 min with gentle agitation) and achieve the lowest limit of detection (LOD; 10 CFU/g in tomato samples) possible. This SL-based immunoassay with its relatively low LOD and short detection time may meet the need for rapid, simple, on-site analysis of pathogens in fresh produce. The novel switchable linker-based immunoassay is a rapid, specific, and sensitive method that has potential applications for routine diagnostics of Salmonella in tomato products. These advantages make it a practical approach for general use in the processing industry to detect Salmonella rapidly and to implement appropriate regulatory procedures. Furthermore, it could be applied to other fresh products including cantaloupe, strawberry, and cucumbers. © 2017 Institute of Food Technologists®.

  18. The First MS-Cleavable, Photo-Thiol-Reactive Cross-Linker for Protein Structural Studies

    Science.gov (United States)

    Iacobucci, Claudio; Piotrowski, Christine; Rehkamp, Anne; Ihling, Christian H.; Sinz, Andrea

    2018-04-01

    Cleavable cross-linkers are gaining increasing importance for chemical cross-linking/mass spectrometry (MS) as they permit a reliable and automated data analysis in structural studies of proteins and protein assemblies. Here, we introduce 1,3-diallylurea (DAU) as the first CID-MS/MS-cleavable, photo-thiol-reactive cross-linker. DAU is a commercially available, inexpensive reagent that efficiently undergoes an anti-Markovnikov hydrothiolation with cysteine residues in the presence of a radical initiator upon UV-A irradiation. Radical cysteine cross-linking proceeds via an orthogonal "click reaction" and yields stable alkyl sulfide products. DAU reacts at physiological pH and cross-linking reactions with peptides, and proteins can be performed at temperatures as low as 4 °C. The central urea bond is efficiently cleaved upon collisional activation during tandem MS experiments generating characteristic product ions. This improves the reliability of automated cross-link identification. Different radical initiators have been screened for the cross-linking reaction of DAU using the thiol-containing compounds cysteine and glutathione. Our concept has also been exemplified for the biologically relevant proteins bMunc13-2 and retinal guanylyl cyclase-activating protein-2. [Figure not available: see fulltext.

  19. Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.

    Science.gov (United States)

    Yan, Qingrong; Barros, Tiago; Visperas, Patrick R; Deindl, Sebastian; Kadlecek, Theresa A; Weiss, Arthur; Kuriyan, John

    2013-06-01

    Serial activation of the tyrosine kinases Lck and ZAP-70 initiates signaling downstream of the T cell receptor. We previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine. We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. The revised model identifies distinct roles for these two tyrosines. As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly phosphorylated peptides by the SH2 domains. Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 only ∼5-fold in vitro. In contrast, phosphorylation by Lck activates ZAP-70 ∼100-fold. This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck.

  20. Iminodiacetic acid as bifunctional linker for dimerization of cyclic RGD peptides

    International Nuclear Information System (INIS)

    Xu, Dong; Zhao, Zuo-Quan; Chen, Shu-Ting; Yang, Yong; Fang, Wei; Liu, Shuang

    2017-01-01

    Introduction: In this study, I2P-RGD 2 was used as the example to illustrate a novel approach for dimerization of cyclic RGD peptides. The main objective of this study was to explore the impact of bifunctional linkers (glutamic acid vs. iminodiacetic acid) on tumor-targeting capability and excretion kinetics of the 99m Tc-labeled dimeric cyclic RGD peptides. Methods: HYNIC-I2P-RGD 2 was prepared by reacting I2P-RGD 2 with HYNIC-OSu in the presence of diisopropylethylamine, and was evaluated for its α v β 3 binding affinity against 125 I-echistatin bound to U87MG glioma cells. 99m Tc-I2P-RGD 2 was prepared with high specific activity (~185 GBq/μmol). The athymic nude mice bearing U87MG glioma xenografts were used to evaluate its biodistribution properties and image quality in comparison with those of 99m Tc-3P-RGD 2 . Results: The IC 50 value for HYNIC-I2P-RGD 2 was determined to be 39 ± 6 nM, which was very close to that (IC 50 = 33 ± 5 nM) of HYNIC-3P-RGD 2 . Replacing glutamic acid with iminodiacetic acid had little impact on α v β 3 binding affinity of cyclic RGD peptides. 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 shared similar tumor uptake values over the 2 h period, and its α v β 3 -specificity was demonstrated by a blocking experiment. The uptake of 99m Tc-I2P-RGD 2 was significantly lower than 99m Tc-3P-RGD 2 in the liver and kidneys. The U87MG glioma tumors were visualized by SPECT with excellent contrast using both 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 . Conclusion: Iminodiacetic acid is an excellent bifunctional linker for dimerization of cyclic RGD peptides. Bifunctional linkers have significant impact on the excretion kinetics of 99m Tc radiotracers. Because of its lower liver uptake and better tumor/liver ratios, 99m Tc-I2P-RGD 2 may have advantages over 99m Tc-3P-RGD 2 for diagnosis of tumors in chest region. -- Graphical abstract: This report presents novel approach for dimerization of cyclic RGD peptides using iminodiacetic acid as a

  1. Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers

    Directory of Open Access Journals (Sweden)

    Yu Huang

    2018-01-01

    Full Text Available A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV–Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV–Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.

  2. Mutations in Biosynthetic Enzymes for the Protein Linker Region of Chondroitin/Dermatan/Heparan Sulfate Cause Skeletal and Skin Dysplasias

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2015-01-01

    Full Text Available Glycosaminoglycans, including chondroitin, dermatan, and heparan sulfate, have various roles in a wide range of biological events such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Their polysaccharides covalently attach to the serine residues on specific core proteins through the common linker region tetrasaccharide, -xylose-galactose-galactose-glucuronic acid, which is produced through the stepwise addition of respective monosaccharides by four distinct glycosyltransferases. Mutations in the human genes encoding the glycosyltransferases responsible for the biosynthesis of the linker region tetrasaccharide cause a number of genetic disorders, called glycosaminoglycan linkeropathies, including Desbuquois dysplasia type 2, spondyloepimetaphyseal dysplasia, Ehlers-Danlos syndrome, and Larsen syndrome. This review focused on recent studies on genetic diseases caused by defects in the biosynthesis of the common linker region tetrasaccharide.

  3. Linker length dependent binding of a focal adhesion kinase derived peptide to the Src SH3-SH2 domains.

    Science.gov (United States)

    Lindfors, Hanna E; Venkata, Bharat Somireddy; Drijfhout, Jan W; Ubbink, Marcellus

    2011-02-18

    The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry. The binding to both motifs is anti-cooperative. Reduction of the long linker connecting the motifs does not lead to cooperativity. Short linkers that do not allow simultaneous intramolecular binding of the peptide to both motifs cause peptide-mediated dimerisation, even with a linker of only three amino acids. The role of the SH3 binding motif is discussed in view of the independent nature of the SH interactions. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Are neck flexion, neck rotation, and sitting at work risk factors for neck pain? Results of a prospective cohort study

    NARCIS (Netherlands)

    Ariens, G.A.M.; Bongers, P.M.; Douwes, M.; Miedema, M.C.; Hoogendoorn, W.E.; van der Wal, G.; Bouter, L.M.; van Mechelen, W.

    2001-01-01

    Objective: To study the relation between neck pain and work related neck flexion, neck rotation, and sitting. Methods: A prospective cohort study was performed with a follow up of 3 years among 1334 workers from 34 companies. Work related physical load was assessed by analysing objectively measured

  5. Are neck flexion, neck rotation, and sitting at work risk factors for neck pain? : Results of a prospective cohort study

    NARCIS (Netherlands)

    Ariëns, G A; Bongers, P M; Douwes, M; Miedema, M C; Hoogendoorn, W E; van der Wal, G; Bouter, L M; van Mechelen, W

    OBJECTIVE: To study the relation between neck pain and work related neck flexion, neck rotation, and sitting. METHODS: A prospective cohort study was performed with a follow up of 3 years among 1334 workers from 34 companies. Work related physical load was assessed by analysing objectively measured

  6. The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.

    Directory of Open Access Journals (Sweden)

    Chai Ann Ng

    Full Text Available Human ether-à-go-go-related gene (hERG K(+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.

  7. ESSENCE OF THE PROBLEM OF ENSURING FOOD SECURITY

    OpenAIRE

    Lalayan G. G.

    2013-01-01

    In this article we have revealed the essence of the problem of ensuring food security in detail. The components of economic safety at macroeconomic level are described, defining conditions of ensuring national food security are shown

  8. Head and Neck Cancer—Patient Version

    Science.gov (United States)

    Head and neck cancers include cancers in the larynx (voice box), throat, lips, mouth, nose, and salivary glands. Start here to find information on head and neck cancer treatment in adults and children, causes and prevention, screening, research, and statistics.

  9. Neck and arm pain syndromes

    DEFF Research Database (Denmark)

    de las Peñas, César Fernández; Cleland, Joshua; Huijbregts, Peter

    approaches.It uniquely addresses the expanding role of the various health care professions which require increased knowledge and skills in screening for contra-indications and recognizing the need for medical-surgical referral. Neck and Arm Pain Syndromes also stresses the integration of experiential......The first of its kind, Neck and Arm Pain Syndromes is a comprehensive evidence- and clinical-based book, covering research-based diagnosis, prognosis and management of neuromusculoskeletal pathologies and dysfunctions of the upper quadrant, including joint, muscle, myofascial and neural tissue...... of the most commonly seen pain syndromes in clinical practice over 800 illustrations demonstrating examination procedures and techniques....

  10. Five-Week Outcomes From a Dosing Trial of Therapeutic Massage for Chronic Neck Pain

    Science.gov (United States)

    Sherman, Karen J.; Cook, Andrea J.; Wellman, Robert D.; Hawkes, Rene J.; Kahn, Janet R.; Deyo, Richard A.; Cherkin, Daniel C.

    2014-01-01

    PURPOSE This trial was designed to evaluate the optimal dose of massage for individuals with chronic neck pain. METHODS We recruited 228 individuals with chronic nonspecific neck pain from an integrated health care system and the general population, and randomized them to 5 groups receiving various doses of massage (a 4-week course consisting of 30-minute visits 2 or 3 times weekly or 60-minute visits 1, 2, or 3 times weekly) or to a single control group (a 4-week period on a wait list). We assessed neck-related dysfunction with the Neck Disability Index (range, 0–50 points) and pain intensity with a numerical rating scale (range, 0–10 points) at baseline and 5 weeks. We used log-linear regression to assess the likelihood of clinically meaningful improvement in neck-related dysfunction (≥5 points on Neck Disability Index) or pain intensity (≥30% improvement) by treatment group. RESULTS After adjustment for baseline age, outcome measures, and imbalanced covariates, 30-minute treatments were not significantly better than the wait list control condition in terms of achieving a clinically meaningful improvement in neck dysfunction or pain, regardless of the frequency of treatments. In contrast, 60-minute treatments 2 and 3 times weekly significantly increased the likelihood of such improvement compared with the control condition in terms of both neck dysfunction (relative risk = 3.41 and 4.98, P = .04 and .005, respectively) and pain intensity (relative risk = 2.30 and 2.73; P = .007 and .001, respectively). CONCLUSIONS After 4 weeks of treatment, we found multiple 60-minute massages per week more effective than fewer or shorter sessions for individuals with chronic neck pain. Clinicians recommending massage and researchers studying this therapy should ensure that patients receive a likely effective dose of treatment. PMID:24615306

  11. Preparation of value-added metal-organic frameworks (MOFs) using waste PET bottles as source of acid linker

    CSIR Research Space (South Africa)

    Dyosiba, Xoliswa

    2016-12-01

    Full Text Available of Value-added Metal-organic Frameworks (MOFs) Using Waste PET Bottles as Source of Acid Linker Xoliswa Dyosiba, Jianwei Ren, Nicholas M. Musyoka, Henrietta W. Langmi, Mkhulu Mathe, Maurice S. Onyango PII: S2214-9937(16)30053-7 DOI: doi:10.1016/j..., Hen- rietta W. Langmi, Mkhulu Mathe, Maurice S. Onyango, Preparation of Value-added Metal-organic Frameworks (MOFs) Using Waste PET Bottles as Source of Acid Linker, Sustainable Materials and Technologies (2016), doi:10.1016/j.susmat.2016...

  12. A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

    DEFF Research Database (Denmark)

    Bang, Claus Gunnar; Jensen, Jakob Feldthusen; Cohrt, Anders Emil O'Hanlon

    2017-01-01

    We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control...... and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay....

  13. Novel cross-linkers for PDMS networks for controlled and well distributed grafting of functionalities by click chemistry

    DEFF Research Database (Denmark)

    Bahrt, Frederikke; Dimitrov, Ivaylo; Daugaard, Anders Egede

    2013-01-01

    by 35%. The contact angle of PDMS films was increased from 108° to 116° by the introduction of a small poly(pentafluorostyrene) chain. Finally, 17α-ethynyl-1,3,5(10)-estratriene-3,17β-diol and 1-ethynyl-3,5- bis(trifluoromethyl)benzene were incorporated as examples of other functional groups. © 2013......-linkers have been utilized to prepare novel polydimethylsiloxane (PDMS) networks. All functional cross-linkers were successfully incorporated into the networks and were demonstrated to be well distributed within the PDMS films. This was substantiated by fluorescence microscopy of a film prepared with the 4...

  14. Perspectives of Security Ensuring within the Framework of Barcelona Process

    Directory of Open Access Journals (Sweden)

    T N Kirabaev

    2009-06-01

    Full Text Available Barcelona process was aimed to become an important mechanism in the realization of ideas of peace, stability and security ensuring in the Mediterranean Sea region. Cooperation in the sphere of security ensuring means openness of the regional states, social and economic reforms, human rights protection. The article deals with the problem of security ensuring by nonmilitary means.

  15. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... cancer of the head, neck and mouth. The Oral Cancer Foundation estimates that close to 42,000 Americans ... diagnosed with oral or pharyngeal cancer this year. Oral cancer’s mortality is particularly high, not because it is ...

  16. Necked-in superdeformed nuclei

    International Nuclear Information System (INIS)

    Joensson, L.O.

    1997-03-01

    In this dissertation the possibility of forming superdeformed states related to two connected spheres, having a more or less pronounced neck, is investigated. Detailed Nilsson-Strutinsky calculations with the cranked Woods-Saxon potential and a finite-range liquid drop model are carried out in the 180 Hg region, where superdeformed states related to two overlapping 90 Zr are predicted. Detailed spectroscopic properties are calculated. The effect of the necking degree of freedom on the giant dipole resonance, GDR, is investigated. The calculations are carried out with the Woods-saxon potential for the single-particle states, and the random phase approximation formalism for the phonon states. The residual interaction and coupling constants are determined by requirements of transitional invariance. The lower energy component of the GDR spectrum for superdeformed shapes, corresponding to vibrations along the symmetry axis, is diminished with increasing necking, and the mean energy of the GDR is increased. The folded Yukawa-plus-exponential liquid drop models take into account the finite range of the nuclear force, which is important when elongated and necked-in nuclear shapes are considered. However, it is shown that they are unstable towards higher multipole deformations, and that unphysical shapes are obtained in free minimizations when too high multipole deformations are included. Limits on multipolarity are given as functions of mass number. 9 refs., 4 figs

  17. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... lump in the neck Your mouth is one of your body's most important early warning systems. Don't ignore any suspicious lumps or sores. Should you discover something, make an appointment for a prompt examination. Early treatment may well be the key to complete ... Oral and maxillofacial ...

  18. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are ... more. TMJ and Facial Pain TMJ and Facial ... Teeth Management Wisdom Teeth Management An impacted wisdom tooth can ...

  19. Preferential 5-Methylcytosine Oxidation in the Linker Region of Reconstituted Positioned Nucleosomes by Tet1 Protein.

    Science.gov (United States)

    Kizaki, Seiichiro; Zou, Tingting; Li, Yue; Han, Yong-Woon; Suzuki, Yuki; Harada, Yoshie; Sugiyama, Hiroshi

    2016-11-07

    Tet (ten-eleven translocation) family proteins oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC), and are suggested to be involved in the active DNA demethylation pathway. In this study, we reconstituted positioned mononucleosomes using CpG-methylated 382 bp DNA containing the Widom 601 sequence and recombinant histone octamer, and subjected the nucleosome to treatment with Tet1 protein. The sites of oxidized methylcytosine were identified by bisulfite sequencing. We found that, for the oxidation reaction, Tet1 protein prefers mCs located in the linker region of the nucleosome compared with those located in the core region. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker

    DEFF Research Database (Denmark)

    Crestey, François; Ottesen, Lars Korsgaard; Jaroszewski, Jerzy Witold

    2008-01-01

    The Letter describes an improved, rapid and mild strategy for the loading of primary alcohols onto a polystyrene trityl resin via a highly reactive trityl bromide linker. This protocol facilitates an efficient resin loading even of acid-sensitive or heat-labile alcohols, which otherwise require...... expensive or non-commercial resin types. Secondary alcohols were only attached in moderate to low yields, while attempts to load a tertiary alcohol expectedly failed. Importantly, selective attachment of diols via a primary alcohol group in the presence of more hindered alcohol groups proved possible....... The effects of activation time and reagent excess as well as alcohol structure were investigated. This improved method provides a convenient access to O-linked resin-bound N-Fmoc-protected amino alcohols that may be employed in SPS of peptides with C-terminal alcohol functionalities. In the case...

  1. Temperature-triggered release of a liquid cross-linker micro-encapsulated in a glassy polymer for low temperature curing

    NARCIS (Netherlands)

    Senatore, D.; Cate, ten A.T.; Laven, J.; Benthem, van R.A.T.M.; With, de G.

    2013-01-01

    In order to prevent a liquid epoxy cross-linker from premature, Arrhenius-law predicted, reaction with an acid-functional polyester resin, the liquid cross-linker has been physically separated from the resin by encapsulation while release is only possible by a temperature-controlled trigger. The

  2. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    Energy Technology Data Exchange (ETDEWEB)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-04-15

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

  3. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    International Nuclear Information System (INIS)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho; Won, Mooho

    2013-01-01

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC 50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC 50 = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM

  4. Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

    Science.gov (United States)

    Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

    2016-01-21

    Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Eviction of linker histone H1 by NAP-family histone chaperones enhances activated transcription.

    Science.gov (United States)

    Zhang, Qian; Giebler, Holli A; Isaacson, Marisa K; Nyborg, Jennifer K

    2015-01-01

    In the Metazoan nucleus, core histones assemble the genomic DNA to form nucleosome arrays, which are further compacted into dense chromatin structures by the linker histone H1. The extraordinary density of chromatin creates an obstacle for accessing the genetic information. Regulation of chromatin dynamics is therefore critical to cellular homeostasis, and histone chaperones serve as prominent players in these processes. In the current study, we examined the role of specific histone chaperones in negotiating the inherently repressive chromatin structure during transcriptional activation. Using a model promoter, we demonstrate that the human nucleosome assembly protein family members hNap1 and SET/Taf1β stimulate transcription in vitro during pre-initiation complex formation, prior to elongation. This stimulatory effect is dependent upon the presence of activators, p300, and Acetyl-CoA. We show that transcription from our chromatin template is strongly repressed by H1, and that both histone chaperones enhance RNA synthesis by overcoming H1-induced repression. Importantly, both hNap1 and SET/Taf1β directly bind H1, and function to enhance transcription by evicting the linker histone from chromatin reconstituted with H1. In vivo studies demonstrate that SET/Taf1β, but not hNap1, strongly stimulates activated transcription from the chromosomally-integrated model promoter, consistent with the observation that SET/Taf1β is nuclear, whereas hNap1 is primarily cytoplasmic. Together, these observations indicate that SET/Taf1β may serve as a critical regulator of H1 dynamics and gene activation in vivo. These studies uncover a novel function for SET that mechanistically couples transcriptional derepression with H1 dynamics. Furthermore, they underscore the significance of chaperone-dependent H1 displacement as an essential early step in the transition of a promoter from a dense chromatin state into one that is permissive to transcription factor binding and robust

  6. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    Directory of Open Access Journals (Sweden)

    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

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

    International Nuclear Information System (INIS)

    Jang, Na Young; Lee, Keun-Wook; Ahn, Soon-Hyun; Kim, Jae-Sung; Ah Kim, In

    2012-01-01

    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. 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. 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. 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

  8. Synthesis of two new alkyne-bearing linkers used for the preparation of siRNA for labeling by click chemistry with fluorine-18

    International Nuclear Information System (INIS)

    Flagothier, Jessica; Kaisin, Geoffroy; Mercier, Frederic; Thonon, David; Teller, Nathalie; Wouters, Johan; Luxen, André

    2012-01-01

    Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [ 18 F] labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two new linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [ 18 F] prosthetic group. - Highlights: ► Synthesis of two new alkyne linkers. ► Functionalization at the 3′-end siRNA by alkyne linker derived of proline. ► Click chemistry between alkyne modified siRNA and [ 18 F] prosthetic group.

  9. One-pot preparation of mRNA/cDNA display by a novel and versatile puromycin-linker DNA.

    Science.gov (United States)

    Mochizuki, Yuki; Biyani, Manish; Tsuji-Ueno, Sachika; Suzuki, Miho; Nishigaki, Koichi; Husimi, Yuzuru; Nemoto, Naoto

    2011-09-12

    A rapid, easy, and robust preparation method for mRNA/cDNA display using a newly designed puromycin-linker DNA is presented. The new linker is structurally simple, easy to synthesize, and cost-effective for use in "in vitro peptide and protein selection". An introduction of RNase T1 nuclease site to the new linker facilitates the easy recovery of mRNA/cDNA displayed protein by an improvement of the efficiency of ligating the linker to mRNAs and efficient release of mRNA/cDNA displayed protein from the solid-phase (magnetic bead). For application demonstration, affinity selections were successfully performed. Furthermore, we introduced a "one-pot" preparation protocol to perform mRNA display easy. Unlike conventional approaches that require tedious and downstream multistep process including purification, this protocol will make the mRNA/cDNA display methods more practical and convenient and also facilitate the development of next-generation, high-throughput mRNA/cDNA display systems amenable to automation.

  10. Mechanistic Evaluation of Motion in Redox-Driven Rotaxanes Reveals Longer Linkers Hasten Forward Escape's and Hinder Backward Translations

    DEFF Research Database (Denmark)

    Andersen, S. S.; Share, A. I.; Poulsen, B. L.

    2014-01-01

    temperatures to provide activation enthalpies (Delta H-double dagger) and entropies (Delta S-double dagger). Longer glycol linkers led to modest increases in the forward escape (t(1/2) = 60 to 69 s); though not because of a diffusive walk. The reduced rate of motion backward depended on folded structures...

  11. The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

    DEFF Research Database (Denmark)

    Rivas, Matilde De Las; Lira-Navarrete, Erandi; Daniel, Earnest James Paul

    2017-01-01

    The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation ...

  12. Synthesis and catalytic evaluation in the Heck reaction of deposited palladium catalysts immobilized via amide linkers and their molecular analogues

    Czech Academy of Sciences Publication Activity Database

    Semler, M.; Čejka, Jiří; Štěpnička, P.

    2014-01-01

    Roč. 227, MAY 2014 (2014), s. 207-214 ISSN 0920-5861 R&D Projects: GA ČR GA104/09/0561; GA ČR(CZ) GA13-08944S Institutional support: RVO:61388955 Keywords : deposited catalysts * palladium * amide linkers Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.893, year: 2014

  13. Differential solvation of intrinsically disordered linkers drives the formation of spatially organized droplets in ternary systems of linear multivalent proteins

    Science.gov (United States)

    Harmon, Tyler S.; Holehouse, Alex S.; Pappu, Rohit V.

    2018-04-01

    Intracellular biomolecular condensates are membraneless organelles that encompass large numbers of multivalent protein and nucleic acid molecules. The bodies assemble via a combination of liquid–liquid phase separation and gelation. A majority of condensates included multiple components and show multilayered organization as opposed to being well-mixed unitary liquids. Here, we put forward a simple thermodynamic framework to describe the emergence of spatially organized droplets in multicomponent systems comprising of linear multivalent polymers also known as associative polymers. These polymers, which mimic proteins and/or RNA have the architecture of domains or motifs known as stickers that are interspersed by flexible spacers known as linkers. Using a minimalist numerical model for a four-component system, we have identified features of linear multivalent molecules that are necessary and sufficient for generating spatially organized droplets. We show that differences in sequence-specific effective solvation volumes of disordered linkers between interaction domains enable the formation of spatially organized droplets. Molecules with linkers that are preferentially solvated are driven to the interface with the bulk solvent, whereas molecules that have linkers with negligible effective solvation volumes form cores in the core–shell architectures that emerge in the minimalist four-component systems. Our modeling has relevance for understanding the physical determinants of spatially organized membraneless organelles.

  14. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network

    Science.gov (United States)

    Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

    2014-01-01

    Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers. PMID:25296246

  15. High-resolution two-dimensional liquid chromatography analysis of key linker drug intermediate used in antibody drug conjugates.

    Science.gov (United States)

    Venkatramani, C J; Huang, Shu Rong; Al-Sayah, Mohammad; Patel, Ila; Wigman, Larry

    2017-10-27

    In this manuscript, the application of high-resolution sampling (HRS) two-dimensional liquid chromatography (2D-LC) in the detailed analysis of key linker drug intermediate is presented. Using HRS, selected regions of the primary column eluent were transferred to a secondary column with fidelity enabling qualitative and quantitative analysis of linker drugs. The primary column purity of linker drug intermediate ranged from 88.9% to 94.5% and the secondary column purity ranged from 99.6% to 99.9%, showing lot-to-lot variability, significant differences between the three lots, and substantiating the synthetic and analytical challenges of ADCs. Over 15 impurities co-eluting with the linker drug intermediate in the primary dimension were resolved in the secondary dimension. The concentrations of most of these impurities were over three orders of magnitude lower than the linker drug. Effective peak focusing and high-speed secondary column analysis resulted in sharp peaks in the secondary dimension, improving the signal-to-noise ratios. The sensitivity of 2D-LC separation was over five fold better than conventional HPLC separation. The limit of quantitation (LOQ) was less than 0.01%. Many peaks originating from primary dimension were resolved into multiple components in the complementary secondary dimension, demonstrating the complexity of these samples. The 2D-LC was highly reproducible, showing good precision between runs with%RSD of peak areas less than 0.1 for the main component. The absolute difference in the peak areas of impurities less than 0.1% were within ±0.01% and for impurities in the range of 0.1%-0.3%, the absolute difference were ±0.02%, which are comparable to 1D-LC. The overall purity of the linker drug intermediate was determined from the product of primary and secondary column purity (HPLC Purity=%peak area of main component in the primary dimension×%peak area of main component in the secondary dimension). Additionally, the 2D-LC separation enables

  16. Neck muscle function in violinists/violists with and without neck pain.

    Science.gov (United States)

    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 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.

  17. Neck muscle endurance and head posture: A comparison between adolescents with and without neck pain.

    Science.gov (United States)

    Oliveira, Ana Carolina; Silva, Anabela G

    2016-04-01

    The main aims of this study were to compare the neck flexor and extensor endurance and forward head posture between adolescents with and without neck pain. The secondary aims were to explore potential associations between muscles endurance, head posture and neck pain characteristics and to assess intra-rater reliability of the measurements used. Adolescents with neck pain (n = 35) and age-matched asymptomatic adolescents (n = 35) had their forward head posture, neck flexor endurance and neck extensor endurance measured using clinical tests. Intra-rater reliability was also assessed. Forward head posture and neck flexor and extensor endurance tests showed moderate to almost perfect intra-rater reliability (ICC between 0.58 and 0.88). Adolescents with neck pain showed significantly less forward head posture (neck pain = 46.62 ± 4.92; asymptomatic = 44.18°± 3.64°, p > 0.05) and less neck flexor (neck pain = 24.50 ± 23.03s; asymptomatic = 35.89 ± 21.53s, p > 0.05) and extensor endurance (neck pain = 12.6.64 ± 77.94s; asymptomatic = 168.66 ± 74.77s, p > 0.05) than asymptomatic adolescents. Results suggest that changes in posture and neck muscle endurance are a feature of adolescents with neck pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

    Science.gov (United States)

    Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

    2015-01-02

    G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Evaluation of ¹¹¹in-labelled exendin-4 derivatives containing different meprin β-specific cleavable linkers.

    Directory of Open Access Journals (Sweden)

    Andreas Jodal

    Full Text Available Cleavable linkers, which are specifically cleaved by defined conditions or enzymes, are powerful tools that can be used for various purposes. Amongst other things, they have been successfully used to deliver toxic payloads as prodrugs into target tissues. In this work novel linker sequences targeting meprin β, a metalloprotease expressed in the kidney brush-border membrane, were designed and included in the sequence of three radiolabelled exendin-4 derivatives. As radiolabelled exendin-4 derivatives strongly accumulate in the kidneys, we hypothesised that specific cleavage of the radiolabelled moiety at the kidney brush-border membrane would allow easier excretion of the activity into the urine and therefore improve the pharmacological properties of the peptide.The insertion of a cleavable linker did not negatively influence the in vitro properties of the peptides. They showed a good affinity to the GLP-1 receptor expressed in CHL cells, a high internalisation and sufficiently high stability in fresh human blood plasma. In vitro digestion with recombinant meprin β rapidly metabolised the corresponding linker sequences. After 60 min the majority of the corresponding peptides were digested and at the same time the anticipated fragments were formed. The peptides were also quickly metabolised in CD1 nu/nu mouse kidney homogenates. Immunofluorescence staining of meprin β in kidney sections confirmed the expression of the protease in the kidney brush-border membrane. Biodistribution in GLP-1 receptor positive tumour-xenograft bearing mice revealed high specific uptake of the 111In-labelled tracers in receptor positive tissue. Accumulation in the kidneys, however, was still high and comparable to the lead compound 111In-Ex4NOD40.In conclusion, we show that the concept of cleavable linkers specific for meprin β is feasible, as the peptides are rapidly cleaved by the enzyme while retaining their biological properties.

  20. Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

    Science.gov (United States)

    Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

    2017-05-08

    Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and

  1. Text neck and neck pain in 18-21-year-old young adults.

    Science.gov (United States)

    Damasceno, Gerson Moreira; Ferreira, Arthur Sá; Nogueira, Leandro Alberto Calazans; Reis, Felipe José Jandre; Andrade, Igor Caio Santana; Meziat-Filho, Ney

    2018-06-01

    The aim of this study was to investigate whether there is an association between text neck and neck pain in young adults. Observational cross-sectional study with 150 18-21-year-old young adults from a public high school in the state of Rio de Janeiro was performed. In the self-report questionnaire, the participants answered questions on sociodemographic factors, anthropometric factors, time spent texting or playing on a mobile phone, visual impairments, and concern with the body posture. The neck posture was assessed by participants' self-perception and physiotherapists' judgment during a mobile phone texting message task. The Young Spine Questionnaire was used to evaluate the neck pain. Four multivariate logistic regression models were fitted to investigate the association between neck posture during mobile phone texting and neck pain, considering potential confounding factors. There is no association between neck posture, assessed by self-perception, and neck pain (OR = 1.66, p = 0.29), nor between neck posture, assessed by physiotherapists' judgment, and neck pain (OR = 1.23, p = 0.61). There was also no association between neck posture, assessed by self-perception, and frequency of neck pain (OR = 2.19, p = 0.09), nor between neck posture, assessed by physiotherapists' judgment, and frequency of neck pain (OR = 1.17, p = 0.68). This study did not show an association between text neck and neck pain in 18-21-year-old young adults. The findings challenge the belief that neck posture during mobile phone texting is associated to the growing prevalence of neck pain.

  2. The Use of Neck Support Pillows and Postural Exercises in the Management of Chronic Neck Pain.

    Science.gov (United States)

    Jamal, Alisha N; Feldman, Brian M; Pullenayegum, Eleanor

    2016-10-01

    Chronic neck pain is a common problem with a profound effect on quality of life. Identifying evidence-based management strategies is fundamental in improving patient outcomes. This study is a reanalysis of the data from Helewa, et al to further characterize the effects of postural exercises and neck support pillows on neck pain. A full factorial model was used. All interactions were analyzed adjusting for the Northwick Park Neck Pain Questionnaire (NPQ) at baseline. Postural exercises significantly decreased NPQ scores at ≥ 3 weeks, and the use of a neck support pillow significantly decreased NPQ scores at ≥ 12 weeks. These interventions could be beneficial in reducing neck pain symptoms.

  3. Methods for ensuring compliance with regulatory requirements: regulators and operators

    International Nuclear Information System (INIS)

    Fleischmann, A.W.

    1989-01-01

    Some of the methods of ensuring compliance with regulatory requirements contained in various radiation protection documents such as Regulations, ICRP Recommendations etc. are considered. These include radiation safety officers and radiation safety committees, personnel monitoring services, dissemination of information, inspection services and legislative power of enforcement. Difficulties in ensuring compliance include outmoded legislation, financial and personnel constraints

  4. Ensuring services to the poor : learning from LLPMS

    International Development Research Centre (IDRC) Digital Library (Canada)

    fajardojp

    necessary steps to delivery services to ensure providing basic facilities but poverty remains central ... services, technological transfer, imparting training, input supply within reasonable ... Providing education, ensuring health facility, safe ..... a workshop organised to get feedback on the methodology of LLPMS the officials of.

  5. An evaluation of adequacy of water policy stipulation in ensuring ...

    African Journals Online (AJOL)

    An evaluation of adequacy of water policy stipulation in ensuring water security in the context of climate change. ... Ethiopian Journal of Environmental Studies and Management ... The aim of the study was to establish how responsive the Water Policy (2010) is to ensure water security in the context of climate change.

  6. Modification of Titanium Substrates with Chimeric Peptides Comprising Antimicrobial and Titanium-Binding Motifs Connected by Linkers To Inhibit Biofilm Formation.

    Science.gov (United States)

    Liu, Zihao; Ma, Shiqing; Duan, Shun; Xuliang, Deng; Sun, Yingchun; Zhang, Xi; Xu, Xinhua; Guan, Binbin; Wang, Chao; Hu, Meilin; Qi, Xingying; Zhang, Xu; Gao, Ping

    2016-03-02

    Bacterial adhesion and biofilm formation are the primary causes of implant-associated infection, which is difficult to eliminate and may induce failure in dental implants. Chimeric peptides with both binding and antimicrobial motifs may provide a promising alternative to inhibit biofilm formation on titanium surfaces. In this study, chimeric peptides were designed by connecting an antimicrobial motif (JH8194: KRLFRRWQWRMKKY) with a binding motif (minTBP-1: RKLPDA) directly or via flexible/rigid linkers to modify Ti surfaces. We evaluated the binding behavior of peptides using quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques and investigated the effect of the modification of titanium surfaces with these peptides on the bioactivity of Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). Compared with the flexible linker (GGGGS), the rigid linker (PAPAP) significantly increased the adsorption of the chimeric peptide on titanium surfaces (p chimeric peptide with the rigid linker exhibited more effective antimicrobial ability than the peptide with the flexible linker. This finding was ascribed to the ability of the rigid linker to separate functional domains and reduce their interference to the maximum extent. Consequently, the performance of chimeric peptides with specific titanium-binding motifs and antimicrobial motifs against bacteria can be optimized by the proper selection of linkers. This rational design of chimeric peptides provides a promising alternative to inhibit the formation of biofilms on titanium surfaces with the potential to prevent peri-implantitis and peri-implant mucositis.

  7. Multivalent cyclic RGD ligands: influence of linker lengths on receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Kubas, Holger; Schaefer, Martin; Bauder-Wuest, Ulrike; Eder, Matthias; Oltmanns, Doerte [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Haberkorn, Uwe; Mier, Walter [Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Eisenhut, Michael, E-mail: m.eisenhut@dkfz.d [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2010-11-15

    Peptides involving the RGD motive (arginine-glycine-aspartic acid) recognize members of the integrin receptor family. Since the receptors are located mainly on the surface of endothelial cells, structural modifications including multimers of c(RGDfE) were recently found to improve the binding avidity for {alpha}{sub v{beta}3} integrin significantly. The multivalent RGD peptides exhibited rather loose linkages partly including oligo(ethylene glycol) spacers (EG{sub n}) with different chain lengths. Therefore, the dependence of multivalent RGD systems with and without EG{sub n} linkers were investigated on their binding properties to cultured {alpha}{sub v{beta}3} integrin-expressing U87MG cells. Methods: We synthesized a series of di-, tri- and tetravalent rigid scaffolds (terephthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic acid) conjugated to c(RGDyK) ligands, which were linked contiguously or separated by the oligo(ethylene glycol) spacers. The inhibition constants of these c(RGDyK) derivatives were determined by competition assays with {sup 125}I-labeled echistatin. Results: While c(RGDyK) function is a relative weak competitor against [{sup 125}I]echistatin (K{sub i}, 329{+-}18 nM) for {alpha}{sub v{beta}3} integrin-expressing U87MG cells, RGD dimers improved the competition potency considerably (K{sub i}, 64{+-}23 nM). This effect was even more pronounced with the RGD trimers (K{sub i}, 40{+-}7 nM) and tetramers (K{sub i}, 26{+-}9 nM). The introduction of EG{sub n} spacers and the increase of linker lengths proved to be detrimental since more competitors were needed to compete with [{sup 125}I]echistatin. The EG{sub 6} group, for example, reduced the inhibition constants by 29% (dimer), 57% (trimer) and 97% (tetramer). Conclusion: The binding experiments performed with the three forms of multivalent RGD ligands indicate the weakening of competitive potency against [{sup 125}I]echistatin with the introduction of EG{sub n} spacers. This effect

  8. Thyroid Emphysema Following Penetrating Neck Trauma

    Directory of Open Access Journals (Sweden)

    Demet Karadağ

    2011-03-01

    Full Text Available Although traumatic thyroid gland rupture or hemorrhage is usually seen in goitrous glands, injuries of the normal thyroid gland after neck trauma have rarely been described in the literature. We describe a 44-year-old man who presented with thyroid emphysema and subcutaneous emphysema (SCE that occurred after penetrating neck trauma. CT images showed complete resolution of thyroid emphysema and subcutaneous emphysema at follow-up examination. Neck injuries can be life threatening. After penetrating neck traumas, physicians should consider subtle esophageal or tracheal laceration. Thyroid emphysema can occur as the result of penetrating neck trauma. The mechanism of emphysema of the thyroid parenchyma can be explained by the thyroid gland’s presence in a single visceral compartment that encompasses the larynx, trachea and thyroid gland. We describe an unusual case of thyroid emphysema of a normal thyroid gland following a penetrating neck injury.

  9. Head and neck position sense.

    Science.gov (United States)

    Armstrong, Bridget; McNair, Peter; Taylor, Denise

    2008-01-01

    Traumatic minor cervical strains are common place in high-impact sports (e.g. tackling) and premature degenerative changes have been documented in sports people exposed to recurrent impact trauma (e.g. scrummaging in rugby) or repetitive forces (e.g. Formula 1 racing drivers, jockeys). While proprioceptive exercises have been an integral part of rehabilitation of injuries in the lower limb, they have not featured as prominently in the treatment of cervical injuries. However, head and neck position sense (HNPS) testing and re-training may have relevance in the management of minor sports-related neck injuries, and play a role in reducing the incidence of ongoing pain and problems with function. For efficacious programmes to be developed and tested, fundamental principles associated with proprioception in the cervical spine should be considered. Hence, this article highlights the importance of anatomical structures in the cervical spine responsible for position sense, and how their interaction with the CNS affects our ability to plan and execute effective purposeful movements. This article includes a review of studies examining position sense in subjects with and without pathology and describes the effects of rehabilitation programmes that have sought to improve position sense. In respect to the receptors providing proprioceptive information for the CNS, the high densities and complex arrays of spindles found in cervical muscles suggest that these receptors play a key role. There is some evidence suggesting that ensemble encoding of discharge patterns from muscle spindles is relayed to the CNS and that a pattern recognition system is used to establish joint position and movement. Sensory information from neck proprioceptive receptors is processed in tandem with information from the vestibular system. There are extensive anatomical connections between neck proprioceptive inputs and vestibular inputs. If positional information from the vestibular system is inaccurate or

  10. Increased neck muscle activity and impaired balance among females with whiplash-related chronic neck pain

    DEFF Research Database (Denmark)

    Juul-Kristensen, Birgit; Clausen, Brian; Ris Hansen, Inge

    2013-01-01

    To investigate neck muscle activity and postural control in patients with whiplash-associated disorder compared with healthy controls.......To investigate neck muscle activity and postural control in patients with whiplash-associated disorder compared with healthy controls....

  11. Oncologic safety of cervical nerve preservation in neck dissection for head and neck cancer.

    Science.gov (United States)

    Honda, Keigo; Asato, Ryo; Tsuji, Jun; Miyazaki, Masakazu; Kada, Shinpei; Tsujimura, Takashi; Kataoka, Michiko

    2017-09-01

    Although the functional merits of preserving cervical nerves in neck dissection for head and neck cancer have been reported, the oncologic safety has not yet been determined. Therefore, the purpose of this study was to evaluate the safety of cervical nerve preservation. A retrospective chart review was performed on patients with head and neck cancer who had been treated by neck dissection between 2009 and 2014 at Kyoto Medical Center. Management of cervical nerves and clinical results were analyzed. A total of 335 sides of neck dissection had been performed in 222 patients. Cervical nerves were preserved in 175 neck sides and resected in 160 sides. The 5-year overall survival (OS) rate calculated by the Kaplan-Meier method was 71%. The 5-year neck control rate was 95% in cervical nerve preserved sides and 89% in cervical nerve resected sides. Preserving cervical nerves in neck dissection is oncologically safe in selected cases. © 2017 Wiley Periodicals, Inc.

  12. Neck massage induced dural sinus thrombosis

    Directory of Open Access Journals (Sweden)

    Verma Ashish

    2007-01-01

    Full Text Available Thrombosis of the intracranial dural sinuses and internal jugular veins may occur as a complication of head and neck infections, surgery, central venous access, local malignancy, polycythemia, hyperhomocysteinemia, neck massage and intravenous drug abuse. A high degree of clinical suspicion followed by adequate imaging is prerequisite to early diagnosis and management. We report a young man who had dural sinus thrombosis with jugular venous thrombosis following neck massage.

  13. An Unusual Neck Mass: Ingested Chicken Bone

    OpenAIRE

    Demirhan, Erhan; İber, Metin; Yağız, Özlem; Kandoğan, Tolga; Çukurova, İbrahim

    2016-01-01

    Background: Foreign bodies in the upper aerodigestive tract are frequently seen in otolaryngological practice, but migration of an ingested foreign body to the neck is a very rare condition. Case Report: We present a 66-year-old woman admitted to our outpatient department with a painful neck mass. She had a history of emergency department admission 4 months prior with odynophagia after eating chicken meal. A physical examination revealed a painful and hyperemic mass on the left neck. Ant...

  14. Clinical analysis of deep neck space infections

    International Nuclear Information System (INIS)

    Hatano, Atsushi; Ui, Naoya; Shigeta, Yasushi; Iimura, Jiro; Rikitake, Masahiro; Endo, Tomonori; Kimura, Akihiro

    2009-01-01

    Deep neck space infections, which affect soft tissues and fascial compartments of the head and neck, can lead to lethal complications unless treated carefully and quickly, even with the advanced antibiotics available. We reviewed our seventeen patients with deep neck abscesses, analyzed their location by reviewing CT images, and discussed the treatment. Deep neck space infections were classified according to the degree of diffusion of infection diagnosed by CT images. Neck space infection in two cases was localized to the upper neck space above the hyoid bone (Stage I). Neck space infection in 12 cases extended to the lower neck space (Stage II), and further extended to the mediastinum in one case (Stage III). The two cases of Stage I and the four cases of Stage II were managed with incision and drainage through a submental approach. The seven cases of Stage II were managed with incision and drainage parallel to the anterior border of the sternocleidomastoid muscle, the ''Dean'' approach. The one case of Stage III received treatment through transcervicotomy and anterior mediastinal drainage through a subxiphodal incision. The parapharyngeal space played an important role in that the inflammatory change can spread to the neck space inferiorly. The anterior cervical space in the infrahyoid neck was important for mediastinal extension of parapharyngeal abscesses. It is important to diagnose deep neck space infections promptly and treat them adequately, and contrast-enhanced CT is useful and indispensable for diagnosis. The point is which kind of drainage has to be performed. If the surgical method of drainage is chosen according to the level of involvement in the neck space and mediastinum, excellent results may be obtained in terms of survival and morbidity. (author)

  15. Thyroid Emphysema Following Penetrating Neck Trauma

    OpenAIRE

    Karadağ, Demet; Doner, Egemen; Adapınar, Baki

    2014-01-01

    Although traumatic thyroid gland rupture or hemorrhage is usually seen in goitrous glands, injuries of the normal thyroid gland after neck trauma have rarely been described in the literature. We describe a 44-year-old man who presented with thyroid emphysema and subcutaneous emphysema (SCE) that occurred after penetrating neck trauma. CT images showed complete resolution of thyroid emphysema and subcutaneous emphysema at follow-up examination. Neck injuries can be life threatening. After pene...

  16. Modeling neck mobility in fossil turtles

    OpenAIRE

    Werneburg, Ingmar; Hinz, Juliane K.; Gumpenberger, Michaela; Volpato, Virginie; Natchev, Nikolay; Joyce, Walter G.

    2014-01-01

    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 cent...

  17. Inverse Effects on Gating and Modulation Caused by a Mutation in the M2-M3 Linker of the GABAA Receptor γ SubunitS⃞

    OpenAIRE

    O'Shea, Sean M.; Williams, Carrie A.; Jenkins, Andrew

    2009-01-01

    M2-M3 linkers are receptor subunit domains known to be critical for the normal function of cysteine-loop ligand-gated ion channels. Previous studies of α and β subunits of type “A” GABA receptors suggest that these linkers couple extracellular elements involved in GABA binding to the transmembrane segments that control the opening of the ion channel. To study the importance of the γ subunit M2-M3 linker, we examined the macroscopic and single-channel effects of an engi...

  18. Inter-Vertebral Flexibility of the Ostrich Neck: Implications for Estimating Sauropod Neck Flexibility

    OpenAIRE

    Cobley, Matthew J.; Rayfield, Emily J.; Barrett, Paul M.

    2013-01-01

    The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal o...

  19. A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study.

    Science.gov (United States)

    Sadaf, Aiman; Mortensen, Jonas S; Capaldi, Stefano; Tikhonova, Elena; Hariharan, Parameswaran; de Castro Ribeiro, Orquidea; Loland, Claus J; Guan, Lan; Byrne, Bernadette; Chae, Pil Seok

    2016-03-01

    Membrane proteins are amphipathic bio-macromolecules incompatible with the polar environments of aqueous media. Conventional detergents encapsulate the hydrophobic surfaces of membrane proteins allowing them to exist in aqueous solution. Membrane proteins stabilized by detergent micelles are used for structural and functional analysis. Despite the availability of a large number of detergents, only a few agents are sufficiently effective at maintaining the integrity of membrane proteins to allow successful crystallization. In the present study, we describe a novel class of synthetic amphiphiles with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively. Members of this class conferred enhanced stability on target membrane proteins compared to conventional detergents. Because of straightforward synthesis of the novel agents and their favourable effects on a range of membrane proteins, these agents should be of wide applicability to membrane protein science.

  20. Gold nanoparticles deposited on linker-free silicon substrate and embedded in aluminum Schottky contact.

    Science.gov (United States)

    Gorji, Mohammad Saleh; Razak, Khairunisak Abdul; Cheong, Kuan Yew

    2013-10-15

    Given the enormous importance of Au nanoparticles (NPs) deposition on Si substrates as the precursor for various applications, we present an alternative approach to deposit Au NPs on linker-free n- and p-type Si substrates. It is demonstrated that, all conditions being similar, there is a significant difference between densities of the deposited NPs on both substrates. The Zeta-potential and polarity of charges surrounding the hydroxylamine reduced seeded growth Au NPs, are determined by a Zetasizer. To investigate the surface properties of Si substrates, contact angle measurement is performed. Field-emission scanning electron microscope is then utilized to distinguish the NPs density on the substrates. Finally, Al/Si Schottky barrier diodes with embedded Au NPs are fabricated, and their structural and electrical characteristics are further evaluated using an energy-filtered transmission electron microscope and current-voltage measurements, respectively. The results reveal that the density of NPs is significantly higher on n-type Si substrate and consequently has more pronounced effects on the electrical characteristics of the diode. It is concluded that protonation of Si-OH group on Si surface in low pH is responsible for the immobilization of Au NPs, which eventually contributes to the lowering of barrier height and enhances the electrical characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Preparation and in vivo evaluation of novel linkers for 211At labeling of proteins

    International Nuclear Information System (INIS)

    Talanov, Vladimir S.; Yordanov, Alexander T.; Garmestani, Kayhan; Milenic, Diane E.; Arora, Hans C.; Plascjak, Paul S.; Eckelman, William C.; Waldmann, Thomas A.; Brechbiel, Martin W.

    2004-01-01

    The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for 211 At labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with 211 At to form succinimidyl 4-methoxymethyl-3-[ 211 At]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[ 211 At]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[ 211 At]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability. Each agent is conjugated with Herceptin in parallel with their respective 125 I analogue, succinimidyl 4-methoxymethyl-3-[ 125 I]iodobenzoate (10), succinimidyl 4-methylthiomethyl-3-[ 125 I]iodobenzoate (12) and succinimidyl N-{4-[ 125 I]iodophenethyl}succinamate (SIPS), respectively, for comparative assessment in LS-174T xenograft-bearing mice. With 9 and 11, inclusion of an electron pair donor in the ortho position does not appear to provide in vivo stability comparable to SAPS. Variables in radiolabeling chemistry of these three agents with 211 At are notable. Sequential elimination of acetic acid and oxidizing agent, N-chlorosuccinimide (NCS), from the 211 At radiolabeling protocol for forming SAPS improves yield, product purity and consistency. NCS appears to be critical for the radiolabeling of 6 with 211 At. Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions

  2. Effect of the Linker in Terephthalate-Functionalized Conducting Redox Polymers

    International Nuclear Information System (INIS)

    Yang, Li; Huang, Xiao; Gogoll, Adolf; Strømme, Maria; Sjödin, Martin

    2016-01-01

    The combination of high capacity redox active pendent groups and conducting polymers, realized in conducting redox polymers (CRPs), provides materials with high charge storage capacity that are electronically conducting which makes CRPs attractive for electrical energy storage applications. In this report, six polythiophene and poly(3,4-ethylenedioxythiophene)(PEDOT)-based CRPs with a diethyl terephthalate unit covalently bound to the polymer chain by various linkers have been synthesized and characterized electrochemically. The effects of the choice of polymer backbone and of the nature of the link on the electrochemistry, and in particular the cycling stability of these polymers, are discussed. All CRPs show both the doping of the polymer backbone as well as the redox behavior of the pendent groups and the redox potential of the pendent groups in the CRPs is close to that of corresponding monomer, indicating insignificant interaction between the pendant and the polymer backbone. While all CRPs show various degrees of charge decay upon electrochemical redox conversion, the PEDOT-based CRPs show significantly improved stability compared to the polythiophene counterparts. Moreover, we show that by the right choice of link the cycling stability of diethyl terephthalate substituted PEDOT-based CRPs can be significantly improved.

  3. Missing Linker Defects in a Homochiral Metal-Organic Framework: Tuning the Chiral Separation Capacity.

    Science.gov (United States)

    Slater, Benjamin; Wang, Zeru; Jiang, Shanxue; Hill, Matthew R; Ladewig, Bradley P

    2017-12-20

    Efficient chiral separation remains a very challenging task due to the identical physical and chemical properties of the enantiomers of a molecule. Enantiomers only behave differently from each other in the presence of other chiral species. Homochiral metal-organic frameworks (MOFs) have received much attention for their promising enantioseparation properties. However, there are still challenges to overcome in this field such as high enantiomeric separation. Structural defects play an important role in the properties of MOFs and can significantly change the pore architecture. In this work, we introduced missing linker defects into a homochiral metal-organic framework [Zn 2 (bdc)(l-lac)(dmf)] (ZnBLD; bdc = 1,4-benzenedicarboxylic acid, l-lac = l-lactic acid, dmf = N,N'-dimethylformamide) and observed an increase in enantiomeric excess for 1-phenylethanol of 35% with the defective frameworks. We adjusted the concentration of monocarboxylic acid ligand l-lactic acid by varying the ratio of Zn 2+ to ligand from 0.5 to 0.85 mmol. Additionally, a defective framework was synthesized with propanoic acid as modulator. In order to elucidate the correlation between defects and enantiomeric excess, five characterization techniques (FTIR, TGA, 1 H NMR, ICP, and PXRD) were employed. Full width at half-maximum analysis (fwhm) was performed on the powder X-ray diffraction traces and showed that the higher concentration of monocarboxylic acid MOFs were isostructural but suffered from increased fwhm values.

  4. Enhanced Charge Separation Efficiency in Pyridine-Anchored Phthalocyanine-Sensitized Solar Cells by Linker Elongation.

    Science.gov (United States)

    Ikeuchi, Takuro; Agrawal, Saurabh; Ezoe, Masayuki; Mori, Shogo; Kimura, Mutsumi

    2015-11-01

    A series of zinc phthalocyanine sensitizers (PcS22-24) having a pyridine anchoring group are designed and synthesized to investigate the structural dependence on performance in dye-sensitized solar cells. The pyridine-anchor zinc phthalocyanine sensitizer PcS23 shows 79 % incident-photon to current-conversion efficiency (IPCE) and 6.1 % energy conversion efficiency, which are comparable with similar phthalocyanine dyes having a carboxylic acid anchoring group. Based on DFT calculations, the high IPCE is attributed with the mixture of an excited-state molecular orbital of the sensitizer and the orbitals of TiO2 . Between pyridine and carboxylic acid anchor dyes, opposite trends are observed in the linker-length dependence of the IPCE. The red-absorbing PcS23 is applied for co-sensitization with a carboxyl-anchor organic dye D131 that has a complementary spectral response. The site-selective adsorption of PcS23 and D131 on the TiO2 surface results in a panchromatic photocurrent response for the whole visible-light region of sun light. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Construction of porous cationic frameworks by crosslinking polyhedral oligomeric silsesquioxane units with N-heterocyclic linkers

    Science.gov (United States)

    Chen, Guojian; Zhou, Yu; Wang, Xiaochen; Li, Jing; Xue, Shuang; Liu, Yangqing; Wang, Qian; Wang, Jun

    2015-06-01

    In fields of materials science and chemistry, ionic-type porous materials attract increasing attention due to significant ion-exchanging capacity for accessing diversified applications. Facing the fact that porous cationic materials with robust and stable frameworks are very rare, novel tactics that can create new type members are highly desired. Here we report the first family of polyhedral oligomeric silsesquioxane (POSS) based porous cationic frameworks (PCIF-n) with enriched poly(ionic liquid)-like cationic structures, tunable mesoporosities, high surface areas (up to 1,025 m2 g-1) and large pore volumes (up to 0.90 cm3 g-1). Our strategy is designing the new rigid POSS unit of octakis(chloromethyl)silsesquioxane and reacting it with the rigid N-heterocyclic cross-linkers (typically 4,4‧-bipyridine) for preparing the desired porous cationic frameworks. The PCIF-n materials possess large surface area, hydrophobic and special anion-exchanging property, and thus are used as the supports for loading guest species PMo10V2O405- the resultant hybrid behaves as an efficient heterogeneous catalyst for aerobic oxidation of benzene and H2O2-mediated oxidation of cyclohexane.

  6. Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

    Science.gov (United States)

    Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

    2017-01-01

    Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255

  7. Role of H1 linker histones in mammalian development and stem cell differentiation.

    Science.gov (United States)

    Pan, Chenyi; Fan, Yuhong

    2016-03-01

    H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Metastasis to neck from unknown primary tumor

    International Nuclear Information System (INIS)

    Jose, B.; Bosch, A.; Caldwell, W.L.; Frias, Z.

    1979-01-01

    The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance. (Auth.)

  9. Subcutaneous fibrosis after whole neck irradiation

    International Nuclear Information System (INIS)

    Hirota, Saeko; Tsujino, Kayoko; Oshitani, Takashi; Hishikawa, Yoshio; Takada, Yoshiki; Kono, Michio; Abe, Mitsuyuki

    2002-01-01

    Purpose: To identify the risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. Methods and Materials: We analyzed 233 cases of patients who had undergone whole neck irradiation with 4-MV X-ray or 8-10-MeV electrons, or both, and had been followed with regard to their skin condition for at least 1 year. The prescribed dose to the whole neck ranged from 19.2 to 72.4 Gy (median 50). The skin-absorbed dose was specified as that at a depth of 4.1 mm (d4.1-mm depth ), and a biologically equivalent dose (BED) of d4.1-mm depth was also estimated (BED 1.8 4.1-mm depth ). Results: Univariate analysis revealed that previous neck dissection, concurrent chemotherapy, corticosteroid administration as a part of chemotherapy, fractionation, and BED 1.8 4.1-mm depth were significant prognostic variables. Multivariate analysis showed that BED 1.8 4.1-mm depth and previous neck dissection were the only prognostic variables for moderate to severe subcutaneous fibrosis. Conclusion: A high dose to a 4.1-mm depth of the skin and a history of neck dissection were identified as the predominant risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. A subcutaneous dose should be considered in radiotherapy treatment planning involving the whole neck, especially in cases in which patients have undergone previous neck dissection

  10. Modelling the System of Ensuring the Investment Security

    Directory of Open Access Journals (Sweden)

    Moroz Maxim O.

    2017-11-01

    Full Text Available The article explores approaches to modelling the system of ensuring the investment security. Necessity of observance of investment security of Ukraine has been substantiated. The author’s own vision of the modelling essentials has been provided. The eligibility for consideration of the system of ensuring the investment security of Ukraine in the functional, structural, process, formative, and factor aspects has been proved. The target setting and tasks of a functional model of the system of ensuring the investment security have been defined. The functions, subjects, organizational-economic mechanisms of the system of ensuring the investment security of Ukraine have been characterized. A structural model of the system of ensuring the investment security has been presented. Special attention has been given to the definition of objects of direct and indirect influence, control and controlled subsystems, aggregate of indicators, safe levels, principles of formation of the investment security system. The process and formative models of the system of ensuring the investment security, as well as the algorithm of the complex assessment of the level of investment security, were analyzed in detail. Measures to ensure the investment security of Ukraine have been defined.

  11. Treatment results of the neck by concurrent chemoradiotherapy for advanced head and neck cancer

    International Nuclear Information System (INIS)

    Tokumaru, Yutaka; Fujii, Masato; Habu, Noboru; Yajima, Yoko; Yorozu, Atsunori

    2009-01-01

    Concurrent chemoradiotherapy (CCRT) is one of the recent emerging modalities for advanced squamous cell carcinoma of the head and neck (HNSCC). However some of the patients treated by CCRT have residual or recurrent cervical lymph nodes. In these cases, neck dissection is considered to be useful in the point of locolegional control and disease free survival. This study aims to analyze neck control rate by CCRT and usefulness of the neck dissection after CCRT for HNSCC. The medical records of 69 consecutive patients (stage III: 4%, stage IV: 96%) treated with CCRT for SCCHN (hypopharynx: 40, oropharynx: 25, larynx: 4) from 2003 through 2007 were reviewed. Clinical complete response (CR) rates of N1, N2a, N2b, N2c and N3 were 75%, 100%, 71%, 74% and 43% respectively. Among the patients with complete neck response, only 2 patients (5%) had an isolated neck recurrence. Eleven patients underwent surgical neck procedures including 7 planned neck dissections and 4 salvage neck dissections. All the 11 patients with neck dissections had good regional control except 1 case. There were a few minor complications such as wound infection and laryngeal edema. Patients who have a complete clinical regional response to CCRT have a low probability of an isolated recurrence in the neck. Planned and salvage neck dissections can be safely performed and considered to be useful in the point of regional control after intensive CCRT. (author)

  12. Dual-purpose linker for alpha helix stabilization and imaging agent conjugation to glucagon-like peptide-1 receptor ligands.

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Liao, Jianshan; Thurber, Greg M

    2015-02-18

    Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel α-helix-stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enable this technique to potentially be used as a general method for labeling α helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents.

  13. [Application of virtual reality in surgical treatment of complex head and neck carcinoma].

    Science.gov (United States)

    Zhou, Y Q; Li, C; Shui, C Y; Cai, Y C; Sun, R H; Zeng, D F; Wang, W; Li, Q L; Huang, L; Tu, J; Jiang, J

    2018-01-07

    Objective: To investigate the application of virtual reality technology in the preoperative evaluation of complex head and neck carcinoma and he value of virtual reality technology in surgical treatment of head and neck carcinoma. Methods: The image data of eight patients with complex head and neck carcinoma treated from December 2016 to May 2017 was acquired. The data were put into virtual reality system to built the three-dimensional anatomical model of carcinoma and to created the surgical scene. The process of surgery was stimulated by recognizing the relationship between tumor and surrounding important structures. Finally all patients were treated with surgery. And two typical cases were reported. Results: With the help of virtual reality, surgeons could adequately assess the condition of carcinoma and the security of operation and ensured the safety of operations. Conclusions: Virtual reality can provide the surgeons with the sensory experience in virtual surgery scenes and achieve the man-computer cooperation and stereoscopic assessment, which will ensure the safety of surgery. Virtual reality has a huge impact on guiding the traditional surgical procedure of head and neck carcinoma.

  14. Interventional neuroradiology of the head and neck.

    Science.gov (United States)

    Turowski, Bernd; Zanella, Friedhelm E

    2003-08-01

    Vascular interventions are important and helpful for treatment of various pathologies of the head and neck. Interventional neuroradiology of the head and neck includes image-guided biopsies, vessel occlusion, and local chemotherapy. Knowledge of anatomy, functional relationships between intra- and extracranial vessels, and pathology are the basis for therapeutic success. The interventional neuroradiologist is responsible for appropriate selection of patients based on clinical information, indications, and risk assessment. Neuroradiologic imaging, especially CT and MR imaging, and appropriate analysis of angiographic findings help ensure indication for treatment and plan an intervention. Technical equipment, including an angiographic unit, catheters, needles, embolizing materials, and so forth, are important. Knowledge of hemodynamics is relevant to avoid complications and to find the optimal technique for solving the clinical problem. Indications for image-guided biopsies are preverterbal fluid-collections, spinal and paraspinal inflammations and abscesses, deep cervical malignancies, vertebral body, and skull base tumors. Special care should be taken to preserve critical structures in this region, including spinal nerve roots, cervical plexus, main peripheral nerves, and vessels. Indications for vessel occlusion are emergency situations to stop bleeding in vascular lesions (traumatic, malformation, or tumors) by reduction of pressure, preoperative reduction of blood flow to minimize the surgical risk, palliative occlusion of feeding vessels to produce tumor necrosis, or potential curative (or presurgical) occlusion of vascular malformations. Pressure reduction to support normal coagulation, such as epistaxis, in hereditary hemorrhagic telangiectasia can be achieved by proximal vessel occlusion with large particles or platinum coils. Prevention of intraoperative bleeding requires occlusion of the microvascular bed with small particles. Examples of these

  15. Optimizing the relaxivity of GdIII complexes appended to InP/ZnS quantum dots by linker tuning.

    Science.gov (United States)

    Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Gateau, Christelle; Reiss, Peter; Fries, Pascal; Mazzanti, Marinella

    2013-06-21

    Three bimodal MRI/optical nanosized contrast agents with high per-nanoparticle relaxivity (up to 2523 mM(-1) s(-1) at 35 MHz and 932 mM(-1) s(-1) at 200 MHz) have been prepared connecting up to 115 tris-aqua Gd(III) complexes to fluorescent non-toxic InP/ZnS quantum dots. The structure of the linker has an important effect on the relaxivity of the final multimeric contrast agent.

  16. A Small Number of Residues Can Determine if Linker Histones Are Bound On or Off Dyad in the Chromatosome.

    Science.gov (United States)

    Zhou, Bing-Rui; Feng, Hanqiao; Ghirlando, Rodolfo; Li, Shipeng; Schwieters, Charles D; Bai, Yawen

    2016-10-09

    Linker histones bind to the nucleosome and regulate the structure and function of chromatin. We have previously shown that the globular domains of chicken H5 and Drosophila H1 linker histones bind to the nucleosome with on- or off-dyad modes, respectively. To explore the determinant for the distinct binding modes, we investigated the binding of a mutant globular domain of H5 to the nucleosome. This mutant, termed GH5_pMut, includes substitutions of five globular domain residues of H5 with the corresponding residues in the globular domain of Drosophila H1. The residues at these five positions play important roles in nucleosome binding by either H5 or Drosophila H1. NMR and spin-labeling experiments showed that GH5_pMut bound to the nucleosome off the dyad. We further found that the nucleosome array condensed by either the GH5_pMut or the globular domain of Drosophila H1 displayed a similar sedimentation coefficient, whereas the same nucleosome array condensed by the wild-type globular domain of H5 showed a much larger sedimentation coefficient. Moreover, NMR and spin-labeling results from the study of the nucleosome in complex with the full-length human linker histone H1.0, whose globular domain shares high sequence conservation with the corresponding globular domain of H5, are consistent with an on-dyad binding mode. Taken together, our results suggest that a small number of residues in the globular domain of a linker histone can control its binding location on the nucleosome and higher-order chromatin structure. Copyright © 2016. Published by Elsevier Ltd.

  17. Genetics Home Reference: head and neck squamous cell carcinoma

    Science.gov (United States)

    ... and neck squamous cell carcinoma Head and neck squamous cell carcinoma Printable PDF Open All Close All Enable Javascript ... Consumer Version: Overview of Mouth, Nose, and Throat Cancers Orphanet: Squamous cell carcinoma of head and neck University of Michigan ...

  18. Head and Neck Cancer—Health Professional Version

    Science.gov (United States)

    Head and neck cancers include hypopharyngeal, laryngeal, lip and oral cavity, metastatic squamous neck, nasopharyngeal, oropharyngeal, paranasal sinus, and salivary gland cancers. Find evidence-based information on head and neck cancer treatment, causes and prevention, research, screening, and statistics.

  19. Design of Tail-Clamp Peptide Nucleic Acid Tethered with Azobenzene Linker for Sequence-Specific Detection of Homopurine DNA

    Directory of Open Access Journals (Sweden)

    Shinjiro Sawada

    2017-10-01

    Full Text Available DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA offers advantages since it has two homopyrimidine PNA strands connected via a flexible ethylene glycol-type linker that can recognize complementary homopurine sequences via Watson-Crick and Hoogsteen base pairings and form thermally-stable PNA/PNA/DNA triplex structures. Here, we synthesized a series of TC-PNAs that can possess different lengths of azobenzene-containing linkers and studied their binding behaviours to homopurine single-stranded DNA. Introduction of azobenzene at the N-terminus amine of PNA increased the thermal stability of PNA-DNA duplexes. Further extension of the homopyrimidine PNA strand at the N-terminus of PNA-AZO further increased the binding stability of the PNA/DNA/PNA triplex to the target homopurine sequence; however, it induced TC-PNA/DNA/TC-PNA complex formation. Among these TC-PNAs, 9W5H-C4-AZO consisting of nine Watson-Crick bases and five Hoogsteen bases tethered with a beta-alanine conjugated azobenzene linker gave a stable 1:1 TC-PNA/ssDNA complex and exhibited good mismatch recognition. Our design for TC-PNA-AZO can be utilized for detecting homopurine sequences in various genes.

  20. Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation

    Science.gov (United States)

    Park, Sujin; Yang, Kyung-Min; Park, Yuna; Hong, Eunji; Hong, Chang Pyo; Park, Jinah; Pang, Kyoungwha; Lee, Jihee; Park, Bora; Lee, Siyoung; An, Haein; Kwak, Mi-Kyung; Kim, Junil; Kang, Jin Muk; Kim, Pyunggang; Xiao, Yang; Nie, Guangjun; Ooshima, Akira

    2018-01-01

    Background Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. Results In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. Conclusions These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers. PMID:29629343

  1. Strategy to Ensure Institutional Control Implementation at Superfund Sites

    Science.gov (United States)

    This document sets forth EPA’s strategy (Strategy) for ensuring that institutional controls (ICs) are successfully implemented at Superfund sites, with an emphasis on evaluating ICs at sites where all construction of all remedies is complete (construction complete sites).

  2. A multipronged approach to ensuring food security | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-02-01

    Feb 1, 2011 ... ... nations committed themselves to ensuring an enabling environment and ... to eradicate poverty and guarantee access to sufficient, safe food to all. They also agreed to promote a fair world trade system, and to work to ...

  3. ENSURING THE SAFETY OF ROAD TRANSPORTATION OF GOODS

    Directory of Open Access Journals (Sweden)

    Liudmila Nikolaevna Andronikova

    2017-05-01

    Full Text Available The article investigates Russian and foreign regulatory documents, governing the issues of cargo securing in road transport, and sets out recommendations to ensure the safety of road transportation of goods by means of their attachment.

  4. The Role of Communication in Ensuring Sustained Behavior Change

    Science.gov (United States)

    Webinar series on communications strategies and methods addresses how communications tools can be used throughout the implementation of climate and clean energy programs to achieve behavior change and ensure sustained.

  5. Strategies for Ensuring Quality in the Business Education ...

    African Journals Online (AJOL)

    Strategies for Ensuring Quality in the Business Education Programme of Tertiary Institutions in ... The survey method was employed. One research question guided the study while two null hypotheses were tested at 0.05 degree of significance.

  6. Advancing Evidence Based Policymaking and Regulation to Ensure ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Advancing Evidence Based Policymaking and Regulation to Ensure Greater ... which is Communications Policy Research South (CPRsouth), a yearly conference that ... policy intellectuals through tutorials for young scholars and internships.

  7. Exploring the scope of community-based rehabilitation in ensuring ...

    African Journals Online (AJOL)

    ... the scope of community-based rehabilitation in ensuring the holistic ... Rehabilitation is defined as the process of combined ... psychological measures for enabling individuals to at- ... inclusion, meeting basic needs and facilitating access to.

  8. Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region

    DEFF Research Database (Denmark)

    Das, Manabendra; Du, Yang; Mortensen, Jonas S.

    2017-01-01

    of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing...

  9. Inter-vertebral flexibility of the ostrich neck: implications for estimating sauropod neck flexibility.

    Science.gov (United States)

    Cobley, Matthew J; Rayfield, Emily J; Barrett, Paul M

    2013-01-01

    The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal of muscle groups and measures of flexibility of the neck in a living analogue, the ostrich (Struthio camelus). The possible effect of cartilage on flexibility is also examined, as this was previously overlooked in osteological estimates of sauropod neck function. These comparisons show that soft tissues are likely to have limited the flexibility of the neck beyond the limits suggested by osteology alone. In addition, the inferred presence of cartilage, and varying the inter-vertebral spacing within the synovial capsule, also affect neck flexibility. One hypothesis proposed that flexibility is constrained by requiring a minimum overlap between successive zygapophyses equivalent to 50% of zygapophyseal articular surface length (ONP50). This assumption is tested by comparing the maximum flexibility of the articulated cervical column in ONP50 and the flexibility of the complete neck with all tissues intact. It is found that this model does not adequately convey the pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may not be useful in determining neck function if considered in isolation from myological and other soft tissue data.

  10. Inter-vertebral flexibility of the ostrich neck: implications for estimating sauropod neck flexibility.

    Directory of Open Access Journals (Sweden)

    Matthew J Cobley

    Full Text Available The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal of muscle groups and measures of flexibility of the neck in a living analogue, the ostrich (Struthio camelus. The possible effect of cartilage on flexibility is also examined, as this was previously overlooked in osteological estimates of sauropod neck function. These comparisons show that soft tissues are likely to have limited the flexibility of the neck beyond the limits suggested by osteology alone. In addition, the inferred presence of cartilage, and varying the inter-vertebral spacing within the synovial capsule, also affect neck flexibility. One hypothesis proposed that flexibility is constrained by requiring a minimum overlap between successive zygapophyses equivalent to 50% of zygapophyseal articular surface length (ONP50. This assumption is tested by comparing the maximum flexibility of the articulated cervical column in ONP50 and the flexibility of the complete neck with all tissues intact. It is found that this model does not adequately convey the pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may not be useful in determining neck function if considered in isolation from myological and other soft tissue data.

  11. Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

    OpenAIRE

    Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie

    2013-01-01

    Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a sever...

  12. X-Ray Exam: Neck (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español X-Ray Exam: Neck KidsHealth / For Parents / X-Ray Exam: ... Neck Enlarged Adenoids Croup Sinusitis Getting an X-ray (Video) X-Ray (Video) View more Partner Message About Us ...

  13. Physical risk factors for neck pain

    NARCIS (Netherlands)

    Ariëns, Geertje A M; Van Mechelen, Willem; Bongers, Paulien M.; Bouter, Lex M.; Van Der Wal, Gerrit

    2000-01-01

    To identify physical risk factors for neck pain, a systematic review of the literature was carried out. Based on methodological quality and study design, 4 levels of evidence were defined to establish the strength of evidence for the relationship between risk factors and neck pain. Altogether, 22

  14. Asymmetry of neck motion and activation of the cervical paraspinal muscles during prone neck extension in subjects with unilateral posterior neck pain.

    Science.gov (United States)

    Park, Kyue-Nam; Kwon, Oh-Yun; Kim, Su-Jung; Kim, Si-Hyun

    2017-01-01

    Although unilateral posterior neck pain (UPNP) is more prevalent than central neck pain, little is known about how UPNP affects neck motion and the muscle activation pattern during prone neck extension. To investigate whether deviation in neck motion and asymmetry of activation of the bilateral cervical paraspinal muscles occur during prone neck extension in subjects with UPNP compared to subjects without UPNP. This study recruited 20 subjects with UPNP and 20 age- and sex-matched control subjects without such pain. Neck motion and muscle onset time during prone neck extension were measured using a three-dimensional motion-analysis system and surface electromyography. The deviation during prone neck extension was greater in the UPNP group than in the controls (p cervical extensor muscle activation in the UPNP group was significantly delayed on the painful side during prone neck extension (p cervical extensors, triggering a need for specific evaluation and exercises in the management of patients with UPNP.

  15. Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein

    International Nuclear Information System (INIS)

    Talanov, Vladimir S.; Garmestani, Kayhan; Regino, Celeste A.S.; Milenic, Diane E.; Plascjak, Paul S.; Waldmann, Thomas A.; Brechbiel, Martin W.

    2006-01-01

    Significant improvement of in vivo stability of 211 At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[ 211 At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The 211 At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 o C for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstannylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with 211 At generates succinimidyl N-2-(4-[ 211 At]astatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with 125 I generated succinimidyl N-2-(4-[ 125 I]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[ 125 I]iodophenethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product

  16. X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex.

    Science.gov (United States)

    Imaizumi, Hiromasa; Sato, Katsutoshi; Nishihara, Asuka; Minami, Kazumasa; Koizumi, Masahiko; Matsuura, Nariaki; Hieda, Miki

    2018-04-01

    The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation-enhanced cell migration and invasion. A sublethal dose of X-ray radiation promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose-dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X-ray-enhanced migration and invasion. In addition, the results suggested that X-ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon-enhanced cell migration and invasion. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Public knowledge of head and neck cancer.

    LENUS (Irish Health Repository)

    O'Connor, T E

    2010-04-01

    Studies show 60% of patients with newly diagnosed Head & Neck Squamous Cell Cancer in Ireland, present with advanced disease. A poor level of knowledge and awareness among the public of Head & Neck Cancer, is an important consideration in the often delayed presentation for medical attention in many of these cases. Our study surveyed 200 members of the public to assess their knowledge and awareness of Head & Neck Cancer. One hundred and forty (70%) of respondents had never encountered the term "Head & Neck Cancer". One hundred and forty six (73%) failed to identify excessive alcohol consumption as a risk factor. Less than 100 (50%) would have concern about persisting hoarseness or a prolonged oral ulcer. An urgent need exists to raise awareness of Head & Neck Cancer among the public in Ireland.

  18. Primary Hydatid Cyst of the Neck

    International Nuclear Information System (INIS)

    Mujtaba, S. S.; Faridi, N.; Haroon, S.

    2013-01-01

    Hydatid cysts in the neck are relatively exceptional, even in areas where Echinococcus granulosis is endemic, such as Asia. Although liver and lung are frequent sites of involvement, it can involve all tissues, with neck remaining one of the most rare sites. It should come in the differential diagnosis of cystic lesion of neck, as the treatment options differ widely from common neck cysts. The role of radiological investigation is important and, in these cases, the involvement of other organs should be investigated. Serological tests may be helpful. The major treatment modality is surgical and the cyst should be excised as a whole, without being ruptured, to prevent any treatment complications, as the cyst fluid can initiate an anaphylactic reaction. Postoperative albendazole therapy is recommended particularly when there is intra-operative spillover. We report a case of an isolated hydatid cyst localized in the anterior triangle of the neck without any pulmonary or hepatic involvement. (author)

  19. Distribution of linker histone variants during plant cell differentiation in the developmental zones of the maize root, dedifferentiation in callus culture after auxin treatment

    Directory of Open Access Journals (Sweden)

    ANASTASIOS ALATZAS

    2008-01-01

    Full Text Available Although several linker histone variants have been studied in both animal and plant organisms, little is known about their distribution during processes that involve alterations in chromatin function, such as differentiation, dedifferentiation and hormone treatment. In this study, we identified linker histone variants by using specific anti-histone Hl antibodies. Each variant's ratio to total Hl in the three developmental zones of maize (Zea mays L. root and in callus cultures derived from them was estimated in order to define possible alterations either during plant cell differentiation or during their dedifferentiation. We also evaluated linker histone variants' ratios in the developmental zones of maize roots treated with auxin in order to examine the effects of exogenous applied auxin to linker histone variant distribution. Finally, immunohistochemical detection was used to identify the root tissues containing each variant and correlate them with the physiological status of the plant cells. According to the results presented in this study, linker histone variants' ratios are altered in the developmental zones of maize root, while they are similar to the meristematic zone in samples from callus cultures and to the differentiation zone in samples from roots treated with auxin. We propose that the alterations in linker histone variants' ratios are correlated with plant cell differentiation and dedifferentiation.

  20. Prevalence, incidence, and risk factors for shoulder and neck dysfunction after neck dissection: A systematic review.

    Science.gov (United States)

    Gane, E M; Michaleff, Z A; Cottrell, M A; McPhail, S M; Hatton, A L; Panizza, B J; O'Leary, S P

    2017-07-01

    Shoulder pain and dysfunction may occur following neck dissection among people being treated for head and neck cancer. This systematic review aims to examine the prevalence and incidence of shoulder and neck dysfunction after neck dissection and identify risk factors for these post-operative complications. Electronic databases (Pubmed, CINAHL, EMBASE, Cochrane) were searched for articles including adults undergoing neck dissection for head and neck cancer. Studies that reported prevalence, incidence or risk factors for an outcome of the shoulder or neck were eligible and assessed using the Critical Review Form - Quantitative Studies. Seventy-five articles were included in the final review. Prevalence rates for shoulder pain were slightly higher after RND (range, 10-100%) compared with MRND (range, 0-100%) and SND (range, 9-25%). The incidence of reduced shoulder active range of motion depended on surgery type (range, 5-20%). The prevalence of reduced neck active range of motion after neck dissection was 1-13%. Type of neck dissection was a risk factor for shoulder pain, reduced function and health-related quality of life. The prevalence and incidence of shoulder and neck dysfunction after neck dissection varies by type of surgery performed and measure of dysfunction used. Pre-operative education for patients undergoing neck dissection should acknowledge the potential for post-operative shoulder and neck problems to occur and inform patients that accessory nerve preservation lowers, but does not eliminate, the risk of developing musculoskeletal complications. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  1. Clinical analysis of neck dissection patients

    International Nuclear Information System (INIS)

    Sato, Katsuro; Takahashi, Sugata

    2008-01-01

    Neck dissection is a highly important surgical procedure in the treatment of squamous cell carcinoma (SCC) of the head and neck since the control of the nodal disease is highly important in these patients. In this paper, 131 patients (210 necks) treated in our department were analyzed. The most frequent primary lesion site was the oral cavity, followed by larynx, hypopharynx and mesopharynx, and treatment of metastatic nodes was considered important especially in patients with SCC in those regions. As the surgical procedure for neck dissection, (modified) radical neck dissection was chosen for higher N stage cases, although it was also applied to lower N stage cases. Postoperative irradiation was performed for 70% of the patients, and control of the neck was considered good as recurrent neck disease occurred in 8% of the patients, and only 20% of those died of recurrent neck disease. The most common primary site showing cervical recurrence was the oral cavity, and control of neck disease is considered important, especially in patients with SCC of the oral cavity. Patients with ≤number of pN 1 receiving postoperative irradiation, and patients with pN (-) and ≤number of pN 1 without postoperative irradiation showed significantly higher survival rates. Postoperative irradiation should be done for patients with ≥number of pN 2, and follow-up without postoperative treatment should be considered for the cases of ≤number of pN 1. Further consideration of patient selection with regard to the area of dissection and the indication for postoperative irradiation without decreasing the survival rate is needed to further improve the treatment of head and neck SCCs. (author)

  2. INTERNAL CONTROLS IN ENSURING GOOD CORPORATE GOVERNANCE IN FINANCIAL INSTITUTIONS

    Directory of Open Access Journals (Sweden)

    KOSMAS NJANIKE

    2011-01-01

    Full Text Available This paper assessed factors that influence the internal controls in ensuring good corporate governance in financial institutions in developing economies with special reference to Zimbabwe. The research paper assessed how lack of internal controls affected good corporate governance and aimed to bring out elements of good corporate governance. It emerged that failure to effectively implement internal controls contributed significantly to poor corporate governance. The study discovered that internal control system overrides and the issue of “fact cat” directors also contributed to poor corporate governance. The study recommended that there is need for the board of directors to guarantee an organizational structure that clearly defines management responsibilities, authority and reporting relationships. There is also need to ensure that delegated responsibilities are effectively carried out to ensure compliance with internal controls of the financial institution concerned.

  3. Neck and Upper Limb Dysfunction in Patients following Neck Dissection: Looking beyond the Shoulder.

    Science.gov (United States)

    Gane, Elise M; O'Leary, Shaun P; Hatton, Anna L; Panizza, Benedict J; McPhail, Steven M

    2017-10-01

    Objective To measure patient-perceived upper limb and neck function following neck dissection and to investigate potential associations between clinical factors, symptoms, and function. Study Design Cross-sectional. Setting Two tertiary hospitals in Brisbane, Australia. Subjects and Methods Inclusion criteria: patients treated with neck dissection (2009-2014). aged <18 years, accessory nerve or sternocleidomastoid sacrifice, previous neck dissection, preexisting shoulder/neck injury, and inability to provide informed consent (cognition, insufficient English). Primary outcomes were self-reported function of the upper limb (Quick Disabilities of the Arm, Shoulder, and Hand) and neck (Neck Disability Index). Secondary outcomes included demographics, oncological management, self-efficacy, and pain. Generalized linear models were prepared to examine relationships between explanatory variables and self-reported function. Results Eighty-nine participants (male n = 63, 71%; median age, 62 years; median 3 years since surgery) reported mild upper limb and neck dysfunction (median [quartile 1, quartile 3] scores of 11 [3, 32] and 12 [4, 28], respectively). Significant associations were found between worse upper limb function and longer time since surgery (coefficient, 1.76; 95% confidence interval [CI], 0.01-3.51), having disease within the thyroid (17.40; 2.37-32.44), postoperative radiation therapy (vs surgery only) (13.90; 6.67-21.14), and shoulder pain (0.65; 0.44-0.85). Worse neck function was associated with metastatic cervical lymph nodes (coefficient, 6.61; 95% CI, 1.14-12.08), shoulder pain (0.19; 0.04-0.34), neck pain (0.34; 0.21-0.47), and symptoms of neuropathic pain (0.61; 0.25-0.98). Conclusion Patients can experience upper limb and neck dysfunction following nerve-preserving neck dissection. The upper quadrant as a whole should be considered when assessing rehabilitation priorities after neck dissection.

  4. Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

    Science.gov (United States)

    Flook, Adam M; Yang, Jianquan; Miao, Yubin

    2014-11-13

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

  5. MALLASEZIA FOLLICULITIS ON THE NECK

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2010-10-01

    Full Text Available Folliculitis caused by Malassezia spp. classified as yeasts in our climate (Poland is fairly rare disease . MF is most commonly found on the chest, back, upper arms, and less frequently on the face. Permanent symptom is persistent itching. The favorable external conditions, which are largely due to high temperature and humidity, and endogenous factors, such as immunosuppression, there is a lipophilic yeast multiplication in the hair follicles. The aim of this article is presentation of the patient with Malassezia Folliculitis on the neck. Patient age 33 with 1- to 2-mm monomorphic papules and pustules on chest. Skin lesions accompanied by itching. In the treatment used topical: ketoconazole containing shampoo, 1% clindamycin cream, 0,5% hydrocortisonum cream, fluconazole 400 mg once p.o.

  6. Neck lift my way: an update.

    Science.gov (United States)

    Feldman, Joel J

    2014-12-01

    The author updates prior descriptions of an approach to the surgical neck lift that aims for a maximum degree of control over the size, shape, and position of every anatomical feature of the neck that is negatively affecting its appearance. A 38-year clinical experience guided the development of the operative tactics that define the strategy. Data collected from a records review of 522 consecutive neck lifts performed during the 10-year period 2004 through 2013 further inform the report. The approach has eight features: (1) nearly routine use of open submental access to all tissue layers of the central neck, including a regimen that curbed the problems that may attend an extensive tissue dissection; (2) management of lax neck skin by lateral excision using a specific postauricular incision, or by using the nonexcisional method of redistribution; (3) open lipectomy for precise removal of excess subcutaneous neck and jawline fat; (4) individualized modifications to subplatysmal fat, perihyoid fascia, and anterior digastric muscles; (5) treatment of large, ptotic, or malpositioned submandibular salivary glands by partial excision using a transcutaneous traction suture; (6) the current version of the corset platysmaplasty, which is used to treat static paramedian platysma muscle bands, and to avoid contour imperfections following subplatysmal maneuvers; (7) an approach that facilitates an isolated neck lift; and (8) durable results. Case examples demonstrate outcomes. Although the updated approach remains relatively complex and invasive, the author believes that the ends justify the means.

  7. Rupture of the neck in nuclear fission

    International Nuclear Information System (INIS)

    Davies, K.T.R.; Managan, R.A.; Nix, J.R.; Sierk, A.J.

    1977-01-01

    We introduce a degree of freedom to describe the rupture of the neck in nuclear fission and calculate the point at which the neck ruptures as the nucleus descends dynamically from its fission saddle point. This is done by mentally slicing the system into two portions at its minimum neck radius and calculating the force required to separate the two portions while keeping their shapes fixed. This force is obtained by differentiating with respect to separation the sum of the Coulomb and nuclear interaction energies between the two portions. For nuclei throughout the Periodic Table we calculate this force along dynamical paths leading from the fission saddle point. The force is initially attractive but becomes repulsive when the neck reaches a critical size. For actinide nuclei the neck radius at which rupture occurs is about 2 fm. This increases the calculated translational kinetic energy of the fission fragments at infinity relative to that calculated for scission occurring at zero neck radius. With the effect of neck rupture taken into account, we calculate and compare with experimental results fission-fragment kinetic energies for two types of nuclear dissipation: ordinary two-body viscosity and one-body dissipation

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Fabrication of electrospun HPGL scaffolds via glycidyl methacrylate cross-linker: Morphology, mechanical and biological properties

    Energy Technology Data Exchange (ETDEWEB)

    Baratéla, Fernando José Costa; Zazuco Higa, Olga [Biotechnology Center, Institute of Energy and Nuclear Research (IPEN), Av. Professor Lineu Prestes 2242, 05508-000 São Paulo, SP (Brazil); Duarte dos Passos, Esdras [PostGraduate Program in Materials for Engineering, Federal University of Itajubá (UNIFEI), Av. BPS 1303, 37500-903 Itajubá, MG (Brazil); Alencar de Queiroz, Alvaro Antonio, E-mail: alencar@unifei.edu.br [Physics and Chemistry Institute (IFQ), Federal University of Itajubá (UNIFEI), Av. BPS 1303, 37500-903 Itajubá, MG (Brazil); High Voltage Laboratory (LAT-EFEI), Federal University of Itajubá (UNIFEI), Av. BPS 1303, 37500-903 Itajubá, MG (Brazil)

    2017-04-01

    Electrospinning is a suitable method to produce scaffolds composed of nanoscale to microscale fibers, which are comparable to the extracellular matrix (ECM). Hyperbranched polyglycerol (HPGL) is a highly biocompatible polyether polyol potentially useful for the design of fibrous scaffolds mimicking the ECM architecture. However, scaffolds developed from HPGL have poor mechanical properties and morphological stability in the aqueous environments required for tissue engineering applications. This work reports the production of stable electrospun HPGL scaffolds (EHPGLS) using glycidyl methacrylate (GMA) as cross-linker to enhance the water stability and mechanical property of electrospun HPGL. The diameter and morphology of the produced EHPGLS were analyzed by scanning electron microscopy (SEM). It was observed that electrical fields in the range of 0.2 kV·cm{sup −1} to 1.0 kV·cm{sup −1} decrease the average fiber diameter of EHPGLS. The increase in porosity of EHPGLS with GMA concentration indicates the in situ formation of a heterogeneous structure resultant from the phase separation during crosslinking of HPGL by GMA. EHPGLS containing 20% (w/w) GMA concentration possessed highest tensile strength (295.4 ± 11.32 kPa), which is approximately 58 times higher than that of non-crosslinked EHPGLS (5.1 ± 2.12 kPa). The MTS cell viability results showed that the EHPGLS have no significant cytotoxicity effect on Chinese hamster ovary (CHO-K1) cells. Scanning electron microscopy (SEM) indicates that the cultured BALB/3T3 fibroblasts cells were able to keep contact each other's, thus forming a homogeneous monolayer on the internal surface of the EHPGLS. - Highlights: • A hyperbranched polyglycerol (HPGL) scaffold with elastic modulus of 295.4 ± 11.32 kPa was developed for soft tissue repair. • HPGL scaffold was prepared by electrospinning method. • The porosity of HPGL scaffolds can be tuned by selecting the degree of GMA in HPGL. • Electrospun HPGL

  10. Integrity of the Linker of Nucleoskeleton and Cytoskeleton Is Required for Efficient Herpesvirus Nuclear Egress.

    Science.gov (United States)

    Klupp, Barbara G; Hellberg, Teresa; Granzow, Harald; Franzke, Kati; Dominguez Gonzalez, Beatriz; Goodchild, Rose E; Mettenleiter, Thomas C

    2017-10-01

    Herpesvirus capsids assemble in the nucleus, while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process, the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes. The linker of nucleoskeleton and cytoskeleton (LINC) complex consists of INM proteins with a luminal SUN (Sad1/UNC-84 homology) domain connected to ONM proteins with a KASH (Klarsicht, ANC-1, SYNE homology) domain and is thought to be responsible for spacing the nuclear membranes. To investigate the role of the LINC complex during herpesvirus infection, we generated cell lines constitutively expressing dominant negative (dn) forms of SUN1 and SUN2. Ultrastructural analyses revealed a significant expansion of the PNS and the contiguous intracytoplasmic lumen, most likely representing endoplasmic reticulum (ER), especially in cells expressing dn-SUN2. After infection, primary virions accumulated in these expanded luminal regions, also very distant from the nucleus. The importance of the LINC complex was also confirmed by reduced progeny virus titers in cells expressing dn-SUN2. These data show that the intact LINC complex is required for efficient nuclear egress of herpesviruses, likely acting to promote fusion of primary enveloped virions with the ONM. IMPORTANCE While the viral factors for primary envelopment of nucleocapsids at the inner nuclear membrane are known to the point of high-resolution structures, the roles of cellular components and regulators remain enigmatic. Furthermore, the machinery responsible for fusion with the outer nuclear membrane is unsolved. We show here

  11. MR of head and neck hemangiomas

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Zimmerman, R.A.; Gusnard, D.A.

    1990-01-01

    This paper defines the MR characteristics of head and neck hemangiomas and to evaluate the role of MR in their diagnosis and management. Eighteen pediatric and young adult patients with head and neck hemangiomas (six neck, six face, three eyelid, two scalp, and one parotid) underwent high-field-strength 1.5-T MR imaging. Conventional spin-echo sequences with T1 and T2 weighting were performed. In addition, one-third of patients underwent MR angiography and gadolinium enhancement. The hemangiomas were isointense to muscle on T1-weighted images and hyperintense on proton-density and T2-weighted images

  12. Treatment of neglected femoral neck fracture

    Directory of Open Access Journals (Sweden)

    Anil K Jain

    2015-01-01

    Full Text Available Intra-capsular femoral neck fractures are seen commonly in elderly people following a low energy trauma. Femoral neck fracture has a devastating effect on the blood supply of the femoral head, which is directly proportional to the severity of trauma and displacement of the fracture. Various authors have described a wide array of options for treatment of neglected/nonunion (NU femoral neck fracture. There is lack of consensus in general, regarding the best option. This Instructional course article is an analysis of available treatment options used for neglected femoral neck fracture in the literature and attempt to suggest treatment guides for neglected femoral neck fracture. We conducted the "Pubmed" search with the keywords "NU femoral neck fracture and/or neglected femoral neck fracture, muscle-pedicle bone graft in femoral neck fracture, fibular graft in femoral neck fracture and valgus osteotomy in femoral neck fracture." A total of 203 print articles were obtained as the search result. Thirty three articles were included in the analysis and were categorized into four subgroups based on treatment options. (a treated by muscle-pedicle bone grafting (MPBG, (b closed/open reduction internal fixation and fibular grafting (c open reduction and internal fixation with valgus osteotomy, (d miscellaneous procedures. The data was pooled from all groups for mean neglect, the type of study (prospective or retrospective, classification used, procedure performed, mean followup available, outcome, complications, and reoperation if any. The outcome of neglected femoral neck fracture depends on the duration of neglect, as the changes occurring in the fracture area and fracture fragments decides the need and type of biological stimulus required for fracture union. In stage I and stage II (Sandhu′s staging neglected femoral neck fracture osteosynthesis with open reduction and bone grafting with MPBG or Valgus Osteotomy achieves fracture union in almost 90

  13. Ensuring Equal Access to High-Quality Education. Revised

    Science.gov (United States)

    Office for Civil Rights, US Department of Education, 2011

    2011-01-01

    The Office for Civil Rights (OCR) in the U.S. Department of Education (Department) is a law enforcement agency charged with enforcing federal civil rights laws to ensure that educational institutions receiving federal financial assistance do not engage in discriminatory conduct. OCR enforces the federal civil rights laws that prohibit…

  14. Role of Head Teachers in Ensuring Sound Climate

    Science.gov (United States)

    Kor, Jacob; Opare, James K.

    2017-01-01

    The school climate is outlined in literature as one of the most important within school factors required for effective teaching in learning. As leaders in any organisations are assigned the role of ensuring sound climates for work, head teachers also have the task of creating and maintaining an environment conducive for effective academic work…

  15. The Problem of Ensuring Reliability of Gas Turbine Engines

    Science.gov (United States)

    Nozhnitsky, Yu A.

    2018-01-01

    Requirements to advanced engines for civil aviation are discussing. Some significant problems of ensuring reliability of advanced gas turbine engines are mentioned. Special attention is paid to successful utilization of new materials and critical technologies. Also the problem of excluding failure of engine part due to low cycle or high cycle fatigue is discussing.

  16. Elementary Mathematics Specialists: Ensuring the Intersection of Research and Practice

    Science.gov (United States)

    McGatha, Maggie B.

    2017-01-01

    This paper provides a historical overview of the role and impact of elementary mathematics specialists as well as current implications and opportunities for the field. Furthermore, suggestions are offered for the mathematics education field for ensuring the intersection of practice and research. [For complete proceedings, see ED581294.

  17. Good Work Ensures Employment Success. Myths and Realities No. 2.

    Science.gov (United States)

    Brown, Bettina Lankard

    It is a myth that skills alone ensure employment. Other keys to workplace success include continuous learning, emotional intelligence, networking, flexibility, and commitment to business objectives. Although academic degrees, skill certifications, and other documentation of accomplishments provide access to employment, they are significant only at…

  18. Ensuring Effective Mentoring in Tertiary Institutions in Anambra State ...

    African Journals Online (AJOL)

    This paper concerns itself only with ascertaining the strategies that could ensure effective mentoring in tertiary institutions. The survey method was employed. The study population comprised 78 teacher educators in tertiary institutions in Anambra State. One research question guided the study while one null hypothesis was ...

  19. Ensuring quality control of forensic accounting for efficient and ...

    African Journals Online (AJOL)

    This study focuses on ensuring quality control of forensic accounting for efficient and effective corporate management. Over the years, fraud has taken the center stage in every discussion whether in business or social. “3m” have been identified to be the tool used to effect this crime namely; misappropriation, misapplication ...

  20. Strategies for Ensuring Trustworthiness in Qualitative Research Projects

    Science.gov (United States)

    Shenton, Andrew K.

    2004-01-01

    Although many critics are reluctant to accept the trustworthiness of qualitative research, frameworks for ensuring rigour in this form of work have been in existence for many years. Guba's constructs, in particular, have won considerable favour and form the focus of this paper. Here researchers seek to satisfy four criteria. In addressing…

  1. Improving consent in patients undergoing surgery for fractured neck of femur.

    Science.gov (United States)

    Thiruchandran, Gajendiran; McKean, Andrew R; Rudran, Branavan; Imam, Mohamed A; Yeong, Keefai; Hassan, Abdel

    2018-05-02

    Background Neck of femur fractures and their subsequent operative fixation are associated with high rates of perioperative morbidity and mortality. Consenting in this setting is suboptimal with the Montgomery court ruling changing the perspective of consent. This quality improvement project assessed the adequacy of consenting against British Orthopaedic Association-endorsed guidance and implemented a series of changes to improve the documentation of risks associated with surgery for fractured neck of femur. Methods Seventy consecutive patients who underwent any operative fixation of a neck of femur fracture were included over a 6-month period at a single centre. Patients unable to consent or without electronic notes were excluded. Consent forms were analysed and the documented potential risks or complications associated with surgery were compared to British Orthopaedic Association-endorsed guidance. A series of changes (using the plan, do study, act (PDSA) approach) was implemented to improve the adequacy of consent. Results Documentation of four out of 12 potential risks or complications was recorded in <50% of cases for patients with intracapsular fractures (n=35), and documentation of seven out of 12 potential risks or complications was recorded in <50% of cases for patients with extracapsular fractures (n=35). Re-audit following raising awareness and attaching consent guidance showed 100% documentation of potential risks or complications in patients with intracapsular and extracapsular fractures (n=70). A neck of femur fracture-specific consent form has been implemented which will hopefully lead to sustained improvement. Conclusions Consenting patients with fractured neck of femur for surgery in the authors' unit was suboptimal when compared to British Orthopaedic Association-endorsed consent guidance. This project has shown that ensuring such guidance is readily available has improved the adequacy of consent. The authors hope that introduction of a neck of

  2. Neck movement and muscle activity characteristics in female office workers with neck pain.

    Science.gov (United States)

    Johnston, V; Jull, G; Souvlis, T; Jimmieson, N L

    2008-03-01

    Cross-sectional study. To explore aspects of cervical musculoskeletal function in female office workers with neck pain. Evidence of physical characteristics that differentiate computer workers with and without neck pain is sparse. Patients with chronic neck pain demonstrate reduced motion and altered patterns of muscle control in the cervical flexor and upper trapezius (UT) muscles during specific tasks. Understanding cervical musculoskeletal function in office workers will better direct intervention and prevention strategies. Measures included neck range of motion; superficial neck flexor muscle activity during a clinical test, the craniocervical flexion test; and a motor task, a unilateral muscle coordination task, to assess the activity of both the anterior and posterior neck muscles. Office workers with and without neck pain were formed into 3 groups based on their scores on the Neck Disability Index. Nonworking women without neck pain formed the control group. Surface electromyographic activity was recorded bilaterally from the sternocleidomastoid, anterior scalene (AS), cervical extensor (CE) and UT muscles. Workers with neck pain had reduced rotation range and increased activity of the superficial cervical flexors during the craniocervical flexion test. During the coordination task, workers with pain demonstrated greater activity in the CE muscles bilaterally. On completion of the task, the UT and dominant CE and AS muscles demonstrated an inability to relax in workers with pain. In general, there was a linear relationship between the workers' self-reported levels of pain and disability and the movement and muscle changes. These results are consistent with those found in other cervical musculoskeletal disorders and may represent an altered muscle recruitment strategy to stabilize the head and neck. An exercise program including motor reeducation may assist in the management of neck pain in office workers.

  3. Structural Polymorphism of the Actin-Espin System: A Prototypical System of Filaments and Linkers in Stereocilia

    International Nuclear Information System (INIS)

    Purdy, Kirstin R.; Wong, Gerard C. L.; Bartles, James R.

    2007-01-01

    We examine the interaction between cytoskeletal F-actin and espin 3A, a prototypical actin bundling protein found in sensory cell microvilli, including ear cell stereocilia. Espin induces twist distortions in F-actin as well as facilitates bundle formation. Mutations in one of the two F-actin binding sites of espin, which have been implicated in deafness, can tune espin-actin interactions and radically transform the system's phase behavior. These results are compared to recent theoretical work on the general phase behavior linker-rod systems

  4. The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

    Czech Academy of Sciences Publication Activity Database

    Maršáková, Lenka; Barvík, I.; Zíma, V.; Zímová, Lucie; Vlachová, Viktorie

    2017-01-01

    Roč. 10, Jan 31 (2017), č. článku 16. ISSN 1662-5099 R&D Projects: GA ČR(CZ) GA15-15839S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : TRP channel * S1-S2 linker * allyl isothiocynate * sensor module Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 5.076, year: 2016

  5. Micropatterning of biomolecules on a glass substrate in fused silica microchannels by using photolabile linker-based surface activation

    International Nuclear Information System (INIS)

    Jang, K.; Mawatari, K.; Kitamori, T.; Xu, Y.; Sato, K.; Tanaka, Y.

    2012-01-01

    We report on a straightforward method for creating micropatterns of multiple biomolecules. The anti-fouling agent 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and a photolabile linker (PL) were covalently linked to an amino-terminated silane surface. Patterns were generated by selective removal of the MPC polymer via UV irradiation. Multiple micropatterns of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) and rhodamine-labeled goat fragment antigen-binding fragments (FAB) were deposited on a same glass substrate. We also employed micropatterning of multiple biomolecules in that Texas red-labeled BSA and FITC-labeled rabbit anti-mouse IgG were placed inside a microchannel. (author)

  6. Three-dimensional measurement of femoral neck anteversion and neck shaft angle.

    Science.gov (United States)

    Sangeux, Morgan; Pascoe, Jessica; Graham, H Kerr; Ramanauskas, Fiona; Cain, Tim

    2015-01-01

    We present a three-dimensional measurement technique for femoral neck anteversion and neck shaft angles which do not require alignment of the femoral and scanner axes. Two assessors performed the measurements on 11 patients (22 femurs). Repeatability between assessors was 2.7 degrees for femoral neck anteversion and 4.8 degrees for neck shaft angle. Measurements compared with an alternative single slice method were different by 2 degrees (3 degrees) in average. The method was repeatable and appropriate for clinical practice.

  7. Drugs Approved for Head and Neck Cancer

    Science.gov (United States)

    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.

  8. A customized head and neck support system

    International Nuclear Information System (INIS)

    Bentel, Gunilla C.; Marks, Lawrence B.; Sherouse, George W.; Spencer, David P.

    1995-01-01

    Purpose: To describe a customized head and neck immobilization system for patients receiving radiotherapy including a head support that conforms to the posterior contour of the head and neck. Methods: The system includes a customized headrest to support the posterior head and neck. This is fixed to a thermoplastic face mask that molds to the anterior head/face contours. The shape of these customized head and neck supports were compared to 'standard' supports. Results: This system is comfortable for the patients and appears to be effective in reproducing the setup of the treatment. Conclusions: The variability in the size and shape of the customized posterior supports exceeded that of 'standard' headrests. It is our clinical impression that the customized supports improve reproducibility and are now a standard part of our immobilization system. The quantitative analysis of the customized headrests and some commonly used 'standard' headrests suggests that the customized supports are better able to address variabilities in patient shape

  9. Neck and scleral hemorrhage in drowning.

    Science.gov (United States)

    Alexander, Russell T; Jentzen, Jeffrey M

    2011-03-01

    The determination of the cause and manner of death for a body recovered from the water can be difficult because of a lack of autopsy findings specific for drowning. This case report describes a 30-year-old man found submerged at the bottom of a hotel pool. An autopsy revealed scleral hemorrhages and fascial hemorrhages of multiple muscles of the anterior and posterior neck bilaterally. No evidence of traumatic injury was on the surface of the body. An investigation by law enforcement found no evidence of foul play. The occurrence of petechial and neck hemorrhage in a body recovered from the water is controversial, and a review of this literature will be given. We suggest that fascial hemorrhages of the muscles of the neck, as well as cephalic hemorrhages, can be explained by drowning-related elevated central venous pressure that is communicated to the head through the valveless veins of the neck. © 2010 American Academy of Forensic Sciences.

  10. Quality of life after planned neck dissection

    International Nuclear Information System (INIS)

    Iwae, Shigemichi; Hirayama, Yuji; Komatsu, Hirokazu

    2009-01-01

    We evaluated the effect of planned neck dissection (PND) after concurrent chemoradiotherapy (CCRT) on quality of life (QOL) by using a self-administered neck dissection questionnaire and an arm abduction test. Subjects are fourteen patients who had undergone CCRT followed by planned selective neck dissection for the treatment of mesopharyngeal and hypopharyngeal cancer. The findings of the survey were compared with thirty-two patients who had undergone CCRT alone. Patients without PND had better scores on measures of pain, constriction, numbness and appearance of the neck, but had no advantage about arm abduction. After PND, the patients who had dissected dominant hand side had lower satisfaction compared with those who had dissected non-dominant hand side. (author)

  11. Unusual Cancers of the Head and Neck

    Science.gov (United States)

    ... more information). Unusual Cancers of the Head and Neck Nasopharyngeal Cancer See the PDQ summary on Childhood ... of PDQ documents can be used freely as text. It cannot be identified as an NCI PDQ ...

  12. Ipsilateral femoral neck and trochanter fracture

    Directory of Open Access Journals (Sweden)

    Devdatta S Neogi

    2011-01-01

    Full Text Available Ipsilateral fractures in the neck and trochanteric region of the femur are very rare and seen in elderly osteoporotic patients. We present a case of a young man who presented with ipsilateral fracture of the femoral neck and a reverse oblique fracture in the trochanteric region following a motor vehicle accident. A possible mechanism, diagnostic challenge, and awareness required for identifying this injury are discussed.

  13. Fragmentation of neck-like structures

    International Nuclear Information System (INIS)

    Montoya, C.; Bowman, D.R.; Peaslee, G.F.; Michigan State Univ., East Lansing, MI

    1994-01-01

    Evidence for intermediate mass fragment emission from neck-like structures joining projectile- and target-like residues has been observed for peripheral 129 Xe+ nat Cu collisions at E/A=50 MeV. These framents are emitted primarily at velocities intermediate between those of the projectile and the target. Relative to the charge distribution for fragments evaporated from the projectile-like residue, the distribution for ''neck'' emission shows an enhanced emission for fragments with 4 f < 8. (orig.)

  14. Schwannomas of the head and neck

    Directory of Open Access Journals (Sweden)

    Anastasios Kanatas

    2011-12-01

    Full Text Available Schwannomas are benign encapsulated nerve sheath tumors composed of Schwann cells. Malignant change in head and neck schwannomas is rare, with the incidence varying between 8 and 13.9%. In this review, we discuss the presentation and the management of head and neck schwannomas. The issues and difficulties based on our own experience as well as the experience of published reports from the literature are presented.

  15. Impact of cathepsin B-sensitive triggers and hydrophilic linkers on in vitro efficacy of novel site-specific antibody-drug conjugates.

    Science.gov (United States)

    Bryden, Francesca; Martin, Camille; Letast, Stéphanie; Lles, Eva; Viéitez-Villemin, Inmaculada; Rousseau, Anaïs; Colas, Cyril; Brachet-Botineau, Marie; Allard-Vannier, Emilie; Larbouret, Christel; Viaud-Massuard, Marie-Claude; Joubert, Nicolas

    2018-03-14

    Herein we describe the synthesis and evaluation of four novel HER2-targeting, cathepsin B-sensitive antibody-drug conjugates bearing a monomethylauristatin E (MMAE) cytotoxic payload, constructed via the conjugation of cleavable linkers to trastuzumab using a site-specific bioconjugation methodology. These linkers vary by both cleavable trigger motif and hydrophilicity, containing one of two cathepsin B sensitive dipeptides (Val-Cit and Val-Ala), and engendered with either hydrophilic or hydrophobic character via application of a PEG 12 spacer. Through evaluation of physical properties, in vitro cytotoxicity, and receptor affinity of the resulting antibody-drug conjugates (ADCs), we have demonstrated that while both dipeptide triggers are effective, the increased hydrophobicity of the Val-Ala pair limits its utility within this type of linker. In addition, while PEGylation augments linker hydrophilicity, this change does not translate to more favourable ADC hydrophilicity or potency. While all described structures demonstrated excellent and similar in vitro cytotoxicity, the ADC with the ValCitPABMMAE linker shows the most promising combination of in vitro potency, structural homogeneity, and hydrophilicity, warranting further evaluation into its therapeutic potential.

  16. Strategies for ensuring quality data from Indian investigational sites

    Directory of Open Access Journals (Sweden)

    Antal K Hajos

    2011-01-01

    Full Text Available The topic of ensuring quality and compliance is and must be a top priority in the conduct of clinical trials, as warranted by regulatory guidelines as well as the inherent responsibility of the professionals conducting such research. Fast-growing emerging clinical geographies such as India demand special attention due to rapid growth and associated factors that may put study quality at risk. In this paper, we used the basic principle of PDCA (Plan, Do, Check, and Adjust to structure the processes of a clinical trial from protocol to final analysis in order to highlight the interactive nature of involved people and processes required to ensure quality of data and site functioning.

  17. Enhancing Scientific Foundations to Ensure Reproducibility: A New Paradigm.

    Science.gov (United States)

    Hsieh, Terry; Vaickus, Max H; Remick, Daniel G

    2018-01-01

    Progress in science is dependent on a strong foundation of reliable results. The publish or perish paradigm in research, coupled with an increase in retracted articles from the peer-reviewed literature, is beginning to erode the trust of both the scientific community and the public. The NIH is combating errors by requiring investigators to follow new guidelines addressing scientific premise, experimental design, biological variables, and authentication of reagents. Herein, we discuss how implementation of NIH guidelines will help investigators proactively address pitfalls of experimental design and methods. Careful consideration of the variables contributing to reproducibility helps ensure robust results. The NIH, investigators, and journals must collaborate to ensure that quality science is funded, explored, and published. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Ensuring the Validity of the Micro Foundation in DSGE Models

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller

    & Primiceri (American Economic Review, forth- coming) and Fernández-Villaverde & Rubio-Ramírez (Review of Economic Studies, 2007) do not satisfy these sufficient conditions, or any other known set of conditions ensuring finite values for the objective functions. Thus, the validity of the micro foundation......The presence of i) stochastic trends, ii) deterministic trends, and/or iii) stochastic volatil- ity in DSGE models may imply that the agents' objective functions attain infinite values. We say that such models do not have a valid micro foundation. The paper derives sufficient condi- tions which...... ensure that the objective functions of the households and the firms are finite even when various trends and stochastic volatility are included in a standard DSGE model. Based on these conditions we test the validity of the micro foundation in six DSGE models from the literature. The models of Justiniano...

  19. Ensuring long-term availability of TELEPERM XS

    International Nuclear Information System (INIS)

    Bock, H.-W.; Richter, S.

    1998-01-01

    With putting in operation the first digital TELEPERM XS I and C systems for functions important to safety in nuclear power plants, ensuring long-term availability and reliable operation of TELEPERM XS systems gains increasing importance. On the one hand, the modular structure of TELEPERM XS has already been optimized during system development such that the application-specific functions are independent of the version of hardware components and system software. On the other hand, hardware-independent, tool-based engineering procedures ensure that the application software of installed I and C systems can be flexibly adapted to modified plant requirements while at the same time the very high software quality is retained. Quality-assured procedures and an actively organized configuration management guarantee that the functionality and the availability of the I and C systems keep their qualified standard. This paper discusses aspects of the configuration management for TELEPERM XS I and C systems. (author)

  20. Ensuring rigour and trustworthiness of qualitative research in clinical pharmacy.

    Science.gov (United States)

    Hadi, Muhammad Abdul; José Closs, S

    2016-06-01

    The use of qualitative research methodology is well established for data generation within healthcare research generally and clinical pharmacy research specifically. In the past, qualitative research methodology has been criticized for lacking rigour, transparency, justification of data collection and analysis methods being used, and hence the integrity of findings. Demonstrating rigour in qualitative studies is essential so that the research findings have the "integrity" to make an impact on practice, policy or both. Unlike other healthcare disciplines, the issue of "quality" of qualitative research has not been discussed much in the clinical pharmacy discipline. The aim of this paper is to highlight the importance of rigour in qualitative research, present different philosophical standpoints on the issue of quality in qualitative research and to discuss briefly strategies to ensure rigour in qualitative research. Finally, a mini review of recent research is presented to illustrate the strategies reported by clinical pharmacy researchers to ensure rigour in their qualitative research studies.

  1. Bilateral femoral neck fractures following pelvic irradiation

    International Nuclear Information System (INIS)

    Mitsuda, Kenji; Nishi, Hosei; Oba, Hiroshi

    1977-01-01

    Over 300 cases of femoral neck fractures following radiotherapy for intrapelvic malignant tumor have been reported in various countries since Baensch reported this disease in 1927. In Japan, 40 cases or so have been reported, and cases of bilateral femoral neck fractures have not reached to ten cases. The authors experienced a case of 75 year-old female who received radiotherapy for cancer of the uterus, and suffered from right femoral neck fracture 3 months after and left femoral neck fracture one year and half after. As clinical symptoms, she had not previous history of trauma in bilateral femurs, but she complained of a pain in a hip joint and of gait disturbance. The pain in left femoral neck continued for about one month before fracture was recognized with roentgenogram. As histopathological findings, increase of fat marrow, decrease of bone trabeculae, and its marked degeneration were recognized. Proliferation of some blood vessels was found out, but thickness of the internal membrane and thrombogenesis were not recognized. Treatment should be performed according to degree of displacement of fractures. In this case, artificial joint replacement surgery was performed to the side of fracture of this time, because this case was bilateral femoral neck fractures and the patient had received artificial head replacement surgery in the other side of fracture formerly. (Tsunoda, M.)

  2. Chronic neck pain and masticatory dysfunction.

    Science.gov (United States)

    Catanzariti, Jean-François; Debuse, Thierry; Duquesnoy, Bernard

    2005-12-01

    Chronic nonspecific neck pain is a common problem in rheumatology and may resist conventional treatment. Pathophysiological links exist between the cervical spine and masticatory system. Occlusal disorders may cause neck pain and may respond to dental treatment. The estimated prevalence of occlusal disorders is about 45%, with half the cases being due to functional factors. Minor repeated masticatory dysfunction (MD) with craniocervical asymmetry is the most common clinical picture. The pain is usually located in the suboccipital region and refractory to conventional treatment. The time pattern may be suggestive, with nocturnal arousals or triggering by temporomandibular movements. MD should be strongly suspected in patients with at least two of the following: history of treated or untreated MD, unilateral temporomandibular joint pain and clicking, lateral deviation during mouth opening, and limitation of mouth opening (less than three fingerbreadths). Rheumatologists should consider MD among causes of neck pain, most notably in patients with abnormal craniocervical posture, signs linking the neck pain to mastication, and clinical manifestations of MD. Evidence suggesting that MD may cause neck pain has been published. However, studies are needed to determine whether treatment of MD can relieve neck pain.

  3. Modeling neck mobility in fossil turtles.

    Science.gov (United States)

    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. © 2014 Wiley Periodicals, Inc.

  4. KEY ASPECTS OF ENSURING ENERGY EFFICIENCY OF BUILDINGS AND STRUCTURES

    Directory of Open Access Journals (Sweden)

    S.G. Abramyan

    2017-06-01

    Full Text Available The paper is based on the review of the foreign and national academic literature and intended to emphasize the issues of ensuring energy efficiency of buildings and structures applicable to all the countries as for reconstruction of existing buildings as for erection of new ones . The author highlights the key aspects of the provision of energy efficiency of buildings and structures in some foreign countries. The conclusion is made that the studies are mainly aimed at discovering new heat insulation materials, whereby polystyrene insulation is found to be the most widespread wall insulation material in a number of countries. At the same time, it is observed that the ongoing research is focused on solutions to optimize the structure of walling systems in terms of both insulant thickness and the number and sequence of insulation layers in the walling structure. A conclusion is made that hyper insulation of external walls leads to considerable expenses arising due to cooling during the summer season. The use of prefabricated vacuum panels as a heat insulation layer and off-the-shelf single-layer structures, subject to their heat insulation characteristics, appears a more constructive way to meet the energy efficiency requirements, as the arrangement of ideal air space in multilayered walls proves a significant challenge today. One of the most promising ways to ensure energy efficiency is the use of multifunctional polyvalent walls and provision of polyvalent heat supply from renewable energy sources. Since energy efficiency depends on the spatial arrangement of buildings, construction must ensure a minimum ratio of the area of enclosing structures to the overall building volume (by adding on new facilities in case of reconstruction. It is noted that a systemic approach to ensuring energy efficiency of buildings is impossible without proper regard to the environmental parameters of heat insulation materials.

  5. Cep63 and cep152 cooperate to ensure centriole duplication.

    Directory of Open Access Journals (Sweden)

    Nicola J Brown

    Full Text Available Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.

  6. Ensuring Sustainable Development through Urban Planning in Pakistan

    Directory of Open Access Journals (Sweden)

    Mohammad Qasim

    2013-04-01

    Full Text Available Urban planning includes land use management and environmental change. It makes arrangement for community facilities and services. Since, sustainable development has been included as a vital end product of all planning goals it also provides for balanced use of land, housing and transportation and better quality of life. Present urban planning in Pakistan is not ensuring sustainable development in Pakistan. This is tested through the case study of master planning in Rawalpindi and its implementation through housing schemes in Rawalpindi, Pakistan. Large portions of provisions of master plans are not implemented. This paper explains how the urban planning will be made enabled to ensure sustainable development in Pakistan. Six numbers of housing schemes and two squatter settlements have been surveyed through questionnaires, secondary data, the opinions of the experts from related fields and site observations. Amenities and social services at far distance, very less green area, Less quantity and bad quality of water, absence of comprehensive solid waste management and sewage disposal system and nontreatment of solid waste, effluent and sewage, prevalent unhygienic conditions and air and water pollution are the existing factors effecting the sustainability. There is a need to revisit the urban planning and a comprehensive Urban and Environment Planning Law at national level and at provincial level is recommended to enable the urban planning to ensure the sustainable development in Pakistan

  7. Ensuring sustainable development through urban planing in pakistan

    International Nuclear Information System (INIS)

    Qasim, M.; Zaidi, S.S.U.

    2013-01-01

    Urban planning includes land use management and environmental change. It makes arrangement for community facilities and services. Since, sustainable development has been included as a vital end product of all planning goals it also provides for balanced use of land, housing and transportation and better quality of life. Present urban planning in Pakistan is not ensuring sustainable development in Pakistan. This is tested through the case study of master planning in Rawalpindi and its implementation through housing schemes in Rawalpindi, Pakistan. Large portions of provisions of master plans are not implemented. This paper explains how the urban planning will be made enabled to ensure sustainable development in Pakistan. Six numbers of housing schemes and two squatter settlements have been surveyed through questionnaires, secondary data, the opinions of the experts from related fields and site observations. Amenities and social services at far distance, very less green area, Less quantity and bad quality of water, absence of comprehensive solid waste management and sewage disposal system and non- treatment of solid waste, effluent and sewage, prevalent unhygienic conditions and air and water pollution are the existing factors effecting the sustainability. There is a need to revisit the urban planning and a comprehensive Urban and Environment Planning Law at national level and at provincial level is recommended to enable the urban planning to ensure the sustainable development in Pakistan. (author)

  8. Modern Paradigm of Ensuring Competitive Advantages of an Enterprise

    Directory of Open Access Journals (Sweden)

    Klymchuk Alyona O.

    2014-01-01

    Full Text Available The article considers evolution of development of the paradigm of ensuring competitive advantages of an enterprise. Foreign and domestic scientists focus on individual directions of development of competitive advantages and pay insufficient attention to new management concepts – development of the information society, knowledge economy and dynamism of integration processes. The goal of the study is formation of the modern paradigm of ensuring competitive advantages of an enterprise with consideration of tendencies of development of the knowledge economy, information society and integration processes. Enterprise competitiveness is a synergetic characteristic, which reflects enterprise capability of dynamic response to changes of the market situation with the aim of keeping predominance over other economic subjects. Management of the future, on the basis of the management 2.0 concept, should take into account interests not only of top management and shareholders but also employees, local communities and territories and meet requirements of the society in general, individual groups of consumers and tendencies of development of managerial and information technologies. The paradigm of the modern theory of ensuring competitive advantages should include models of keeping competitive advantages in the existing markets and models of development of future markets; strategy of development of enterprise competitiveness, human capital development and efficient enterprise management.

  9. Neck dissection following chemo radiation for node positive head and neck carcinomas

    International Nuclear Information System (INIS)

    Thariat, J.; Thariat, J.; Marcy, P.Y.; Bozec, A.; Peyrade, F.; Hofman, P.; Hamoir, M.; Janot, F.; De Mones, E.; Marcy, P.Y.; Carrier, P.; Bozec, I.; Guevara, J.; Santini, J.; Albert, S.; Vedrine, P.O.; Graff, P.; Peyrade, F.; Hofman, P.; Bourhis, J.; Lapeyre, M.

    2009-01-01

    The optimal timing and extent of neck dissection in the context of chemo radiation for head and neck cancer remains controversial. For some institutions, it is uncertain whether neck dissection should still be performed up front especially for cystic nodes. For others, neck dissection can be performed after chemo radiation and can be omitted for N1 disease as long as a complete response to chemo radiation is obtained. The question is debated for N2 and N3 disease even after a complete response as the correlation between radiological and clinical assessment and pathology may not be reliable. Response rates are greater than or equal to 60% and isolated neck failures are less than or equal to 10% with current chemo radiation protocols. Some therefore consider that systematic up front or planned neck dissection would lead to greater than or equal to 50% unnecessary neck dissections for N2-N3 disease. Positron-emission tomography (PET) scanning to assess treatment response and have shown a very high negative predictive value of greater than or equal to 95% when using a standard uptake value of 3 for patients with a negative PET at four months after the completion of therapy. These data may support the practice of observing PET-negative necks. More evidence-based data are awaited to assess the need for neck dissection on PET. Selective neck dissection based on radiological assessment and preoperative findings and not exclusively on initial nodal stage may help to limit morbidity and to improve the quality of life without increasing the risk of neck failure. Adjuvant regional radiation boosts might be discussed on an individual basis for aggressive residual nodal disease with extra-capsular spread and uncertain margins but evidence is missing. Medical treatments aiming at reducing the metastatic risk especially for N3 disease are to be evaluated

  10. Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

    Science.gov (United States)

    Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

    2012-12-31

    Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Wall to membrane linkers, stretch activated channels, and the detection of tension, voltage, temperature, auxin, and pH

    Science.gov (United States)

    Pickard, B. G.

    1992-01-01

    Introduction. The higher plant is a heterogeneous, mechanically prestressed structure continually subject to shifting forces. When a cell grows in a plant at gravitropic equilibrium, it must create localized maxima of shear in walls of neighboring cells. Such mechanical stress and strain are likely detected in a variety of ways. However, tension-sensitive ion channels are of particular interest because it appears that they are elaborately evolved for sensory function. We hypothesize that 1) the patchy patterns of high shear are focused via wall-to-membrane linkers onto the plasma membrane, where 2) they are translated by mechanosensory cation channels into corresponding patterns of high cytosolic Ca2+, which 3) initiate local enhancement of wall expansion. Further, we hypothesize that the local promotion of enhancement is achieved at least in part by local intensification of auxin transport across the plasma membrane. By implication, when an organ is asymmetrically pressed, rubbed, or bent or when it is displaced in the gravitational field, the net asymmetry of shear stress occurring across the organ would lead to asymmetric redistribution of auxin and corrective asymmetric growth. We shall describe a representative mechanosensitive Ca(2+) -selective cation channel (MCaC) with susceptibilities to xenobiotics implicating it as a force transducer in thigmo- and gravitropism. Then, we shall consider whether a putative wall-to-membrane linker (WML) could be a key feature of the molecular architecture permitting the stress distributed in the wall system to be focused on the channels.

  12. Probing the Influence of Linker Length and Flexibility in the Design and Synthesis of New Trehalase Inhibitors

    Directory of Open Access Journals (Sweden)

    Giampiero D’Adamio

    2018-02-01

    Full Text Available This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards C. riparius trehalase was evaluated and the results showed that 8 was active in the μM range and showed a good selectivity towards the insect trehalase. To reduce the overall number of synthetic steps, simpler and more flexible disaccharide mimetics 9–11 bearing a pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The biological data showed the key role of the linker chain’s length in inducing inhibitory properties, since only compounds 9 (α,β-mixture, bearing a two-carbon atom linker chain, maintained activity as trehalase inhibitors. A proper change in the glucosyl donor-protecting groups allowed the stereoselective synthesis of the β-glucoside 9β, which was active in the low micromolar range (IC50 = 0.78 μM and 12-fold more potent (and more selective than 9α towards the insect trehalase.

  13. Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

    Directory of Open Access Journals (Sweden)

    Zomaya Albert Y

    2006-12-01

    Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

  14. [Head and neck adaptive radiotherapy].

    Science.gov (United States)

    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. Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  15. Comparison of electromyographic activity and range of neck motion in violin students with and without neck pain during playing.

    Science.gov (United States)

    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.

  16. Dose-response relationship for elective neck irradiation of head and neck cancer - facts and controversies

    International Nuclear Information System (INIS)

    Suwinski, R.; Maciejewski, B.; Withers, H.R.

    1998-01-01

    The aim of this study is to assign dose-response relationship for subclinical neck metastases of squamous cell head and neck cancer based on extensive survey of 24 data sets collected from the literature. Neck relapse rates (NRR) without and after elective (ENI) or preoperative irradiation were estimated for each site and stage of primary tumor and the reduction in neck relapse rate was calculated. An average NRR without ENI was 22% (12-35% ) and only 2.5% (0-1 0%) after the ENI with total dose of 46- 50 Gy which gives high reduction rate in the risk of neck recurrences being on the average 89% and 42% (0-46%) after preoperative irradiation using 22-30 Gy. Dose response curve for elective and preoperative irradiation have shown that 50 Gy in 2 Gy fraction reduces the incidence of neck relapses in the NO patients by more than 90% and only by less than 50% after total doses lower than 30 Gy. No correlation between the risk of neck metastases without ENI and the reduction in neck relapses after ENI was found. (authors)

  17. Regional control of melanoma neck node metastasis after selective neck dissection with or without adjuvant radiotherapy

    NARCIS (Netherlands)

    Hamming-Vrieze, Olga; Balm, Alfons J. M.; Heemsbergen, Wilma D.; Hooft van Huysduynen, Thijs; Rasch, Coen R. N.

    2009-01-01

    OBJECTIVE: To examine the effect of adjuvant radiotherapy on regional control of melanoma neck node metastasis. DESIGN: A single-institution retrospective study. SETTING: Tertiary care cancer center. PATIENTS: The study included 64 patients with melanoma neck node metastasis who were treated with

  18. Shoulder and neck morbidity in quality of life after surgery for head and neck cancer

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    2004-01-01

    Background. Quality of life has become a major issue in determining the outcome of treatment in head and neck surgery with curative intent. The aim of our study was to determine which factors in the postoperative care, especially shoulder and neck morbidity, are related to quality of life and how

  19. Psychometric properties of the Neck OutcOme Score, Neck Disability Index, and Short Form-36 were evaluated in patients with neck pain

    DEFF Research Database (Denmark)

    Juul, Tina; Søgaard, Karen; Davis, Aileen M.

    2016-01-01

    Objective:To assess reliability, construct validity, responsiveness, and interpretability for Neck OutcOme Score (NOOS), Neck Disability Index (NDI), and Short Form–36 (SF-36) in neck pain patients. Study Design and Setting: Internal consistency was assessed by Cronbach alpha. Test-retest reliabi...

  20. Treatment of Neck Pain: Noninvasive Interventions

    Science.gov (United States)

    Carragee, Eugene J.; van der Velde, Gabrielle; Carroll, Linda J.; Nordin, Margareta; Guzman, Jaime; Peloso, Paul M.; Holm, Lena W.; Côté, Pierre; Hogg-Johnson, Sheilah; Cassidy, J. David; Haldeman, Scott

    2008-01-01

    Study Design. Best evidence synthesis. Objective. To identify, critically appraise, and synthesize literature from 1980 through 2006 on noninvasive interventions for neck pain and its associated disorders. Summary of Background Data. No comprehensive systematic literature reviews have been published on interventions for neck pain and its associated disorders in the past decade. Methods. We systematically searched Medline and screened for relevance literature published from 1980 through 2006 on the use, effectiveness, and safety of noninvasive interventions for neck pain and associated disorders. Consensus decisions were made about the scientific merit of each article; those judged to have adequate internal validity were included in our best evidence synthesis. Results. Of the 359 invasive and noninvasive intervention articles deemed relevant, 170 (47%) were accepted as scientifically admissible, and 139 of these related to noninvasive interventions (including health care utilization, costs, and safety). For whiplash-associated disorders, there is evidence that educational videos, mobilization, and exercises appear more beneficial than usual care or physical modalities. For other neck pain, the evidence suggests that manual and supervised exercise interventions, low-level laser therapy, and perhaps acupuncture are more effective than no treatment, sham, or alternative interventions; however, none of the active treatments was clearly superior to any other in either the short-or long-term. For both whiplash-associated disorders and other neck pain without radicular symptoms, interventions that focused on regaining function as soon as possible are relatively more effective than interventions that do not have such a focus. Conclusion. Our best evidence synthesis suggests that therapies involving manual therapy and exercise are more effective than alternative strategies for patients with neck pain; this was also true of therapies which include educational interventions

  1. Pocket Proteins Suppress Head and Neck Cancer

    Science.gov (United States)

    Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

    2012-01-01

    Head and neck squamous cell carcinomas (HNSCC) is a common cancer in humans long known to be caused by tobacco and alcohol use, but now an increasing percentage of HNSCC is recognized to be caused by the same human papillomaviruses (HPVs) that cause cervical and other anogenital cancers. HPV-positive HNSCCs differ remarkably from HPV-negative HNSCCs in their clinical response and molecular properties. From studies in mice, we know that E7 is the dominant HPV oncoprotein in head and neck cancer. E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene. However loss of pRb function does not fully account for E7’s potency in causing head and neck cancer. In this study, we characterized the cancer susceptibility of mice deficient in the expression of pRb and either of two related “pocket” proteins, p107 and p130, that are also inactivated by E7. pRb/p107 deficient mice developed head and neck cancer as frequently as do HPV16 E7 transgenic mice. The head and neck epithelia of the pRb/p107 deficient mice also displayed the same acute phenotypes and biomarker readouts as observed in the epithelia of E7 transgenic mice. Mice deficient for pRb and p130 in their head and neck epithelia showed intermediate acute and tumor phenotypes. We conclude that pRb and p107 act together to efficiently suppress head and neck cancer, and are therefore highly relevant targets of HPV16 E7 in its contribution to HPV-positive HNSCC. PMID:22237625

  2. Crystallization and preliminary X-ray analysis of Acetivibrio cellulolyticus cellulosomal type II cohesin module: two versions having different linker lengths

    International Nuclear Information System (INIS)

    Noach, Ilit; Alber, Orly; Bayer, Edward A.; Lamed, Raphael; Levy-Assaraf, Maly; Shimon, Linda J. W.; Frolow, Felix

    2007-01-01

    The cloning, expression, purification, crystallization and preliminary X-ray characterization of two protein constructs of the second type II cohesin module from A. cellulolyticus ScaB are described. Both constructs contain the native N-terminal linker, but only one of them contains the full-length 45-residue C-terminal linker; the other contains a five-residue segment of this linker. The second type II cohesin module of the cellulosomal scaffoldin polypeptide ScaB from Acetivibrio cellulolyticus (CohB2) was cloned into two constructs: one containing a short (five-residue) C-terminal linker (CohB2-S) and the second incorporating the full native 45-residue linker (CohB2-L). Both constructs encode proteins that also include the full native six-residue N-terminal linker. The CohB2-S and CohB2-L proteins were expressed, purified and crystallized in the orthorhombic crystal system, but with different unit cells and symmetries: space group P2 1 2 1 2 1 with unit-cell parameters a = 90.36, b = 68.65, c = 111.29 Å for CohB2-S and space group P2 1 2 1 2 with unit-cell parameters a = 68.76, b = 159.22, c = 44.21 Å for CohB2-L. The crystals diffracted to 2.0 and 2.9 Å resolution, respectively. The asymmetric unit of CohB2-S contains three cohesin molecules, while that of CohB2-L contains two molecules

  3. The linker domain of poly(rC) binding protein 2 is a major determinant in poliovirus cap-independent translation.

    Science.gov (United States)

    Sean, Polen; Nguyen, Joseph H C; Semler, Bert L

    2008-09-01

    Poliovirus, a member of the enterovirus genus in the family Picornaviridae, is the causative agent of poliomyelitis. Translation of the viral genome is mediated through an internal ribosomal entry site (IRES) encoded within the 5' noncoding region (5' NCR). IRES elements are highly structured RNA sequences that facilitate the recruitment of ribosomes for translation. Previous studies have shown that binding of a cellular protein, poly(rC) binding protein 2 (PCBP2), to a major stem-loop structure in the genomic 5' NCR is necessary for the translation of picornaviruses containing type I IRES elements, including poliovirus, coxsackievirus, and human rhinovirus. PCBP1, an isoform that shares approximately 90% amino acid identity to PCBP2, cannot efficiently stimulate poliovirus IRES-mediated translation, most likely due to its reduced binding affinity to stem-loop IV within the poliovirus IRES. The primary differences between PCBP1 and PCBP2 are found in the so-called linker domain between the second and third K-homology (KH) domains of these proteins. We hypothesize that the linker region of PCBP2 augments binding to poliovirus stem-loop IV RNA. To test this hypothesis, we generated six PCBP1/PCBP2 chimeric proteins. The recombinant PCBP1/PCBP2 chimeric proteins were able to interact with poliovirus stem-loop I RNA and participate in protein-protein interactions. We demonstrated that the PCBP1/PCBP2 chimeric proteins with the PCBP2 linker, but not with the PCBP1 linker, were able to interact with poliovirus stem-loop IV RNA, and could subsequently stimulate poliovirus IRES-mediated translation. In addition, using a monoclonal anti-PCBP2 antibody (directed against the PCBP2 linker domain) in mobility shift assays, we showed that the PCBP2 linker domain modulates binding to poliovirus stem-loop IV RNA via a mechanism that is not inhibited by the antibody.

  4. Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

    Directory of Open Access Journals (Sweden)

    Makenzie Saoura

    Full Text Available The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether and functions as a monomer. The amino domain retains the flexible arm responsible for substrate recognition and binding while the carboxy domain retains the active site. The linker region was explored by Ala-scanning through two conserved regions of D. melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain proximal to the linker, and Tflex, a flexible site in the linker. Periodic substitutions in a hydrophobic patch (F329 and L332 at the carboxy end of NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively, accompanied by reduced linker flexibility at N-T inside the Ndom- linker boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher catalytic efficiency than wild type and locally decreased flexibility, while the Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in pre-tRNA processing kinetics and protein flexibility are interpreted in light of a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of local changes in hydrophobicity into the skeleton of the amino domain.

  5. Head and neck cancer: Radiotherapeutic precepts in the management of the neck

    International Nuclear Information System (INIS)

    Million, R.R.; Cassisi, N.J.; Parsons, J.T.; Mendenhall, W.M.

    1986-01-01

    The authors provide a series of statements regarding the use of radiotherapy and surgery for metastatic squamous cancer to the neck. Some of these precepts are established facts requiring no additional documentation - for example, the combination of radiation and neck dissection for effective treatment of N2B neck disease or for subclinical disease, depending on extracapsular spread. Other precepts of the authors are not as generally accepted by head and neck surgeons, such as the mandatory staging of neck dissections following curative radiation therapy or the routine use of computerized tomography (CT) to confirm pathologic adenopathy. Most of the authors' precepts are supported by a combination of their personal clinical experience and hard data from the University of Florida, Gainesville

  6. THE ISSUEOFSTRENGTHENING BUDGET CAPACITY FOR ENSURING THE FINANCIALINDEPENDENCE OFLOCALAUTHORITIES

    Directory of Open Access Journals (Sweden)

    Dmytriy V. Nekhaychuk

    2018-05-01

    Full Text Available The paper deals with the issues on strengthening local governments’ budget capacity in the face of modern challenges. It shows the conceptual in-depth study of local budgets foundations, income and practical recommendations focusing on stability and capacity. The author proves that the revenues of local budgets play a crucial role in ensuring the full and effective performance of the functions and local authorities’ tasks. The paper shows the scientific analysis of modern economists’ views on the local authorities’ financial autonomy and the local budgets’ role in the process. The paper also shows the retrospective comparative analysis of methods, used by local and foreign scientists for the formation of local budgets’ revenues. It considers the economic nature of income in local budgets as a source of finance, ensures the efficient operation of local authorities. It has been found out that the organization of the process of forming local budgets’ revenues is influenced by the organizational and legal forms of management, type of ownership and specifics of enterprises. Taxes are the dominant source of local budgets’ incomes, the financial regulator of production, means of ensuring socio-economic development of the separate administrative and territorial units and the state as a whole. The authors also analyze different types of revenues, including tax, in the revenue part of local budgets. The authors propose to expand the list of local taxes and fees due to the introduction of tax with targeted use of received funds. The conceptual basis of financial independence of local self-government lies in in the optimal interests of the population, local government, state and business structures. The increase of own revenues in the share of local budgets becomes a strategic issue of the financial autonomy and the corresponding administrative and territorial units.

  7. Systems and processes that ensure high quality care.

    Science.gov (United States)

    Bassett, Sally; Westmore, Kathryn

    2012-10-01

    This is the second in a series of articles examining the components of good corporate governance. It considers how the structures and processes for quality governance can affect an organisation's ability to be assured about the quality of care. Complex information systems and procedures can lead to poor quality care, but sound structures and processes alone are insufficient to ensure good governance, and behavioural factors play a significant part in making sure that staff are enabled to provide good quality care. The next article in this series looks at how the information reporting of an organisation can affect its governance.

  8. Ensuring long time access to DELPHI data: the IDEA project

    International Nuclear Information System (INIS)

    Camporesi, T.; Charpentier, P.; Elsing, M.; Liko, D.; Smirnov, N.; Wicke, D.

    2001-01-01

    The long term accessibility of its data is an important concern of the DELPHI collaboration. It is the authors' assumption that the storage of the data itself will be a minor issue due to the progress in storage technologies. Therefore DELPHI focuses on a reorganisation of the data, which should provide a flexible and coherent framework for physics analysis in the future. The authors describe the current status of the IDEA (Improved DElphi Analysis) project which will ensure usability of DELPHI data for future generations of physicists

  9. Effects of neck strength training on isometric neck strength in rugby union players.

    Science.gov (United States)

    Geary, Kevin; Green, Brian S; Delahunt, Eamonn

    2014-11-01

    To investigate the effectiveness of a neck strengthening program on the isometric neck strength profile of male rugby union players. Controlled laboratory study. Professional rugby union club. Fifteen professional and 10 semiprofessional rugby union players. The 15 professional players undertook a 5-week neck strengthening intervention, which was performed twice per week, whereas the 10 semiprofessional players acted as the control group. Isometric strength of the neck musculature was tested using a hand-held dynamometer, for flexion (F), extension (E), left-side flexion (LSF), and right-side flexion (RSF). Preintervention and postintervention evaluations were undertaken. No significant between-group differences in isometric neck strength were noted preintervention. A significant main effect for time was observed (P isometric neck strength in all planes after the 5-week intervention (F preintervention = 334.45 ± 39.31 N vs F postintervention 396.05 ± 75.55 N; E preintervention = 606.19 ± 97.34 vs E postintervention = 733.88 ± 127.16 N; LSF preintervention = 555.56 ± 88.34 N vs LSF postintervention = 657.14 ± 122.99 N; RSF preintervention = 570.00 ± 106.53 N vs RSF postintervention = 668.00 ± 142.18 N). No significant improvement in neck strength was observed for control group participants. The results of the present study indicate that a 5-week neck strengthening program improves isometric neck strength in rugby union players, which may have implications for injury prevention, screening, and rehabilitation. The strengthening program described in the present study may facilitate rehabilitation specialists in the development of neck injury prevention, screening, and rehabilitation protocols.

  10. Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA

    OpenAIRE

    Levy, Anat; Eyal, Miri; Hershkovits, Gitit; Salmon-Divon, Mali; Klutstein, Michael; Katcoff, Don Jay

    2008-01-01

    Nucleosome core particles in eukaryotes are linked by a stretch of DNA that is usually associated with a linker histone. Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA. In vivo deletions of Hho1p sequences showed that the second globular domain is sufficient for that repression, whereas the presence of the N terminus is required for its derepression. In contrast, a run-on assay confirmed by...

  11. Neck motion, motor control, pain and disability: A longitudinal study of associations in neck pain patients in physiotherapy treatment.

    Science.gov (United States)

    Meisingset, Ingebrigt; Stensdotter, Ann-Katrin; Woodhouse, Astrid; Vasseljen, Ottar

    2016-04-01

    Neck pain is associated with several alterations in neck motion and motor control, but most of the findings are based on cross-sectional studies. The aim of this study was to investigate associations between changes in neck motion and motor control, and changes in neck pain and disability in physiotherapy patients during a course of treatment. Prospective cohort study. Subjects with non-specific neck pain (n = 71) participated in this study. Neck flexibility, joint position error (JPE), head steadiness, trajectory movement control and postural sway were recorded before commencement of physiotherapy (baseline), at 2 weeks, and at 2 months. Numerical Rating Scale and Neck Disability Index were used to measure neck pain and disability at the day of testing. To analyze within subjects effects in neck motion and motor control, neck pain, and disability over time we used fixed effects linear regression analysis. Changes in neck motion and motor control occurred primarily within 2 weeks. Reduction in neck pain was associated with increased cervical range of motion in flexion-/extension and increased postural sway when standing with eyes open. Decreased neck disability was associated with some variables for neck flexibility and trajectory movement control. Cervical range of motion in flexion-/extension was the only variable associated with changes in both neck pain and neck disability. This study shows that few of the variables for neck motion and motor control were associated with changes neck pain and disability over a course of 2 months with physiotherapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide

    International Nuclear Information System (INIS)

    Dijkgraaf, Ingrid; Liu, Shuang; Kruijtzer, John A.W.; Soede, Annemieke C.; Oyen, Wim J.G.; Liskamp, Rob M.J.; Corstens, Frans H.M.; Boerman, Otto C.

    2007-01-01

    Introduction: Due to the selective expression of the α v β 3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N ' ,N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. Methods: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG 4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111 In, and their in vitro and in vivo α v β 3 -binding characteristics were determined. Results: LogP values varied between -2.82±0.06 and -3.95±0.33. The IC 50 values for DOTA-E-[c(RGDfK)] 2 , DOTA-PEG 4 -E-[c(RGDfK)] 2 , DOTA-E-E-[c(RGDfK)] 2 and DOTA-K-E-[c(RGDfK)] 2 were comparable. Two hours after injection, the tumor uptakes of the 111 In-labeled compounds were not significantly different. The kidney accumulation of [ 111 In]-DOTA-K-E-[c(RGDfK)] 2 [4.05±0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (2.63±0.19% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.16±0.21% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.12±0.09% ID/g) was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (1.64±0.1% ID/g; P 111 In]-DOTA-K-E-[c(RGDfK)] 2 (1.52±0.04% ID/g; P v β 3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG 4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver

  13. Ensuring the 50 year life of a fissile material container

    International Nuclear Information System (INIS)

    Glass, R.E.; Towne, T.L.

    1997-12-01

    Sandia was presented with an opportunity in 1993 to design containers for the long term storage and transport of fissile material. This program was undertaken at the direction of the US Department of Energy and in cooperation with Lawrence Livermore National Laboratory and Los Alamos National Laboratory which were tasked with developing the internal fixturing for the contents. The hardware is being supplied by Allied Signal Federal Manufacturing and Technologies, and the packaging will occur at Mason and Hangar Corporation's Pantex Plant. The unique challenge was to design a container that could be sealed with the fissile material contents; and, anytime during the next 50 years, the container could be transported with only the need for the pre-shipment leak test. This required not only a rigorous design capable of meeting the long term storage and transportation requirements, but also resulted in development of a surveillance program to ensure that the container continues to perform as designed over the 50-year life. This paper addresses the design of the container, the testing that was undertaken to demonstrate compliance with US radioactive materials transport regulations, and the surveillance program that has been initiated to ensure the 50-year performance

  14. [Ensure - complete and balanced nutrition, convenient on work].

    Science.gov (United States)

    Kurenkov, A V; Iuriatin, A A

    2013-01-01

    The work conditions often may compromise a company ability to supply their employees with adequate, hot meals. For heavy labor workers and some office employees it is important to restore energy and nutrients with food, balanced in nutrients. The lack of adequate nutritive support can give a negative impact on different organs functions. One of the main principles of healthy nutrition is - diet must be balanced in nutrients. Which is easy to say, but difficult to implement, especially on some industries. Complete and balanced liquid and ready-to-use nutrition is new trend in nutrition of healthy people who cannot consume optimal diet, and in people with the risk of nutrient deficiencies. One-two packs of Ensure daily can significantly improve a worker ration. 2 and more packs could serve as a real complete and balanced lunch (>or=780 kcal). Also Ensure is easy to store and to deliver in distant places of work and can be recommended for use as a convenient, complete and balanced nutrition on work.

  15. THE ROLE OF MORTGAGE CREDIT IN ENSURING ECONOMIC GROWTH

    Directory of Open Access Journals (Sweden)

    Z. L. Garipova

    2014-04-01

    Full Text Available The decision of the important social task - ensuring the availability of housing for the mass of the population of the country, on the one hand, allowed to launch investment, savings, financial and credit mechanisms for ensuring economic growth of the Russian economy on the other. Despite the high degree of sophistication in the scientific literature of the organization of mortgage lending system, a study of its impact on economic growth factors in the scientific literature clearly insufficient. The original article was the theory of economic growth, which allowed on the basis of research of interaction of demand for residential property, it deals with the housing mortgage credit to justify a conclusion about its importance not only for solution of social tasks, availability of housing, but also a significant impact on the demand and supply on the residential property market. Based on the analysis of statistical data for the period from 2006 to 2012, and their correlation analysis carried out research of factors of development of housing markets and mortgage lending, namely incomes, housing prices, interest rates on loans, «channel lending conditions, the terms of banking mortgage.Purchase on Elibrary.ru > Buy now

  16. Innovations as a Factor for Ensuring Economic Safety

    Directory of Open Access Journals (Sweden)

    Maxim SANDU

    2017-06-01

    Full Text Available In modern conditions of development of the competitive environment, one of the main ways to solve economic, social and environmental problems is to use the latest achievements of science and technology. Each enterprise seeks to ensure that economic growth is intense, i.e. to be a consequence of the application of more sophisticated factors of production and technology. The prerequisite for intensive growth is the use of innovative strategy in the practical activities of enterprises. The end result of innovations is the materialization and industrial development of innovation, the idea of which can be the scientific and technical activity, and marketing research to identify unmet needs. The innovations are an effective defensive reaction of the firm to the emerging threats of losing market place, constant pressure from competitors, the challenge of new technologies, shortening the life of products, legislative restrictions and changing the market situation. In the offensive version, the innovation is a mean of exploiting new opportunities to preserve or gain a competitive advantage. In the long term aspect, the company has no choice but to pursue an innovation policy, which is the only source of lasting success. The main objective of researching the innovation activity of any organization is to ensure competitiveness in market conditions in order to identify risk factors and ways to overcome them.

  17. Investment-innovation mechanism of ensuring competitiveness of industrial enterprises

    Directory of Open Access Journals (Sweden)

    Kozyk Vasyl V.

    2014-01-01

    Full Text Available The article considers the process of formation of the investment-innovation mechanism of ensuring competitiveness of industrial enterprises. It identifies the essence, composition, goals and means of functioning of this mechanism. It establishes sequence of the process of functioning of the investment-innovation mechanism of ensuring competitiveness of economic subjects. It marks out such particular types of this mechanism: mechanism of renovation of fixed assets of an enterprise, mechanism of formation of channels and network of sales of enterprise products, mechanism of expansion of production capacity of the enterprise on manufacture of traditional types of products, mechanism of introduction of new progressive production processes, mechanism of development and production of innovation products, and mechanism of reduction of the level of risk of investment activity of the enterprise. The article conducts modelling of the process of development and realisation of investment solutions on introduction of progressive technologies of manufacture of products at the enterprise. It offers a method of selection of the most competitive variant of technology of manufacture of products depending on the level of quality and also specific current capital outlays for their manufacture.

  18. FACTOR IN ENSURING A BALANCED BUDGET NORTHERN TERRITORIES

    Directory of Open Access Journals (Sweden)

    Tatiana Anatol’evna Naidenova

    2016-02-01

    Full Text Available The main tools of sustainable development of the country as a whole and its individual regions are federal and regional budgets. At the same time a prerequisite for the use of this tool is its equilibrium. It is the basic principle of a responsible fiscal policy. The article describes the factors to equilibrium. on the budgets of the northern regions of the Russian Federation. The measures to ensure budgetary equilibrium in the northern regions of the Russian Federation are offered.The purpose of the article. Substantiating the measures to balance the budgets of the northern Russian Federation subjects on the basis of analysis of the factors that directly affect the mobilization of potential tax revenues to regional budgets.Method and methodology of work. Theoretical and empirical methods, analysis, synthesis, induction, deduction.Results of the study. To ensure factors unbalanced budgets northern territories. The proposals the balance of revenues and expenditures of the regional budgets of the northern regions of the Russian Federation are submitted.Application area. Finance authorities of subjects of the Russian Federation.

  19. A Knowledge Translation Programme to Increase the Utilization of Thoracic Spine Mobilization and Manipulation for Patients with Neck Pain.

    Science.gov (United States)

    Karas, Steve; Westerheide, Angela; Daniel, Laura

    2016-06-01

    There is extensive evidence that mobilization and manipulation of the thoracic spine is associated with improved outcomes in patients with neck pain. However, these evidence-based techniques are not always utilized. Successful knowledge translation programmes are needed to move the best available evidence to clinical practice. The purpose of the present research was to evaluate the effects of a structured knowledge translation programme on the frequency of manual therapy techniques performed by physical therapists on patients with neck pain. Prior to our intervention, we assessed physical therapists' use of thoracic spine intervention for the treatment of neck pain and their knowledge of the evidence. We delivered a multimodal knowledge translation programme and then reassessed their use and knowledge of the interventions. The majority of our physical therapists increased the use of thoracic spine techniques for their patients with neck pain. The increase was greater in those who used the techniques infrequently. Overall knowledge of the evidence appeared unchanged. Knowledge translation programmes are essential in ensuring clinical use of evidence-based practice. Our programme results, although on a small scale and not statistically significant, showed a positive trend toward increased thoracic spine manual therapy use for neck pain. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. The Danish Head and Neck Cancer database

    DEFF Research Database (Denmark)

    Overgaard, Jens; Jovanovic, Aleksandar; Godballe, Christian

    2016-01-01

    of continuous clinical trials and subsequent implementation in national guidelines. The database has furthermore been used to describe the effect of reduced waiting time, changed epidemiology, and influence of comorbidity and socioeconomic parameters. CONCLUSION: Half a century of registration of head and neck......AIM OF THE DATABASE: The Danish Head and Neck Cancer database is a nationwide clinical quality database that contains prospective data collected since the early 1960s. The overall aim of this study was to describe the outcome of the national strategy for multidisciplinary treatment of head and neck......) of cancer in the nasal sinuses, salivary glands, or thyroid gland (corresponding to the International Classification of Diseases, tenth revision, classifications C.01-C.11, C.30-C.32, C.73, and C.80). MAIN VARIABLES: The main variables used in the study were symptoms and the duration of the symptoms...

  1. Scientific Research & Subsistence: Protocols to Ensure Co-Existence

    Science.gov (United States)

    Nachman, C.; Holman, A.; DeMaster, D.

    2017-12-01

    Commercial, industrial, and research interests in the Arctic are expanding rapidly. Potentials are numerous and exciting, giving rise to the need for guidelines to ensure interactions among waterway users do not conflict. Of particular concern is the potential for adverse impacts to U.S. Arctic coastal communities that rely on living marine resources for nutritional and cultural health, through subsistence hunts from small craft, ice edges, and shore. Recent events raised concerns over research surveys potentially interfering with subsistence hunts in the Bering, Chukchi, and Beaufort Seas. Incidents led to calls by Native Alaskan communities to restrict science activities with a mixed response from the scientific community (i.e., some sympathetic, some defensive). With a common goal of wanting to mitigate this potential interaction, Federal agencies made a commitment in the National Strategy for the Arctic Region to coordinate and consult with Alaska Natives and also to pursue responsible Arctic stewardship, with understanding through scientific research and traditional knowledge. The effort to create a "Standard of Care" for research surveys incorporates years of experience by subsistence hunters working to mitigate impacts of other anthropogenic activities in the region, as well as best practices by many in the research community. The protocols are designed to ensure potential conflicts between the scientific research community and subsistence hunters are avoided and to encourage mutual assistance and collaboration between researchers and hunters. The guidelines focus on enhancing communication between researchers and subsistence hunters before, during, and after research occurs. The best management practices outlined in the Standard of Care assist those overseeing and funding scientific research in making decisions about how best to accomplish the goals of the research while ensuring protection of the Alaska subsistence lifestyle. These protocols could also be

  2. CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell-Specific Adaptor Protein.

    Science.gov (United States)

    Hem, C D; Ekornhol, M; Granum, S; Sundvold-Gjerstad, V; Spurkland, A

    2017-02-01

    The T cell-specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline-rich region and phosphotyrosines have been identified, including the Src and Tec family kinases lymphocyte-specific protein tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signalling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known. Through the use of in silico ligand prediction, peptide spot arrays, pull-down and immunoprecipitation experiments, we here report novel interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr) 629 and linker of activated T cells (LAT) pTyr 171 , pTyr 191 and pTyr 226 . © 2016 The Foundation for the Scandinavian Journal of Immunology.

  3. Self-organization of Au–CdSe hybrid nanoflowers at different length scales via bi-functional diamine linkers

    Energy Technology Data Exchange (ETDEWEB)

    AbouZeid, Khaled Mohamed [Virginia Commonwealth University, Department of Chemistry (United States); Mohamed, Mona Bakr [Cairo University, National Institute of Laser Enhanced Science (NILES) (Egypt); El-Shall, M. Samy, E-mail: mselshal@vcu.edu [Virginia Commonwealth University, Department of Chemistry (United States)

    2016-01-15

    This work introduces a series of molecular bridging bi-functional linkers to produce laterally self-assembled nanostructures of the Au–CdSe nanoflowers on different length scales ranging from 10 nm to 100 microns. Assembly of Au nanocrystals within amorphous CdSe rods is found in the early stages of the growth of the Au–CdSe nanoflowers. The Au–CdSe nanoflowers are formed through a one-pot low temperature (150 °C) process where CdSe clusters are adsorbed on the surface of the Au cores, and they then start to form multiple arms and branches resulting in flower-shaped hybrid nanostructures. More complex assembly at a micron length scale can be achieved by means of bi-functional capping agents with appropriate alkyl chain lengths, such as 1,12-diaminododecane.

  4. Ag2S Quantum Dot-Sensitized Solar Cells by First Principles: The Effect of Capping Ligands and Linkers.

    Science.gov (United States)

    Amaya Suárez, Javier; Plata, Jose J; Márquez, Antonio M; Fernández Sanz, Javier

    2017-09-28

    Quantum dots solar cells, QDSCs, are one of the candidates for being a reliable alternative to fossil fuels. However, the well-studied CdSe and CdTe-based QDSCs present a variety of issues for their use in consumer-goods applications. Silver sulfide, Ag 2 S, is a promising material, but poor efficiency has been reported for QDSCs based on this compound. The potential influence of each component of QDSCs is critical and key for the development of more efficient devices based on Ag 2 S. In this work, density functional theory calculations were performed to study the nature of the optoelectronic properties for an anatase-TiO 2 (101) surface sensitized with different silver sulfide nanoclusters. We demonstrated how it is possible to deeply tune of its electronic properties by modifying the capping ligands and linkers to the surface. Finally, an analysis of the electron injection mechanism for this system is presented.

  5. Arm and neck pain in ultrasonographers.

    Science.gov (United States)

    Claes, Frank; Berger, Jan; Stassijns, Gaëtane

    2015-03-01

    The aim of this study was to evaluate the prevalence of upper-body-quadrant pain among ultrasonographers and to evaluate the association between individual ergonomics, musculoskeletal disorders, and occurrence of neck pain. A hundred and ten (N = 110) Belgian and Dutch male and female hospital ultrasonographers were consecutively enrolled in the study. Data on work-related ergonomic and musculoskeletal disorders were collected with an electronic inquiry, including questions regarding ergonomics (position of the screen, high-low table, and ergonomic chair), symptoms (neck pain, upper-limb pain), and work-related factors (consecutive working hours a day, average working hours a week). Subjects with the screen on their left had significantly more neck pain (odds ratio [OR] = 3.6, p = .0286). Depending on the workspace, high-low tables increased the chance of developing neck pain (OR = 12.9, p = .0246). A screen at eye level caused less neck pain (OR = .22, p = .0610). Employees with a fixed working space were less susceptible to arm pain (OR = 0.13, p = .0058). The prevalence of arm pain was significantly higher for the vascular department compared to radiology, urology, and gynecology departments (OR = 9.2, p = .0278). Regarding prevention of upper-limb pain in ultrasonograph, more attention should be paid to the work environment and more specialty to the ultrasound workstation layout. Primary ergonomic prevention could provide a painless work situation for the ultrasonographer. Further research on the ergonomic conditions of ultrasonography is necessary to develop ergonomic solutions in the work environment that will help to alleviate neck and arm pain. © 2014, Human Factors and Ergonomics Society.

  6. Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    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.

    2012-01-01

    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'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. Neck muscle fatigue alters the cervical flexion relaxation ratio in sub-clinical neck pain patients.

    Science.gov (United States)

    Zabihhosseinian, Mahboobeh; Holmes, Michael W R; Ferguson, Brad; Murphy, Bernadette

    2015-06-01

    The cervical flexion relaxation ratio is lower in neck pain patients compared to healthy controls. Fatigue modulates the onset and offset angles of the silent period in both the lumbar and cervical spine in healthy individuals; however, this response has not been studied with neck pain patients. The purpose of this study was to determine if cervical extensor fatigue would alter the parameters of the cervical flexion relaxation more in a neck pain group than a healthy control group. Thirteen healthy and twelve neck pain patients participated. Cervical extensor activity was examined bilaterally and kinematics of the neck and head were collected. An isometric, repetitive neck extension task at 70% of maximum elicited fatigue. Participants performed 3 trials of maximal cervical flexion both pre and post fatigue. The healthy controls and neck pain groups fatigued after 56 (41) and 39 (31) repetitions, respectively. There was a significant interaction effect for the flexion relaxation ratio between the control and neck pain groups from pre to post fatigue trials (F1,96=22.67, P=0.0001), but not for onset and offset angles (F1, 96=0.017, P=0.897), although the onset and offset angles did decrease significantly for both groups following fatigue (F1,96=9.26, P=0.002). Individuals with mild to moderate neck pain have significant differences in their neuromuscular control relative to controls, experienced myoelectric fatigue with fewer repetitions in a shorter time, had a lower cervical flexion relaxation ratio at baseline and had an inability to decrease this ratio further in response to fatigue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Regulating repression: roles for the sir4 N-terminus in linker DNA protection and stabilization of epigenetic states.

    Directory of Open Access Journals (Sweden)

    Stephanie Kueng

    Full Text Available Silent information regulator proteins Sir2, Sir3, and Sir4 form a heterotrimeric complex that represses transcription at subtelomeric regions and homothallic mating type (HM loci in budding yeast. We have performed a detailed biochemical and genetic analysis of the largest Sir protein, Sir4. The N-terminal half of Sir4 is dispensable for SIR-mediated repression of HM loci in vivo, except in strains that lack Yku70 or have weak silencer elements. For HM silencing in these cells, the C-terminal domain (Sir4C, residues 747-1,358 must be complemented with an N-terminal domain (Sir4N; residues 1-270, expressed either independently or as a fusion with Sir4C. Nonetheless, recombinant Sir4C can form a complex with Sir2 and Sir3 in vitro, is catalytically active, and has sedimentation properties similar to a full-length Sir4-containing SIR complex. Sir4C-containing SIR complexes bind nucleosomal arrays and protect linker DNA from nucleolytic digestion, but less effectively than wild-type SIR complexes. Consistently, full-length Sir4 is required for the complete repression of subtelomeric genes. Supporting the notion that the Sir4 N-terminus is a regulatory domain, we find it extensively phosphorylated on cyclin-dependent kinase consensus sites, some being hyperphosphorylated during mitosis. Mutation of two major phosphoacceptor sites (S63 and S84 derepresses natural subtelomeric genes when combined with a serendipitous mutation (P2A, which alone can enhance the stability of either the repressed or active state. The triple mutation confers resistance to rapamycin-induced stress and a loss of subtelomeric repression. We conclude that the Sir4 N-terminus plays two roles in SIR-mediated silencing: it contributes to epigenetic repression by stabilizing the SIR-mediated protection of linker DNA; and, as a target of phosphorylation, it can destabilize silencing in a regulated manner.

  9. Distributed Design of a Central Service to Ensure Deterministic Behavior

    Directory of Open Access Journals (Sweden)

    Imran Ali Jokhio

    2012-10-01

    Full Text Available A central authentication service to EPC (Electronic Product Code system architecture is proposed in our previous work. A challenge for a central service always arises that how it can ensure a certain level of delay while processing emergent data. The increasing data in the EPC system architecture is tags data. Therefore, authenticating increasing number of tag in the central authentication service with a deterministic time response is investigated and a distributed authentication service is designed in a layered approach. A distributed design of tag searching services in SOA (Service Oriented Architecture style is also presented. Using the SOA architectural style a self-adaptive authentication service over Cloud is also proposed for the central authentication service, that may also be extended for other applications.

  10. Standardization by ISO to Ensure the Sustainability of Space Activities

    Science.gov (United States)

    Kato, A.; Lazare, B.; Oltrogge, D.; Stokes, H.

    2013-08-01

    The ISO / Technical Committee 20 / Sub-committee 14 develops debris-related standards and technical reports to mitigate debris and help ensure mission and space sustainability. While UN Guidelines and the IADC Guidelines encourage national governments and agencies to promote debris mitigation design and operation, the ISO standards will help the global space industry promote and sustain its space-related business. In this paper the scope and status of each ISO standard is discussed within an overall framework. A comparison with international guidelines is also provided to demonstrate the level of consistency. Finally, as a case study, the ISO standards are applied to a CubeSat mission, thus demonstrating their usability on a relatively recent and popular class of satellite.

  11. Ensuring the safety of nuclear facilities located in large cities

    International Nuclear Information System (INIS)

    Ryazantsev, E.P.; Kolyadin, V.I.; Bylkin, B.K.; Zverkov, Yu.A.

    2002-01-01

    The problems of ensuring the safety of nuclear facilities and other facilities representing a radiation hazard (hereinafter referred to as 'nuclear facilities') which are located in large cities are considered in the light of the experience with the 'Kurchatov Institute' Russian Research Centre. The accumulation of substantial quantities of spent nuclear fuel and radwaste at the Centre was an inevitable consequence of the military and civilian nuclear research programmes which started there in 1943. A comprehensive programme has been developed for reducing the impact of ionizing radiation on the Centre's personnel, the population living near the Centre and the local environment. The authors describe the basic elements of a programme for decommissioning reactor facilities and eliminating spent fuel and radwaste storage sites and also describe how the programme is progressing. (author)

  12. Creative payment strategy helps ensure a future for teaching hospitals.

    Science.gov (United States)

    Vancil, D R; Shroyer, A L

    1998-11-01

    The Colorado Medicaid Program in years past relied on disproportionate share hospital (DSH) payment programs to increase access to hospital care for Colorado citizens, ensure the future financial viability of key safety-net hospitals, and partially offset the state's cost of funding the Medicaid program. The options to finance Medicaid care using DSH payments, however, recently have been severely limited by legislative and regulatory changes. Between 1991 and 1997, a creative Medicaid refinancing strategy called the major teaching hospital (MTH) payment program enabled $131 million in net payments to be distributed to the two major teaching hospitals in Colorado to provide enhanced funding related to their teaching programs and to address the ever-expanding healthcare needs of their low-income patients. This new Medicaid payment mechanism brought the state $69.5 million in Federal funding that otherwise would not have been received.

  13. frequency of ipsilateral femoral neck fractures in patients

    African Journals Online (AJOL)

    Background: Ipsilateral associated femoral neck and shaft fractures are reported to occur in 2.5-6% of all femoral shaft ... nailing of the shaft fracture, which makes treatment of the neck ... chest, spine), while the other had maxillofacial injuries.

  14. Neck Muscle Fatigue with Helmet-Mounted Systems

    National Research Council Canada - National Science Library

    Eveland, Edward S; Pellettiere, Joseph A

    2006-01-01

    .... Changes in neck muscle strength were identified along with EMG evidence of fatigue. When flights occurred on an almost daily basis over 4 days, the force imparted to the neck was reduced each day...

  15. Treatment of Childhood Head and Neck Cancer - Patient Version

    Science.gov (United States)

    Find diagnosis, staging, and treatment information for these head and neck cancers: hypopharynx, larynx, lip and oral cavity, neck cancer with occult primary, nasopharynx, oropharynx, paranasal sinus and nasal cavity, and salivary gland cancer.

  16. Treatment of Head and Neck Cancer in Adults - Patient Version

    Science.gov (United States)

    Find diagnosis, staging, and treatment information for these head and neck cancers: hypopharynx, larynx, lip and oral cavity, neck cancer with occult primary, nasopharynx, oropharynx, paranasal sinus and nasal cavity, and salivary gland cancer.

  17. PET-CT–Guided Surveillance of Head and Neck Cancers

    Science.gov (United States)

    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.

  18. Safety and excellence--is regulation ensuring their achievement

    International Nuclear Information System (INIS)

    Levesque, R.J.A.

    1992-01-01

    Canada has a large, vigorous nuclear industry staffed by competent people, and a vigourous, independent regulatory agency similarly staffed. Nevertheless, there have been many signs over the last few years that the level of operating and engineering excellence needed to ensure a high level of safety was not being achieved in some key sections of the industry. Years of successful, accident-free operation - a hallmark of Canadian nuclear generating stations - are not by themselves a proof of adequate safety. Signs that the level of excellence is not being met in the nuclear reactor business have been seen, for example, in reviews of significant events, in the standard of generating documentation, and in the time taken to implement necessary design modifications. In the radioisotope business, the number of violations of licence conditions has been growing steadily, and there are an unacceptable number of workers exceeding regulatory dose limits. While many of these violations are minor in themselves, their prevalence suggests a degree of complacency has been developing which will be an enemy of excellence. Equally, the level of review, assessment, inspection and confirmatory research carried out in the past by the Atomic Energy Control Board (AECB) has been clearly inadequate. The paper discusses these and other examples of a lack of excellence, particularly in organization and management within its licensees and its effect on safety,. and identifies some of the performance indicators used. The paper also identifies some of the actions that are being taken by the AECB and the licensees to ensure an adequate level of safety is being maintained. The AECB is increasing, for example, its frequency of inspections in several industrial sectors and increasing its depth of safety review of nuclear generating stations

  19. Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

    Science.gov (United States)

    de Wilde, Sofieke; de Jong, Maria G H; Le Brun, Paul P H; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

    2018-01-01

    Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical

  20. A clinical study on deep neck abscess

    International Nuclear Information System (INIS)

    Ota, Yumi; Ogawa, Yoshiko; Takemura, Teiji; Sawada, Toru

    2007-01-01

    Although various effective antibiotics have been synthesized, deep neck abscess is still a serious and life-threatening infection. It is important to diagnose promptly and treat adequately, and contrast-enhanced CT is useful and indispensable for diagnosis. We reviewed our patients with deep neck abscess, and analyzed the location by reviewing CT images, and discussed the treatment. Surgical drainage is a fundamental treatment for abscess but if it exists in only one area such as the parotid gland space, it can be cured with needle aspiration and suitable antibiotics. (author)

  1. Hyperparathyroidism following head and neck irradiation

    International Nuclear Information System (INIS)

    Rao, S.D.; Frame, B.; Miller, M.J.; Kleerskoper, M.; Block, M.A.; Parfitt, A.M.

    1980-01-01

    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

  2. Pediatric nontraumatic myositis ossificans of the neck

    Energy Technology Data Exchange (ETDEWEB)

    Kokkosis, Angela A. [Stony Brook University Medical Center, Stony Brook University School of Medicine, Stony Brook, NY (United States); Balsam, Dvorah [Stony Brook University Medical Center, Department of Radiology, Stony Brook, NY (United States); Lee, Thomas K. [Stony Brook University Medical Center, Department of Pediatric Surgery, Stony Brook, NY (United States); Schreiber, Z.J. [Stony Brook University Medical Center, Department of Pathology, Stony Brook, NY (United States)

    2009-04-15

    Nontraumatic myositis ossificans circumscripta (MOC) is a rarely reported benign heterotopic ossification characterized by the aberrant formation of bone in extraskeletal soft tissues. Although a history of trauma can be elicited in 75% of MOC patients, the etiology is unclear in patients without inciting injury. MOC is associated with young male athletes, and is most often localized to the muscle groups of the extremities. Rare cases have been reported in children and adolescents of nontraumatic MOC in the neck. We present a 15-year-old adolescent with a rapidly growing, painful neck mass without traumatic stimulus. (orig.)

  3. Complications of neck liposuction and submentoplasty.

    Science.gov (United States)

    Koehler, James

    2009-02-01

    Patients desiring improved neck and jawline contours often are looking for minimally invasive procedures and are not interested in undergoing extensive face-lifting procedures. Realizing the limitations, surgeons may offer their patient such procedures as liposuction and submentoplasty. Even though these procedures are less involved than a facelift, many pitfalls can occur, leading to an unfavorable result and a disappointed patient. Proper patient selection and choosing the correct operation are crucial to avoiding these situations. This article focuses on the common complications of neck liposuction and submentoplasty and reviews the management and avoidance of these complications.

  4. Hyperparathyroidism following head and neck irradiation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Pediatric nontraumatic myositis ossificans of the neck

    International Nuclear Information System (INIS)

    Kokkosis, Angela A.; Balsam, Dvorah; Lee, Thomas K.; Schreiber, Z.J.

    2009-01-01

    Nontraumatic myositis ossificans circumscripta (MOC) is a rarely reported benign heterotopic ossification characterized by the aberrant formation of bone in extraskeletal soft tissues. Although a history of trauma can be elicited in 75% of MOC patients, the etiology is unclear in patients without inciting injury. MOC is associated with young male athletes, and is most often localized to the muscle groups of the extremities. Rare cases have been reported in children and adolescents of nontraumatic MOC in the neck. We present a 15-year-old adolescent with a rapidly growing, painful neck mass without traumatic stimulus. (orig.)

  6. Are People With Whiplash-Associated Neck Pain Different from People With Nonspecific Neck Pain?

    DEFF Research Database (Denmark)

    Anstey, Ricci; Kongsted, Alice; Kamper, Steven

    2016-01-01

    Study Design Secondary analysis of a prospective cohort study with cross sectional and longitudinal analyses. Background The clinical importance of a history of whiplash associated disorder (WAD) in people with neck pain remains uncertain. Objective To compare people with WAD to people with non......-specific neck pain, in terms of their baseline characteristics, and pain and disability outcomes over 1 year. Methods Consecutive patients with neck pain presenting to a secondary care spine centre answered a comprehensive self-report questionnaire and underwent a physical examination. Patients were classified...

  7. Microencapsulation of Epoxidized Linseed Oil Liquid Cross-Linker in Poly(N-vinyl-pyrrolidone): Optimization by a Design-of-Experiments Approach

    NARCIS (Netherlands)

    Senatore, D.; Laven, J.; Benthem, van R.A.T.M.; La Camera, D.; With, de G.

    2010-01-01

    A liquid cross-linker, epoxidized linseed oil (ELO), was encapsulated in a plastic with a high glass transition temperature (poly(N-vinyl-2-pyrrolidone); PVP). The process parameters of the spray-drying employed were optimized by a Design-of-Experiments (DoE) approach. Three factors concerning both

  8. Modulation of procaspase-7 self-activation by PEST amino acid residues of the N-terminal prodomain and intersubunit linker.

    Science.gov (United States)

    Alves, Juliano; Garay-Malpartida, Miguel; Occhiucci, João M; Belizário, José E

    2017-12-01

    Procaspase-7 zymogen polypeptide is composed of a short prodomain, a large subunit (p20), and a small subunit (p10) connected to an intersubunit linker. Caspase-7 is activated by an initiator caspase-8 and -9, or by autocatalysis after specific cleavage at IQAD 198 ↓S located at the intersubunit linker. Previously, we identified that PEST regions made of amino acid residues Pro (P), Glu (E), Asp (D), Ser (S), Thr (T), Asn (N), and Gln (Q) are conserved flanking amino acid residues in the cleavage sites within a prodomain and intersubunit linker of all caspase family members. Here we tested the impact of alanine substitution of PEST amino acid residues on procaspase-7 proteolytic self-activation directly in Escherichia coli. The p20 and p10 subunit cleavage were significantly delayed in double caspase-7 mutants in the prodomain (N18A/P26A) and intersubunit linker (S199A/P201A), compared with the wild-type caspase-7. The S199A/P201A mutants effectively inhibited the p10 small subunit cleavage. However, the mutations did not change the kinetic parameters (k cat /K M ) and optimal tetrapeptide specificity (DEVD) of the purified mutant enzymes. The results suggest a role of PEST-amino acid residues in the molecular mechanism for prodomain and intersubunit cleavage and caspase-7 self-activation.

  9. Micromachined silicon acoustic delay line with 3D-printed micro linkers and tapered input for improved structural stability and acoustic directivity

    International Nuclear Information System (INIS)

    Cho, Y; Kumar, A; Xu, S; Zou, J

    2016-01-01

    Recent studies have shown that micromachined silicon acoustic delay lines can provide a promising solution to achieve real-time photoacoustic tomography without the need for complex transducer arrays and data acquisition electronics. To achieve deeper imaging depth and wider field of view, a longer delay time and therefore delay length are required. However, as the length of the delay line increases, it becomes more vulnerable to structural instability due to reduced mechanical stiffness. In this paper, we report the design, fabrication, and testing of a new silicon acoustic delay line enhanced with 3D printed polymer micro linker structures. First, mechanical deformation of the silicon acoustic delay line (with and without linker structures) under gravity was simulated by using finite element method. Second, the acoustic crosstalk and acoustic attenuation caused by the polymer micro linker structures were evaluated with both numerical simulation and ultrasound transmission testing. The result shows that the use of the polymer micro linker structures significantly improves the structural stability of the silicon acoustic delay lines without creating additional acoustic attenuation and crosstalk. In addition, the improvement of the acoustic acceptance angle of the silicon acoustic delay lines was also investigated to better suppress the reception of unwanted ultrasound signals outside of the imaging plane. These two improvements are expected to provide an effective solution to eliminate current limitations on the achievable acoustic delay time and out-of-plane imaging resolution of micromachined silicon acoustic delay line arrays. (paper)

  10. Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R- and (S-aminopropanediol as an acyclic linker

    Directory of Open Access Journals (Sweden)

    Daniel Lachmann

    2010-02-01

    Full Text Available The Nile Blue chromophore was incorporated into oligonucleotides using “click” chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R-3-amino-1,2-propanediol was applied as the linker between the phosphodiester bridges. Two sets of DNA duplexes were prepared. One set carried the chromophore in an A-T environment, the second set in a G-C environment. Both were characterized by optical spectroscopy. Sequence-dependent fluorescence quenching was applied as a sensitive tool to compare the stacking interactions with respect to the chirality of the acyclic linker attachment. The results were compared to recent results from duplexes that carried the Nile Blue label in a sequentially and structurally identical context, except for the opposite chirality of the linker ((S-3-amino-1,2-propandiol. Only minor, negligible differences were observed. Melting temperatures, UV–vis absorption spectra together with fluorescence quenching data indicate that Nile Blue stacks perfectly between the adjacent base pairs regardless of whether it has been attached via an S- or R-configured linker. This result was supported by geometrically optimized DNA models.

  11. Radioiodination of protein using 2,3,5,6-tetrafluorophenyl 3-(nido-carboranyl) propionate (TCP) as a potential bi-functional linker: Synthesis and biodistribution in mice

    International Nuclear Information System (INIS)

    Lin Rushan; Liu Ning; Yang Yuanyou; Li Bing; Liao Jiali; Jin Jiannan

    2009-01-01

    2,3,5,6-Tetrafluorophenyl 3-(nido-carboranyl) propionate (TCP), as a new potential bi-functional linker for radiohalogenation of proteins or peptides, was synthesized. With this bi-functional linker, the first attempt to conjugate bovine serum albumin (BSA) with 125 I was made and the biodistribution of the conjugated BSA ( 125 I-TCP-BSA) was investigated in NIH strain mice. By the use of TCP as the linker, BSA was conjugated with 125 I in a labeling yield of 58-75% and with radiochemical purity of 99.8% after purification by Sephadex TM G-50. Even after being kept at room temperature for 72 h, the radiochemical purity of 125 I-TCP-BSA was still more than 98%, much higher than that of the directly 125 I-labeled BSA ( 125 I-BSA). Meanwhile, biodistribution experiments in mice indicated that the uptake of 125 I with 125 I-TCP-BSA into thyroid was obviously less than that with 125 I-BSA post-injection. All the results implied that the 125 I-conjugated BSA ( 125 I-TCP-BSA) was considerably stable in vivo as well as in vitro, and TCP was regarded as a promising bi-functional linker for radiohalogenation of proteins

  12. Traceless Azido Linker for the Solid-Phase Synthesis of NH-1,2,3-Triazoles via Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions

    DEFF Research Database (Denmark)

    Cohrt, Anders Emil; Jensen, Jakob Feldthusen; Nielsen, Thomas Eiland

    2010-01-01

    A broadly useful acid-labile traceless azido linker for the solid-phase synthesis of NH-1,2,3-triazoles is presented. A variety of alkynes were efficiently immobilized on a range of polymeric supports by Cu(I)-mediated azide-alkyne cycloadditions. Supported triazoles showed excellent compatibility...

  13. The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid-labile handle for solid-phase synthesis

    DEFF Research Database (Denmark)

    Boas, Ulrik; Brask, Jesper; Christensen, J.B.

    2002-01-01

    The tris(alkoxy)benzyl backbone amide linker (BAL) has found widespread application in solid-phase synthesis. The key intermediate for preparation of para BAL (p-BAL) is 2,6-dimethoxy-4-hydroxybenzaldehyde; several reports on its synthesis have appeared. However, the ortho analogue of the handle (o...

  14. Diols and anions can control the formation of an exciplex between a pyridinium boronic acid with an aryl group connected via a propylene linker.

    Science.gov (United States)

    Huang, Yan-Jun; Jiang, Yun-Bao; Bull, Steven D; Fossey, John S; James, Tony D

    2010-11-21

    The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of its cation-π stacking interaction causing a four-fold fluorescence enhancement.

  15. Doxorubicin conjugation and drug linker chemistry alter the intravenous and pulmonary pharmacokinetics of a PEGylated Generation 4 polylysine dendrimer in rats.

    Science.gov (United States)

    Leong, Nathania J; Mehta, Dharmini; McLeod, Victoria M; Kelly, Brian D; Pathak, Rashmi; Owen, David J; Porter, Christopher Jh; Kaminskas, Lisa M

    2018-05-28

    PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumours from the blood and highly selective, yet rapid liberation in the tumour microenvironment. This study sought to characterise how the nature of cathepsin B cleavable peptide linkers, used to conjugate doxorubicin to a PEGylated (PEG570) G4 polylysine dendrimer, affect drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats. The construct bearing a self-emolative diglycolic acid-V-Citrulline linker exhibited faster doxorubicin release kinetics compared to constructs bearing self emolative diglycolic acid-GLFG, or non-self emolative glutaric acid-GLFG linkers. The V-Citrulline construct exhibited slower plasma clearance, but faster absorption from the lungs than a GLFG construct, although mucociliary clearance and urinary elimination were unchanged. Doxorubicin-conjugation enhanced localisation in the bronchoalveolar lavage fluid compared to lung tissue, suggesting that projection of doxorubicin from the dendrimer surface reduced tissue uptake. These data show that the linker chemistry employed to conjugate drugs to PEGylated carriers can affect drug release profiles and systemic and lung disposition. Copyright © 2018. Published by Elsevier Inc.

  16. Synthesis of highly fluorescent and thio-linkers stabilize gold quantum dots and nano clusters in DMF for bio-labeling

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Shiva K., E-mail: srastogi@uidaho.edu [University of Idaho, Department of Chemistry (United States); Denn, Benjamin D.; Branen, A. Larry [University of Idaho, Coeur D' Alene, Biosensors and Nanotechnology Application Laboratory (BNAL) (United States)

    2012-01-15

    This study demonstrates a one versus two-step synthesis of fluorescent gold quantum dots (F-AuQDs) and nano clusters (F-AuNCs) functionalized with thiolated organic linkers using reduction of gold precursor in N,N Prime -dimethylformamide in 1 h of reaction. The F-AuQDs and F-AuNCs show fluorescence emission at 425 {+-} 5 nm upon excitation at 345 {+-} 5 nm of wavelength, with good water solubility and stability. Five different thiolated organic binary linkers consisting of various functional groups including: carboxylic acid, hydroxyl, and aromatic amine, were conjugated with the F-AuQDs and F-AuNCs. The formation mechanism and functionalization of the F-AuQDs and F-AuNCs was characterized using UV-vis absorption spectra, UV-vis light, fluorescent emission spectra, pH, TEM, and FTIR. The fluorescence emission of the F-AuQDs and F-AuNCs is greatly dependent on the thio-linker. This novel one-step approach provides facile and fast synthesis of F-AuQDs and F-AuNCs over the two-step method, with less than 5 h of reaction and workup compared to more than 28 h of reaction for the two-step approach. These thio-linker functionalized F-AuQDs and F-AuNCs have a wide application in fluorescent labeling of biomolecules, optical devices, imaging, energy transfer, and biosensing.

  17. Desorption of 3,3′-diindolylmethane from imprinted particles: An impact of cross-linker structure on binding capacity and selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Klejn, Dorota; Luliński, Piotr; Maciejewska, Dorota, E-mail: dorota.maciejewska@wum.edu.pl

    2015-11-01

    Here, seven cross-linkers (six polar diacrylates or dimethacrylates of different lengths between double bonds, and one aromatic-divinylbenzene) were used to examine the impact of the cross-linker on binding capacity and selectivity of 3,3′-diindolylmethane (DIM) imprinted material. DIM participates in the suppression of viability of human ovarian and human breast cancer cell lines, but has low bioavailability. The investigations of novel imprinted polymer matrices for improvement of DIM release could allow to utilize not only a potency of DIM but also similar alkaloids, which are the important compounds with pharmacological activity. The bulk, thermal radical copolymerization of the cross-linkers in the presence of 3,3′-diindolylmethane (the template) and allylamine (the functional monomer) in dimethyl sulfoxide or in carbon tetrachloride (porogens) was carried out. The binding capacities of imprinted and non-imprinted polymers were compared, and two polymers (these were prepared using ethylene glycol dimethacrylate and polyethylene glycol dimethacrylate as the cross-linkers) with the highest selectivity and binding capacity were selected to desorption test. The desorption profile of polymer prepared using polyethylene glycol dimethacrylate as the cross-linker revealed sustained release of 3,3′-diindolylmethane, and this system was selected for further optimization of the cross-linker amounts. The morphology and structure of the selected particles were analyzed using SEM micrographs, {sup 13}C CP/MAS NMR spectroscopy, and BET measurements. The desorption of 3,3′-diindolylmethane from poly(allylamine-co-polyethylene glycol dimethacrylate) particles was in accordance with pseudo-second-order kinetics and the simplified Higuchi model indicated the diffusion controlled release of 3,3′-diindolylmethane. - Graphical abstract: Sustained release of 3,3′-diindolylmethane from cavity in imprinted poly(allylamine-co-polyethylene glycol dimethacrylate

  18. The Effects of Anchor Groups on (1) TiO2-Catalyzed Photooxidation and (2) Linker-Assisted Assembly on TiO2

    Science.gov (United States)

    Anderson, Ian Mark

    Quantum dot-sensitized solar cells (QDSSCs) are a popular target for research due to their potential for highly efficient, easily tuned absorption. Typically, light is absorbed by quantum dots attached to a semiconductor substrate, such as TiO2, via bifunctional linker molecules. This research aims to create a patterned monolayer of linker molecules on a TiO2 film, which would in turn allow the attachment of a patterned layer of quantum dots. One method for the creation of a patterned monolayer is the functionalization of a TiO2 film with a linker molecule, followed by illumination with a laser at 355 nm. This initiates a TiO 2-catalyzed oxidation reaction, causing loss of surface coverage. A second linker molecule can then be adsorbed onto the TiO2 surface in the illuminated area. Towards that end, the behaviors of carboxylic and phosphonic acids adsorbed on TiO2 have been studied. TiO2 films were functionalized by immersion in solutions a single adsorbate and surface coverage was determined by IR spectroscopy. It is shown that phosphonic acids attain higher surface coverage than carboxylic acids, and will displace them from TiO2 when in a polar solvent. Alkyl chain lengths, which can influence stabilities of monolayers, are shown not to have an effect on this relationship. Equilibrium binding data for the adsorption of n-hexadecanoic acid to TiO2 from a THF solution are presented. It is shown that solvent polarity can affect monolayer stability; carboxylates and phosphonates undergo more desorption into polar solvents than nonpolar. Through illumination, it was possible to remove nearly all adsorbed linkers from TiO2. However, the illuminated areas were found not to be receptive to attachment by a second adsorbate. A possible reason for this behavior is presented. I also report on the synthesis and characterization of a straight-chain, thiol-terminated phosphonic acid. Initial experiments involving monolayer formation and quantum dot attachment are presented

  19. Desorption of 3,3′-diindolylmethane from imprinted particles: An impact of cross-linker structure on binding capacity and selectivity

    International Nuclear Information System (INIS)

    Klejn, Dorota; Luliński, Piotr; Maciejewska, Dorota

    2015-01-01

    Here, seven cross-linkers (six polar diacrylates or dimethacrylates of different lengths between double bonds, and one aromatic-divinylbenzene) were used to examine the impact of the cross-linker on binding capacity and selectivity of 3,3′-diindolylmethane (DIM) imprinted material. DIM participates in the suppression of viability of human ovarian and human breast cancer cell lines, but has low bioavailability. The investigations of novel imprinted polymer matrices for improvement of DIM release could allow to utilize not only a potency of DIM but also similar alkaloids, which are the important compounds with pharmacological activity. The bulk, thermal radical copolymerization of the cross-linkers in the presence of 3,3′-diindolylmethane (the template) and allylamine (the functional monomer) in dimethyl sulfoxide or in carbon tetrachloride (porogens) was carried out. The binding capacities of imprinted and non-imprinted polymers were compared, and two polymers (these were prepared using ethylene glycol dimethacrylate and polyethylene glycol dimethacrylate as the cross-linkers) with the highest selectivity and binding capacity were selected to desorption test. The desorption profile of polymer prepared using polyethylene glycol dimethacrylate as the cross-linker revealed sustained release of 3,3′-diindolylmethane, and this system was selected for further optimization of the cross-linker amounts. The morphology and structure of the selected particles were analyzed using SEM micrographs, 13 C CP/MAS NMR spectroscopy, and BET measurements. The desorption of 3,3′-diindolylmethane from poly(allylamine-co-polyethylene glycol dimethacrylate) particles was in accordance with pseudo-second-order kinetics and the simplified Higuchi model indicated the diffusion controlled release of 3,3′-diindolylmethane. - Graphical abstract: Sustained release of 3,3′-diindolylmethane from cavity in imprinted poly(allylamine-co-polyethylene glycol dimethacrylate). - Highlights:

  20. The variation of the strength of neck extensor muscles and semispinalis capitis muscle size with head and neck position.

    Science.gov (United States)

    Rezasoltani, A; Nasiri, R; Faizei, A M; Zaafari, G; Mirshahvelayati, A S; Bakhshidarabad, L

    2013-04-01

    Semispinalis capitis muscle (SECM) is a massive and long cervico-thoracic muscle which functions as a main head and neck extensor muscle. The aim of this study was to detect the effect of head and neck positions on the strength of neck extensor muscles and size of SECM in healthy subjects. Thirty healthy women students voluntarily participated in this study. An ultrasonography apparatus (Hitachi EUB 525) and a system of tension-meter were used to scan the right SECM at the level of third cervical spine and to measure the strength of neck extensor muscles at three head and neck positions. Neck extensor muscles were stronger in neutral than flexion or than extension positions while the size of SECM was larger in extension than neutral or than flexion position. The force generation capacity of the main neck extensor muscle was lower at two head and neck flexion and extension positions than neutral position. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Neck Pain in Military Helicopter Pilots: Prevalence and Associated Factors

    NARCIS (Netherlands)

    van den Oord, Marieke H. A. H.; de Loose, Veerle; Meeuwsen, Ted; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

    2010-01-01

    Our aim is to estimate the self-reported one-year prevalence of neck pain in military helicopter pilots and to compare work-related, individual, and health-related factors in the pilots with (neck pain group) and without (reference group) regular or continuous neck pain. A questionnaire was

  2. Neck injury tolerance under inertial loads in side impacts.

    Science.gov (United States)

    McIntosh, Andrew S; Kallieris, Dimitrios; Frechede, Bertrand

    2007-03-01

    Neck injury remains a major issue in road safety. Current side impact dummies and side impact crashworthiness assessments do not assess the risk of neck injury. These assessments are limited by biofidelity and knowledge regarding neck injury criteria and tolerance levels in side impacts. Side impact tests with PMHS were performed at the Heidelberg University in the 1980s and 1990s to improve primarily the understanding of trunk dynamics, injury mechanisms and criteria. In order to contribute to the definition of human tolerances at neck level, this study presents an analysis of the head/neck biomechanical parameters that were measured in these tests and their relationship to neck injury severity. Data from 15 impact tests were analysed. Head accelerations, and neck forces and moments were calculated from 9-accelerometer array head data, X-rays and anthropometric data. Statistically significant relationships were observed between resultant head acceleration and neck force and neck injury severity. The average resultant head acceleration for AIS 2 neck injuries was 112 g, while resultant neck force was 4925 N and moment 241 Nm. The data compared well to other test data on cadavers and volunteers. It is hoped that the paper will assist in the understanding of neck injuries and the development of tolerance criteria.

  3. Topographic Pattern Distribution of Head And Neck Squamous Cell ...

    African Journals Online (AJOL)

    FINEPRINT

    value of 71% of SCC in Turkey. Nevertheless a similar report documented a relatively lower value especially in. Yemen where head and neck SCC constituted only 8% of all head and neck cancers. Reports from Yemen revealed that oral cavity SCC was the most common topographic site of all head and. 3 neck cancers.

  4. Neck sprain after motor vehicle accidents in drivers and passengers

    NARCIS (Netherlands)

    Versteegen, GJ; Kingma, J; Meijler, WJ; ten Duis, HJ

    2000-01-01

    Neck sprain is a general term denoting a soft tissue injury of the neck, which seldom causes major disability but is considered a modem epidemic. The purpose of the present study was to determine the prevalence of sprain of the neck injury due to motor vehicle accidents (MVAs) in both drivers and

  5. Effect of neck warming and cooling on thermal comfort

    Science.gov (United States)

    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.

  6. Prevention of flight-related neck pain in military aircrew

    NARCIS (Netherlands)

    van den Oord, M.H.A.H.

    2012-01-01

    Military pilots and rear aircrew members are occupations with several occupational exposures that might cause neck pain. In addition to the negative impact of neck pain on health, safety is one of the main concerns for the military aviation, because neck pain may interfere with flying performance.

  7. Shoulder morbidity after non-surgical treatment of the neck.

    NARCIS (Netherlands)

    van Wouwe, V.; de Bree, R.; Kuik, D.J.; de Goede, C.J.T.; de Leeuw, I.M.; Leemans, C.R.

    2009-01-01

    Background and purpose: Reports on shoulder function after non-surgical treatment are not available. In the present study shoulder morbidity after surgical and non-surgical treatment of the neck is determined and compared. Materials and methods: In 100 head and neck cancer patients 174 neck sides

  8. Failure pattern and salvage treatment after radical treatment of head and neck cancer

    DEFF Research Database (Denmark)

    Pagh, Anja; Grau, Cai; Overgaard, Jens

    2016-01-01

    Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal...... recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T...

  9. Structural and Functional Analysis of the Signal-Transducing Linker in the pH-Responsive One-Component System CadC of Escherichia coli.

    Science.gov (United States)

    Buchner, Sophie; Schlundt, Andreas; Lassak, Jürgen; Sattler, Michael; Jung, Kirsten

    2015-07-31

    The pH-responsive one-component signaling system CadC in Escherichia coli belongs to the family of ToxR-like proteins, whose members share a conserved modular structure, with an N-terminal cytoplasmic winged helix-turn-helix DNA-binding domain being followed by a single transmembrane helix and a C-terminal periplasmic pH-sensing domain. In E. coli CadC, a cytoplasmic linker comprising approximately 50 amino acids is essential for transmission of the signal from the sensor to the DNA-binding domain. However, the mechanism of transduction is poorly understood. Using NMR spectroscopy, we demonstrate here that the linker region is intrinsically disordered in solution. Furthermore, mutational analyses showed that it tolerates a range of amino acid substitutions (altering polarity, rigidity and α-helix-forming propensity), is robust to extension but is sensitive to truncation. Indeed, truncations either reversed the expression profile of the target operon cadBA or decoupled expression from external pH altogether. CadC dimerizes via its periplasmic domain, but light-scattering analysis provided no evidence for dimerization of the isolated DNA-binding domain, with or without the linker region. However, bacterial two-hybrid analysis revealed that CadC forms stable dimers in a stimulus- and linker-dependent manner, interacting only at pHpH. Thus, we propose that the disordered CadC linker is required for transducing the pH-dependent response of the periplasmic sensor into a structural rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding domain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Unusual and highly tunable missing-linker defects in zirconium metal-organic framework UiO-66 and their important effects on gas adsorption.

    Science.gov (United States)

    Wu, Hui; Chua, Yong Shen; Krungleviciute, Vaiva; Tyagi, Madhusudan; Chen, Ping; Yildirim, Taner; Zhou, Wei

    2013-07-17

    UiO-66 is a highly important prototypical zirconium metal-organic framework (MOF) compound because of its excellent stabilities not typically found in common porous MOFs. In its perfect crystal structure, each Zr metal center is fully coordinated by 12 organic linkers to form a highly connected framework. Using high-resolution neutron power diffraction technique, we found the first direct structural evidence showing that real UiO-66 material contains significant amount of missing-linker defects, an unusual phenomenon for MOFs. The concentration of the missing-linker defects is surprisingly high, ∼10% in our sample, effectively reducing the framework connection from 12 to ∼11. We show that by varying the concentration of the acetic acid modulator and the synthesis time, the linker vacancies can be tuned systematically, leading to dramatically enhanced porosity. We obtained samples with pore volumes ranging from 0.44 to 1.0 cm(3)/g and Brunauer-Emmett-Teller surface areas ranging from 1000 to 1600 m(2)/g, the largest values of which are ∼150% and ∼60% higher than the theoretical values of defect-free UiO-66 crystal, respectively. The linker vacancies also have profound effects on the gas adsorption behaviors of UiO-66, in particular CO2. Finally, comparing the gas adsorption of hydroxylated and dehydroxylated UiO-66, we found that the former performs systematically better than the latter (particularly for CO2) suggesting the beneficial effect of the -OH groups. This finding is of great importance because hydroxylated UiO-66 is the practically more relevant, non-air-sensitive form of this MOF. The preferred gas adsorption on the metal center was confirmed by neutron diffraction measurements, and the gas binding strength enhancement by the -OH group was further supported by our first-principles calculations.

  11. Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

    Science.gov (United States)

    Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

    2010-11-12

    Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

  12. Neck pain and disability due to neck pain: what is the relation?

    DEFF Research Database (Denmark)

    Fejer, René; Hartvigsen, Jan

    2008-01-01

    Pain and disability are interrelated, but the relationship between pain and disability is not straightforward. The objective of this study was to investigate the relationship between neck pain (NP) intensity, NP duration, and disability based on the population-based 'Funen Neck and Chest Pain......' study. Pain intensity was measured using 11-box numerical rating scales, pain duration was measured using the Standardized Nordic Questionnaire, and disability was measured by the Copenhagen Neck Functional Disability Scale. Spearman rank correlation coefficients and logistic regression analyses were...... used to measure correlations and strength of associations between pain intensity, pain duration, and disability given domain specific characteristics (socioeconomic, health and physical, comorbidity, and variables related to consequences of NP). Neck pain was very common, but mainly mild and did...

  13. Radiation processing of leafy vegetables to ensure their microbial safety

    International Nuclear Information System (INIS)

    Khade, H.D.; Jain, M.P.; Satyendra, Gautam

    2015-01-01

    Leafy vegetables which are consumed in raw form such as spinach, coriander and mint were found to be heavily burdened with microbial load including presumptive coliform, an indicator of pathogenic contaminations. Total aerobic plate counts in fresh spinach, coriander and mint samples collected from different location of Mumbai and nearby cities were found to be in the order of ∼ 10 7 to ∼ 10 8 CFU/g. In these samples yeast and mould count was in the order of ∼10 5 CFU/g and presumptive coliform in the order of ∼ 10 4 to ∼10 5 CFU/g. As per USFDA coliform load in the food commodity should be nil. The finding thus indicates that these fresh vegetables are not safe for raw consumption. Hence there is utmost need of process which can ensure the safety by reducing their microbial load below permissible level (<10 4 CFU/gm) and coliform load to nil without affecting the appearance and quality of such produce. In this study gamma radiation was used for hygienization of leafy vegetables. The sample were first cleaned in potable water followed by sodium hypochlorite wash (200 ppm for 20 min), air dried, packed in styrofoam based tray, wrapped with cling film and radiation processed at 1 to 2.5 kGy and stored at 4 and 10℃ . Post irradiation microbiological analysis of radiation processed samples was carried out at in 2 kGy irradiated samples total plate count was below ∼10 3 CFU/g and presumptive coliform count was below detectable level. Yeast and mould count in these samples also reduced to below ∼ 10 3 CFU/g. Based on the study the following combination treatment can be given to raw leafy vegetables, washing with potable water (5 min) → sodium hypochlorite (200 ppm 20 min) wash → Air drying → Packaging in styrofoam based tray and wrapping with cling film → Irradiation at 2 kGy → storage at 4℃ . Besides ensuring safety the treatment also resulted in increased shelf life extension of the commodities up to 20 days. (author)

  14. Isolated Enteric Cyst in the Neck

    Directory of Open Access Journals (Sweden)

    Amit Mahore

    2014-01-01

    Full Text Available We report an extremely rare case of isolated enteric cyst in the neck region which was diagnosed on the histopathological examination. It was suspected to be duplication cyst on radiology. We have also evaluated the differential diagnosis and management issues.

  15. Fibrous dysplasia of the femoral neck

    International Nuclear Information System (INIS)

    Savage, P.E.; Stoker, D.J.

    1984-01-01

    Fibrous dysplasia of the femur is usually observed in the intertrochanteric region. It is rarely confined to the femoral neck. We present four cases illustrating the radiographic appearance and spectrum of this condition which all showed the relatively lucent variety of fibrous dysplasia with varying degrees of expansion and surrounding sclerosis. The natural history of this condition is discussed. (orig.)

  16. Manipulation or Mobilisation for Neck Pain

    NARCIS (Netherlands)

    Gross, Anita; Miller, Jordan; D'Sylva, Jonathan; Burnie, Stephen J.; Goldsmith, Charles H.; Graham, Nadine; Haines, Ted; Brønfort, Gert; Hoving, Jan L.

    2010-01-01

    Background Manipulation and mobilisation are often used, either alone or combined with other treatment approaches, to treat neck pain. Objectives To assess if manipulation or mobilisation improves pain, function/disability, patient satisfaction, quality of life, and global perceived effect in adults

  17. Management of common head and neck masses.

    Science.gov (United States)

    Tracy, Thomas F; Muratore, Christopher S

    2007-02-01

    Head and neck masses are a common clinical concern in infants, children, and adolescents. The differential diagnosis for a head or neck mass includes congenital, inflammatory, and neoplastic lesions. An orderly and thorough examination of the head and neck with an appropriate directed workup will facilitate the diagnosis. The most common entities occur repeatedly within the various age groups and can be differentiated with a clear understanding of embryology and anatomy of the region, and an understanding of the natural history of a specific lesion. Congenital lesions most commonly found in the pediatric population include the thyroglossal duct cyst and the branchial cleft and arch anomalies. The inflammatory masses are secondary to local or systemic infections. The most common etiology for cervical adenopathy in children is reactive lymphadenopathy following a viral or bacterial illness. Persistent adenopathy raises more concerns, especially enlarged lymph nodes within the posterior triangle or supraclavicular space, nodes that are painless, firm, and not mobile, or a single dominant node that persists for more than 6 weeks should all heighten concern for malignancy. In this review, we discuss the current principles of surgical management of the most common head and neck masses that present to pediatricians and pediatric surgeons.

  18. Cystic malformations of the neck in children

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2005-05-01

    The most common cystic malformations of the neck are the result of abnormal embryogenesis involving the thyroglossal duct (TGD), lymphatic primordia and the branchial apparatus. When the basic embryology of these structures is considered, a reasonable differential diagnosis - and in some cases a definitive diagnosis - can be achieved based on the location and the imaging characteristics of the cystic mass. (orig.)

  19. Cystic malformations of the neck in children

    International Nuclear Information System (INIS)

    Koch, Bernadette L.

    2005-01-01

    The most common cystic malformations of the neck are the result of abnormal embryogenesis involving the thyroglossal duct (TGD), lymphatic primordia and the branchial apparatus. When the basic embryology of these structures is considered, a reasonable differential diagnosis - and in some cases a definitive diagnosis - can be achieved based on the location and the imaging characteristics of the cystic mass. (orig.)

  20. The Funen Neck and Chest Pain study

    DEFF Research Database (Denmark)

    Fejer, René; Hartvigsen, Jan; Kyvik, Kirsten Ohm

    2006-01-01

    OBJECTIVE: To describe the Funen Neck and Chest Pain (FNCP) study and carry out a comprehensive non-response analysis of the quality of the survey. METHODS: The FNCP questionnaire was sent out to 7000 randomly selected individuals aged 20-71 years living in Funen County, Denmark. A full description...

  1. Head And Neck Rhabdomyosacroma In Childhood: An ...

    African Journals Online (AJOL)

    Background: Rhabdomyosarcoma may be histologically indistinguishable from other undifferentiated childhood tumours occurring in the head and neck region on routine heamatoxylin and eosin staining. Aim: aimed at assessing the usefulness of employing immunohistochemistry, as an adjunct to routine H&E staining, ...

  2. BLADDER NECK RESECTION WITH PRESERVATION OF ...

    African Journals Online (AJOL)

    Conclusion The complication of retrograde ejaculation in young patients who are in need of fertililty may be avoided by preservation of > 1 cm of the supramontanal part during bladder neck resection. La Résection du Col de Vessie avec Préservation de l'Ejaculation Antégrade Objectif Evaluer une nouvelle méthode de ...

  3. Target definition in prostate, head, and neck

    NARCIS (Netherlands)

    Rasch, Coen; Steenbakkers, Roel; van Herk, Marcel

    2005-01-01

    Target definition is a major source of errors in both prostate and head and neck external-beam radiation treatment. Delineation errors remain constant during the course of radiation and therefore have a large impact on the dose to the tumor. Major sources of delineation variation are visibility of

  4. AN APPROACH TO THE NECK MASS

    African Journals Online (AJOL)

    Enrique

    thirds of the neck respectively. Level V contains the nodes in the posterior tri- angle. These are ... Level VI lies between the carotid sheaths in the anterior ... over 40 years of age. ... This brings us back ..... is often necessary for the classification.

  5. Shoulder complaints after nerve sparing neck dissections

    NARCIS (Netherlands)

    van Wilgen, CP; Dijkstra, PU; van der Laan, BFAM; Plukker, JTM; Roodenburg, JLN

    The purpose of the study was to analyse the prevalence of shoulder complaints after nerve sparing neck dissection at least I year after surgery, and to analyse the influence of radiation therapy on shoulder complaints. Patients were interviewed for shoulder complaints, and patients filled out the

  6. 49 CFR 572.183 - Neck assembly.

    Science.gov (United States)

    2010-10-01

    ... midsagittal plane of the neck-headform assembly is vertical and perpendicular to the plane of motion of the... history of the pendulum falls inside the corridor determined by the upper and lower boundaries specified... maximum rotation in the lateral direction of the reference plane of the headform (175-9000) as shown in...

  7. Oral sequelae of head and neck radiotherapy

    NARCIS (Netherlands)

    Vissink, A; Jansma, J; Spijkervet, FKL; Burlage, FR; Coppes, RP

    In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e. g., salivary glands, oral mucosa, bone, dentition,

  8. Quantitative Ultrasonic Nakagami Imaging of Neck Fibrosis After Head and Neck Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaofeng [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Yoshida, Emi [Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (United States); Cassidy, Richard J.; Beitler, Jonathan J.; Yu, David S.; Curran, Walter J. [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Tian, E-mail: tliu34@emory.edu [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2015-06-01

    Purpose: To investigate the feasibility of ultrasound Nakagami imaging to quantitatively assess radiation-induced neck fibrosis, a common sequela of radiation therapy (RT) to the head and neck. Methods and Materials: In a pilot study, 40 study participants were enrolled and classified into 3 subgroups: (1) a control group of 12 healthy volunteers; (2) an asymptomatic group of 11 patients who had received intensity modulated RT for head and neck cancer and had experienced no neck fibrosis; and (3) a symptomatic group of 17 post-RT patients with neck fibrosis. Each study participant underwent 1 ultrasound study in which scans were performed in the longitudinal orientation of the bilateral neck. Three Nakagami parameters were calculated to quantify radiation-induced tissue injury: Nakagami probability distribution function, shape, and scaling parameters. Physician-based assessments of the neck fibrosis were performed according to the Radiation Therapy Oncology Group late morbidity scoring scheme, and patient-based fibrosis assessments were rated based on symptoms such as pain and stiffness. Results: Major discrepancies existed between physician-based and patient-based assessments of radiation-induced fibrosis. Significant differences in all Nakagami parameters were observed between the control group and 2 post-RT groups. Moreover, significant differences in Nakagami shape and scaling parameters were observed among asymptomatic and symptomatic groups. Compared with the control group, the average Nakagami shape parameter value increased by 32.1% (P<.001), and the average Nakagami scaling parameter increased by 55.7% (P<.001) for the asymptomatic group, whereas the Nakagami shape parameter increased by 74.1% (P<.001) and the Nakagami scaling parameter increased by 83.5% (P<.001) for the symptomatic group. Conclusions: Ultrasonic Nakagami imaging is a potential quantitative tool to characterize radiation-induced asymptomatic and symptomatic neck fibrosis.

  9. Quantitative Ultrasonic Nakagami Imaging of Neck Fibrosis After Head and Neck Radiation Therapy

    International Nuclear Information System (INIS)

    Yang, Xiaofeng; Yoshida, Emi; Cassidy, Richard J.; Beitler, Jonathan J.; Yu, David S.; Curran, Walter J.; Liu, Tian

    2015-01-01

    Purpose: To investigate the feasibility of ultrasound Nakagami imaging to quantitatively assess radiation-induced neck fibrosis, a common sequela of radiation therapy (RT) to the head and neck. Methods and Materials: In a pilot study, 40 study participants were enrolled and classified into 3 subgroups: (1) a control group of 12 healthy volunteers; (2) an asymptomatic group of 11 patients who had received intensity modulated RT for head and neck cancer and had experienced no neck fibrosis; and (3) a symptomatic group of 17 post-RT patients with neck fibrosis. Each study participant underwent 1 ultrasound study in which scans were performed in the longitudinal orientation of the bilateral neck. Three Nakagami parameters were calculated to quantify radiation-induced tissue injury: Nakagami probability distribution function, shape, and scaling parameters. Physician-based assessments of the neck fibrosis were performed according to the Radiation Therapy Oncology Group late morbidity scoring scheme, and patient-based fibrosis assessments were rated based on symptoms such as pain and stiffness. Results: Major discrepancies existed between physician-based and patient-based assessments of radiation-induced fibrosis. Significant differences in all Nakagami parameters were observed between the control group and 2 post-RT groups. Moreover, significant differences in Nakagami shape and scaling parameters were observed among asymptomatic and symptomatic groups. Compared with the control group, the average Nakagami shape parameter value increased by 32.1% (P<.001), and the average Nakagami scaling parameter increased by 55.7% (P<.001) for the asymptomatic group, whereas the Nakagami shape parameter increased by 74.1% (P<.001) and the Nakagami scaling parameter increased by 83.5% (P<.001) for the symptomatic group. Conclusions: Ultrasonic Nakagami imaging is a potential quantitative tool to characterize radiation-induced asymptomatic and symptomatic neck fibrosis

  10. Why sauropods had long necks; and why giraffes have short necks

    OpenAIRE

    Taylor, Michael P.; Wedel, Mathew J.

    2013-01-01

    The necks of the sauropod dinosaurs reached 15 m in length: six times longer than that of the world record giraffe and five times longer than those of all other terrestrial animals. Several anatomical features enabled this extreme elongation, including: absolutely large body size and quadrupedal stance providing a stable platform for a long neck; a small, light head that did not orally process food; cervical vertebrae that were both numerous and individually elongate; an efficient air-sac-bas...

  11. Is Planned Neck Dissection Necessary for Head and Neck Cancer After Intensity-Modulated Radiotherapy?

    International Nuclear Information System (INIS)

    Yao Min; Hoffman, Henry T.; Chang, Kristi; Funk, Gerry F.; Smith, Russell B.; Tan Huaming; Clamon, Gerald H.; Dornfeld, Ken; Buatti, John M.

    2007-01-01

    Purpose: The objective of this study was to determine regional control of local regional advanced head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT), along with the role and selection criteria for neck dissection after IMRT. Methods and Materials: A total of 90 patients with stage N2A or greater HNSCC were treated with definitive IMRT from December 1999 to July 2005. Three clinical target volumes were defined and were treated to 70 to 74 Gy, 60 Gy, and 54 Gy, respectively. Neck dissection was performed for selected patients after IMRT. Selection criteria evolved during this period with emphasis on post-IMRT [ 18 F] fluorodeoxyglucose positron emission tomography in recent years. Results: Median follow-up for all patients was 29 months (range, 0.2-74 months). All living patients were followed at least 9 months after completing treatment. Thirteen patients underwent neck dissection after IMRT because of residual lymphadenopathy. Of these, 6 contained residual viable tumor. Three patients with persistent adenopathy did not undergo neck dissection: 2 refused and 1 had lung metastasis. Among the remaining 74 patients who were observed without neck dissection, there was only 1 case of regional failure. Among all 90 patients in this study, the 3-year local and regional control was 96.3% and 95.4%, respectively. Conclusions: Appropriately delivered IMRT has excellent dose coverage for cervical lymph nodes. A high radiation dose can be safely delivered to the abnormal lymph nodes. There is a high complete response rate. Routine planned neck dissection for patients with N2A and higher stage after IMRT is not necessary. Post-IMRT [ 18 F] fluorodeoxyglucose positron emission tomography is a useful tool in selecting patients appropriate for neck dissection

  12. Ensuring the sustainability of EDF power plant operating capacity

    International Nuclear Information System (INIS)

    Francois, J.

    2009-01-01

    The life extension of the power plants is considered whereas EDF must face an acceleration of the retirement rates due to the fact that the first generations of the baby-boom are ageing 60 years, now. Between 2000 and 2006, EDF gradually set up a system of management of competencies. On the one hand, EDF moved from logic of relatively standardized training to a more individualized logic of acquisition of competencies. In addition, the objective of maintenance of internat competencies defined in 2000 was supplemented in 2003 by a prospective dimension intended to anticipate the departures in inactivity. Then in 2006 competencies of sub-contractors were taken into account. During this period I.R.S.N. has assessed 3 times this system of management. This article briefly presents the principal lessons driven from these evaluations. It accounts for the undeniable effort made by EDF to ensure the maintenance of its competencies. However, it stresses that a high level of vigilance is still needed because it is not stabilized already. (author)

  13. Robust mitotic entry is ensured by a latching switch

    Directory of Open Access Journals (Sweden)

    Chloe Tuck

    2013-07-01

    Cell cycle events are driven by Cyclin dependent kinases (CDKs and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011. Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust.

  14. Robust mitotic entry is ensured by a latching switch.

    Science.gov (United States)

    Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novák, Béla

    2013-01-01

    Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust.

  15. Ensuring quality in qualitative inquiry: using key concepts as guidelines

    Directory of Open Access Journals (Sweden)

    Debra Frances Campbell

    2013-09-01

    Full Text Available The field of qualitative scientific inquiry employs a fast-growing variety of approaches, whose traditions, procedures, and structures vary, depending on the type of study design and methodology (i.e., phenomenological, ethnographic, grounded theory, case study, action research, etc.. With the interpretive approach, researchers do not utilize the same measures of validity used in positivist approaches to scientific inquiry, since there is "...no one standard or accepted structure as one typically finds in quantitative research" (Creswell, 2007. With the absence of a single standard, how, then, is it possible for qualitative researchers to know whether or not their study was done with rigor, that it has validity, that it is ready to submit to their peers? The research literature is sprinkled with references to quality in qualitative inquiry, which helps to construe a study's validity. Markula (2008 suggests that we validate our study's findings by assuring readers that it was done "in the best possible way." While each research tradition has its own set of criteria for judging quality, we present here general concepts drawn from the literature. We hope this article will provide a framework from which qualitative researchers can judge their work before submitting it to their peers¸ one which will help ensure that their study was done "in the best possible way."

  16. Failure assessment techniques to ensure shipping container integrity

    International Nuclear Information System (INIS)

    McConnell, P.

    1986-02-01

    This report discusses several methodologies which may be used to ensure the structural integrity of containment systems to be used for the transport and storage of high-level radioactive substances. For economic reasons, shipping containers constructed of ferritic materials are being considered for manufacture by vendors in the US and Europe. Ferritic show an inherent transition from a ductile, high energy failure mode to a brittle, low energy fracture mode with decreasing temperature. Therefore, formal consideration of means by which to avoid unstable brittle fracture is necessary prior to the licensing of ferritic casks. It is suggested that failure of a shipping container wall be defined as occurring when a flaw extends through the outer wall of the containment system. Crack initiation which may lead to unstable brittle crack growth should therefore be prevented. It is suggested that a fundamental linear elastic fracture mechanics (lefm) approach be adopted on a case-by-case basis, applied perhaps by means of appropriate modifications to ASMA Section III or Section XI. A lefm analysis requires information concerning service temperatures, loading rates, flaw sizes, and applied stresses. Tentative judgments regarding these parameters for typical shipping containers have been made

  17. Ensuring microbiological safety of commercial eggs by gamma irradiation

    International Nuclear Information System (INIS)

    Hammad, A.A; Swailam, H.M.; Abd El-Rahim, E.A.; Shallan, M.A; Aly, W.F.

    2009-01-01

    Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (balady, white and brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of balady eggs. The effect of gamma irradiation at dose of 0,2,3 and 4 kGy on microbiological quality of balady eggs during storage at 4± 1 deg c for 35 days as well as on total cholesterol , ph, and total carotenoids contents were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Whereas completely eliminated coliform bacteria, E.coli and salmonella spp. Total cholesterol and total carotenoids were decreased in yolk egg. irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life of balady eggs

  18. Ensuring Microbiological Safety of Fresh Eggs by Using Gamma Irradiation

    International Nuclear Information System (INIS)

    Hammad, A. A.; Swailam, H.M.; Aly, W. F.

    2008-01-01

    Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (Balady, White and Brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that Balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of Balady eggs. The effect of gamma irradiation at dose of 0, 2, 3 and 4 kGy on microbiological quality of Balady eggs during storage at 4±1 degree C for 35 days was studied. The effects of irradiation and storage on total cholesterol, and total carotenoids contents in Balady eggs were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Coliform bacteria, E. coli and Salmonella spp. were completely eliminated. Total cholesterol and total carotenoids were decreased in yolk egg as a result of irradiation. Treated Balady eggs with irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life.

  19. Nuclear safeguards: power tool for ensuring nuclear safety and security

    International Nuclear Information System (INIS)

    Ramakumar, K.L.

    2016-01-01

    The quantitative measurement of fissile nuclear materials through independent measurements is one of the cornerstones of the Nuclear Material Accounting and Control (NUMAC) edifice. The verification of the accountancy also represents one of the key elements of international nuclear materials Safeguards. The very basis of NUMAC is to ensure safeguarding nuclear material and to state with confidence, “no significant amount of nuclear material has been withdrawn from its intended civilian use.” Thus, materials accounting systems are designed to account for or keep track of the amounts and locations of sensitive nuclear materials by periodic measurements. The purpose of this activity is to detect missing items (gross defects). A variety of C/S techniques are used, primarily optical surveillance and sealing. These measures serve to back up nuclear material accountancy by providing means by which access to nuclear material can be monitored. Unattended monitoring is a special mode of application of NDA or C/S techniques, or a combination of these, that operates for extended periods of time. The complexity and diversity of facilities containing safeguarded nuclear material require a correspondingly diverse set of verification techniques and equipment. The equipment and techniques used in safeguards are briefly described in this talk

  20. Future of Assurance: Ensuring that a System is Trustworthy

    Science.gov (United States)

    Sadeghi, Ahmad-Reza; Verbauwhede, Ingrid; Vishik, Claire

    Significant efforts are put in defining and implementing strong security measures for all components of the comput-ing environment. It is equally important to be able to evaluate the strength and robustness of these measures and establish trust among the components of the computing environment based on parameters and attributes of these elements and best practices associated with their production and deployment. Today the inventory of techniques used for security assurance and to establish trust -- audit, security-conscious development process, cryptographic components, external evaluation - is somewhat limited. These methods have their indisputable strengths and have contributed significantly to the advancement in the area of security assurance. However, shorter product and tech-nology development cycles and the sheer complexity of modern digital systems and processes have begun to decrease the efficiency of these techniques. Moreover, these approaches and technologies address only some aspects of security assurance and, for the most part, evaluate assurance in a general design rather than an instance of a product. Additionally, various components of the computing environment participating in the same processes enjoy different levels of security assurance, making it difficult to ensure adequate levels of protection end-to-end. Finally, most evaluation methodologies rely on the knowledge and skill of the evaluators, making reliable assessments of trustworthiness of a system even harder to achieve. The paper outlines some issues in security assurance that apply across the board, with the focus on the trustworthiness and authenticity of hardware components and evaluates current approaches to assurance.

  1. Ensuring the operational safety of finnish nuclear power plants

    International Nuclear Information System (INIS)

    Vuorinen, A.

    1991-01-01

    The Finnish nuclear energy programme has been successful both from the safety and economical point of view. These achievements are based on different factors which are discussed in the paper. Finnish Centre for Radiation and Nuclear Safety (STUK) has specified the technical requirements and procedures to be followed in the design, construction, commissioning and operation of NPPs in a series of guides. The guides are quite demanding and latest results of safety research and technical development are taken into account. Regulatory supervision of Finnish NPPs is comprehensive. As an example of this the regulatory inspection program for operational phase is presented. An important way to ensure operational safety of a NPP is to define a set of limits and conditions to identify limiting safety envelope for plant operation. Practices in Finland are reviewed in the paper. The strategy of Defence in Depth is amongst the fundamental principles of nuclear safety. Two corollary principles of defence of depth are accident prevention and accident mitigation. Means used in following these principles are discussed. (author)

  2. Neck muscle vibration can improve sensorimotor function in patients with neck pain.

    Science.gov (United States)

    Beinert, Konstantin; Keller, Martin; Taube, Wolfgang

    2015-03-01

    People with neck pain display a diminished joint position sense and disturbed postural control, which is thought to be a result of impaired somatosensory afferent activity and/or integration. Afferent processing can be artificially manipulated by vibration and was shown to reduce motor performance in healthy subjects. However, the effect of vibration on sensorimotor function in neck pain patients is scarcely investigated. To assess the effect of neck muscle vibration on joint position sense and postural control in neck pain subjects and healthy controls. Case control study. Thirteen neck pain patients and 10 healthy controls participated in the present study. Cervical joint position sense and dynamic and static postural stability. Short-term, targeted neck muscle vibration with 100 Hz was applied after baseline measurement. Vibration had opposite effects in patients and healthy subjects. Patients showed improved joint position sense (pneck pain. Thus, vibration may be used to counteract sensorimotor impairment of the cervical spine. Potential underlying mechanisms are discussed. Copyright © 2015. Published by Elsevier Inc.

  3. Why sauropods had long necks; and why giraffes have short necks

    Science.gov (United States)

    Wedel, Mathew J.

    2013-01-01

    The necks of the sauropod dinosaurs reached 15 m in length: six times longer than that of the world record giraffe and five times longer than those of all other terrestrial animals. Several anatomical features enabled this extreme elongation, including: absolutely large body size and quadrupedal stance providing a stable platform for a long neck; a small, light head that did not orally process food; cervical vertebrae that were both numerous and individually elongate; an efficient air-sac-based respiratory system; and distinctive cervical architecture. Relevant features of sauropod cervical vertebrae include: pneumatic chambers that enabled the bone to be positioned in a mechanically efficient way within the envelope; and muscular attachments of varying importance to the neural spines, epipophyses and cervical ribs. Other long-necked tetrapods lacked important features of sauropods, preventing the evolution of longer necks: for example, giraffes have relatively small torsos and large, heavy heads, share the usual mammalian constraint of only seven cervical vertebrae, and lack an air-sac system and pneumatic bones. Among non-sauropods, their saurischian relatives the theropod dinosaurs seem to have been best placed to evolve long necks, and indeed their necks probably surpassed those of giraffes. But 150 million years of evolution did not suffice for them to exceed a relatively modest 2.5 m. PMID:23638372

  4. Why sauropods had long necks; and why giraffes have short necks.

    Science.gov (United States)

    Taylor, Michael P; Wedel, Mathew J

    2013-01-01

    The necks of the sauropod dinosaurs reached 15 m in length: six times longer than that of the world record giraffe and five times longer than those of all other terrestrial animals. Several anatomical features enabled this extreme elongation, including: absolutely large body size and quadrupedal stance providing a stable platform for a long neck; a small, light head that did not orally process food; cervical vertebrae that were both numerous and individually elongate; an efficient air-sac-based respiratory system; and distinctive cervical architecture. Relevant features of sauropod cervical vertebrae include: pneumatic chambers that enabled the bone to be positioned in a mechanically efficient way within the envelope; and muscular attachments of varying importance to the neural spines, epipophyses and cervical ribs. Other long-necked tetrapods lacked important features of sauropods, preventing the evolution of longer necks: for example, giraffes have relatively small torsos and large, heavy heads, share the usual mammalian constraint of only seven cervical vertebrae, and lack an air-sac system and pneumatic bones. Among non-sauropods, their saurischian relatives the theropod dinosaurs seem to have been best placed to evolve long necks, and indeed their necks probably surpassed those of giraffes. But 150 million years of evolution did not suffice for them to exceed a relatively modest 2.5 m.

  5. Why sauropods had long necks; and why giraffes have short necks

    Directory of Open Access Journals (Sweden)

    Michael P. Taylor

    2013-02-01

    Full Text Available The necks of the sauropod dinosaurs reached 15 m in length: six times longer than that of the world record giraffe and five times longer than those of all other terrestrial animals. Several anatomical features enabled this extreme elongation, including: absolutely large body size and quadrupedal stance providing a stable platform for a long neck; a small, light head that did not orally process food; cervical vertebrae that were both numerous and individually elongate; an efficient air-sac-based respiratory system; and distinctive cervical architecture. Relevant features of sauropod cervical vertebrae include: pneumatic chambers that enabled the bone to be positioned in a mechanically efficient way within the envelope; and muscular attachments of varying importance to the neural spines, epipophyses and cervical ribs. Other long-necked tetrapods lacked important features of sauropods, preventing the evolution of longer necks: for example, giraffes have relatively small torsos and large, heavy heads, share the usual mammalian constraint of only seven cervical vertebrae, and lack an air-sac system and pneumatic bones. Among non-sauropods, their saurischian relatives the theropod dinosaurs seem to have been best placed to evolve long necks, and indeed their necks probably surpassed those of giraffes. But 150 million years of evolution did not suffice for them to exceed a relatively modest 2.5 m.

  6. Ipsilateral humeral neck and shaft fractures

    Directory of Open Access Journals (Sweden)

    Zhu Bin

    2017-01-01

    Full Text Available Background/Aim. Fractures of the proximal humerus or shaft are common, however, ipsilateral neck and shaft humerus fracture is a rare phenomenon. This combination injury is challenging for orthopaedic surgeons because of its complex treatment options at present. The purpose of this study was to review a series of ipsilateral humeral neck and shaft fractures to study the fracture pattern, complications and treatment outcomes of each treatment options used. Methods. A total of six patients (four female and two male with the average age of 42.8 years (range: 36–49 years was collected and reviewed retrospectively. Two of them were treated with double plates and four with antegrade intramedullary nail. According to the Neer’s classification, all proximal fractures were two-part surgical neck fractures. All humeral shaft fractures were located at the middle of one third. Five fractures were simple transverse (A3, one fragmented wedge fracture (B3. One patient had associated radial nerve palsy. Results. All surgical neck fractures except one united uneventfully in the average time span of 8.7 weeks. Four humeral shaft fractures healed in near anatomic alignment. The remaining two patients had the nonunion with no radiological signs of fracture healing. The average University of California, Los Angeles End-Results (UCLA score was 23.1. On the contrary, the average American Shoulder and Elbow Surgeon's (ASES score was 73.3. The patients treated with antegrade intramedullary nails presented 70.5 points. The ASES scores were 79 in the double plates group. Conclusions. Ipsilateral humeral shaft and neck fracture is extremely rare. Both antegrade intramedullar nailing and double plates result in healing of fractures. However the risk of complication is lower in the double plating group.

  7. Selective neck dissection: a review of the evidence.

    Science.gov (United States)

    Pagedar, Nitin A; Gilbert, Ralph W

    2009-01-01

    The management of regional metastatic disease in patients with oral cancer is a topic of controversy. Comprehensive neck dissection has been the mainstay of treatment historically, but clinicians have sought alternatives to limit the morbidity of the classic radical neck dissection. This article will review evidence on the applicability of selective neck dissection in two settings: as primary treatment of the clinically positive neck and as salvage treatment of recurrent neck disease after radiotherapy. In the text, for each article cited we supply the level of evidence thereof according to the Oxford Centre for Evidence-based medicine.

  8. Series of mixed uranyl-lanthanide (Ce, Nd) organic coordination polymers with aromatic polycarboxylates linkers.

    Science.gov (United States)

    Mihalcea, Ionut; Volkringer, Christophe; Henry, Natacha; Loiseau, Thierry

    2012-09-17

    Three series of mixed uranyl-lanthanide (Ce or Nd) carboxylate coordination polymers have been successfully synthesized by means of a hydrothermal route using either conventional or microwave heating methods. These compounds have been prepared from mixtures of uranyl nitrate, lanthanide nitrate together with phthalic acid (1,2), pyromellitic acid (3,4), or mellitic acid (5,6) in aqueous solution. The X-ray diffraction (XRD) single-crystal revealed that the phthalate complex (UO(2))(4)O(2)Ln(H(2)O)(7)(1,2-bdc)(4)·NH(4)·xH(2)O (Ln = Ce(1), Nd(2); x = 1 for 1, x = 0 for 2), is based on the connection of tetranuclear uranyl-centered building blocks linked to discrete monomeric units LnO(2)(H(2)O)(7) via the organic species to generate infinite chains, intercalated by free ammonium cations. The pyromellitate phase (UO(2))(3)Ln(2)(H(2)O)(12)(btec)(3)·5H(2)O (Ce(3), Nd(4)) contains layers of monomeric uranyl-centered hexagonal and pentagonal bipyramids linked via the carboxylate arms of the organic molecules. The three-dimensionality of the structure is ensured by the connection of remaining free carboxylate groups with isolated monomeric units LnO(2)(H(2)O)(7). The network of the third series (UO(2))(2)(OH)Ln(H(2)O)(7)(mel)·5H(2)O (Ce(5), Nd(6)) is built up from dinuclear uranyl units forming layers through connection with the mellitate ligands, which are further linked to each other through discrete monomers LnO(3)(H(2)O)(6). The thermal decomposition of the various coordination complexes led to the formation of mixed uranium-lanthanide oxide, with the fluorite-type structure at 1500 °C (for 1, 2) or 1400 °C for 3-6. Expected U/Ln ratio from the crystal structures were observed for compounds 1-6.

  9. Ensuring the population living safety in the contaminated areas

    Directory of Open Access Journals (Sweden)

    S. I. Voronov

    2016-01-01

    Full Text Available The state policy of the Russian Federation to ensure population, living in the contaminated areas, life safety is implemented by means of federal programs.12 programs for overcoming the Chernobyl accident consequences, children’s population protection and housing provision for the Chernobyl accident liquidators are adopted and realized during this time. Total financing amount from the federal budget is more than 9,2 billion rubles. The main efforts are directed to create necessary infrastructure in settlements, development and deployment rehabilitation measures for agricultural lands and forests, creation of radiation situation monitoring systems, increase housekeeping safety culture in the contaminated territories, informational support and social and psychological rehabilitation of the population. Within the state programs are developing complex systems of a radiation situation monitoring in 12 subjects of the Russian Federation. Experts training for the outreach work with population, concerning radiation safety, increasing population knowledge level about radiation in a format of seminars, conferences, with use of online technologies is provided. The project on creation the uniform interdepartmental information system on overcoming radiation accidents aftermath, integrating the operating information systems of The Ministry of the Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters, Federal Service for Hydrometeorology and Environmental Monitoring, the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing and the Russian Academy of Sciences is realized.However, the problem of overcoming the radiation accidents aftermath remains relevant up to date.In 14 subjects of the Russian Federation there are territories contaminated by radioactive materials as a result of the Chernobyl accident where more than 1,5 million people live.

  10. WISE recommendations to ensure the safety of injections in diabetes.

    Science.gov (United States)

    Strauss, K

    2012-01-01

    Injections and fingersticks administered to patients with diabetes in health care settings present a risk of blood exposure to the injector as well as other workers in potential contact with sharps. Such exposures could lead to transmission of bloodborne pathogens such as hepatitis and HIV. A recent EU Directive requires that where such risks have been identified, processes and devices must be put in place to reduce or eliminate the risk. The aim of this paper is to provide formal guidelines on the application of this Directive to diabetes care settings. These evidence-based recommendations were written and vetted by a large group of international safety experts. A systematic literature search was conducted for all peer-reviewed studies and publications which bear on sharps safety in diabetes. Initially a group of experts reviewed this literature and drafted the recommendations. These were then presented for review, debate and revision to 57 experts from 14 countries at the WISE workshop in October, 2011. After the WISE meeting, the revised Recommendations were circulated electronically to attendees on three occasions, each time in a new iteration with revisions. Each recommendation was graded by the weight it should have in daily practice and by its degree of support in the medical literature. The topics covered include Risks of Sharps Injury and Muco-cutaneous Exposure, The EU Directive, Device Implications, Injection Technique Implications, Education and Training (Creating a "Safety Culture"), Value, Awareness and Responsibility. These safety recommendations provide practical guidance and fill an important gap in diabetes management. If followed, they should help ensure safe, effective and largely injury-free injections and fingersticks. They will serve as the roadmap for applying the new EU Directive to diabetes care. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Head and neck cancer information on the internet: type, accuracy and content.

    LENUS (Irish Health Repository)

    Ni Riordain, Richeal

    2009-08-01

    This study aimed to determine the type, accuracy and content of information available on the internet regarding head and neck cancer. The search engine Google was used to generate a list of the top 100 websites about head and neck cancer. The websites were evaluated using the DISCERN instrument and the JAMA benchmarks and whether the site displayed the Health on the Net seal was also recorded. The search yielded 1,650,000 sites on the Google website. Of the top 100 sites, a total of 33 sites were suitable for analysis due to duplicate links, non-functioning links and irrelevant website. 45% achieved all four JAMA benchmarks and 18% achieved only 1 benchmark. No website receiving the maximum mark on the overall score and four websites received the lowest overall score regarding the DISCERN instrument. The question with the poorest response score was \\'Does it describe how the treatment choices affect overall quality of life?\\' 39% of the websites displayed the Health on the Net (HON) seal. A wide variety of types of information are available on the internet regarding head and neck cancer with variable accuracy levels based on both Journal of the American Medical Association (JAMA) benchmarks and DISCERN. The onus lies with the practitioner to guide the patient regarding scientific reliability of information and to direct the patient in filtering the information sourced. The inclusion of quality of life related information is currently lacking and should be addressed to ensure a more comprehensive understanding for patients of treatment options.

  12. Staging of primary head and neck tumors and detection of recurrences

    International Nuclear Information System (INIS)

    Adams, S.; Baum, R.P.; Knecht, R.; Hoer, G.

    2001-01-01

    Squamous cell carcinomas represent the vast majority of all malignant tumors of the head and neck region. Lymph node involvement is the most important prognostic factor affecting survival of patients with head and neck cancer. The effectiveness of surgical treatment depends on the complete excision of all tumor tissue and an accurate preoperative diagnosis. Tumor-node-metastasis (TNM) staging is therefore mandatory. In comparison to positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG PET), morphological imaging modalities (CT, MRI) have been applied for the localization of primary head and neck tumors because of their better anatomical resolution. Metabolic tumor imaging using FDG PET is superior to morphological imaging by CT and MRI in the detection of small cervical lymph node metastases (Class 1a indication). Increased FDG uptake has also been observed in benign inflammatory lesions after radiation therapy, therefore detection of local recurrence with FDG PET can be problematic. To ensure a high diagnostic accuracy it is been suggested to perform FDG PET not earlier than 3 months after radiation therapy (Class 1a indication for the diagnosis of local recurrence). (orig.) [de

  13. Directing the breathing behavior of pillared-layered metal-organic frameworks via a systematic library of functionalized linkers bearing flexible substituents.

    Science.gov (United States)

    Henke, Sebastian; Schneemann, Andreas; Wütscher, Annika; Fischer, Roland A

    2012-06-06

    Flexible metal-organic frameworks (MOFs), also referred to as soft porous crystals (SPCs), show reversible structural transitions dependent on the nature and quantity of adsorbed guest molecules. In recent studies it has been reported that covalent functionalization of the organic linker can influence or even integrate framework flexibility ("breathing") in MOFs. However, rational fine-tuning of such responsive properties is very desirable but challenging as well. Here we present a powerful approach for the targeted manipulation of responsiveness and framework flexibility of an important family of pillared-layered MOFs based on the parent structure [Zn(2)(bdc)(2)(dabco)](n) (bdc = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane). A library of functionalized bdc-type linkers (fu-bdc), which bear additional dangling side groups at different positions of the benzene core (alkoxy groups of varying chain length with diverse functionalities and polarity), was generated. Synthesis of the materials [Zn(2)(fu-bdc)(2)(dabco)](n) yields the respective collection of highly responsive MOFs. The parent MOF is only weakly flexible; however, the substituted frameworks of [Zn(2)(fu-bdc)(2)(dabco)](n) contract drastically upon guest removal and expand again upon adsorption of DMF (N,N-dimethylformamide), EtOH, or CO(2), etc., while N(2) is hardly adsorbed and does not open the narrow-pored form. These "breathing" dynamics are attributed to the dangling side chains that act as immobilized "guests", which interact with mobile guest molecules as well as with themselves and with the framework backbone. The structural details of the guest-free, contracted form and the gas sorption behavior (phase transition pressure, hysteresis loop) are highly dependent on the nature of the substituent at the linker and can therefore be adjusted using our approach. Combining our library of functionalized linkers with the concept of mixed-component MOFs (solid solutions) offers very rich

  14. Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinu; Shin, Eun Seow; Kim, Jeong Eon; Yoon, Sang Pil [Jeju National University School of Medicine, Jeju (Korea, Republic of); Kim, Young Suk [Dept. of Radiation Oncology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of)

    2015-12-15

    Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.

  15. Detection of alloimmunization to ensure safer transfusion practice

    Directory of Open Access Journals (Sweden)

    Rashmi Sood

    2013-01-01

    significant role in improving blood safety. Centers that have incorporated antibody screen test and identification have ensured safe transfusion. Identified patients should be flagged in a database and information shared. Such patients can be given carry-on cards and educated about the names of the identified antibodies. Full red cell phenotyping of individuals, patients and donors, can be feasibility.

  16. Confirmatory factory analysis of the Neck Disability Index in a general problematic neck population indicates a one-factor model.

    Science.gov (United States)

    Gabel, Charles Philip; Cuesta-Vargas, Antonio I; Osborne, Jason W; Burkett, Brendan; Melloh, Markus

    2014-08-01

    The Neck Disability Index frequently is used to measure outcomes of the neck. The statistical rigor of the Neck Disability Index has been assessed with conflicting outcomes. To date, Confirmatory Factor Analysis of the Neck Disability Index has not been reported for a suitably large population study. Because the Neck Disability Index is not a condition-specific measure of neck function, initial Confirmatory Factor Analysis should consider problematic neck patients as a homogenous group. We sought to analyze the factor structure of the Neck Disability Index through Confirmatory Factor Analysis in a symptomatic, homogeneous, neck population, with respect to pooled populations and gender subgroups. This was a secondary analysis of pooled data. A total of 1,278 symptomatic neck patients (67.5% female, median age 41 years), 803 nonspecific and 475 with whiplash-associated disorder. The Neck Disability Index was used to measure outcomes. We analyzed pooled baseline data from six independent studies of patients with neck problems who completed Neck Disability Index questionnaires at baseline. The Confirmatory Factor Analysis was considered in three scenarios: the full sample and separate sexes. Models were compared empirically for best fit. Two-factor models have good psychometric properties across both the pooled and sex subgroups. However, according to these analyses, the one-factor solution is preferable from both a statistical perspective and parsimony. The two-factor model was close to significant for the male subgroup (pfactor structure when analyzed by Confirmatory Factor Analysis in a pooled, homogenous sample of neck problem patients. However, a two-factor model did approach significance for male subjects where questions separated into constructs of mental and physical function. Further investigations in different conditions, subgroup and sex-specific populations are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The burden of neck pain: its meaning for persons with neck pain and healthcare providers, explored by concept mapping.

    Science.gov (United States)

    van Randeraad-van der Zee, Carlijn H; Beurskens, Anna J H M; Swinkels, Raymond A H M; Pool, Jan J M; Batterham, Roy W; Osborne, Richard H; de Vet, Henrica C W

    2016-05-01

    To empirically define the concept of burden of neck pain. The lack of a clear understanding of this construct from the perspective of persons with neck pain and care providers hampers adequate measurement of this burden. An additional aim was to compare the conceptual model obtained with the frequently used Neck Disability Index (NDI). Concept mapping, combining qualitative (nominal group technique and group consensus) and quantitative research methods (cluster analysis and multidimensional scaling), was applied to groups of persons with neck pain (n = 3) and professionals treating persons with neck pain (n = 2). Group members generated statements, which were organized into concept maps. Group members achieved consensus about the number and description of domains and the researchers then generated an overall mind map covering the full breadth of the burden of neck pain. Concept mapping revealed 12 domains of burden of neck pain: impaired mobility neck, neck pain, fatigue/concentration, physical complaints, psychological aspects/consequences, activities of daily living, social participation, financial consequences, difficult to treat/difficult to diagnose, difference of opinion with care providers, incomprehension by social environment, and how person with neck pain deal with complaints. All ten items of the NDI could be linked to the mind map, but the NDI measures only part of the burden of neck pain. This study revealed the relevant domains for the burden of neck pain from the viewpoints of persons with neck pain and their care providers. These results can guide the identification of existing measurements instruments for each domain or the development of new ones to measure the burden of neck pain.

  18. Test Characteristics of Neck Fullness and Witnessed Neck Pulsations in the Diagnosis of Typical AV Nodal Reentrant Tachycardia

    Science.gov (United States)

    Sakhuja, Rahul; Smith, Lisa M; Tseng, Zian H; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Scheinman, Melvin M; Olgin, Jeffrey E; Marcus, Gregory M

    2011-01-01

    Summary Background Claims in the medical literature suggest that neck fullness and witnessed neck pulsations are useful in the diagnosis of typical AV nodal reentrant tachycardia (AVNRT). Hypothesis Neck fullness and witnessed neck pulsations have a high positive predictive value in the diagnosis of typical AVNRT. Methods We performed a cross sectional study of consecutive patients with palpitations presenting to a single electrophysiology (EP) laboratory over a 1 year period. Each patient underwent a standard questionnaire regarding neck fullness and/or witnessed neck pulsations during their palpitations. The reference standard for diagnosis was determined by electrocardiogram and invasive EP studies. Results Comparing typical AVNRT to atrial fibrillation (AF) or atrial flutter (AFL) patients, the proportions with neck fullness and witnessed neck pulsations did not significantly differ: in the best case scenario (using the upper end of the 95% confidence interval [CI]), none of the positive or negative predictive values exceeded 79%. After restricting the population to those with supraventricular tachycardia other than AF or AFL (SVT), neck fullness again exhibited poor test characteristics; however, witnessed neck pulsations exhibited a specificity of 97% (95% CI 90–100%) and a positive predictive value of 83% (95% CI 52–98%). After adjustment for potential confounders, SVT patients with witnessed neck pulsations had a 7 fold greater odds of having typical AVNRT, p=0.029. Conclusions Although neither neck fullness nor witnessed neck pulsations are useful in distinguishing typical AVNRT from AF or AFL, witnessed neck pulsations are specific for the presence of typical AVNRT among those with SVT. PMID:19479968

  19. Progressive shoulder-neck exercise on cervical muscle functions in middle-aged and senior patients with chronic neck pain.

    Science.gov (United States)

    Lin, I-Hsien; Chang, Kwang-Hwa; Liou, Tsan-Hon; Tsou, Chih-Min; Huang, Yi-Ching

    2018-02-01

    Although neck pain is a common musculoskeletal disorder, there is no consensus on suitable exercise methods for middle-aged and senior patients with chronic neck pain. Therefore, this study investigated the effectiveness of a 6-week shoulder-neck exercise intervention program on cervical muscle function improvement in patients aged 45 years or older with chronic neck pain. The aim of the present study was to evaluate the effects of progressive shoulder-neck exercise on cervical muscle functions of middle-aged and senior patients with chronic neck pain. A randomized controlled single-blind trial. Rehabilitation department of a hospital. A total of 72 subjects aged ≥45 years with chronic neck pain were randomly allocated to either an experimental group (N.=36; age 57.3±8.74 years) or a control group (N.=36; age 58.15±8.17 years). The control group received only traditional physiotherapy, whereas the experimental group participated in a 6-week shoulder-neck exercise program consisting of cranio-cervical flexion and progressive resistance exercises in addition to receiving traditional physiotherapy. The muscle functions of subjects in both groups were tested before the experiment and also after the intervention program. The pretest and posttest measured the cranio-cervical flexion test (CCFT) and the superficial cervical muscle strength. After the intervention, the experimental group had a 56.48 point improvement in the performance index of the CCFT (Pcervical muscle functions. This study confirmed that the 6-week progressive shoulder-neck exercise program can effectively improve cervical muscle function in middle-aged and senior patients with chronic neck pain. Progressive shoulder-neck exercise might provide positive effect on deep and superficial neck muscle strength in patients with chronic neck pain. Therefore, this study may serve as a reference for the clinical rehabilitation of patients with chronic neck pain.

  20. Usefulness of fat suppression MR imagings for head and neck cancers

    International Nuclear Information System (INIS)

    Kitagawa, Yoshimasa; Ishii, Yasuo; Morihiro, Hironori; Ogasawara, Toshiyuki

    1996-01-01

    Large amounts of fat and complex anatomy make the head and neck region one of the more challenging areas for MR imagings. The high signal intensity of fat on T1 weighted images (T1W1) has limited the utility of Gd-DTPA in imaging of head and neck lesions. The contrast enhanced lesions may have T1W1 signal intensity similar to fat, which results in diagnostic difficulty. A fat suppression technique used in conjunction with Gd-DTPA ensures that enhancing lesions will not be obscured by high signal from the surrounding fat or by chemical shift artifact. We evaluated the role or chemical shift imagings for fat suppression in the depiction of 15 patients with head and neck cancers. Gd-DTPA-enhanced fat suppression T1W1 were compared with conventional pre and postcontrast T1- and T2W1 using a four-point grading system (Grade 0-3) in detecting and defining the extent of primary lesions and lymphnodes. Gd-DTPA-enhanced fat suppression T1W1 (average score 2.93) which had a score of 3 in 14 patients, were superior to conventional T1W1 (0.73), postcontrast T1W1 (1.80) and T2W1 (1.67). Gd-DTPA enhanced fat suppression T1W1 were particularly beneficial in the detection of central necrosis or extracapsular invasion of neck lymphnodes as well as in defining the extent of tumor invasion to fat-containing areas such as bone marrow or cheek. Our data suggested that fat suppression technique was extremely useful to delineate the primary tumors and regional lymphnodes without increasing scan time or image postprocessing. (author)

  1. Imaging of head and neck venous malformations

    International Nuclear Information System (INIS)

    Flis, Christine M.; Connor, Stephen E.

    2005-01-01

    Venous malformations (VMs) are non proliferative lesions that consist of dysplastic venous channels. The aim of imaging is to characterise the lesion and define its anatomic extent. We will describe the plain film, ultrasound (US) (including colour and duplex Doppler), computed tomography (CT), magnetic resonance imaging (MRI), conventional angiographic and direct phlebographic appearances of venous malformations. They will be illustrated at a number of head and neck locations, including orbit, oral cavity, superficial and deep facial space, supraglottic and intramuscular. An understanding of the classification of such vascular anomalies is required to define the correct therapeutic procedure to employ. Image-guided sclerotherapy alone or in combination with surgery is now the first line treatment option in many cases of head and neck venous malformations, so the radiologist is now an integral part of the multidisciplinary management team. (orig.)

  2. Linker-free 3D assembly of nanocrystals with tunable unit size for reversible lithium ion storage

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Da; Lee, Jim Yang, E-mail: cheleejy@nus.edu.sg [Department of Chemical and Biomolecular Engineering, Faculty of Engineering, National University of Singapore, 10 Kent Ridge Crescent, 119260 (Singapore)

    2011-09-02

    A simple and scalable procedure combining hydrothermal synthesis with post-synthesis calcination was developed to produce a linker-free, thermally stable, mesoscale 3D ordered assembly of spinel-type ZnCo{sub 2}O{sub 4} nanocrystals. The mesoscale assembly with distinctively sharp edges was formed by close-packing the ZnCo{sub 2}O{sub 4} nanocrystal building blocks with a unit size changeable by the synthesis temperature. A self-templating mechanism based on the topotactic transformation of an oxalato-bridged precursor coordination compound was proposed for the assembly. The packaging of crystalline ZnCo{sub 2}O{sub 4} nanoparticles, an active lithium ion storage compound, into a dense organized structure is an effective way to increase the volumetric capacity of ZnCo{sub 2}O{sub 4} nanoparticles for reversible lithium ion storage. The highly ordered 3D assembly of ZnCo{sub 2}O{sub 4} demonstrated excellent reversible lithium ion storage properties and a specific capacity ({approx}800 mAh g{sup -1}) much higher than that of carbon (typically {approx} 350 mAh g{sup -1}).

  3. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Directory of Open Access Journals (Sweden)

    Sujiet Puthenveetil

    Full Text Available Antibody drug conjugates (ADCs are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  4. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Science.gov (United States)

    Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

    2017-01-01

    Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  5. Biocompatible Porous Polyester-Ether Hydrogel Scaffolds with Cross-Linker Mediated Biodegradation and Mechanical Properties for Tissue Augmentation

    Directory of Open Access Journals (Sweden)

    Berkay Ozcelik

    2018-02-01

    Full Text Available Porous polyester-ether hydrogel scaffolds (PEHs were fabricated using acid chloride/alcohol chemistry and a salt templating approach. The PEHs were produced from readily available and cheap commercial reagents via the reaction of hydroxyl terminated poly(ethylene glycol (PEG derivatives with sebacoyl, succinyl, or trimesoyl chloride to afford ester cross-links between the PEG chains. Through variation of the acid chloride cross-linkers used in the synthesis and the incorporation of a hydrophobic modifier (poly(caprolactone (PCL, it was possible to tune the degradation rates and mechanical properties of the resulting hydrogels. Several of the hydrogel formulations displayed exceptional mechanical properties, remaining elastic without fracture at compressive strains of up to 80%, whilst still displaying degradation over a period of weeks to months. A subcutaneous rat model was used to study the scaffolds in vivo and revealed that the PEHs were infiltrated with well vascularised tissue within two weeks and had undergone significant degradation in 16 weeks without any signs of toxicity. Histological evaluation for immune responses revealed that the PEHs incite only a minor inflammatory response that is reduced over 16 weeks with no evidence of adverse effects.

  6. Optimization and characterization of biomolecule immobilization on silicon substrates using (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde linker

    International Nuclear Information System (INIS)

    Gunda, Naga Siva Kumar; Singh, Minashree; Norman, Lana; Kaur, Kamaljit; Mitra, Sushanta K.

    2014-01-01

    In the present work, we developed and optimized a technique to produce a thin, stable silane layer on silicon substrate in a controlled environment using (3-aminopropyl)triethoxysilane (APTES). The effect of APTES concentration and silanization time on the formation of silane layer is studied using spectroscopic ellipsometry and Fourier transform infrared spectroscopy (FTIR). Biomolecules of interest are immobilized on optimized silane layer formed silicon substrates using glutaraldehyde linker. Surface analytical techniques such as ellipsometry, FTIR, contact angle measurement system, and atomic force microscopy are employed to characterize the bio-chemically modified silicon surfaces at each step of the biomolecule immobilization process. It is observed that a uniform, homogenous and highly dense layer of biomolecules are immobilized with optimized silane layer on the silicon substrate. The developed immobilization method is successfully implemented on different silicon substrates (flat and pillar). Also, different types of biomolecules such as anti-human IgG (rabbit monoclonal to human IgG), Listeria monocytogenes, myoglobin and dengue capture antibodies were successfully immobilized. Further, standard sandwich immunoassay (antibody–antigen–antibody) is employed on respective capture antibody coated silicon substrates. Fluorescence microscopy is used to detect the respective FITC tagged detection antibodies bound to the surface after immunoassay.

  7. Silica-bound copper(II)triazacyclononane as a phosphate esterase: effect of linker length and surface hydrophobicity.

    Science.gov (United States)

    Bodsgard, Brett R; Clark, Robert W; Ehrbar, Anthony W; Burstyn, Judith N

    2009-04-07

    A series of silica-bound Cu(ii) triazacyclononane materials was prepared to study the effect of linker length and surface hydrophobicity on the hydrolysis of phosphate esters. The general synthetic approach for these heterogeneous reagents was rhodium-catalyzed hydrosilation between an alkenyl-modified triazacyclononane and hydride-modified silica followed by metallation with a Cu(ii) salt. Elemental analysis confirmed that organic functionalization of the silica gel was successful and provided an estimate of the surface concentration of triazacyclononane. EPR spectra were consistent with square pyramidal Cu(ii), indicating that Cu(ii) ions were bound to the immobilized macrocycles. The hydrolytic efficacies of these heterogeneous reagents were tested with bis(p-nitrophenyl)phosphate (BNPP) and diethyl 4-nitrophenyl phosphate (paraoxon). The agent that performed best was an octyl-linked, propanol-blocked material. This material had the most hydrophilic surface and the most accessible active site, achieving a rate maximum on par with the other materials, but in fewer cycles and without an induction period.

  8. Solid phase synthesis of mitochondrial triphenylphosphonium-vitamin E metabolite using a lysine linker for reversal of oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohanad Mossalam

    Full Text Available Mitochondrial targeting of antioxidants has been an area of interest due to the mitochondria's role in producing and metabolizing reactive oxygen species. Antioxidants, especially vitamin E (α-tocopherol, have been conjugated to lipophilic cations to increase their mitochondrial targeting. Synthetic vitamin E analogues have also been produced as an alternative to α-tocopherol. In this paper, we investigated the mitochondrial targeting of a vitamin E metabolite, 2,5,7,8-tetramethyl-2-(2'-carboxyethyl-6-hydroxychroman (α-CEHC, which is similar in structure to vitamin E analogues. We report a fast and efficient method to conjugate the water-soluble metabolite, α-CEHC, to triphenylphosphonium cation via a lysine linker using solid phase synthesis. The efficacy of the final product (MitoCEHC to lower oxidative stress was tested in bovine aortic endothelial cells. In addition the ability of MitoCEHC to target the mitochondria was examined in type 2 diabetes db/db mice. The results showed mitochondrial accumulation in vivo and oxidative stress decrease in vitro.

  9. The bacterial tubulin FtsZ requires its intrinsically disordered linker to direct robust cell wall construction.

    Science.gov (United States)

    Sundararajan, Kousik; Miguel, Amanda; Desmarais, Samantha M; Meier, Elizabeth L; Casey Huang, Kerwyn; Goley, Erin D

    2015-06-23

    The bacterial GTPase FtsZ forms a cytokinetic ring at midcell, recruits the division machinery and orchestrates membrane and peptidoglycan cell wall invagination. However, the mechanism for FtsZ regulation of peptidoglycan metabolism is unknown. The FtsZ GTPase domain is separated from its membrane-anchoring C-terminal conserved (CTC) peptide by a disordered C-terminal linker (CTL). Here we investigate CTL function in Caulobacter crescentus. Strikingly, production of FtsZ lacking the CTL (ΔCTL) is lethal: cells become filamentous, form envelope bulges and lyse, resembling treatment with β-lactam antibiotics. This phenotype is produced by FtsZ polymers bearing the CTC and a CTL shorter than 14 residues. Peptidoglycan synthesis still occurs downstream of ΔCTL; however, cells expressing ΔCTL exhibit reduced peptidoglycan crosslinking and longer glycan strands than wild type. Importantly, midcell proteins are still recruited to sites of ΔCTL assembly. We propose that FtsZ regulates peptidoglycan metabolism through a CTL-dependent mechanism that extends beyond simple protein recruitment.

  10. Synthesis of Cassava Waste Pulp-Acrylamide Super Absorbent: Effect of Initiator and Cross-Linker Concentration

    Directory of Open Access Journals (Sweden)

    Zainal Alim Mas’ud

    2013-05-01

    Full Text Available Cassava waste pulp (CWP contains high carbohydrates that can be modified into super absorbent polymer (SAP through grafting and cross-linking copolymerization. Acrylamide (AM was grafted onto CWP with ammonium persulfate (APS as the initiator and N,N'-methylene-bis-acrylamide (MBA as the cross-linker under atmospheric nitrogen. The effect of APS and MBA concentrations on water absorption capacity of saponified SAP was studied, while the evaluation of grafting ratio (GR and grafting efficiency (GRE was conducted on unsaponified SAP. The grafting success was indicated by the occurrence of IR peaks at wave numbers of 573, 765, 858, and 1667 cm-1. In the saponified SAP, the very intense characteristic band at 1562 cm-1 is due to C=O asymmetric stretching in the carboxylate anion. Saponification increases significantly water absorption capacity compared to that of unsaponified SAP (from 39.79 g/g to 578.23 g/g. The highest water absorption capacity is reached at 0.74% APS and 0.09% MBA. The percentage of GRE and GR tends to increase with increasing APS concentration until reaching the highest value and then decreases. Effect of MBA concentration on water absorption capacity, GR, and on GRE is similar to the effect of initiator concentration on GR and GRE.

  11. NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring.

    Science.gov (United States)

    Komljenovic, Dorde; Wiessler, Manfred; Waldeck, Waldemar; Ehemann, Volker; Pipkorn, Ruediger; Schrenk, Hans-Hermann; Debus, Jürgen; Braun, Klaus

    2016-01-01

    Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner.

  12. Linker-free 3D assembly of nanocrystals with tunable unit size for reversible lithium ion storage

    International Nuclear Information System (INIS)

    Deng, Da; Lee, Jim Yang

    2011-01-01

    A simple and scalable procedure combining hydrothermal synthesis with post-synthesis calcination was developed to produce a linker-free, thermally stable, mesoscale 3D ordered assembly of spinel-type ZnCo 2 O 4 nanocrystals. The mesoscale assembly with distinctively sharp edges was formed by close-packing the ZnCo 2 O 4 nanocrystal building blocks with a unit size changeable by the synthesis temperature. A self-templating mechanism based on the topotactic transformation of an oxalato-bridged precursor coordination compound was proposed for the assembly. The packaging of crystalline ZnCo 2 O 4 nanoparticles, an active lithium ion storage compound, into a dense organized structure is an effective way to increase the volumetric capacity of ZnCo 2 O 4 nanoparticles for reversible lithium ion storage. The highly ordered 3D assembly of ZnCo 2 O 4 demonstrated excellent reversible lithium ion storage properties and a specific capacity (∼800 mAh g -1 ) much higher than that of carbon (typically ∼ 350 mAh g -1 ).

  13. Construction, Structural Diversity and Properties of Five Coordination Polymers Based on 5-Nitroisophthalate and Bis(imidazole) Linkers

    Science.gov (United States)

    Arıcı, Mürsel

    2018-06-01

    Five coordination polymers, namely, [Cd(μ3-5-nip)(μ-obix)]n (1), [Co(μ3-5-nip)(μ-obix)]n (2), [Zn(μ-5-nip)(μ-obix)]n (3 and 4) and [Cd(μ-5-nip)(μ-bisobix)]n (5) (5-nip: 5-nitroisophthalate, obix: 1,2-bis(imidazol-1ylmethyl)benzene, bisobix: 1,2-bis(2-isopropylimidazol-1ylmethyl)benzene) were hydrothermally synthesized and characterized by IR spectroscopy, elemental analysis, single crystal and powder X-ray diffraction and thermal analysis (TG/DTA). X-ray results showed that the complexes displayed structural diversity depending on metal ions and conformations of bis(imidazole) linkers. Complexes 1 and 2 were 1D structures and obix ligand displayed cis-conformation. Complexes 3 and 4 exhibited 2D and 3D structures with same components depending on obix conformation. In complex 5, 3D+3D→3D interpenetrated structure was obtained with dia topology when bisobix having sterically hindered groups on imidazole rings was used. Moreover, thermal, photoluminescence and optical properties of the complexes were also investigated.

  14. Demonstration of Improved Charge Transfer in Graphene/Au Nanorods Plasmonic Hybrids Stabilized by Benzyl Thiol Linkers

    Directory of Open Access Journals (Sweden)

    Giuseppe Valerio Bianco

    2016-01-01

    Full Text Available Hybrids based on graphene decorated with plasmonic gold (Au nanostructures are being investigated as possible materials combination to add to graphene functionalities of tunable plasmon resonance and enhanced absorption at selected wavelength in the visible-near-infrared region of the spectrum. Here, we report a solution drop-casting approach for fabricating stable hybrids based on chemical vapor deposition (CVD graphene and Au nanorods, which are able to activate effective charge transfer from graphene. We demonstrate that CVD graphene functionalization by benzyl thiol (BZT provides the linker to strong anchoring, via S-Au bonds, Au nanorods to graphene. Optical measurements by spectroscopic ellipsometry give evidence of the introduction of plasmon resonances at 1.85 and 2.25 eV in the Au nanorods/BZT/graphene hybrids, which enable surface enhanced Raman scattering (SERS detection. Furthermore, an effective electron transfer from graphene to Au nanorods, resulting in an enhancement of p-type doping of graphene with a consequent decrease of its sheet resistance, is probed by Raman spectroscopy and corroborated by electrical measurements.

  15. Phosphonate self-assembled monolayers as organic linkers in solid-state quantum dot sensetized solar cells

    KAUST Repository

    Ardalan, Pendar

    2010-06-01

    We have employed X-ray photoelectron spectroscopy (XPS), ultraviolet-visible (UV-vis) spectroscopy, infrared (IR) spectroscopy, water contact angle (WCA) measurements, ellipsometry, and electrical measurements to study the effects of self-assembled monolayers (SAMs) with phosphonic acid headgroups on the bonding and performance of cadmium sulfide (CdS) solid-state quantum dot sensitized solar cells (QDSSCs). ∼2 to ∼6 nm size CdS quantum dots (QDs) were grown on the SAM-passivated TiO2 surfaces by successive ionic layer adsorption and reaction (SILAR). Our results show differences in the bonding of the CdS QDs at the TiO2 surfaces with a SAM linker. Moreover, our data indicate that presence of a SAM increases the CdS uptake on TiO2 as well as the performance of the resulting devices. Importantly, we observe ∼2 times higher power conversion efficiencies in the devices with a SAM compared to those that lack a SAM. © 2010 IEEE.

  16. Optimization and characterization of biomolecule immobilization on silicon substrates using (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde linker

    Energy Technology Data Exchange (ETDEWEB)

    Gunda, Naga Siva Kumar [Department of Mechanical Engineering, University of Alberta, Edmonton, Canada T6G 2G8 (Canada); Singh, Minashree [Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada T6G 1C9 (Canada); Norman, Lana [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada T6G 2V4 (Canada); Kaur, Kamaljit [Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada T6G 1C9 (Canada); Mitra, Sushanta K., E-mail: sushanta.mitra@ualberta.ca [Department of Mechanical Engineering, University of Alberta, Edmonton, Canada T6G 2G8 (Canada)

    2014-06-01

    In the present work, we developed and optimized a technique to produce a thin, stable silane layer on silicon substrate in a controlled environment using (3-aminopropyl)triethoxysilane (APTES). The effect of APTES concentration and silanization time on the formation of silane layer is studied using spectroscopic ellipsometry and Fourier transform infrared spectroscopy (FTIR). Biomolecules of interest are immobilized on optimized silane layer formed silicon substrates using glutaraldehyde linker. Surface analytical techniques such as ellipsometry, FTIR, contact angle measurement system, and atomic force microscopy are employed to characterize the bio-chemically modified silicon surfaces at each step of the biomolecule immobilization process. It is observed that a uniform, homogenous and highly dense layer of biomolecules are immobilized with optimized silane layer on the silicon substrate. The developed immobilization method is successfully implemented on different silicon substrates (flat and pillar). Also, different types of biomolecules such as anti-human IgG (rabbit monoclonal to human IgG), Listeria monocytogenes, myoglobin and dengue capture antibodies were successfully immobilized. Further, standard sandwich immunoassay (antibody–antigen–antibody) is employed on respective capture antibody coated silicon substrates. Fluorescence microscopy is used to detect the respective FITC tagged detection antibodies bound to the surface after immunoassay.

  17. Influence of vibronic contribution on light harvesting efficiency of NKX-2587 derivatives with oligothiophene as π-conjugated linker

    Science.gov (United States)

    Yang, Pan; Zhang, Yang; Li, Ming; Shen, Wei; He, Rongxing

    2018-01-01

    Based on the NKX-2587 molecule we designed ten sensitizers with 1-10 thiophene moieties to investigate how the number of thiophene unit in the spacer influences the absorption spectra of sensitizer in dye sensitized solar cells (DSSCs). The parameters of short-circuit current density (Jsc), open circuit voltage (Voc), the light harvesting efficiency (LHE), injection driving force (Δ Ginject), and transferred electron number (nc), were calculated and discussed in detail. Results indicated that the increasing of thiophene units makes for the enhancement of oscillator strengths (f), although the red shift of vertical electronic absorption spectra is small. For the designed sensitizers with 1-5 thiophene units, their ΔGinject and nc raise gradually with the increasing of thiophene number. However, for those sensitizers with 6-10 thiophene units, the ΔGinject and nc decrease continuously with the increasing of thiophene units. In order to study how the oligothiophene as π-conjugated linker affects light harvesting efficiency of DSSCs, the vibrationally resolved electronic spectra of five metal-free NKX-2587 derivatives with 1-5 thiophene units were simulated within the Franck-Condon approximation including the Herzberg-Teller and Duschinsky effects. The present theoretical results provided helpful guidance for understanding the sources of spectral intensities of dye molecules, and a valuable method for rational design of new molecules to improve the energy conversion efficiency (η) of DSSCs.

  18. Structure and properties of Al-MIL-53-ADP, a breathing MOF based on the aliphatic linker molecule adipic acid.

    Science.gov (United States)

    Reinsch, Helge; Pillai, Renjith S; Siegel, Renée; Senker, Jürgen; Lieb, Alexandra; Maurin, Guillaume; Stock, Norbert

    2016-03-14

    The new aluminium based metal-organic framework [Al(OH)(O2C-C4H8-CO2)]·H2O denoted as Al-MIL-53-ADP-lp (lp stands for large pore) was synthesised under solvothermal conditions. This solid is an analogue of the archetypical aluminium terephthalate Al-MIL-53 based on the aliphatic single-chain linker molecule adipic acid (H2ADP, hexanedioic acid). In contrast to its aromatic counterparts, Al-MIL-53-ADP exhibits a structural breathing behaviour solely upon dehydration/rehydration. The crystal structure of the anhydrous compound denoted as Al-MIL-53-ADP-np (np stands for narrow pore) was determined by a combination of forcefield-based computations and Rietveld refinement of the powder X-ray diffraction data while the structure of the hydrated form Al-MIL-53-ADP-lp was derived computationally by a combination of force field based methods and Density Functional Theory calculations. Both structures were further supported by (1)H, (13)C and (27)Al high-resolution NMR MAS 1D data coupled again with simulations. Al-MIL-53-ADP was further characterised by means of vibrational spectroscopy, elemental analysis, thermogravimetry and water vapour sorption.

  19. Quality of life and neck pain in nurses

    Directory of Open Access Journals (Sweden)

    Lucy Joslin

    2014-04-01

    Full Text Available Objectives: To investigate the association between neck pain and psychological stress in nurses. Material and Methods: Nurses from the Avon Orthopaedic Centre completed 2 questionnaires: the Short Form-36 (SF-36 and 1 exploring neck pain and associated psychological stress. Results: Thirty four nurses entered the study (68% response. Twelve (35.3% had current neck pain, 13 (38.2% reported neck pain within the past year and 9 (26.5% had no neck pain. Subjects with current neck pain had significantly lower mental health (47.1 vs. 70.4; p = 0.002, physical health (60.8 vs. 76.8; p = 0.010 and overall SF-36 scores (56.8 vs. 74.9; p = 0.003. Five (41.7% subjects with current neck pain and 5 (38.5% subjects with neck pain in the previous year attributed it to psychological stress. Conclusions: Over 1/3 of nurses have symptomatic neck pain and significantly lower mental and physical health scores. Managing psychological stress may reduce neck pain, leading to improved quality of life for nurses, financial benefits for the NHS, and improved patient care.

  20. Purse-string platysmaplasty: the third dimension for neck contouring.

    Science.gov (United States)

    Gentile, Richard D

    2005-11-01

    Techniques and concepts for treatment of the aging neck have been evolving since the late 1960s and rely on two-dimensional anterior approximation with lateral imbrication of the platysma with or without submental fat reduction, However, the medial approximation can sometimes give a "boxy" appearance to the anterior neck, especially if anterior shifting of the platysma recurs after platysmaplasty with laxity redeveloping in this midline location. The "purse-string" platysmaplasty (PSP) is a new concept in neck contouring that facilitates an enhanced definition for the cervicomandibular transition to better simulate the well-defined contour of this transition that is present in youth. It aids in the contouring of difficult poorly defined necks and in male patients. The PSP adds a "third dimension" to neck recontouring by invaginating the platysma with a plication suture and pexing the platysma, without incising it, to deeper neck fascia with a technique that adds support and definition to the neck contour. The PSP can be performed in patients undergoing a full rhytidectomy as well as in individuals having isolated neck rejuvenation. The PSP is especially helpful in rejuvenating the male lower face and neck because of the relatively heavier deeper structures of the male neck and the need to enhance definition along the jawline.

  1. Musculoskeletal networks reveal topological disparity in mammalian neck evolution.

    Science.gov (United States)

    Arnold, Patrick; Esteve-Altava, Borja; Fischer, Martin S

    2017-12-13

    The increase in locomotor and metabolic performance during mammalian evolution was accompanied by the limitation of the number of cervical vertebrae to only seven. In turn, nuchal muscles underwent a reorganization while forelimb muscles expanded into the neck region. As variation in the cervical spine is low, the variation in the arrangement of the neck muscles and their attachment sites (i.e., the variability of the neck's musculoskeletal organization) is thus proposed to be an important source of neck disparity across mammals. Anatomical network analysis provides a novel framework to study the organization of the anatomical arrangement, or connectivity pattern, of the bones and muscles that constitute the mammalian neck in an evolutionary context. Neck organization in mammals is characterized by a combination of conserved and highly variable network properties. We uncovered a conserved regionalization of the musculoskeletal organization of the neck into upper, mid and lower cervical modules. In contrast, there is a varying degree of complexity or specialization and of the integration of the pectoral elements. The musculoskeletal organization of the monotreme neck is distinctively different from that of therian mammals. Our findings reveal that the limited number of vertebrae in the mammalian neck does not result in a low musculoskeletal disparity when examined in an evolutionary context. However, this disparity evolved late in mammalian history in parallel with the radiation of certain lineages (e.g., cetartiodactyls, xenarthrans). Disparity is further facilitated by the enhanced incorporation of forelimb muscles into the neck and their variability in attachment sites.

  2. Review of patients with dysphasia after a neck dissection

    International Nuclear Information System (INIS)

    Yokoyama, Junkichi

    2007-01-01

    The most useful modality for treating neck metastasis is a neck dissection. A neck dissection was previously performed as a radical neck dissection. However, disabilities in shoulder movement and swallowing function often occur after this procedure. Recently, a functional neck dissection has therefore been performed in order to avoid such postoperative complications. The current study for dysphasia after a neck dissection investigates patients with primary unknown neck metastasis and neck recurrence after chemoradiation. Eleven cases of dysphasia occurred after a neck dissection between 2003 and 2006. These cases resected the lower cranial nerves (IX, X, XII), or paralysis of these nerves occurred despite their preservation after surgery. Patients with dysphasia underwent rehabilitation to regain their swallowing function. However, rehabilitation was unsuccessful and the patients were thus required to undergo further surgery. A neck dissection with resection of the lower cranial nerves (IX, X, XII) may sometimes result in dysphasia. Consequently, surgery to prevent dysphasia should be performed simultaneously so that timely postoperative therapy can be carried out. (author)

  3. The role of USG in neck monitoring after surgery of malignant neoplasms of head and neck

    International Nuclear Information System (INIS)

    Szmeja, Z.; Kordylewska, M.; Dziamska, K.; Szyfter, W.; Kruk-Zagajewska, A.

    1994-01-01

    Metastases to regional lymph nodes of the neck in patients with larynx cancer are a more frequent cause of death in comparison to local recurrence. Thus it is necessary to thoroughly examine the treatment and after the treatment. The ultrasound examination introduced significant diagnostic value in the diagnosis of malignant cancers. Ultrasound monitoring of the lymphatic system after surgical treatment or radiation allows to diagnose early metastases which are not visible in palpation examination. In over 200 patients after surgical treatment of larynx cancer several ultrasound examinations of the neck were carried out. The time following the end of the treatment was 4 months to l 8 years. In the ultrasound examination of the neck changes in the lymphatic system were observed, which were not clinically manifested in 10 patients. Metastases to regional lymph nodes of the neck were most frequently observed in the first year after the operation. Patients who were diagnosed with metastases before operation and patients with supraglottic cancers were at more risk of having metastases. The ultrasound examination of the neck should be a routine, systematically repeated examination in the observation of patients after larynx cancer operation. (author)

  4. Neck circumference as a measure of neck fat and abdominal visceral fat in Chinese adults.

    Science.gov (United States)

    Li, Hong-Xing; Zhang, Fen; Zhao, Dong; Xin, Zhong; Guo, Shu-Qin; Wang, Shu-Mei; Zhang, Jian-Jun; Wang, Jun; Li, Yan; Yang, Guang-Ran; Yang, Jin-Kui

    2014-04-04

    Visceral adipose tissue (VAT) is a unique pathogenic fatty deposit, in that it is closely correlated with risk of cardiovascular diseases. The present study is to investigate the usefulness of neck circumference (NC) to indicate VAT. Participants aged 35 to 75 years who had taken abdomen and neck computer tomography (CT) examination were included in this study. Neck adipose tissue, abdominal VAT and subcutaneous adipose tissue (SAT) areas, as well as sagittal abdominal diameter (SAD) were measured by CT. Body anthropometrics and metabolic parameters including blood glucose, lipid profiles and blood pressure were also measured. A lower abdomen CT examination was carried out on a total of 177 patients (87 male and 90 female) with a mean age of 59 years. Of the 177 participants, 15 men and 15 women also took a neck CT examination. With a comparable age and BMI, neck adipose area was correlated with abdominal VAT area significantly in men (r = 0.57, p = 0.028) and women (r = 0.53, p = 0.041). NC is positively correlated with VAT both in men (r = 0.49, p fat both in men (r = 0.83, p fat area is significantly correlated with abdominal VAT. Meanwhile, SAD is the best predictor for visceral fat in the Chinese population.

  5. Effects of neck exercise on high-school students' neck-shoulder posture.

    Science.gov (United States)

    Lee, Myoung-Hyo; Park, Su-Jin; Kim, Jin-Sang

    2013-05-01

    [Purpose] This study examined the effects of deep flexor muscle-strengthening exercise on the neck-shoulder posture, and the strength and endurance of the deep flexor muscles of high-school students. [Subjects] The subjects were 30 seventeen-year-old female high-school students who complained about bad posture and chronic neck-shoulder pain. They were randomly divided into an experimental group of 15 subjects, who performed a deep flexor muscle-strengthening exercise and a control group of 15 subjects, who performed a basic stretching exercise. [Methods] The experimental group of 15 subjects performed a deep flexor muscle-strengthening exercise consisting of low-load training of the cranio-cervical flexor muscle, and the control group of 15 subjects performed a basic stretching exercise consisting of seven motions. [Results] The experimental group showed statistically significant changes in head tilt angle, neck flexion angle, forward shoulder angle, and the result of the cranio-cervical flexion test after the training. In contrast, the control group showed no statistically significant changes in these measures following the training. When the results of the groups were compared, statistically significant differences were found for all items between the experimental group and the control group. [Conclusion] Strengthening cranio-cervical flexor muscles is important for the adjustment of neck posture, and maintaining their stability is required to improve neck-shoulder posture.

  6. A disappearing left-sided neck mass.

    Science.gov (United States)

    Lutwak, Nancy; Dill, Curt

    2012-07-04

    The patient was a 48-year-old man who presented to the emergency department with complaints of a left-sided painful neck mass, which changed in size relative to ingestion of meals. He denied voice change, fever, chills, weight loss, dysphagia and hoarseness. Physical examination was unremarkable. CT scan demonstrated a 3.9 mm calculus of the submandibular gland duct. Therapeutic sialendocopy was successfully performed.

  7. Clinical and Surgical Anatomy of the Neck

    OpenAIRE

    Fernández Russo, Gustavo A.H.

    2012-01-01

    Introduction: to bring relevance on morphological details pertaining to medical and surgical applicability and demonstrate its value as an unavoidable mainstay for diagnosis and mangement of head and neck pathology.Materials and method: a. standarized dissections, of preserved adult human corpses, to obtain anatomical pieces for teaching purposes in school of medicine, axial slices and its comparative study with computed tomography (CT) images. b.application of normalized surgical techniques...

  8. Femoral neck fracture following groin irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Grigsby, Perry W; Roberts, Heidi L; Perez, Carlos A

    1995-04-30

    Purpose: The incidence and risk factors are evaluated for femoral neck fracture following groin irradiation for gynecologic malignancies. Methods and Materials: The radiation therapy records of 1313 patients with advanced and recurrent cancer of the vagina, vulva, cervix, and endometrium, treated at the Mallinckrodt Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was 12.7 years. From this group, 207 patients were identified who received irradiation to the pelvis and groins with anterposterior-posterior anterior (AP-PA), 18 MV photons. Data were reviewed regarding irradiation dose to the femoral neck and other presumed risk factors including age, primary site, stage, groin node status, menopausal status, estrogen use, cigarette use, alcohol consumption, and osteoporosis. Results: The per-patient incidence of femoral neck fracture was 4.8% (10 out of 207). Four patients developed bilateral fractures. However, the cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10 years. Cox multivariate analysis of age, weight, and irradiation dose showed that only irradiation dose may be important to developing fracture. Step-wise logistic regression of presumed prognostic factors revealed that only cigarette use and x-ray evidence of osteoporosis prior to irradiation treatment were predictive of fracture. Conclusion: Femoral head fracture is a common complication of groin irradiation for gynecologic malignancies. Fracture in our database appears to be related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis. Special attention should be given in treatment planning (i.e., shielding of femoral head/neck and use of appropriate electron beam energies for a portion of treatment) to reduce the incidence of this complication.

  9. Cancer of the head and neck

    International Nuclear Information System (INIS)

    Leignel, D.; Toledano, A.; Calais, G.; Gardner, M.; Valinta, D.; Halimi, P.; Alberini, J.L.; Plantet, M.M.; Banal, A.; Hans, S.; Floiras, J.L.; Labib, A.; Djemaa, A.; Naoun, L.; Bali, M.; Melais, K.; George, L.; Cazalet, M.; Gross, E.; Padovani, L.; Cowen, D.; Pignon, T.; Bannour, N.; Guedouar, R.; Bouaouina, N.; Mege, A.; Lapeyre, M.; Graff, P.; Marchesi, V.; Aletti, P.; Marchal, C.; Peiffert, D.; Serre, A.; Ailleres, N.; Lemanski, C.; Hay, M.H.; Llacer Moscardo, C.; Allaw, A.; Azria, D.; Dubois, J.B.; Fenoglietto, P.; Maalej, M.; Nasr, C.; Chaari, N.; Hentati, D.; Kochbati, L.; Besbes, M.; Benjelloun, H.; Benchakroun, N.; Houjami, M.; Jouhadi, H.; Tawfiq, N.; Acharki, A.; Sahraoui, S.; Benider, A.; Racadot, S.; Mercier, M.; Dessard-Diana, B.; Bensadoun, R.J.; Martin, M.; Malaurie, E.; Favrel, V.; Housset, M.; Journel, C.; Calais, G.; Huet, J.; Pillet, G.; Hennequin, C.; Haddad, E.; Diana, C.; Blaska-Jaulerry, B.; Henry-Amar, M.; Gehanno, P.; Baillet, F.; Mazeron, J.J.; Chaouache, C.K.; Tebra Mrad, T.M.S.; Bannour, B.N.S.; Bouaouina, B.N.; Favrel, V.; Khodri, M.; Chapet, O.; Nguyen, D.; Ardiet, J.; Romestaing, P.; Thillays, F.; Bardet, E.; Rolland, F.; Maingan, P.; Campion, L.; Mahe, M.A.

    2005-01-01

    Thirteen articles are presented in relation with head and neck cancer. Chemoradiotherapy, medical examinations using nuclear techniques such PET scanning, fractionated radiotherapy after a chemotherapy, analysis of dose volume for patients treated by irradiation with a combined chemotherapy, dosimetry, conformal radiotherapy with intensity modulation, dosimetry in brachytherapy, association of radiotherapy and chemotherapy in the treatment of nose pharynx carcinomas, recurrence, are the different subjects treated in this part. (N.C.)

  10. Femoral neck fracture following groin irradiation

    International Nuclear Information System (INIS)

    Grigsby, Perry W.; Roberts, Heidi L.; Perez, Carlos A.

    1995-01-01

    Purpose: The incidence and risk factors are evaluated for femoral neck fracture following groin irradiation for gynecologic malignancies. Methods and Materials: The radiation therapy records of 1313 patients with advanced and recurrent cancer of the vagina, vulva, cervix, and endometrium, treated at the Mallinckrodt Institute of Radiology from 1954 to 1992, were reviewed. Median follow-up was 12.7 years. From this group, 207 patients were identified who received irradiation to the pelvis and groins with anterposterior-posterior anterior (AP-PA), 18 MV photons. Data were reviewed regarding irradiation dose to the femoral neck and other presumed risk factors including age, primary site, stage, groin node status, menopausal status, estrogen use, cigarette use, alcohol consumption, and osteoporosis. Results: The per-patient incidence of femoral neck fracture was 4.8% (10 out of 207). Four patients developed bilateral fractures. However, the cumulative actuarial incidence of fracture was 11% at 5 years and 15% at 10 years. Cox multivariate analysis of age, weight, and irradiation dose showed that only irradiation dose may be important to developing fracture. Step-wise logistic regression of presumed prognostic factors revealed that only cigarette use and x-ray evidence of osteoporosis prior to irradiation treatment were predictive of fracture. Conclusion: Femoral head fracture is a common complication of groin irradiation for gynecologic malignancies. Fracture in our database appears to be related to irradiation dose, cigarette use, and x-ray evidence of osteoporosis. Special attention should be given in treatment planning (i.e., shielding of femoral head/neck and use of appropriate electron beam energies for a portion of treatment) to reduce the incidence of this complication

  11. Skin Cancer of the Head and Neck

    OpenAIRE

    Ouyang, Yun-Hsuan

    2010-01-01

    The majority of skin cancers of the head and neck are nonmelanoma skin cancers (NMSC). Basal cell carcinoma and squamous cell carcinoma are the most frequent types of NMSC. Malignant melanoma is an aggressive neoplasm of skin, and the ideal adjuvant therapy has not yet been found, although various options for treatment of skin cancer are available to the patient and physician, allowing high cure rate and excellent functional and cosmetic outcomes. Sunscreen protection and early evaluation of ...

  12. Predictors of Persistent Axial Neck Pain After Cervical Laminoplasty.

    Science.gov (United States)

    Kimura, Atsushi; Shiraishi, Yasuyuki; Inoue, Hirokazu; Endo, Teruaki; Takeshita, Katsushi

    2018-01-01

    Retrospective analysis of prospective data. The aim of this study was to reveal baseline predictors of persistent postlaminoplasty neck pain. Axial neck pain is one of the most common complications after cervical laminoplasty; however, baseline predictors of persistent postlaminoplasty neck pain are unclear. We analyzed data from 156 patients who completed a 2-year follow-up after double-door laminoplasty for degenerative cervical myelopathy. Patients rated the average intensity of axial neck pain in the last month using an 11-point numerical rating scale preoperatively and at the 2-year follow-up. The dependent variable was the presence of moderate-to-severe neck pain (numerical rating scale ≥4) at the 2-year follow-up. The independent variables included patient characteristics, baseline radiological parameters, surgical variables, baseline axial neck pain intensity, and baseline functions, which were measured by the Japanese Orthopaedic Association score and the Short Form-36 survey (SF-36). Logistic regression analysis was performed to identify independent predictors of moderate-to-severe neck pain after laminoplasty. At the 2-year follow-up, 51 patients (32%) had moderate-to-severe neck pain, and 106 patients (68%) had no or mild pain. Univariate analysis revealed that the ratio of cervical anterolisthesis, ratio of current smoking, baseline neck pain intensity, and baseline SF-36 Mental Component Summary differed significantly between the groups. Multivariate logistic regression analysis showed that independent predictors of moderate-to-severe neck pain at the 2-year follow-up include the presence of anterolisthesis, current smoking, moderate-to-severe baseline neck pain, and lower SF-36 Mental Component Summary. The presence of anterolisthesis and moderate-to-severe baseline neck pain were also associated with significantly poorer physical function after surgery. The presence of anterolisthesis was associated not only with the highest odds ratio of

  13. Ensuring Credit to Data Creators: A Case Study for Geodesy

    Science.gov (United States)

    Boler, F. M.; Gorman, A.

    2011-12-01

    facilitate citation for the purpose of ensuring credit to the data creators. UNAVCO's archiving and metadata management systems are generally well-suited to assigning and maintaining DOIs for two styles of logical collections of data: campaigns, which are spatially and temporally well-defined; and stations, which represent ongoing collection at a single spatial position at the Earth's surface. These two styles form the basis for implementing approximately 3,000 DOIs that can encompass the current holdings in the UNAVCO Archive. In addition, aggregations of DOIs into a superset DOI is advantageous for numerous cases where groupings of stations are naturally used in research studies. There are about 100 such natural collections of stations. However, research using GNSS data can also utilize several hundred or more stations in unique combinations, where tallying the individual DOIs within a reference list is cumbersome. We are grappling with the complexities that inevitably crop up when assigning DOIs, including subsetting, versioning, and aggregating. We also foresee the need for mechanisms for users to go beyond our predefined collections and/or aggregations to define their own ad-hoc collections. Our goal is to create a system for DOI assignment and utilization that succeeds in facilitating data citation within our community of geodesy scientists.

  14. Global Uranium Supply Ensured for Long Term, New Report Shows

    International Nuclear Information System (INIS)

    2012-01-01

    Full text: Uranium resources and production are on the rise with the security of uranium supply ensured for the long term, according to a new report by the OECD Nuclear Energy Agency (NEA) and the International Atomic Energy Agency (IAEA). Uranium 2011: Resources, Production and Demand, commonly referred to as the ''Red Book'', shows that total identified uranium resources have grown 12.5% since 2008. However, the costs of production have also increased, leading to reductions in lower cost category resources. These figures, which reflect the situation as of 1 January 2011, mean that total identified resources are sufficient for over 100 years of supply based on current requirements. Global uranium mine production increased by over 25% between 2008 and 2010 because of significantly increased production in Kazakhstan, currently the world's leading producer. The increased resource base has been achieved thanks to a 22% increase in uranium exploration and mine development expenditures between 2008 and 2010, which in 2010 totalled over $2 billion. Demand for uranium is expected to continue to rise for the foreseeable future. Although the Fukushima Daiichi nuclear accident has affected nuclear power projects and policies in some countries, nuclear power remains a key part of the global energy mix. Several governments have plans for new nuclear power plant construction, with the strongest expansion expected in China, India, the Republic of Korea and the Russian Federation. The speed and magnitude of growth in generating capacity elsewhere is still to be determined. By the year 2035, according to the joint NEA-IAEA Secretariat, world nuclear electricity generating capacity is projected to grow from 375 GWe net (at the end of 2010) to between 540 GWe net in the low demand case and 746 GWe net in the high demand case, increases of 44% and 99% respectively. Accordingly, world annual reactor-related uranium requirements are projected to rise from 63 875 tonnes of uranium metal

  15. Neck muscle biomechanics and neural control.

    Science.gov (United States)

    Fice, Jason Bradley; Siegmund, Gunter P; Blouin, Jean-Sebastien

    2018-04-18

    The mechanics, morphometry, and geometry of our joints, segments and muscles are fundamental biomechanical properties intrinsic to human neural control. The goal of our study was to investigate if the biomechanical actions of individual neck muscles predicts their neural control. Specifically, we compared the moment direction & variability produced by electrical stimulation of a neck muscle (biomechanics) to their preferred activation direction & variability (neural control). Subjects sat upright with their head fixed to a 6-axis load cell and their torso restrained. Indwelling wire electrodes were placed into the sternocleidomastoid (SCM), splenius capitis (SPL), and semispinalis capitis (SSC) muscles. The electrically stimulated direction was defined as the moment direction produced when a current (2-19mA) was passed through each muscle's electrodes. Preferred activation direction was defined as the vector sum of the spatial tuning curve built from RMS EMG when subjects produced isometric moments at 7.5% and 15% of their maximum voluntary contraction (MVC) in 26 3D directions. The spatial tuning curves at 15% MVC were well-defined (unimodal, pbiomechanics but, as activation increases, biomechanical constraints in part dictate the activation of synergistic neck muscles.

  16. Updates in Head and Neck Reconstruction.

    Science.gov (United States)

    Largo, Rene D; Garvey, Patrick B

    2018-02-01

    After reading this article, the participant should be able to: 1. Have a basic understanding of virtual planning, rapid prototype modeling, three-dimensional printing, and computer-assisted design and manufacture. 2. Understand the principles of combining virtual planning and vascular mapping. 3. Understand principles of flap choice and design in preoperative planning of free osteocutaneous flaps in mandible and midface reconstruction. 4. Discuss advantages and disadvantages of computer-assisted design and manufacture in reconstruction of advanced oncologic mandible and midface defects. Virtual planning and rapid prototype modeling are increasingly used in head and neck reconstruction with the aim of achieving superior surgical outcomes in functionally and aesthetically critical areas of the head and neck compared with conventional reconstruction. The reconstructive surgeon must be able to understand this rapidly-advancing technology, along with its advantages and disadvantages. There is no limit to the degree to which patient-specific data may be integrated into the virtual planning process. For example, vascular mapping can be incorporated into virtual planning of mandible or midface reconstruction. Representative mandible and midface cases are presented to illustrate the process of virtual planning. Although virtual planning has become helpful in head and neck reconstruction, its routine use may be limited by logistic challenges, increased acquisition costs, and limited flexibility for intraoperative modifications. Nevertheless, the authors believe that the superior functional and aesthetic results realized with virtual planning outweigh the limitations.

  17. CT perfusion study of neck lymph nodes

    International Nuclear Information System (INIS)

    Zhong Jin; Liu Jun; Hua Rui; Qiao Hui; Gong Yi

    2011-01-01

    Objective: To study the CT perfusion features of various lymph nodes in the neck. Methods: Dynamic perfusion CT scanning was performed in 83 neck lymph nodes proved by pathology, including tuberculosis lymph nodes, lymphoma and metastatic lymph nodes. The shapes, blood flow modes, and perfusion parameters of these lymph nodes were compared among 3 groups. Statistical analysis of L/T and CT perfusion parameters was performed by one-way ANOVA and LSD test. Results: The values of MTT of tuberculosis lymph nodes, lymphoma and metastatic lymph nodes were (28.13±5.08), (31.08±5.82), and (11.24±5.31) s, respectively. The MTT of metastatic lymph nodes was statistically lower than that of tuberculosis lymph nodes and lymphoma (P -1 · 100 g -1 , respectively. The values of BV were (24.68±2.84), (25.30±3.16), and (25.15± 8.81) ml·100 g -1 respectively. The values of TTP were (40.90±8.85), (40.67±6.45), and (40.98±6.62) s, respectively. There were no significant differences in L/T, BF, BV and TTP among tuberculosis lymph nodes, lymphoma and metastatic lymph nodes (P>0.05). Conclusion: CT perfusion, especially combination functional imaging with perfusion images may be helpful in judging the nature of neck lymph nodes. (authors)

  18. Head and Neck Cancers in Developing Countries

    Directory of Open Access Journals (Sweden)

    Poonam Joshi

    2014-04-01

    Full Text Available Head and neck cancers are the most common cancers in developing countries, especially in Southeast Asia. Head and neck cancers are more common in males compared to females. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC. HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The annual GDP (gross domestic product spent on health care is very low in developing countries compared to the developed countries. Cancer treatment leads to a significant financial burden on the cancer patients and their families. Several health programs have been implemented to curb this rising burden of disease. The main aims of these health programs are to increase awareness among people regarding tobacco and to improve access to health care facilities, early diagnosis, treatment, and palliative care.

  19. Talar Neck Fracture after United Tibiotalar Fusion

    Directory of Open Access Journals (Sweden)

    W. Platt

    2015-01-01

    Full Text Available Tibiotalar arthrodesis is a well-established treatment for tibiotalar arthritis, for example, in younger high demand patients. Talar neck fractures are less common though well-recognised sequelae of foot ankle trauma. Here we present the clinical case of a 69-year-old male who presented to our institution with a nonunion of a talar neck fracture, having undergone a left tibiotalar fusion 24 years previously. To the authors’ knowledge, this injury has only been described once previously in the literature. However, the original case described a fracture sustained in the very early postoperative period following tibiotalar fusion, postulated to be secondary to postimmobilisation osteopaenia or stress risers from metalwork. The aetiology in this case is likely due to axial compression transmitted to the talar neck via the calcaneus. The predisposing factors for nonunion are discussed, highlighting the importance of vigilance for this injury in any patient with concomitant tibiotalar fusion and foot trauma. The management of this patient is discussed.

  20. A Dual-Purpose Linker for Alpha Helix Stabilization and Imaging Agent Conjugation to Glucagon-Like Peptide-1 Receptor Ligands

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Liao, Jianshan; Thurber, Greg M.

    2016-01-01

    Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using the glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel alpha helix stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enables this technique to potentially be used as a general method for labeling alpha helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents. PMID:25594741