WorldWideScience

Sample records for single mouse click

  1. Flexible Piezoelectric Energy Harvesting from Mouse Click Motions

    Directory of Open Access Journals (Sweden)

    Youngsu Cha

    2016-07-01

    Full Text Available In this paper, we study energy harvesting from the mouse click motions of a robot finger and a human index finger using a piezoelectric material. The feasibility of energy harvesting from mouse click motions is experimentally and theoretically assessed. The fingers wear a glove with a pocket for including the piezoelectric material. We model the energy harvesting system through the inverse kinematic framework of parallel joints in a finger and the electromechanical coupling equations of the piezoelectric material. The model is validated through energy harvesting experiments in the robot and human fingers with the systematically varying load resistance. We find that energy harvesting is maximized at the matched load resistance to the impedance of the piezoelectric material, and the harvested energy level is tens of nJ.

  2. Aiming and clicking in young children's use of the computer mouse

    NARCIS (Netherlands)

    Donker, A.; Reitsma, P.

    2007-01-01

    The present study investigated the abilities of young children to aim and click with a computer mouse. Young children have not yet fully developed their motor skills and they are therefore more likely than adults to click next to targets on the computer screen. Because in educational software

  3. Brain potentials after clicking a mouse: a new psychophysiological approach to human-computer interaction.

    Science.gov (United States)

    Nittono, Hiroshi; Hamada, Aya; Hori, Tadao

    As a first step in developing a new psychophysiological technique to assess mental workload in human-computer interaction (HCI), we recorded event-related brain potentials for visual stimuli triggered by voluntary mouse clicks. Twelve university students clicked a mouse button at their own pace. Each click triggered 1 of 3 alphabetic letters assigned to frequent standard, rare target, and rare nontarget stimuli. Counting target stimuli was required. Both rare stimuli elicited a P3 (P300) wave, the amplitude of which was larger when the stimuli were triggered by mouse clicks than when the same stimuli were presented automatically without mouse clicks. Postmotor potentials associated with clicking were small in amplitude (<2 microV) and did not temporally overlap with the P3. The findings suggest that the P3 can be recorded for a computer's response to the user's intentional action and may be used as a measure of perceptual-central processing resources allocated to the HCI task. Actual or potential applications of this research include the evaluation of the user's attentional state during HCI byrecording brain potentials in the "mouse click" or action-perception paradigm.

  4. Neglect of bandwidth of Odontocetes echo location clicks biases propagation loss and single hydrophone population estimates

    NARCIS (Netherlands)

    Ainslie, M.A.

    2013-01-01

    Passive acoustic monitoring with a single hydrophone has been suggested as a cost-effective method to monitor population density of echolocating marine mammals, by estimating the distance at which the hydrophone is able to intercept the echolocation clicks and distinguish these from the background.

  5. Large-scale separation of single-walled carbon nanotubes by electronic type using click chemistry

    Science.gov (United States)

    Um, Jo-Eun; Song, Sun Gu; Yoo, Pil J.; Song, Changsik; Kim, Woo-Jae

    2018-01-01

    Single-walled carbon nanotubes (SWCNTs) can be either metallic or semiconducting, making their separation critical for applications in nanoelectronics, biomedical materials, and solar cells. Herein, we investigate a novel solution-phase separation method based on click chemistry (azide-alkyne Huisgen cycloaddition) and determine its efficiency and scalability. In this method, metallic SWCNTs in metallic/semiconducting SWCNT mixtures are selectively functionalized with alkyne groups by being reacted with 4-propargyloxybenezenediazonium tetrafluoroborate. Subsequently, silica nanoparticles are functionalized with azide groups and reacted with alkyne-bearing metallic SWCNTs in the SWCNT mixture in the presence of a Cu catalyst. As a result, metallic SWCNTs are anchored on silica powder, whereas non-functionalized semiconducting SWCNTs remain in solution. Low-speed centrifugation effectively removes the silica powder with attached metallic SWCNTs, furnishing a solution of highly pure semiconducting SWCNTs, as confirmed by Raman and UV-vis/near-infrared absorption measurements. This novel separation scheme exhibits the advantage of simultaneously separating both metallic and semiconducting SWCNTs from their mixtures, being cost-effective and therefore applicable at an industrial scale.

  6. Automatic Classification of Users' Health Information Need Context: Logistic Regression Analysis of Mouse-Click and Eye-Tracker Data.

    Science.gov (United States)

    Pian, Wenjing; Khoo, Christopher Sg; Chi, Jianxing

    2017-12-21

    Users searching for health information on the Internet may be searching for their own health issue, searching for someone else's health issue, or browsing with no particular health issue in mind. Previous research has found that these three categories of users focus on different types of health information. However, most health information websites provide static content for all users. If the three types of user health information need contexts can be identified by the Web application, the search results or information offered to the user can be customized to increase its relevance or usefulness to the user. The aim of this study was to investigate the possibility of identifying the three user health information contexts (searching for self, searching for others, or browsing with no particular health issue in mind) using just hyperlink clicking behavior; using eye-tracking information; and using a combination of eye-tracking, demographic, and urgency information. Predictive models are developed using multinomial logistic regression. A total of 74 participants (39 females and 35 males) who were mainly staff and students of a university were asked to browse a health discussion forum, Healthboards.com. An eye tracker recorded their examining (eye fixation) and skimming (quick eye movement) behaviors on 2 types of screens: summary result screen displaying a list of post headers, and detailed post screen. The following three types of predictive models were developed using logistic regression analysis: model 1 used only the time spent in scanning the summary result screen and reading the detailed post screen, which can be determined from the user's mouse clicks; model 2 used the examining and skimming durations on each screen, recorded by an eye tracker; and model 3 added user demographic and urgency information to model 2. An analysis of variance (ANOVA) analysis found that users' browsing durations were significantly different for the three health information contexts

  7. Efficient One-click Browsing of Large Trajectory Sets

    DEFF Research Database (Denmark)

    Krogh, Benjamin Bjerre; Andersen, Ove; Lewis-Kelham, Edwin

    2014-01-01

    presents a novel query type called sheaf, where users can browse trajectory data sets using a single mouse click. Sheaves are very versatile and can be used for location-based advertising, travel-time analysis, intersection analysis, and reachability analysis (isochrones). A novel in-memory trajectory...

  8. Engineering single-molecule, nanoscale, and microscale bio-functional materials via click chemistry

    Science.gov (United States)

    Daniele, Michael Angelo-Anthony

    To expand the design envelope and supplement the materials library available to biomaterials scientists, the copper(I)-catalyzed azide-alkyne cycloaddition (CuCAAC) was explored as a route to design, synthesize and characterize bio-functional small-molecules, nanoparticles, and microfibers. In each engineered system, the use of click chemistry provided facile, bio-orthogonal control for materials synthesis; moreover, the results provided a methodology and more complete, fundamental understanding of the use of click chemistry as a tool for the synergy of biotechnology, polymer and materials science. Fluorophores with well-defined photophysical characteristics (ranging from UV to NIR fluorescence) were used as building blocks for small-molecule, fluorescent biosensors. Fluorophores were paired to exhibit fluorescence resonant energy transfer (FRET) and used to probe the metabolic activity of carbazole 1,9a-dioxygenase (CARDO). The FRET pair exhibited a significant variation in PL response with exposure to the lysate of Pseudomonas resinovorans CA10, an organism which can degrade variants of both the donor and acceptor fluorophores. Nanoparticle systems were modified via CuCAAC chemistry to carry affinity tags for CARDO and were subsequently utilized for affinity based bioseparation of CARDO from crude cell lysate. The enzymes were baited with an azide-modified carbazolyl-moiety attached to a poly(propargyl acrylate) nanoparticle. Magnetic nanocluster systems were also modified via CuCAAC chemistry to carry fluorescent imaging tags. The iron-oxide nanoclusters were coated with poly(acrylic acid-co-propargyl acrylate) to provide a clickable surface. Ultimately, alternate Cu-free click chemistries were utilized to produce biohybrid microfibers. The biohybrid microfibers were synthesized under benign photopolymerization conditions inside a microchannel, allowing the encapsulation of viable bacteria. By adjusting pre-polymer solutions and laminar flow rates within the

  9. Functionalization of single-walled carbon nanotubes with protein by click chemistry as sensing platform for sensitized electrochemical immunoassay

    International Nuclear Information System (INIS)

    Qi Honglan; Ling Chen; Huang Ru; Qiu Xiaoying; Shangguan Li; Gao Qiang; Zhang Chengxiao

    2012-01-01

    Highlights: ► Single-walled carbon nanotubes were functionalized with protein by click chemistry. ► The SWNTs conjugated with protein showed excellent dispersion in water and kept good bioacitvity. ► A competitive electrochemical immunoassay for the determination of anti-IgG was developed with high sensitivity and good stability. - Abstract: The application of the Cu(I)-catalyzed [3 + 2] Huisgen cycloaddition to the functionalization of single-walled carbon nanotubes (SWNTs) with the protein and the use of the artificial SWNTs as a sensing platform for sensitive immunoassay were reported. Covalent functionalization of azide decorated SWNTs with alkyne modified protein was firstly accomplished by the Cu(I)-catalyzed [3 + 2] Huisgen cycloaddition. FT-IR spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron micrograph were used to characterize the protein-functionalized SWNTs. It was found that the SWNTs conjugated with the proteins showed excellent dispersion in water and kept good bioacitivity when immunoglobulin (IgG) and horseradish peroxidase (HRP) were chosen as model proteins. As a proof-of-concept, IgG-functionalized SWNTs were immobilized onto the surface of a glassy carbon electrode by simple casting method as immunosensing platform and a sensitive competitive electrochemical immunoassay was developed for the determination of anti-immunoglobulin (anti-IgG) using HRP as enzyme label. The fabrication of the immunosensor were characterized by cyclic voltammetry and electrochemical impedance spectroscopy with the redox probe [Fe(CN) 6 ] 3−/4− . The SWNTs as immobilization platform showed better sensitizing effect, a detection limit of 30 pg mL −1 (S/N = 3) was obtained for anti-IgG. The proposed strategy provided a stable immobilization method and sensitized recognition platform for analytes. This work demonstrated that the click coupling of SWNTs with protein was an effective

  10. Covalently {beta}-cyclodextrin modified single-walled carbon nanotubes: a novel artificial receptor synthesized by 'click' chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Guo Zhen; Liang Li [Nankai University, State Key Laboratory and Institute of Elemento-Organic Chemistry (China); Liang Jiajie; Ma Yanfeng; Yang Xiaoying [Nankai University, Center for Nanoscale Science and Technology and Institute of Polymer Chemistry, College of Chemistry (China); Ren Dongmei [Nankai University, State Key Laboratory and Institute of Elemento-Organic Chemistry (China); Chen Yongsheng [Nankai University, Center for Nanoscale Science and Technology and Institute of Polymer Chemistry, College of Chemistry (China); Zheng Jianyu, E-mail: jyzheng@nankai.edu.c [Nankai University, State Key Laboratory and Institute of Elemento-Organic Chemistry (China)

    2008-08-15

    Novel {beta}-cyclodextrin covalently modified single-walled carbon nanotubes have been synthesized via a 'click' coupling reaction. The product was fully characterized with Raman, FTIR, XRD, UV-Vis-NIR spectra as well as TEM and TGA measurements. The effective functionalization via 'click' coupling has set up a facile and versatile route for modular preparation of SWNTs based functional materials. The inclusion complexation behavior of this artificial receptor with quinine has been investigated in aqueous solution by fluorescence spectroscopy.

  11. Effect of computer mouse gain and visual demand on mouse clicking performance and muscle activation in a young and elderly group of experienced computer users

    DEFF Research Database (Denmark)

    Sandfeld, Jesper; Jensen, Bente R.

    2005-01-01

    The present study evaluated the specific effects of motor demand and visual demands on the ability to control motor output in terms of performance and muscle activation. Young and elderly subjects performed multidirectional pointing tasks with the computer mouse. Three levels of mouse gain...... and three levels of target size were used. All subjects demonstrated a reduced working speed and hit rate at the highest mouse gain (1:8) when the target size was small. The young group had an optimum at mouse gain 1:4. The elderly group was most sensitive to the combination of high mouse gain and small...... was only to a minor degree influenced by mouse gain (and target sizes) indicating that stability of the forearm/hand is of significance during computer mouse control. The study has implications for ergonomists, pointing device manufacturers and software developers....

  12. Think Before You Click

    CERN Multimedia

    2001-01-01

    Be aware of what attachments you open and what Internet programs you agree to download, the simple click of a mouse can be enough to introduce a virus at CERN and cause widespread damage. Modern viruses are a serious threat to our computers and networks. CERN limits the security risks that these programs pose through the use of its firewall, by constantly updating its anti-virus software, by detecting un-patched security holes, and by blocking many dangerous attachments as they pass through e-mail gateways, but these defenses do not guarantee 100% security. Our habits of clicking "ok" automatically on the Internet and opening attachments without thinking, are the behaviors that modern viruses are using to get past our security protections. Viruses can sit on the Internet waiting for us to activate them as we surf the web. Many of us simply click 'ok' when presented with dialogue boxes and this is exactly what the virus wants: clicking can be enough to download and infect our computers. Viruses can travel as...

  13. Click bait

    DEFF Research Database (Denmark)

    Blom, Jonas Nygaard; Reinecke Hansen, Kenneth

    2015-01-01

    This is why you should read this article. Although such an opening statement does not make much sense read in isolation, journalists often write headlines like this on news websites. They use the forward-referring technique as a stylistic and narrative luring device trying to induce anticipation...... and curiosity so the readers click (or tap on) the headline and read on. In this article, we map the use of forward-referring headlines in online news journalism by conducting an analysis of 100,000 headlines from 10 different Danish news websites. The results show that commercialization and tabloidization seem...

  14. Thermodynamics and kinetics of DNA nanotube polymerization from single-filament measurements† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c3sc53331j Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

    Science.gov (United States)

    Hariadi, Rizal F.; Yurke, Bernard

    2015-01-01

    DNA nanotubes provide a programmable architecture for molecular self-assembly and can serve as model systems for one-dimensional biomolecular assemblies. While a variety of DNA nanotubes have been synthesized and employed as models for natural biopolymers, an extensive investigation of DNA nanotube kinetics and thermodynamics has been lacking. Using total internal reflection microscopy, DNA nanotube polymerization was monitored in real time at the single filament level over a wide range of free monomer concentrations and temperatures. The measured polymerization rates were subjected to a global nonlinear fit based on polymerization theory in order to simultaneously extract kinetic and thermodynamic parameters. For the DNA nanotubes used in this study, the association rate constant is (5.99 ± 0.15) × 105 M–1 s–1, the enthalpy is 87.9 ± 2.0 kcal mol–1, and the entropy is 0.252 ± 0.006 kcal mol–1 K–1. The qualitative and quantitative similarities between the kinetics of DNA nanotubes, actin filaments, and microtubules polymerization highlight the prospect of building complex dynamic systems from DNA molecules inspired by biological architecture. PMID:29308139

  15. Sperm whale clicks

    DEFF Research Database (Denmark)

    Møhl, Bertel; Wahlberg, Magnus; Madsen, Peter T.

    2000-01-01

    . A sound generator weighing upward of 10 tons and with a cross-section of 1 m is expected to generate high-intensity, directional sounds. This prediction from the Norris and Harvey theory is not supported by published data for sperm whale clicks ~source levels of 180 dB re 1 mPa and little, if any....... This implicates sonar as a possible function of the clicks. Thus, previously published properties of sperm whale clicks underestimate the capabilities of the sound generator and therefore cannot falsify the Norris and Harvey theory.......In sperm whales ~Physeter catodon L. 1758! the nose is vastly hypertrophied, accounting for about one-third of the length or weight of an adult male. Norris and Harvey @in Animal Orientation and Navigation, NASA SP-262 ~1972!, pp. 397–417# ascribed a sound-generating function to this organ complex...

  16. Computer Security: one click and BOOM…

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2016-01-01

    Browsing the World Wide Web is not as easy as it seems… One wrong click and all your passwords (CERN, Facebook, PayPal, Amazon, etc.) could be stolen; all your activities could be clandestinely monitored (mouse movements and clicks, words typed, screenshots, microphone and webcam recordings, etc.); confidential documents could be stolen; and an attack path (a so-called back-door) into CERN could be opened…    As a result, you would have to reinstall your computer from scratch and change all your passwords! One of our colleagues learned this the hard way. One wrong click in summer 2015 permitted malicious attackers to infiltrate CERN but, fortunately, no real damage was done. Still, the cost of investigating the incident ran to several tens of thousands of Swiss francs and a lot of time was wasted trying to understand the attacker’s intent and the extent of the infiltration... With the goal of increasing more awareness of the risk of clicking on li...

  17. Isolation of Kupffer Cells and Hepatocytes from a Single Mouse Liver

    DEFF Research Database (Denmark)

    Aparicio-Vergara, Marcela; Tencerova, Michaela; Morgantini, Cecilia

    2017-01-01

    one viable hepatic cellular fraction from a single mouse; either parenchymal (hepatocytes) or non-parenchymal cells (i.e., Kupffer cells or hepatic stellate cells). Here, we describe a method to isolate both hepatocytes and Kupffer cells from a single mouse liver, thereby providing the unique......Liver perfusion is a common technique used to isolate parenchymal and non-parenchymal liver cells for in vitro experiments. This method allows hepatic cells to be separated based on their size and weight, by centrifugation using a density gradient. To date, other methods allow the isolation of only...... advantage of studying different liver cell types that have been isolated from the same organism....

  18. Click Here To Buy.

    Science.gov (United States)

    Bridgman, Anne

    2000-01-01

    E-commerce is coming slowly to education, but some curious school purchasing officials are clicking on vendors' web sites. Pioneering districts include the Chicago, Detroit, and El Dorado (California) public schools. Vendors include Boise Cascade and Office Depot. Some vendors are joining institutional exchanges like Commerce One or marketing…

  19. Monitoring the native phosphorylation state of plasma membrane proteins from a single mouse cerebellum

    DEFF Research Database (Denmark)

    Schindler, J.; Ye, J. Y.; Jensen, Ole Nørregaard

    2013-01-01

    proteins are major targets of the signalling cascades, we developed a protocol to monitor their phosphorylation state starting from a single mouse cerebellum. An aqueous polymer two-phase system was used to enrich for plasma membrane proteins. Subsequently, calcium phosphate precipitation, immobilized...... metal affinity chromatography, and TiO2 were combined to a sequential extraction procedure prior to mass spectrometric analyses. This strategy resulted in the identification of 1501 different native phosphorylation sites in 507 different proteins. 765 (51%) of these phosphorylation sites were localized...

  20. Effect of BCNU on mouse skin and spinal cord in single drug and radiation exposures

    International Nuclear Information System (INIS)

    Lelieveld, P.; Brown, J.M.; Goffinet, D.R.; Schoeppel, S.L.; Scoles, M.

    1979-01-01

    We set out to determine whether any interaction occurs between BCNU and radiation for the mouse skin and spinal cord. Single doses of BCNU of 10, 20, or 30 mg/kg were injected intraperitoneally as a function of time before or after irradiation of the foot or spinal cord of anesthesized C3H mice. Enhancement of the radiation skin reaction (dose enhancement factor = 1.3) was seen when BCNU (30 mg/kg) was given 1 day, 6 hr, and 2 hr prior to irradiation of the foot with 2,500 rad, and a larger DEF of 1.6 was observed when BCNU was given immediately before the radiation dose. However, with a different mouse strain (BALB/c) not anesthetized at the time of irradiation, no significant enhancement following a dose of 20 mg/kg BCNU was observed. Experiments are in progress to determine the cause of these differences. BCNU (10 mg/kg) was given 24 hr or immediately prior to various single doses of radiation to a 12 mm segment of the mouse spinal cord (T/sub 11-12/ to L/sub 1-2/), and the subsequent myelitis was scored monthly. The addition of BCNU to irradiation did not accelerate the development of myelitis, not the ultimate proportion of animals developing hind limb paralysis: the 50% myelitis dose at 10 months (MD/sub 50/10/sub mo/) values for irradiation alone, BCNU at the time of irradiation and 24 hr before were 3,722, 3,795 and 3,853 rad, respectively

  1. Cryo-imaging of fluorescently labeled single cells in a mouse

    Science.gov (United States)

    Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.

    2009-02-01

    We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron

  2. Click Analytics: Visualizing Website Use Data

    OpenAIRE

    Tabatha A. Farney

    2011-01-01

    Click analytics is a powerful technique that displays what and where users are clicking on a webpage helping libraries to easily identify areas of high and low usage on a page without having to decipher website use data sets. Click analytics is a subset of web analytics, but there is little research that discusses its potential uses for libraries. This paper introduces three click analytics tools, Google Analytics’ In-Page Analytics, ClickHeat, and Crazy Egg, and evaluates their usefulness in...

  3. A bright single-cell resolution live imaging reporter of Notch signaling in the mouse.

    Science.gov (United States)

    Nowotschin, Sonja; Xenopoulos, Panagiotis; Schrode, Nadine; Hadjantonakis, Anna-Katerina

    2013-04-25

    Live imaging provides an essential methodology for understanding complex and dynamic cell behaviors and their underlying molecular mechanisms. Genetically-encoded reporter expressing mouse strains are an important tool for use in live imaging experiments. Such reporter strains can be engineered by placing cis-regulatory elements of interest to direct the expression of desired reporter genes. If these cis-regulatory elements are downstream targets, and thus activated as a consequence of signaling pathway activation, such reporters can provide read-outs of the signaling status of a cell. The Notch signaling pathway is an evolutionary conserved pathway operating in multiple developmental processes as well as being the basis for several congenital diseases. The transcription factor CBF1 is a central evolutionarily conserved component of the Notch signaling pathway. It binds the active form of the Notch receptor (NICD) and subsequently binds to cis-regulatory regions (CBF1 binding sites) in the promoters of Notch responsive genes. In this way, CBF1 binding sites represent a good target for the design of a Notch signaling reporter. To generate a single-cell resolution Notch signaling reporter, we used a CBF responsive element to direct the expression of a nuclear-localized fluorescent protein. To do this, we linked 4 copies of a consensus CBF1 binding site to the basal simian virus 40 (SV40) promoter, placed this cassette in front of a fluorescent protein fusion comprising human histone H2B linked to the yellow fluorescent protein (YFP) Venus, one of the brightest available YFPs. We used the CBF:H2B-Venus construct to generate both transgenic embryonic mouse stem (ES) cell lines and a strain of transgenic mice that would report Notch signaling activity. By using multiple CBF1 binding sites together with a subcellular-localized, genetically-encoded fluorescent protein, H2B-Venus, we have generated a transgenic strain of mice that faithfully recapitulates Notch signaling

  4. Ways to suppress click and pop for class D amplifiers

    Science.gov (United States)

    Haishi, Wang; Bo, Zhang; Jiang, Sun

    2012-08-01

    Undesirable audio click and pop may be generated in a speaker or headphone. Compared to linear (class A/B/AB) amplifiers, class D amplifiers that comprise of an input stage and a modulation stage are more prone to producing click and pop. This article analyzes sources that generate click and pop in class D amplifiers, and corresponding ways to suppress them. For a class D amplifier with a single-ended input, click and pop is likely to be due to two factors. One is from a voltage difference (VDIF) between the voltage of an input capacitance (VCIN) and a reference voltage (VREF) of the input stage, and the other one is from the non-linear switching during the setting up of the bias and feedback voltages/currents (BFVC) of the modulation stage. In this article, a fast charging loop is introduced into the input stage to charge VCIN to roughly near VREF. Then a correction loop further charges or discharges VCIN, substantially equalizing it with VREF. Dummy switches are introduced into the modulation stage to provide switching signals for setting up BFVC, and the power switches are disabled until the BFVC are set up successfully. A two channel single-ended class D amplifier with the above features is fabricated with 0.5 μm Bi-CMOS process. Road test and fast Fourier transform analysis indicate that there is no noticeable click and pop.

  5. Linking Metal Ions via Inorganic Click (iClick) Reactions

    Energy Technology Data Exchange (ETDEWEB)

    Veige, Adam [Univ. of Florida, Gainesville, FL (United States)

    2015-11-17

    This final report discusses the major objectives of the project, a discussion of the objectives achieved, a discussion of the objectives that failed, and finally, a discussion of future directions given the new knowledge obtained. This one-year seed project (with one year no-cost extension) contained three objectives: A) Expand the scope of iClick synthesis beyond AuI/AuI reactions. B) Elucidate a CuI-catalyzed iClick reaction. C) Synthesize and characterize tri- and tetra-metallic complexes as models for metallopolymers. Objectives A and C were achieved, whereas only parts of objective B were achieved.

  6. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels

    2014-01-01

    of sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz......In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator......, 350 ms tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue, LIF) intervals, while force and [Ca(2+)]i were measured. Stimulation continued until force decreased to 30% of its initial value. Fibres were then prepared for analyses of subcellular glycogen distribution...

  7. Grafting of a single donor myofibre promotes hypertrophy in dystrophic mouse muscle.

    Directory of Open Access Journals (Sweden)

    Luisa Boldrin

    Full Text Available Skeletal muscle has a remarkable capability of regeneration following injury. Satellite cells, the principal muscle stem cells, are responsible for this process. However, this regenerative capacity is reduced in muscular dystrophies or in old age: in both these situations, there is a net loss of muscle fibres. Promoting skeletal muscle muscle hypertrophy could therefore have potential applications for treating muscular dystrophies or sarcopenia. Here, we observed that muscles of dystrophic mdx nude host mice that had been acutely injured by myotoxin and grafted with a single myofibre derived from a normal donor mouse exhibited increased muscle area. Transplantation experiments revealed that the hypertrophic effect is mediated by the grafted fibre and does not require either an imposed injury to the host muscle, or the contribution of donor cells to the host muscle. These results suggest the presence of a crucial cross-talk between the donor fibre and the host muscle environment.

  8. Grafting of a Single Donor Myofibre Promotes Hypertrophy in Dystrophic Mouse Muscle

    Science.gov (United States)

    Boldrin, Luisa; Morgan, Jennifer E.

    2013-01-01

    Skeletal muscle has a remarkable capability of regeneration following injury. Satellite cells, the principal muscle stem cells, are responsible for this process. However, this regenerative capacity is reduced in muscular dystrophies or in old age: in both these situations, there is a net loss of muscle fibres. Promoting skeletal muscle muscle hypertrophy could therefore have potential applications for treating muscular dystrophies or sarcopenia. Here, we observed that muscles of dystrophic mdx nude host mice that had been acutely injured by myotoxin and grafted with a single myofibre derived from a normal donor mouse exhibited increased muscle area. Transplantation experiments revealed that the hypertrophic effect is mediated by the grafted fibre and does not require either an imposed injury to the host muscle, or the contribution of donor cells to the host muscle. These results suggest the presence of a crucial cross-talk between the donor fibre and the host muscle environment. PMID:23349935

  9. Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq

    Directory of Open Access Journals (Sweden)

    Ozgun Gokce

    2016-07-01

    Full Text Available The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states.

  10. The Click and Twitch in Contemporary Poetry.

    Science.gov (United States)

    Meredith, Bernard

    It is the creative writing instructor's role to help the student turn "twitch" poems into "click" poems ("twitch" being a kind of verbal hypertension that takes shape in the absence of anything humanly important to say on the poet's part and "click" being the finished poem that makes a sound like the click of the lid on a perfectly made box).…

  11. Click Analytics: Visualizing Website Use Data

    Directory of Open Access Journals (Sweden)

    Tabatha A. Farney

    2011-09-01

    Full Text Available Click analytics is a powerful technique that displays what and where users are clicking on a webpage helping libraries to easily identify areas of high and low usage on a page without having to decipher website use data sets. Click analytics is a subset of web analytics, but there is little research that discusses its potential uses for libraries. This paper introduces three click analytics tools, Google Analytics’ In-Page Analytics, ClickHeat, and Crazy Egg, and evaluates their usefulness in the context of redesigning a library’s homepage.

  12. Structure of a single whisker representation in layer 2 of mouse somatosensory cortex.

    Science.gov (United States)

    Clancy, Kelly B; Schnepel, Philipp; Rao, Antara T; Feldman, Daniel E

    2015-03-04

    Layer (L)2 is a major output of primary sensory cortex that exhibits very sparse spiking, but the structure of sensory representation in L2 is not well understood. We combined two-photon calcium imaging with deflection of many whiskers to map whisker receptive fields, characterize sparse coding, and quantitatively define the point representation in L2 of mouse somatosensory cortex. Neurons within a column-sized imaging field showed surprisingly heterogeneous, salt-and-pepper tuning to many different whiskers. Single whisker deflection elicited low-probability spikes in highly distributed, shifting neural ensembles spanning multiple cortical columns. Whisker-evoked response probability correlated strongly with spontaneous firing rate, but weakly with tuning properties, indicating a spectrum of inherent responsiveness across pyramidal cells. L2 neurons projecting to motor and secondary somatosensory cortex differed in whisker tuning and responsiveness, and carried different amounts of information about columnar whisker deflection. From these data, we derive a quantitative, fine-scale picture of the distributed point representation in L2. Copyright © 2015 the authors 0270-6474/15/353946-13$15.00/0.

  13. Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

    International Nuclear Information System (INIS)

    Doerr, W.; Kummermehr, J.

    1990-01-01

    Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

  14. Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation

    Directory of Open Access Journals (Sweden)

    Hisham Mohammed

    2017-08-01

    Full Text Available The mouse inner cell mass (ICM segregates into the epiblast and primitive endoderm (PrE lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

  15. Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor

    Directory of Open Access Journals (Sweden)

    Ren Guo

    2017-08-01

    Full Text Available Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps using only one transcription factor (TF (Foxa1, Foxa2, or Foxa3 plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah−/− mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps.

  16. Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation.

    Science.gov (United States)

    Mohammed, Hisham; Hernando-Herraez, Irene; Savino, Aurora; Scialdone, Antonio; Macaulay, Iain; Mulas, Carla; Chandra, Tamir; Voet, Thierry; Dean, Wendy; Nichols, Jennifer; Marioni, John C; Reik, Wolf

    2017-08-01

    The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

    Science.gov (United States)

    Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

    2015-12-01

    Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

  18. Cows, clicks, ciphers, and satire

    Directory of Open Access Journals (Sweden)

    Tom Tyler

    2015-04-01

    Full Text Available The social network game Farmville, which allows players to grow crops, raise animals, and produce a variety of goods, proved enormously successful within a year of its launch in 2009, attracting 110 million Facebook users. However, the game has been criticised for its mindless mechanics, which require little more than repeated clicking on its colourful icons. By way of parody, Ian Bogost’s Cow Clicker permits its players to simply click on a picture of a cow once every six hours. In this essay I extend Bogost’s critique and suggest that Cow Clicker highlights not just the soulless inanity of Farmville gameplay but also the paucity of that game’s portrayal of the painful reality of a dairy cow’s punishing daily existence and untimely end.

  19. Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1STEM Mouse

    Directory of Open Access Journals (Sweden)

    Francois E. Mercier

    2016-06-01

    Full Text Available Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs requires in vivo functional analyses. Competitive bone marrow transplants (BMTs compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprca Pepcb/BoyJ (CD45.1, has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2 strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprca Pepcb/BoyJ strain differs is almost 40 Mb encoding ∼300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM mouse strain, CD45.1STEM, which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays.

  20. Single cell analysis of caspase-3 in apoptotic and non-apoptotic cells during mouse limb development

    Czech Academy of Sciences Publication Activity Database

    Adamová, Eva; Klepárník, Karel; Matalová, E.

    2014-01-01

    Roč. 3, - (2014), PP58 ISSN 2052-1219. [European Calcified Tissue Society Congress /41./. 17.05.2014-20.05.2014, Praha] R&D Projects: GA ČR GAP206/11/2377; GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 Keywords : single cell analysis * caspase-3 * mouse limb development Subject RIV: CB - Analytical Chemistry, Separation

  1. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    Science.gov (United States)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels; Westerblad, Håkan

    2014-01-01

    In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator of sarcoplasmic reticulum Ca2+ release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca2+ ([Ca2+]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz, 350 ms tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue, LIF) intervals, while force and [Ca2+]i were measured. Stimulation continued until force decreased to 30% of its initial value. Fibres were then prepared for analyses of subcellular glycogen distribution by transmission electron microscopy. At fatigue, tetanic [Ca2+]i was reduced to 70 ± 4% and 54 ± 4% of the initial in HIF (P glycogen content was 60–75% lower than in rested control fibres (P glycogen was similar to control. Individual fibres showed a good correlation between the fatigue-induced decrease in tetanic [Ca2+]i and the reduction in intermyofibrillar (P = 0.051) and intramyofibrillar (P = 0.0008) glycogen. In conclusion, the fatigue-induced decrease in tetanic [Ca2+]i, and hence force, is accompanied by major reductions in inter- and intramyofibrillar glycogen. The stronger correlation between decreased tetanic [Ca2+]i and reduced intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca2+ release critically depends on energy supply from the intramyofibrillar glycogen pool. PMID:24591577

  2. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres.

    Science.gov (United States)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels; Westerblad, Hakan

    2014-05-01

    In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator of sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz, 350 ms tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue, LIF) intervals, while force and [Ca(2+)]i were measured. Stimulation continued until force decreased to 30% of its initial value. Fibres were then prepared for analyses of subcellular glycogen distribution by transmission electron microscopy. At fatigue, tetanic [Ca(2+)]i was reduced to 70 ± 4% and 54 ± 4% of the initial in HIF (P glycogen content was 60-75% lower than in rested control fibres (P glycogen was similar to control. Individual fibres showed a good correlation between the fatigue-induced decrease in tetanic [Ca(2+)]i and the reduction in intermyofibrillar (P = 0.051) and intramyofibrillar (P = 0.0008) glycogen. In conclusion, the fatigue-induced decrease in tetanic [Ca(2+)]i, and hence force, is accompanied by major reductions in inter- and intramyofibrillar glycogen. The stronger correlation between decreased tetanic [Ca(2+)]i and reduced intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca(2+) release critically depends on energy supply from the intramyofibrillar glycogen pool.

  3. Single cell lineage analysis of mouse embryonic stem cells at the exit from pluripotency

    Directory of Open Access Journals (Sweden)

    Jamie Trott

    2013-08-01

    Understanding how interactions between extracellular signalling pathways and transcription factor networks influence cellular decision making will be crucial for understanding mammalian embryogenesis and for generating specialised cell types in vitro. To this end, pluripotent mouse Embryonic Stem (mES cells have proven to be a useful model system. However, understanding how transcription factors and signalling pathways affect decisions made by individual cells is confounded by the fact that measurements are generally made on groups of cells, whilst individual mES cells differentiate at different rates and towards different lineages, even in conditions that favour a particular lineage. Here we have used single-cell measurements of transcription factor expression and Wnt/β-catenin signalling activity to investigate their effects on lineage commitment decisions made by individual cells. We find that pluripotent mES cells exhibit differing degrees of heterogeneity in their expression of important regulators from pluripotency, depending on the signalling environment to which they are exposed. As mES cells differentiate, downregulation of Nanog and Oct4 primes cells for neural commitment, whilst loss of Sox2 expression primes cells for primitive streak commitment. Furthermore, we find that Wnt signalling acts through Nanog to direct cells towards a primitive streak fate, but that transcriptionally active β-catenin is associated with both neural and primitive streak commitment. These observations confirm and extend previous suggestions that pluripotency genes influence lineage commitment and demonstrate how their dynamic expression affects the direction of lineage commitment, whilst illustrating two ways in which the Wnt signalling pathway acts on this network during cell fate assignment.

  4. In-Depth Functional Diagnostics of Mouse Models by Single-Flash and Flicker Electroretinograms without Adapting Background Illumination.

    Science.gov (United States)

    Tanimoto, Naoyuki; Michalakis, Stylianos; Weber, Bernhard H F; Wahl-Schott, Christian A; Hammes, Hans-Peter; Seeliger, Mathias W

    2016-01-01

    Electroretinograms (ERGs) are commonly recorded at the cornea for an assessment of the functional status of the retina in mouse models. Full-field ERGs can be elicited by single-flash as well as flicker light stimulation although in most laboratories flicker ERGs are recorded much less frequently than singleflash ERGs. Whereas conventional single-flash ERGs contain information about layers, i.e., outer and inner retina, flicker ERGs permit functional assessment of the vertical pathways of the retina, i.e., rod system, cone ON-pathway, and cone OFF-pathway, when the responses are evoked at a relatively high luminance (0.5 log cd s/m(2)) with varying frequency (from 0.5 to 30 Hz) without any adapting background illumination. Therefore, both types of ERGs complement an in-depth functional characterization of the mouse retina, allowing for a discrimination of an underlying functional pathology. Here, we introduce the systematic interpretation of the single-flash and flicker ERGs by demonstrating several different patterns of functional phenotype in genetic mouse models, in which photoreceptors and/or bipolar cells are primarily or secondarily affected.

  5. Click here to view fulltext PDF

    Indian Academy of Sciences (India)

    develop a theory that could successfully explain cancer pathogenesis and resistance to medications. In 1937, the research of Jacob Furth and Morton Kahn indicated that a single leukaemic cell, after being transplanted into a mouse, was able to produce a new hematopoietic malignancy (Furth and Kahn 1937). This led to ...

  6. A microfluidic system supports single mouse embryo culture leading to full-term development

    NARCIS (Netherlands)

    Esteves, Telma Cristina; van Rossem, F.; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele; le Gac, Severine

    2013-01-01

    The present study demonstrates the feasibility of application of a microfluidic system for in vitro culture of pre-implantation mouse embryos, with subsequent development to full-term upon embryo transfer. Specifically, embryos cultured in groups in nL volume chambers achieve pre-implantation

  7. Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

    Science.gov (United States)

    Herbst, Eric A F; Holloway, Graham P

    2015-02-15

    the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  8. Quantitative mouse brain phenotyping based on single and multispectral MR protocols

    Science.gov (United States)

    Badea, Alexandra; Gewalt, Sally; Avants, Brian B.; Cook, James J.; Johnson, G. Allan

    2013-01-01

    Sophisticated image analysis methods have been developed for the human brain, but such tools still need to be adapted and optimized for quantitative small animal imaging. We propose a framework for quantitative anatomical phenotyping in mouse models of neurological and psychiatric conditions. The framework encompasses an atlas space, image acquisition protocols, and software tools to register images into this space. We show that a suite of segmentation tools (Avants, Epstein et al., 2008) designed for human neuroimaging can be incorporated into a pipeline for segmenting mouse brain images acquired with multispectral magnetic resonance imaging (MR) protocols. We present a flexible approach for segmenting such hyperimages, optimizing registration, and identifying optimal combinations of image channels for particular structures. Brain imaging with T1, T2* and T2 contrasts yielded accuracy in the range of 83% for hippocampus and caudate putamen (Hc and CPu), but only 54% in white matter tracts, and 44% for the ventricles. The addition of diffusion tensor parameter images improved accuracy for large gray matter structures (by >5%), white matter (10%), and ventricles (15%). The use of Markov random field segmentation further improved overall accuracy in the C57BL/6 strain by 6%; so Dice coefficients for Hc and CPu reached 93%, for white matter 79%, for ventricles 68%, and for substantia nigra 80%. We demonstrate the segmentation pipeline for the widely used C57BL/6 strain, and two test strains (BXD29, APP/TTA). This approach appears promising for characterizing temporal changes in mouse models of human neurological and psychiatric conditions, and may provide anatomical constraints for other preclinical imaging, e.g. fMRI and molecular imaging. This is the first demonstration that multiple MR imaging modalities combined with multivariate segmentation methods lead to significant improvements in anatomical segmentation in the mouse brain. PMID:22836174

  9. cGMP in Mouse Rods: the spatiotemporal dynamics underlying single photon responses

    Directory of Open Access Journals (Sweden)

    Owen P. Gross

    2015-03-01

    Full Text Available Vertebrate vision begins when retinal photoreceptors transduce photons into membrane hyperpolarization, which reduces glutamate release onto second-order neurons. In rod photoreceptors, transduction of single photons is achieved by a well-understood G-protein cascade that modulates cGMP levels, and in turn, cGMP-sensitive inward current. The spatial extent and depth of the decline in cGMP during the single photon response have been major issues in phototransduction research since the discovery that single photons elicit substantial and reproducible changes in membrane current. The spatial profile of cGMP decline during the single photon response affects signal gain, and thus may contribute to reduction of trial-to-trial fluctuations in the single photon response. Here we summarize the general principles of rod phototransduction, emphasizing recent advances in resolving the spatiotemporal dynamics of cGMP during the single photon response.

  10. Fluorescence of Hydroxyphenyl-Substituted "Click" Triazoles.

    Science.gov (United States)

    Meisner, Quinton J; Accardo, Joseph V; Hu, Guoxiang; Clark, Ronald J; Jiang, De-En; Zhu, Lei

    2018-03-22

    The structural and optical properties of hydroxyphenyl-substituted-1,2,3-triazole molecules ("click" triazoles) are described. "Click" triazoles are prepared from the copper(I)-catalyzed azide-alkyne cycloaddition reactions. The alkyne-derived C4 substituent of a "click" triazole engages in electronic conjugation more effectively with the triazolyl core than the azide-derived N1 substituent. Furthermore, triazolyl group exerts a stronger electron-withdrawing effect on the N1 than the C4 substituent. Therefore, the placement of an electron-donating group at either C4 or N1 position and the presence or the absence of an intramolecular hydrogen bond (HB) have profound influences on the optical properties of these compounds. The reported "click" triazoles have fluorescence quantum yields in the range of 0.1-0.3 and large apparent Stokes shifts (8000-13 000 cm -1 ) in all tested solvents. Deprotonation of "click" triazoles with a C4 hydroxyphenyl group increases their Stokes shifts; while the opposite (or quenching) occurs to the triazoles with an N1 hydroxyphenyl substituent. For the triazoles that contain intramolecular HBs, neither experimental nor computational results support a model of excited state intramolecular proton transfer (ESIPT). Rather, the excited state internal (or intramolecular) charge transfer (ICT) mechanism is more suitable to explain the fluorescence properties of the hydroxyphenyl-substituted "click" triazoles; specifically, the large Stokes shifts of these compounds.

  11. Expression and purification of single cysteine-containing mutant variants of the mouse prion protein by oxidative refolding.

    Science.gov (United States)

    Sengupta, Ishita; Udgaonkar, Jayant B

    2017-12-01

    The folding and aggregation of proteins has been studied extensively, using multiple probes. To facilitate such experiments, introduction of spectroscopically-active moieties in to the protein of interest is often necessary. This is commonly achieved by specifically labelling cysteine residues in the protein, which are either present naturally or introduced artificially by site-directed mutagenesis. In the case of the recombinant prion protein, which is normally expressed in inclusion bodies, the presence of the native disulfide bond complicates the correct refolding of single cysteine-containing mutant variants of the protein. To overcome this major bottleneck, a simple purification strategy for single tryptophan, single cysteine-containing mutant variants of the mouse prion protein is presented, with yields comparable to that of the wild type protein. The protein(s) obtained by this method are correctly folded, with a single reduced cysteine, and the native disulfide bond between residues C178 and C213 intact. The β-sheet rich oligomers formed from these mutant variant protein(s) are identical to the wild type protein oligomer. The current strategy facilitates sample preparation for a number of high resolution spectroscopic measurements for the prion protein, which specifically require thiol labelling. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutant coloboma

    Energy Technology Data Exchange (ETDEWEB)

    Hess, E.J.; Rogan, P.K.; Domoto, M. [Pennsylvania State Univ. College of Medicine, Hershey, PA (United States)] [and others

    1995-12-18

    Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex-influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval. 39 refs., 2 figs., 1 tab.

  13. Single-neuron diversity generated by Protocadherin-β cluster in mouse central and peripheral nervous systems

    Directory of Open Access Journals (Sweden)

    Keizo eHirano

    2012-08-01

    Full Text Available The generation of complex neural circuits depends on the correct wiring of neurons with diverse individual characteristics. To understand the complexity of the nervous system, the molecular mechanisms for specifying the identity and diversity of individual neurons must be elucidated. The clustered protocadherins (Pcdh in mammals consist of approximately 50 Pcdh genes (Pcdh-α, Pcdh-β, and Pcdh-γ that encode cadherin-family cell surface adhesion proteins. Individual neurons express a random combination of Pcdh-α and Pcdh-γ, whereas the expression patterns for the Pcdh-β genes, 22 one-exon genes in mouse, are not fully understood. Here we show that the Pcdh-β genes are expressed in a 3’-polyadenylated form in mouse brain. In situ hybridization using a pan-Pcdh-β probe against a conserved Pcdh-β sequence showed widespread labeling in the brain, with prominent signals in the olfactory bulb, hippocampus, and cerebellum. In situ hybridization with specific probes for individual Pcdh-β genes showed their expression to be scattered in Purkinje cells from P10 to P150. The scattered expression patterns were confirmed by performing a newly developed single-cell 3’-RACE analysis of Purkinje cells, which clearly demonstrated that the Pcdh-β genes are expressed monoallelically and combinatorially in individual Purkinje cells. Scattered expression patterns of individual Pcdh-β genes were also observed in pyramidal neurons in the hippocampus and cerebral cortex, neurons in the trigeminal and dorsal root ganglion, GABAergic interneurons, and cholinergic neurons. Our results extend previous observations of diversity at the single-neuron level generated by Pcdh expression and suggest that the Pcdh-β cluster genes contribute to specifying the identity and diversity of individual neurons.

  14. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

    Science.gov (United States)

    Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

    2016-04-15

    Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

  15. A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse.

    Directory of Open Access Journals (Sweden)

    Masakazu Kataoka

    Full Text Available Synaptosomal-associated protein of 25 kDa (SNAP-25 is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC phosphorylates Ser(187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser(187 of SNAP-25 with Ala using "knock-in" technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.

  16. MRI Findings in Patients with TMJ Click

    Directory of Open Access Journals (Sweden)

    Mahrokh Imanimoghaddam

    2013-12-01

    Full Text Available Introduction: It has been shown that joint click, an initial and common finding in internal derangement (ID, respond to neither conservative treatment nor surgical intervention. This raises the question as to whether it must be treated in the absence of other pertinent signs and symptoms, so the aim of this study was to investigate and compare the MRI findings of TMJ in both normal subjects and patients with click, in order to determine the importance of click in predicting TMJ pathological changes. Methods: A total of 26 patients with clinical symptoms of disk displacement with reduction (DDwR according to RDC/TMD were compared to 14 normal subjects in terms of their MRI findings, including disk displacement, effusion, condylar osteoarthritic changes and disk deformities. Results: Out of 80 joints in total (52 affected joints in 26 patients and 28 joints in control group, 48 were shown with normal disk position in MRI whereas 28 (35% and 4 (5% were categorised as DDwR and (disk displacement without reduction DDwoR, respectively. Statistically significant correlations were established between the following pairs of variables in order: Click and disk displacement, effusion and disk displacement, disk displacement and effusion with disk deformity. Conclusion: The correlation between the presence of click and disk displacement, disk deformity and effusion emphasizes the importance of MRI for an accurate diagnosis and development of an appropriate treatment plan in these cases and shows that clinical examination is not sufficient for these purposes.

  17. Simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues.

    Directory of Open Access Journals (Sweden)

    Giuseppe Orsomando

    Full Text Available A novel assay procedure has been developed to allow simultaneous activity discrimination in crude tissue extracts of the three known mammalian nicotinamide mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1 isozymes. These enzymes catalyse the same key reaction for NAD biosynthesis in different cellular compartments. The present method has been optimized for NMNAT isozymes derived from Mus musculus, a species often used as a model for NAD-biosynthesis-related physiology and disorders, such as peripheral neuropathies. Suitable assay conditions were initially assessed by exploiting the metal-ion dependence of each isozyme recombinantly expressed in bacteria, and further tested after mixing them in vitro. The variable contributions of the three individual isozymes to total NAD synthesis in the complex mixture was calculated by measuring reaction rates under three selected assay conditions, generating three linear simultaneous equations that can be solved by a substitution matrix calculation. Final assay validation was achieved in a tissue extract by comparing the activity and expression levels of individual isozymes, considering their distinctive catalytic efficiencies. Furthermore, considering the key role played by NMNAT activity in preserving axon integrity and physiological function, this assay procedure was applied to both liver and brain extracts from wild-type and Wallerian degeneration slow (Wld(S mouse. Wld(S is a spontaneous mutation causing overexpression of NMNAT1 as a fusion protein, which protects injured axons through a gain-of-function. The results validate our method as a reliable determination of the contributions of the three isozymes to cellular NAD synthesis in different organelles and tissues, and in mutant animals such as Wld(S.

  18. Chasing the precursor of functional hematopoietic stem cells at the single cell levels in mouse embryos.

    Science.gov (United States)

    Wang, Xiaochen; Gong, Yuemin; Ema, Hideo

    2016-07-22

    Adult hematopoietic stem cells (HSCs), the ideal system for regenerative research, were isolated at single cell levels decades ago, whereas studies on embryonic HSCs are much more difficult. Zhou et al identified a new pre-HSC cell surface marker, CD201, by which they isolated pre-HSCs at single cell levels for further analyses. The novel expression pattern of HSC development is revealed, including the fundamental role of mammalian targets of rapamycin (mTOR) signaling pathway in HSCs emergence, and the repopulation potential of S/G2/M phase pre-HSCs. Deeper understandings of the cellular origin and developmental regulatory network of HSCs are essential to develop new strategies of generating HSCs in vitro for clinical application.

  19. Single cell analysis facilitates staging of Blimp1-dependent primordial germ cells derived from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    John J Vincent

    Full Text Available The cell intrinsic programming that regulates mammalian primordial germ cell (PGC development in the pre-gonadal stage is challenging to investigate. To overcome this we created a transgene-free method for generating PGCs in vitro (iPGCs from mouse embryonic stem cells (ESCs. Using labeling for SSEA1 and cKit, two cell surface molecules used previously to isolate presumptive iPGCs, we show that not all SSEA1+/cKit+ double positive cells exhibit a PGC identity. Instead, we determined that selecting for cKit(bright cells within the SSEA1+ fraction significantly enriches for the putative iPGC population. Single cell analysis comparing SSEA1+/cKit(bright iPGCs to ESCs and embryonic PGCs demonstrates that 97% of single iPGCs co-express PGC signature genes Blimp1, Stella, Dnd1, Prdm14 and Dazl at similar levels to e9.5-10.5 PGCs, whereas 90% of single mouse ESC do not co-express PGC signature genes. For the 10% of ESCs that co-express PGC signature genes, the levels are significantly lower than iPGCs. Microarray analysis shows that iPGCs are transcriptionally distinct from ESCs and repress gene ontology groups associated with mesoderm and heart development. At the level of chromatin, iPGCs contain 5-methyl cytosine bases in their DNA at imprinted and non-imprinted loci, and are enriched in histone H3 lysine 27 trimethylation, yet do not have detectable levels of Mvh protein, consistent with a Blimp1-positive pre-gonadal PGC identity. In order to determine whether iPGC formation is dependent upon Blimp1, we generated Blimp1 null ESCs and found that loss of Blimp1 significantly depletes SSEA1/cKit(bright iPGCs. Taken together, the generation of Blimp1-positive iPGCs from ESCs constitutes a robust model for examining cell-intrinsic regulation of PGCs during the Blimp1-positive stage of development.

  20. Single particle tracking of internalized metallic nanoparticles reveals heterogeneous directed motion after clathrin dependent endocytosis in mouse chromaffin cells

    Science.gov (United States)

    Gabriel, Manuela; Moya-Díaz, José; Gallo, Luciana I.; Marengo, Fernando D.; Estrada, Laura C.

    2018-01-01

    Most accepted single particle tracking methods are able to obtain high-resolution trajectories for relatively short periods of time. In this work we apply a straightforward combination of single-particle tracking microscopy and metallic nanoparticles internalization on mouse chromaffin cells to unveil the intracellular trafficking mechanism of metallic-nanoparticle-loaded vesicles (MNP-V) complexes after clathrin dependent endocytosis. We found that directed transport is the major route of MNP-Vs intracellular trafficking after stimulation (92.6% of the trajectories measured). We then studied the MNP-V speed at each point along the trajectory, and found that the application of a second depolarization stimulus during the tracking provokes an increase in the percentage of low-speed trajectory points in parallel with a decrease in the number of high-speed trajectory points. This result suggests that stimulation may facilitate the compartmentalization of internalized MNPs in a more restricted location such as was already demonstrated in neuronal and neuroendocrine cells (Bronfman et al 2003 J. Neurosci. 23 3209-20). Although further experiments will be required to address the mechanisms underlying this transport dynamics, our studies provide quantitative evidence of the heterogeneous behavior of vesicles mobility after endocytosis in chromaffin cells highlighting the potential of MNPs as alternative labels in optical microscopy to provide new insights into the vesicles dynamics in a wide variety of cellular environments.

  1. Secretion of an immunoreactive single-chain variable fragment antibody against mouse interleukin 6 by Lactococcus lactis.

    Science.gov (United States)

    Shigemori, Suguru; Ihara, Masaki; Sato, Takashi; Yamamoto, Yoshinari; Nigar, Shireen; Ogita, Tasuku; Shimosato, Takeshi

    2017-01-01

    Interleukin 6 (IL-6) is an important pathogenic factor in development of various inflammatory and autoimmune diseases and cancer. Blocking antibodies against molecules associated with IL-6/IL-6 receptor signaling are an attractive candidate for the prevention or therapy of these diseases. In this study, we developed a genetically modified strain of Lactococcus lactis secreting a single-chain variable fragment antibody against mouse IL-6 (IL6scFv). An IL6scFv-secretion vector was constructed by cloning an IL6scFv gene fragment into a lactococcal secretion plasmid and was electroporated into L. lactis NZ9000 (NZ-IL6scFv). Secretion of recombinant IL6scFv (rIL6scFv) by nisin-induced NZ-IL6scFv was confirmed by western blotting and was optimized by tuning culture conditions. We found that rIL6scFv could bind to commercial recombinant mouse IL-6. This result clearly demonstrated the immunoreactivity of rIL6scFv. This is the first study to engineer a genetically modified strain of lactic acid bacteria (gmLAB) that produces a functional anti-cytokine scFv. Numerous previous studies suggested that mucosal delivery of biomedical proteins using gmLAB is an effective and low-cost way to treat various disorders. Therefore, NZ-IL6scFv may be an attractive tool for the research and development of new IL-6 targeting agents for various inflammatory and autoimmune diseases as well as for cancer.

  2. Facile design of biomaterials by 'click' chemistry

    DEFF Research Database (Denmark)

    Hvilsted, Søren

    2012-01-01

    The advent of the so‐called ‘click chemistry’ a decade ago has significantly improved the chemical toolbox for producing novel biomaterials. This review focuses primarily on the application of Cu(I)‐catalysed azide–alkyne 1,3‐cycloadditon in the preparation of numerous, diverse biomaterials...... chemistry is elaborated. The present state of creating functional and biologically active surfaces by click chemistry is presented. Finally, conducting surfaces based on an azide‐functionalized polymer with prospective biological sensor potential are introduced. Copyright © 2012 Society of Chemical Industry...

  3. Development of Thermal and Photochemical Strategies for Thiol−Ene Click Polymer Functionalization

    NARCIS (Netherlands)

    Campos, Luis M.; Killops, Kato L.; Sakai, Ryosuke; Paulusse, Jos Marie Johannes; Damiron, Denis; Drockenmuller, Eric; Messmore, Benjamin W.; Hawker, Craig J.

    2008-01-01

    A series of alkene-functional polymers were synthesized by controlled polymerization techniques in order to investigate and compare the efficiency and orthogonality of both photochemically and thermally initiated thiol−ene click coupling reactions. The copolymers were designed to have single or

  4. Optimization of the virtual mouse HeadMouse to foster its classroom use by children with physical disabilities

    Directory of Open Access Journals (Sweden)

    Merce TEIXIDO

    2014-03-01

    Full Text Available This paper presents the optimization of a virtual mouse called HeadMouse in order to foster its classroom use by children with physical disabilities. HeadMouse is an absolute virtual mouse that converts head movements in cursor displacement and facial gestures in click actions. The virtual mouse combines different image processing algorithms: face detection, pattern matching and optical flow in order to emulate the behaviour of a conventional computer mouse. The original implementation of HeadMouse requires large computational power and this paper proposes specific optimizations in order to enable its use by children with disabilities in standard low cost classroom computers.

  5. The Mesoaccumbens Pathway: A Retrograde Labeling and Single-Cell Axon Tracing Analysis in the Mouse.

    Science.gov (United States)

    Rodríguez-López, Claudia; Clascá, Francisco; Prensa, Lucía

    2017-01-01

    Neurons in the ventral tegmental area (VTA) that innervate the nucleus accumbens (Acb) constitute the so-called mesoaccumbens system. Increased activity by these neurons is correlated with the expectation and achievement of reward. The mesoaccumbens projection neurons are regarded as a central node in the brain networks that regulate drive and hedonic experience, and their dysregulation is a common pathophysiological step in addictive behaviors as well as major depression. Despite previous anatomical studies that have analyzed the origin of the mesoaccumbens axons within the VTA, regarded as a unit, the exact contributions of the various cytoarchitectural subdivisions of the VTA to this innervation is still unexplored; understanding these contributions would help further our understanding of their precise anatomical organization. With the aim of deciphering the contribution of the various VTA subdivisions to accumbal innervation, the present study has used retrograde tracer microinjections in the Acb to map the location within the various VTA subdivisions of neurons targeting either the shell or core compartments of the Acb in mice. Furthermore, the dopaminergic nature of these projections has also been analyzed using tyrosine-hydroxylase immunohistochemistry. We demonstrate here that small territories of the Acb core and shell are innervated simultaneously by many VTA subdivisions, contributing dopaminergic as well as non-dopaminergic axons to the accumbal innervation. In fact, single VTA subdivisions harbor both dopaminergic and non-dopaminergic neurons that project to the same accumbal territory. The most medial VTA subnuclei, like the caudal linear nucleus, project abundantly to medial aspects of the Acb core, whereas more lateral territories of the Acb are preferentially targeted by neurons located in the parabrachial pigmented and paranigral nuclei. Overall, about half of the mesoaccumbens neurons are putatively dopaminergic in mice. Anterograde single

  6. Unsupervised Learning (Clustering) of Odontocete Echolocation Clicks

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Unsupervised Learning ( Clustering ) of Odontocete...develop methods for clustering of marine mammal echolocation clicks to learn about species assemblages where little or no prior knowledge exists about...California Bight where many of the species can be acoustically identified, enabling the development of clustering algorithms whose performance can be

  7. Application of Click Chemistry for PET

    NARCIS (Netherlands)

    Mirfeizi, Leila; Campbell-Verduyn, Lachlan; Dierckx, Rudi A.; Feringa, Bernard; Elsinga, Philip H.

    2013-01-01

    Sharpless et al. presented, in 2001, a review in which they introduced the concept of "click chemistry". In this review a "new way" of making chemicals, with a particular emphasis on drugs, is presented. Current drugs are often based on natural products that were first extracted from plants or other

  8. Click Model-Based Information Retrieval Metrics

    NARCIS (Netherlands)

    Chuklin, A.; Serdyukov, P.; de Rijke, M.

    2013-01-01

    In recent years many models have been proposed that are aimed at predicting clicks of web search users. In addition, some information retrieval evaluation metrics have been built on top of a user model. In this paper we bring these two directions together and propose a common approach to converting

  9. Modeling clicks beyond the first result page

    NARCIS (Netherlands)

    Chuklin, A.; Serdyukov, P.; de Rijke, M.

    2013-01-01

    Most modern web search engines yield a list of documents of a fixed length (usually 10) in response to a user query. The next ten search results are usually available in one click. These documents either replace the current result page or are appended to the end. Hence, in order to examine more

  10. SUPPLEMENTARY INFORMATION Efficient click reaction towards ...

    Indian Academy of Sciences (India)

    sudarshana

    SUPPLEMENTARY INFORMATION. Efficient click reaction towards novel sulfonamide hybrids by molecular hybridization strategy as antiproliferative agents. DONG-JUN FU,a. YU-HUI HOU,a. SAI-YANG ZHANGb* and YAN-BING. ZHANGa*. aNew Drug Research & Development Center, School of Pharmaceutical Sciences,.

  11. Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle.

    Science.gov (United States)

    Stecher, Bärbel; Berry, David; Loy, Alexander

    2013-09-01

    The highly diverse intestinal microbiota forms a structured community engaged in constant communication with itself and its host and is characterized by extensive ecological interactions. A key benefit that the microbiota affords its host is its ability to protect against infections in a process termed colonization resistance (CR), which remains insufficiently understood. In this review, we connect basic concepts of CR with new insights from recent years and highlight key technological advances in the field of microbial ecology. We present a selection of statistical and bioinformatics tools used to generate hypotheses about synergistic and antagonistic interactions in microbial ecosystems from metagenomic datasets. We emphasize the importance of experimentally testing these hypotheses and discuss the value of gnotobiotic mouse models for investigating specific aspects related to microbiota-host-pathogen interactions in a well-defined experimental system. We further introduce new developments in the area of single-cell analysis using fluorescence in situ hybridization in combination with metabolic stable isotope labeling technologies for studying the in vivo activities of complex community members. These approaches promise to yield novel insights into the mechanisms of CR and intestinal ecophysiology in general, and give researchers the means to experimentally test hypotheses in vivo at varying levels of biological and ecological complexity. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  12. Repopulation dynamics of single haematopoietic stem cells in mouse transplantation experiments: Importance of stem cell composition in competitor cells.

    Science.gov (United States)

    Ema, Hideo; Uchinomiya, Kouki; Morita, Yohei; Suda, Toshio; Iwasa, Yoh

    2016-04-07

    The transplantation of blood tissues from bone marrow into a lethally irradiated animal is an experimental procedure that is used to study how the blood system is reconstituted by haematopoietic stem cells (HSC). In a competitive repopulation experiment, a lethally irradiated mouse was transplanted with a single HSC as a test cell together with a number of bone marrow cells as competitor cells, and the fraction of the test cell progeny (percentage of chimerism) was traced over time. In this paper, we studied the stem cell kinetics in this experimental procedure. The balance between symmetric self-renewal and differentiation divisions in HSC determined the number of cells which HSC produce and the length of time for which HSC live after transplantation. The percentage of chimerism depended on the type of test cell (long-, intermediate-, or short-term HSC), as well as the type and number of HSC included in competitor cells. We next examined two alternative HSC differentiation models, one-step and multi-step differentiation models. Although these models differed in blood cell production, the percentage of chimerism appeared very similar. We also estimated the numbers of different types of HSC in competitor cells. Based on these results, we concluded that the experimental results inevitably include stochasticity with regard to the number and the type of HSC in competitor cells, and that, in order to detect different types of HSC, an appropriate number of competitor cells needs to be used in transplantation experiments. Copyright © 2016. Published by Elsevier Ltd.

  13. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Claudia V.; Oliveira, Paulo J. [CNC—Center for Neuroscience and Cell Biology, University of Coimbra (Portugal); Will, Yvonne [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States); Nadanaciva, Sashi, E-mail: sashi.nadanaciva@pfizer.com [Compound Safety Prediction, Pfizer Global Research and Development, Groton, CT (United States)

    2012-10-15

    Mitochondrial DNA (mtDNA) variations including single nucleotide polymorphisms (SNPs) have been proposed to be involved in idiosyncratic drug reactions. However, current in vitro and in vivo models lack the genetic diversity seen in the human population. Our hypothesis is that different cell strains with distinct mtDNA SNPs may have different mitochondrial bioenergetic profiles and may therefore vary in their response to drug-induced toxicity. Therefore, we used an in vitro system composed of four strains of mouse embryonic fibroblasts (MEFs) with mtDNA polymorphisms. We sequenced mtDNA from embryonic fibroblasts isolated from four mouse strains, C57BL/6J, MOLF/EiJ, CZECHII/EiJ and PERA/EiJ, with the latter two being sequenced for the first time. The bioenergetic profile of the four strains of MEFs was investigated at both passages 3 and 10. Our results showed that there were clear differences among the four strains of MEFs at both passages, with CZECHII/EiJ having a lower mitochondrial robustness when compared to C57BL/6J, followed by MOLF/EiJ and PERA/EiJ. Seven drugs known to impair mitochondrial function were tested for their effect on the ATP content of the four strains of MEFs in both glucose- and galactose-containing media. Our results showed that there were strain-dependent differences in the response to some of the drugs. We propose that this model is a useful starting point to study compounds that may cause mitochondrial off-target toxicity in early stages of drug development, thus decreasing the number of experimental animals used. -- Highlights: ► mtDNA SNPs may be linked to individual predisposition to drug-induced toxicity. ► CZECHII/EiJ and PERA/EiJ mtDNA was sequenced for the first time in this study. ► Strain-dependent mitochondrial capacity differences were measured. ► Strain-dependent differences in response to mitochondrial toxicants were observed.

  14. Polymer Nanocomposites via Click Chemistry Reactions

    Directory of Open Access Journals (Sweden)

    Mehmet Arslan

    2017-10-01

    Full Text Available The emerging areas of polymer nanocomposites, as some are already in use in industrial applications and daily commodities, have the potential of offering new technologies with all manner of prominent capabilities. The incorporation of nanomaterials into polymeric matrix provides significant improvements, such as higher mechanical, thermal or electrical properties. In these materials, interface/interphase of components play a crucial role bringing additional features on the resulting nanocomposites. Among the various preparation strategies of such materials, an appealing strategy relies on the use of click chemistry concept as a multi-purpose toolbox for both fabrication and modulation of the material characteristics. This review aims to deliver new insights to the researchers of the field by noticing effective click chemistry-based methodologies on the preparation of polymer nanocomposites and their key applications such as optic, biomedical, coatings and sensor.

  15. Modelling the broadband propagation of marine mammal echolocation clicks for click-based population density estimates.

    Science.gov (United States)

    von Benda-Beckmann, Alexander M; Thomas, Len; Tyack, Peter L; Ainslie, Michael A

    2018-02-01

    Passive acoustic monitoring with widely-dispersed hydrophones has been suggested as a cost-effective method to monitor population densities of echolocating marine mammals. This requires an estimate of the area around each receiver over which vocalizations are detected-the "effective detection area" (EDA). In the absence of auxiliary measurements enabling estimation of the EDA, it can be modelled instead. Common simplifying model assumptions include approximating the spectrum of clicks by flat energy spectra, and neglecting the frequency-dependence of sound absorption within the click bandwidth (narrowband assumption), rendering the problem amenable to solution using the sonar equation. Here, it is investigated how these approximations affect the estimated EDA and their potential for biasing the estimated density. EDA was estimated using the passive sonar equation, and by applying detectors to simulated clicks injected into measurements of background noise. By comparing model predictions made using these two approaches for different spectral energy distributions of echolocation clicks, but identical click source energy level and detector settings, EDA differed by up to a factor of 2 for Blainville's beaked whales. Both methods predicted relative density bias due to narrowband assumptions ranged from 5% to more than 100%, depending on the species, detector settings, and noise conditions.

  16. A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors*

    Science.gov (United States)

    Blevitt, Jonathan M.; Hack, Michael D.; Herman, Krystal; Chang, Leon; Keith, John M.; Mirzadegan, Tara; Rao, Navin L.; Lebsack, Alec D.; Milla, Marcos E.

    2016-01-01

    5-Lipoxygenase activating protein (FLAP) plays a critical role in the metabolism of arachidonic acid to leukotriene A4, the precursor to the potent pro-inflammatory mediators leukotriene B4 and leukotriene C4. Studies with small molecule inhibitors of FLAP have led to the discovery of a drug binding pocket on the protein surface, and several pharmaceutical companies have developed compounds and performed clinical trials. Crystallographic studies and mutational analyses have contributed to a general understanding of compound binding modes. During our own efforts, we identified two unique chemical series. One series demonstrated strong inhibition of human FLAP but differential pharmacology across species and was completely inactive in assays with mouse or rat FLAP. The other series was active across rodent FLAP, as well as human and dog FLAP. Comparison of rodent and human FLAP amino acid sequences together with an analysis of a published crystal structure led to the identification of amino acid residue 24 in the floor of the putative binding pocket as a likely candidate for the observed speciation. On that basis, we tested compounds for binding to human G24A and mouse A24G FLAP mutant variants and compared the data to that generated for wild type human and mouse FLAP. These studies confirmed that a single amino acid mutation was sufficient to reverse the speciation observed in wild type FLAP. In addition, a PK/PD method was established in canines to enable preclinical profiling of mouse-inactive compounds. PMID:27129215

  17. General Dialdehyde Click Chemistry for Amine Bioconjugation.

    Science.gov (United States)

    Elahipanah, Sina; O'Brien, Paul J; Rogozhnikov, Dmitry; Yousaf, Muhammad N

    2017-05-17

    The development of methods for conjugating a range of molecules to primary amine functional groups has revolutionized the fields of chemistry, biology, and material science. The primary amine is a key functional group and one of the most important nucleophiles and bases used in all of synthetic chemistry. Therefore, tremendous interest in the synthesis of molecules containing primary amines and strategies to devise chemical reactions to react with primary amines has been at the core of chemical research. In particular, primary amines are a ubiquitous functional group found in biological systems as free amino acids, as key side chain lysines in proteins, and in signaling molecules and metabolites and are also present in many natural product classes. Due to its abundance, the primary amine is the most convenient functional group handle in molecules for ligation to other molecules for a broad range of applications that impact all scientific fields. Because of the primary amine's central importance in synthetic chemistry, acid-base chemistry, redox chemistry, and biology, many methods have been developed to efficiently react with primary amines, including activated carboxylic acids, isothiocyanates, Michael addition type systems, and reaction with ketones or aldehydes followed by in situ reductive amination. Herein, we introduce a new traceless, high-yield, fast click-chemistry method based on the rapid and efficient trapping of amine groups via a functionalized dialdehyde group. The click reaction occurs in mild conditions in organic solvents or aqueous media and proceeds in high yield, and the starting dialdehyde reagent and resulting dialdehyde click conjugates are stable. Moreover, no catalyst or dialdehyde-activating group is required, and the only byproduct is water. The initial dialdehyde and the resulting conjugate are both straightforward to characterize, and the reaction proceeds with high atom economy. To demonstrate the broad scope of this new click

  18. Well-defined silica supported aluminum hydride: another step towards the utopian single site dream?† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc02276b Click here for additional data file.

    Science.gov (United States)

    Werghi, Baraa; Bendjeriou-Sedjerari, Anissa; Sofack-Kreutzer, Julien; Jedidi, Abdesslem; Abou-Hamad, Edy

    2015-01-01

    of a strained siloxane bridge, Si–O–Si but with two different mechanisms, showing that the reality of “single site” catalyst may be an utopia: DFT calculations indicate that isobutyl transfer occurs via a simple metathesis between the Al-isobutyl and O–Si bonds, while hydride transfer occurs via a two steps mechanism, the first one is a β-H elimination to Al with elimination of isobutene, whereas the second is a metathesis step between the formed Al–H bond and a O–Si bond. Thermal treatment of 1a (at 250 °C) under high vacuum (10–5 mbar) generates Al–H through a β-H elimination of isobutyl fragment. These supported well-defined Al–H which are highly stable with time, are tetra, penta and octa coordinated as demonstrated by IR and 27Al–1H J-HMQC NMR spectroscopy. All these observations indicate that surfaces atoms around the site of grafting play a considerable role in the reactivity of a single site system. PMID:28757945

  19. Interfacing click chemistry with automated oligonucleotide synthesis for the preparation of fluorescent DNA probes containing internal xanthene and cyanine dyes

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Wengel, Jesper

    2013-01-01

    for the first time performed solid-phase copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click labeling during the automated phosphoramidite oligonucleotide synthesis followed by postsynthetic click reactions in solution. We demonstrate that our novel strategy is rapid and efficient for the preparation...... Stokes shifts (40-110 nm), quenched fluorescence of single-stranded probes accompanied by up to 7.7-fold light-up effect of emission upon target DNA/RNA binding, remarkable sensitivity to single-nucleotide mismatches, generally high fluorescence brightness values (FB up to 26), and hence low limit...

  20. Modulation of protein A binding allows single-step purification of mouse bispecific antibodies that retain FcRn binding

    Science.gov (United States)

    Armstrong, Anthony A.; Pardinas, Jose R.; Zheng, Songmao; Brosnan, Kerry; Emmell, Eva; Luo, Jeffrey; Chiu, Mark L.

    2017-01-01

    ABSTRACT The increased number of bispecific antibodies (BsAb) under therapeutic development has resulted in a need for mouse surrogate BsAbs. Here, we describe a one-step method for generating highly pure mouse BsAbs suitable for in vitro and in vivo studies. We identify two mutations in the mouse IgG2a and IgG2b Fc region: one that eliminates protein A binding and one that enhances protein A binding by 8-fold. We show that BsAbs harboring these mutations can be purified from the residual parental monoclonal antibodies in one step using protein A affinity chromatography. The structural basis for the effects of these mutations was analyzed by X-ray crystallography. While the mutation that disrupted protein A binding also inhibited FcRn interaction, a bispecific mutant in which one subunit retained the ability to bind protein A could still interact with FcRn. Pharmacokinetic analysis of the serum half-lives of the mutants showed that the mutant BsAb had a serum half-life comparable to a wild-type Ab. The results describe a rapid method for generating panels of mouse BsAbs that could be used in mouse studies. PMID:28898162

  1. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

    Directory of Open Access Journals (Sweden)

    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  2. Classification of echolocation clicks from odontocetes in the Southern California Bight.

    Science.gov (United States)

    Roch, Marie A; Klinck, Holger; Baumann-Pickering, Simone; Mellinger, David K; Qui, Simon; Soldevilla, Melissa S; Hildebrand, John A

    2011-01-01

    This study presents a system for classifying echolocation clicks of six species of odontocetes in the Southern California Bight: Visually confirmed bottlenose dolphins, short- and long-beaked common dolphins, Pacific white-sided dolphins, Risso's dolphins, and presumed Cuvier's beaked whales. Echolocation clicks are represented by cepstral feature vectors that are classified by Gaussian mixture models. A randomized cross-validation experiment is designed to provide conditions similar to those found in a field-deployed system. To prevent matched conditions from inappropriately lowering the error rate, echolocation clicks associated with a single sighting are never split across the training and test data. Sightings are randomly permuted before assignment to folds in the experiment. This allows different combinations of the training and test data to be used while keeping data from each sighting entirely in the training or test set. The system achieves a mean error rate of 22% across 100 randomized three-fold cross-validation experiments. Four of the six species had mean error rates lower than the overall mean, with the presumed Cuvier's beaked whale clicks showing the best performance (<2% error rate). Long-beaked common and bottlenose dolphins proved the most difficult to classify, with mean error rates of 53% and 68%, respectively.

  3. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates temporal suppression of click-evoked otoacoustic emissions (CEOAEs), occurring when a suppressor-click is presented close in time to a test-click (e.g. 0-8ms). Various temporal suppression methods for examining temporal changes in cochlear compression were evaluated...... and measured here for seven subjects, both for short- and long-latency CEOAEs. Long-latency CEOAEs (duration >20ms) typically indicate the presence of synchronised spontaneous otoacoustic emissions (SSOAEs). Temporal suppression can only be linked to changes in CEOAE-compression if the suppressor-click affects...

  4. Get the right mix of bricks & clicks.

    Science.gov (United States)

    Gulati, R; Garino, J

    2000-01-01

    The bright line that once distinguished the dot-com from the incumbent is rapidly fading. Success in the new economy will go to those who can execute clicks-and-mortar strategies that bridge the physical and virtual worlds. But how executives forge such strategies is under considerable debate. Despite the obvious benefits that integration offers--cross-promotion, shared information, purchasing leverage, distribution economies, and the like--many executives now assume that Internet businesses have to be separate to thrive. They believe that the very nature of traditional business--its protectiveness of current customers, its fear of cannibalization, its general myopia--will smother any Internet initiative. Authors Ranjay Gulati and Jason Garino contend that executives don't have to make an either- or choice when it comes to their clicks-and-mortar strategies. The question isn't, "Should we develop our Internet channel in-house or launch a spin-off?" but rather, "What degree of integration makes sense for our company?" To determine the best level of integration for their companies, executives should examine four business dimensions: brand, management, operations, and equity. Drawing on the experiences of three established retailers--Office Depot, KB Toys, and Rite Aid--the authors show the spectrum of strategies available and discuss the trade-offs involved in each choice. By thinking carefully about which aspects of a business to integrate and which to keep distinct, companies can tailor their clicks-and-mortar strategy to their own particular market and competitive situation, dramatically increasing their odds of e-business success.

  5. Solid-state molecular organometallic chemistry. Single-crystal to single-crystal reactivity and catalysis with light hydrocarbon substrates† †Electronic supplementary information (ESI) available: Full details of experimental details, spectroscopic and other analytical data, X-ray crystallography, catalytic conditions, and computational studies. CCDC 1539832–1539836. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc01491k Click here for additional data file. Click here for additional data file. Click here for additional data file.

    Science.gov (United States)

    Chadwick, F. Mark; McKay, Alasdair I.; Martinez-Martinez, Antonio J.; Rees, Nicholas H.; Krämer, Tobias

    2017-01-01

    Single-crystal to single-crystal solid/gas reactivity and catalysis starting from the precursor sigma-alkane complex [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF4] (NBA = norbornane; ArF = 3,5-(CF3)2C6H3) is reported. By adding ethene, propene and 1-butene to this precursor in solid/gas reactions the resulting alkene complexes [Rh(Cy2PCH2CH2PCy2)(alkene)x][BArF4] are formed. The ethene (x = 2) complex, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Oct, has been characterized in the solid-state (single-crystal X-ray diffraction) and by solution and solid-state NMR spectroscopy. Rapid, low temperature recrystallization using solution methods results in a different crystalline modification, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Hex, that has a hexagonal microporous structure (P6322). The propene complex (x = 1) [Rh(Cy2PCH2CH2PCy2)(propene)][BArF4] is characterized as having a π-bound alkene with a supporting γ-agostic Rh···H3C interaction at low temperature by single-crystal X-ray diffraction, variable temperature solution and solid-state NMR spectroscopy, as well as periodic density functional theory (DFT) calculations. A fluxional process occurs in both the solid-state and solution that is proposed to proceed via a tautomeric allyl-hydride. Gas/solid catalytic isomerization of d3-propene, H2C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000

  6. Conductive Polymer Functionalization by Click Chemistry

    DEFF Research Database (Denmark)

    Daugaard, Anders Egede; Hvilsted, Søren; Hansen, Thomas Steen

    2008-01-01

    Click chemistry is used to obtain new conductive polymer films based on poly(3,4-ethylenedioxythiophene) (PEDOT) from a new azide functional monomer. Postpolymerization, 1,3-dipolar cycloadditions in DMF, using a catalyst system of CUS04 and sodium ascorbate, and different alkynes are performed...... to functionalize films of PEDOT-N3 and copolymers prepared from EDOT-N3 and 3,4-ethylenedioxythiophene (EDOT). This approach enables new functionalities on PEDOT that could otherwise not withstand the polymerization conditions. Reactions on the thin polymer films have been optimized using an alkynated fluorophore...

  7. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin.

    Science.gov (United States)

    Murphy, J E; Zhou, S; Giese, K; Williams, L T; Escobedo, J A; Dwarki, V J

    1997-12-09

    The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes mellitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity.

  8. A single bivalent efficiently inhibits cyclin B1 degradation and polar body extrusion in mouse oocytes indicating robust SAC during female meiosis I.

    Directory of Open Access Journals (Sweden)

    Steffen Hoffmann

    Full Text Available The Spindle Assembly Checkpoint (SAC inhibits anaphase until microtubule-to-kinetochore attachments are formed, thus securing correct chromosome separation and preventing aneuploidy. Whereas in mitosis even a single unattached chromosome keeps the SAC active, the high incidence of aneuploidy related to maternal meiotic errors raises a concern about the lower efficiency of SAC in oocytes. Recently it was suggested that in mouse oocytes, contrary to somatic cells, not a single chromosome but a critical mass of chromosomes triggers efficient SAC pointing to the necessity of evaluating the robustness of SAC in oocytes. Two types of errors in chromosome segregation upon meiosis I related to SAC were envisaged: (1 SAC escape, when kinetochores emit SAC-activating signal unable to stop anaphase I; and (2 SAC deceive, when kinetochores do not emit the signal. Using micromanipulations and live imaging of the first polar body extrusion, as well as the dynamics of cyclin B1 degradation, here we show that in mouse oocytes a single bivalent keeps the SAC active. This is the first direct evaluation of SAC efficiency in mouse oocytes, which provides strong evidence that the robustness of SAC in mammalian oocytes is comparable to other cell types. Our data do not contradict the hypothesis of the critical mass of chromosomes necessary for SAC activation, but suggest that the same rule may govern SAC activity also in other cell types. We postulate that the innate susceptibility of oocytes to errors in chromosome segregation during the first meiotic division may not be caused by lower efficiency of SAC itself, but could be linked to high critical chromosome mass necessary to keep SAC active in oocyte of large size.

  9. Assessing the Mitochondrial Membrane Potential in Cells and In Vivo using Targeted Click Chemistry and Mass Spectrometry.

    Science.gov (United States)

    Logan, Angela; Pell, Victoria R; Shaffer, Karl J; Evans, Cameron; Stanley, Nathan J; Robb, Ellen L; Prime, Tracy A; Chouchani, Edward T; Cochemé, Helena M; Fearnley, Ian M; Vidoni, Sara; James, Andrew M; Porteous, Carolyn M; Partridge, Linda; Krieg, Thomas; Smith, Robin A J; Murphy, Michael P

    2016-02-09

    The mitochondrial membrane potential (Δψm) is a major determinant and indicator of cell fate, but it is not possible to assess small changes in Δψm within cells or in vivo. To overcome this, we developed an approach that utilizes two mitochondria-targeted probes each containing a triphenylphosphonium (TPP) lipophilic cation that drives their accumulation in response to Δψm and the plasma membrane potential (Δψp). One probe contains an azido moiety and the other a cyclooctyne, which react together in a concentration-dependent manner by "click" chemistry to form MitoClick. As the mitochondrial accumulation of both probes depends exponentially on Δψm and Δψp, the rate of MitoClick formation is exquisitely sensitive to small changes in these potentials. MitoClick accumulation can then be quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach enables assessment of subtle changes in membrane potentials within cells and in the mouse heart in vivo. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. What clicks actually mean: Exploring digital news user practices

    NARCIS (Netherlands)

    Groot Kormelink, T.; Costera Meijer, I.

    2017-01-01

    This article problematizes the relationship between clicks and audience interests. Clicking patterns are often seen as evidence that news users are mostly interested in junk news, leading to concerns about the state of journalism and the implications for society. Asking and observing how 56 users

  11. A comparative study of click models for web search

    NARCIS (Netherlands)

    Grotov, A.; Chuklin, A.; Markov, I.; Stout, L.; Xumara, F.; de Rijke, M.; Mothe, J.; Savoy, J.; Kamps, J.; Pinel-Sauvagnat, K.; Jones, G.J.F.; SanJuan, E.; Cappellato, L.; Ferro, N.

    2015-01-01

    Click models have become an essential tool for understanding user behavior on a search engine result page, running simulated experiments and predicting relevance. Dozens of click models have been proposed, all aiming to tackle problems stemming from the complexity of user behavior or of contemporary

  12. Morphine dependence in single enteric neurons from the mouse colon requires deletion of β‐arrestin2

    OpenAIRE

    Smith, Tricia H.; Ngwainmbi, Joy; Hashimoto, Atsushi; Dewey, William L.; Akbarali, Hamid I.

    2014-01-01

    Abstract Chronic administration of morphine results in the development of tolerance to the analgesic effects and to inhibition of upper gastrointestinal motility but not to colonic motility, resulting in persistent constipation. In this study we examined the effect of chronic morphine in myenteric neurons from the adult mouse colon. Similar to the ileum, distinct neuronal populations exhibiting afterhyperpolarization (AHP)‐positive and AHP‐negative neurons were identified in the colon. Acute ...

  13. People's Ability to Detect Objects Using Click-Based Echolocation: A Direct Comparison between Mouth-Clicks and Clicks Made by a Loudspeaker.

    Science.gov (United States)

    Thaler, Lore; Castillo-Serrano, Josefina

    2016-01-01

    Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants' was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation.

  14. People’s Ability to Detect Objects Using Click-Based Echolocation: A Direct Comparison between Mouth-Clicks and Clicks Made by a Loudspeaker

    Science.gov (United States)

    Thaler, Lore; Castillo-Serrano, Josefina

    2016-01-01

    Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants’ was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation. PMID:27135407

  15. People's Ability to Detect Objects Using Click-Based Echolocation: A Direct Comparison between Mouth-Clicks and Clicks Made by a Loudspeaker.

    Directory of Open Access Journals (Sweden)

    Lore Thaler

    Full Text Available Echolocation is the ability to use reflected sound to obtain information about the spatial environment. Echolocation is an active process that requires both the production of the emission as well as the sensory processing of the resultant sound. Appreciating the general usefulness of echo-acoustic cues for people, in particular those with vision impairments, various devices have been built that exploit the principle of echolocation to obtain and provide information about the environment. It is common to all these devices that they do not require the person to make a sound. Instead, the device produces the emission autonomously and feeds a resultant sound back to the user. Here we tested if echolocation performance in a simple object detection task was affected by the use of a head-mounted loudspeaker as compared to active clicking. We found that 27 sighted participants new to echolocation did generally better when they used a loudspeaker as compared to mouth-clicks, and that two blind participants with experience in echolocation did equally well with mouth clicks and the speaker. Importantly, performance of sighted participants' was not statistically different from performance of blind experts when they used the speaker. Based on acoustic click data collected from a subset of our participants, those participants whose mouth clicks were more similar to the speaker clicks, and thus had higher peak frequencies and sound intensity, did better. We conclude that our results are encouraging for the consideration and development of assistive devices that exploit the principle of echolocation.

  16. Clicks versus Citations: Click Count as a Metric in High Energy Physics Publishing

    Energy Technology Data Exchange (ETDEWEB)

    Bitton, Ayelet; /UC, San Diego /SLAC

    2011-06-22

    High-energy physicists worldwide rely on online resources such as SPIRES and arXiv to perform gather research and share their own publications. SPIRES is a tool designed to search the literature within high-energy physics, while arXiv provides the actual full-text documents of this literature. In high-energy physics, papers are often ranked according to the number of citations they acquire - meaning the number of times a later paper references the original. This paper investigates the correlation between the number of times a paper is clicked in order to be downloaded and the number of citations it receives following the click. It explores how physicists truly read what they cite.

  17. One Click: The CECS Students’ Assistant Tools

    Directory of Open Access Journals (Sweden)

    FROILAN G. DESTREZA

    2014-02-01

    Full Text Available This study is pursued because the researchers believe that the design project is more convenient to use in a group discussion as students are expected to gain more knowledge during peer to peer discussion. Through this study, some issues in the traditional way of teaching will be resolve like the time-consuming checking of attendance, quizzes dictation, paying of test papers and the fear of students to participate in recitation The researchers used Prototyping model as procedural method for the successful development and implementation of the hardware and software. This method has five phases which include: quick plan, quick design, prototype construction, delivery and feedback and communication. This study was evaluated by the CECS Students and the assessment of the respondent regarding the software and hardware application was measured in different levels of acceptability such as Accuracy, Adaptability, Effectiveness, Efficiency, Interactive, Portability, Reliability, Security and User-friendliness. The overall acceptability of the traditional way of teaching as evaluated by the respondents is satisfactory. With regard to the evaluation of One Click: The CECS Students’ Assistant Tool, the overall acceptability is excellent. Through evaluation, the researchers had determined that there is a significant difference between the levels of acceptability of the traditional way of teaching and the “One Click: The CECS Students’ Assistant Tool” in terms of the given set of criteria. The recommendation of the researchers in the design project are as follows: enhance the system where the users/students can go back and answer the previous questions and add an interface where user/instructor can delete files.

  18. Genesis of the Mechanical Heart Valves' Ultrasonic Closing Clicks

    Science.gov (United States)

    Hasegawa, Jun; Kobayashi, Kenji

    A new in vitro experimental tool was developed to study the mechanism of the ultrasonic closing clicks' genesis of mechanical heart valves. Since the newly developed tester adopted compressed air flow directly instead of the blood analog fluid to drive the mechanical heart valve, it is not possibe to generate any cavitation. Closing clicks were measured with a small accelerometer at the surface of the valve holder made of silicone rubber. Ultrasonic closing clicks as well as audible closing clicks, similar to those measured clinically, could be observed using this setup. Thus, it was confirmed that the ultrasonic closing clicks can be generated without the existence of cavitation. Simultaneous measurements of the valve motion were made with a high-speed video camera, and the analysis of the video frames and clicks showed that higher frequency signal components of more than 50kHz could be generated only at the instant of the closure, which means the collision of the occluder with the housing. Eighteen miniature accelerometers with an area of one square millimeter were developed and stuck on the housing to monitor the distribution of the housing vibrations in detail, and it was found that the vibrations correspond to the ultrasonic closing clicks propagated from the valve stop: the collision point of the occluder with the housing. This fact indicated that the generation of ultrasonic closing clicks are limited to the small area of the collision. From those results, it was concluded that the major origin of the ultrasonic closing clicks' genesis should be the collision of the occluder with the housing.

  19. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs....... The latter is defined as a CEOAE with duration greater than 20 ms, typically observed for test subjects with spontaneous otoacoustic emissions (SOAEs). Previous studies have tended to exclude these test subjects but they are incorporated here. The results from six exemplary subjects demonstrate that temporal...

  20. Intracellular β2-adrenergic receptor signaling specificity in mouse skeletal muscle in response to single-dose β2-agonist clenbuterol treatment and acute exercise.

    Science.gov (United States)

    Sato, Shogo; Shirato, Ken; Mitsuhashi, Ryosuke; Inoue, Daisuke; Kizaki, Takako; Ohno, Hideki; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-05-01

    The aim of this study was to clarify the intracellular β2-adrenergic receptor signaling specificity in mouse slow-twitch soleus and fast-twitch tibialis anterior (TA) muscles, resulting from single-dose β2-agonist clenbuterol treatment and acute exercise. At 1, 4, and 24 h after single-dose treatment with clenbuterol or after acute running exercise, the soleus and TA muscles were isolated and subjected to analysis. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased after single-dose clenbuterol treatment and acute exercise in the soleus muscle but not in the TA muscle. Although there was no change in the phosphorylation of Akt after acute exercise in either muscle, phosphorylation of Akt in the soleus muscle increased after single-dose clenbuterol treatment, whereas that in the TA muscle remained unchanged. These results suggest that p38 MAPK and Akt pathways play a functional role in the adaptation to clenbuterol treatment and exercise, particularly in slow-twitch muscles.

  1. CLoNe is a new method to target single progenitors and study their progeny in mouse and chick.

    Science.gov (United States)

    García-Moreno, Fernando; Vasistha, Navneet A; Begbie, Jo; Molnár, Zoltán

    2014-04-01

    Cell lineage analysis enables us to address pivotal questions relating to: the embryonic origin of cells and sibling cell relationships in the adult body; the contribution of progenitors activated after trauma or disease; and the comparison across species in evolutionary biology. To address such fundamental questions, several techniques for clonal labelling have been developed, each with its shortcomings. Here, we report a novel method, CLoNe that is designed to work in all vertebrate species and tissues. CLoNe uses a cocktail of labelling, targeting and transposition vectors that enables targeting of specific subpopulations of progenitor types with a combination of fluorophores resulting in multifluorescence that describes multiple clones per specimen. Furthermore, transposition into the genome ensures the longevity of cell labelling. We demonstrate the robustness of this technique in mouse and chick forebrain development, and show evidence that CLoNe will be broadly applicable to study clonal relationships in different tissues and species.

  2. Repression of multiple CYP2D genes in mouse primary hepatocytes with a single siRNA construct.

    Science.gov (United States)

    Elraghy, Omaima; Baldwin, William S

    2015-01-01

    The Cyp2d subfamily is the second most abun-dant subfamily of hepatic drug-metabolizing CYPs. In mice, there are nine Cyp2d members that are believed to have redundant catalytic activity. We are testing and optimizing the ability of one short interfering RNA (siRNA) construct to knockdown the expression of multiple mouse Cyp2ds in primary hepatocytes. Expression of Cyp2d10, Cyp2d11, Cyp2d22, and Cyp2d26 was observed in the primary male mouse hepatocytes. Cyp2d9, which is male-specific and growth hormone-dependent, was not expressed in male primary hepatocytes, potentially because of its dependence on pulsatile growth hormone release from the anterior pituitary. Several different siRNAs at different concentrations and with different reagents were used to knockdown Cyp2d expression. siRNA constructs designed to repress only one construct often mildly repressed several Cyp2d isoforms. A construct designed to knockdown every Cyp2d isoform provided the best results, especially when incubated with transfection reagents designed specifically for primary cell culture. Interestingly, a construct designed to knockdown all Cyp2d isoforms, except Cyp2d10, caused a 2.5× increase in Cyp2d10 expression, presumably because of a compensatory response. However, while RNA expression is repressed 24 h after siRNA treatment, associated changes in Cyp2d-mediated metabolism are tenuous. Overall, this study provides data on the expression of murine Cyp2ds in primary cell lines, valuable information on designing siRNAs for silencing multiple murine CYPs, and potential pros and cons of using siRNA as a tool for repressing Cyp2d and estimating Cyp2d's role in murine xenobiotic metabolism.

  3. A site-specific, single-copy transgenesis strategy to identify 5' regulatory sequences of the mouse testis-determining gene Sry.

    Science.gov (United States)

    Quinn, Alexander; Kashimada, Kenichi; Davidson, Tara-Lynne; Ng, Ee Ting; Chawengsaksophak, Kallayanee; Bowles, Josephine; Koopman, Peter

    2014-01-01

    The Y-chromosomal gene SRY acts as the primary trigger for male sex determination in mammalian embryos. Correct regulation of SRY is critical: aberrant timing or level of Sry expression is known to disrupt testis development in mice and we hypothesize that mutations that affect regulation of human SRY may account for some of the many cases of XY gonadal dysgenesis that currently remain unexplained. However, the cis-sequences involved in regulation of Sry have not been identified, precluding a test of this hypothesis. Here, we used a transgenic mouse approach aimed at identifying mouse Sry 5' flanking regulatory sequences within 8 kb of the Sry transcription start site (TSS). To avoid problems associated with conventional pronuclear injection of transgenes, we used a published strategy designed to yield single-copy transgene integration at a defined, transcriptionally open, autosomal locus, Col1a1. None of the Sry transgenes tested was expressed at levels compatible with activation of Sox9 or XX sex reversal. Our findings indicate either that the Col1a1 locus does not provide an appropriate context for the correct expression of Sry transgenes, or that the cis-sequences required for Sry expression in the developing gonads lie beyond 8 kb 5' of the TSS.

  4. A site-specific, single-copy transgenesis strategy to identify 5' regulatory sequences of the mouse testis-determining gene Sry.

    Directory of Open Access Journals (Sweden)

    Alexander Quinn

    Full Text Available The Y-chromosomal gene SRY acts as the primary trigger for male sex determination in mammalian embryos. Correct regulation of SRY is critical: aberrant timing or level of Sry expression is known to disrupt testis development in mice and we hypothesize that mutations that affect regulation of human SRY may account for some of the many cases of XY gonadal dysgenesis that currently remain unexplained. However, the cis-sequences involved in regulation of Sry have not been identified, precluding a test of this hypothesis. Here, we used a transgenic mouse approach aimed at identifying mouse Sry 5' flanking regulatory sequences within 8 kb of the Sry transcription start site (TSS. To avoid problems associated with conventional pronuclear injection of transgenes, we used a published strategy designed to yield single-copy transgene integration at a defined, transcriptionally open, autosomal locus, Col1a1. None of the Sry transgenes tested was expressed at levels compatible with activation of Sox9 or XX sex reversal. Our findings indicate either that the Col1a1 locus does not provide an appropriate context for the correct expression of Sry transgenes, or that the cis-sequences required for Sry expression in the developing gonads lie beyond 8 kb 5' of the TSS.

  5. Applications of Azide-Based Bioorthogonal Click Chemistry in Glycobiology

    Directory of Open Access Journals (Sweden)

    Xiu Zhang

    2013-06-01

    Full Text Available Click chemistry is a powerful chemical reaction with excellent bioorthogonality features: biocompatible, rapid and highly specific in biological environments. For glycobiology, bioorthogonal click chemistry has created a new method for glycan non-invasive imaging in living systems, selective metabolic engineering, and offered an elite chemical handle for biological manipulation and glycomics studies. Especially the [3 + 2] dipolar cycloadditions of azides with strained alkynes and the Staudinger ligation of azides and triarylphosphines have been widely used among the extant click reactions. This review focuses on the azide-based bioorthogonal click chemistry, describing the characteristics and development of these reactions, introducing some recent applications in glycobiology research, especially in glycan metabolic engineering, including glycan non-invasive imaging, glycomics studies and viral surface manipulation for drug discovery as well as other applications like activity-based protein profiling and carbohydrate microarrays.

  6. Efficient click reaction towards novel sulfonamide hybrids by ...

    Indian Academy of Sciences (India)

    Dong-Jun FU

    2018-02-01

    Feb 1, 2018 ... bCollaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan Province,. China ... Twelve novel sulfonamide hybrids were designed by molecular hybridization strategy. The target ... Molecular hybridization strategy; click reaction; sulfonamide; antiproliferative. 1.

  7. Recent advances in click chemistry applied to dendrimer synthesis.

    Science.gov (United States)

    Arseneault, Mathieu; Wafer, Caroline; Morin, Jean-François

    2015-05-20

    Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the "click chemistry" concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field.

  8. Factors influencing clicking of banner ads on the WWW.

    Science.gov (United States)

    Cho, Chang-Hoan

    2003-04-01

    This paper explores various factors influencing the clicking of banner ads on the WWW. The study indicates that several important variables affect the clicking of banner ads: (1) level of product involvement, (2) congruency between the content of a vehicle and the product category of a banner ad, (3) attitude toward the vehicle, and (4) overall attitude toward web advertising. For methodology, this study employed a between-group experimental design and measured real click-through rates with the aid of an online data collection technology called FileMaker Pro. Results of logistic regressions show that people are more likely to click banner ads if they are highly involved with products, perceive high synergy between web pages and ads, have a favorable attitude toward a vehicle, or have a favorable attitude toward web advertising in general. A total of 756 subjects participated in this research.

  9. Evaluation of Kentucky's "Click It or Ticket" 2008 campaign.

    Science.gov (United States)

    2008-07-01

    The objective of this report was to document the results of the "Click It or Ticket" 2008 campaign in Kentucky. The campaign involved a combination of earned media, paid media, and enforcement. : The evaluation of the campaign included documenting th...

  10. Click Bait: You Won’t Believe What Happens Next!

    Directory of Open Access Journals (Sweden)

    Liliana Alves

    2016-12-01

    Full Text Available The goal of this chapter is to investigate Click Bait, one of the strategies most commonly used by online news journalists aiming to make their headlines more attractive to readers. The chapter begins by studying Social Networks and the power they give marketers in spreading information. Next, a historical context to Click Bait is presented through its origins as Yellow Journalism, a 19th century journalism trend focused on hyperbolizing news headlines in order to increase sales. Finally, Click Bait is studied as the online application of techniques like Yellow Journalism. This section analyzes semantics and some of the most popular headline construction formulas. Literature on this matter concluded that the use of certain headline construction formulas yields significant increase in click-through rates. These increases could be beneficial to the publishing organization as they increase advertising impressions, but could also be detrimental, as these hyperbolic headlines may make readers feel manipulated.

  11. Click Chemistry in Peptide-Based Drug Design

    Directory of Open Access Journals (Sweden)

    Irwin Chaiken

    2013-08-01

    Full Text Available Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical and biological fields. In this review, we discuss the application of click chemistry in peptide-based drug design. We highlight how triazoles formed by click reactions have been used for mimicking peptide and disulfide bonds, building secondary structural components of peptides, linking functional groups together, and bioconjugation. The progress made in this field opens the way for synthetic approaches to convert peptides with promising functional leads into structure-minimized and more stable forms.

  12. Young children's ability to use a computer mouse

    NARCIS (Netherlands)

    Donker, A.; Reitsma, P.

    2007-01-01

    Because there is little empirical data available on how well young children are able to use a computer mouse, the present study examined their proficiency in clicking on small objects at various positions on the screen and their skill in moving objects over the screen, using drag-and-drop and

  13. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C(60) fullerenes in the FE1-Mutatrade markMouse lung epithelial cells

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Pojana, Giulio; White, Paul

    2008-01-01

    Viability, cell cycle effects, genotoxicity, reactive oxygen species production, and mutagenicity of C(60) fullerenes (C(60)) and single-walled carbon nanotubes (SWCNT) were assessed in the FE1-Mutatrade markMouse lung epithelial cell line. None of these particles induced cell death within 24 hr...... at doses between 0 and 200 microg/ml or during long-term subculture exposure (576 hr) at 100 microg/ml, as determined by two different assays. However, cell proliferation was slower with SWCNT exposure and a larger fraction of the cells were in the G1 phase. Exposure to carbon black resulted...... by the comet assay. The mutant frequency in the cII gene was unaffected by 576 hr of exposure to either 100 microg/ml C(60) or SWCNT when compared with control incubations, whereas we have previously reported that carbon black and diesel exhaust particles induce mutations using an identical exposure scenario...

  14. Performance of single and multi-atlas based automated landmarking methods compared to expert annotations in volumetric microCT datasets of mouse mandibles.

    Science.gov (United States)

    Young, Ryan; Maga, A Murat

    2015-01-01

    Here we present an application of advanced registration and atlas building framework DRAMMS to the automated annotation of mouse mandibles through a series of tests using single and multi-atlas segmentation paradigms and compare the outcomes to the current gold standard, manual annotation. Our results showed multi-atlas annotation procedure yields landmark precisions within the human observer error range. The mean shape estimates from gold standard and multi-atlas annotation procedure were statistically indistinguishable for both Euclidean Distance Matrix Analysis (mean form matrix) and Generalized Procrustes Analysis (Goodall F-test). Further research needs to be done to validate the consistency of variance-covariance matrix estimates from both methods with larger sample sizes. Multi-atlas annotation procedure shows promise as a framework to facilitate truly high-throughput phenomic analyses by channeling investigators efforts to annotate only a small portion of their datasets.

  15. Clicking in cervids - basic parameters, origin and function?

    OpenAIRE

    POJEROVÁ, Lucie

    2014-01-01

    It is well known that some ungulates produce clicking sound by limbs, but often without more details. This study deals with the clicking sound in five cervid taxons, specifically in Caribou (Rangifer tarandus), Pere David´s Deer (Elaphurus davidianus), Western Red Deer (Cervus elaphus), Moose (Alces alces), Barbary stag (Cervus elaphus barbarus) in detail. Dominant frequency, 25% quartile, 50% quartile, 75% quartile were investigated for these species, with the particular attention to sex, ag...

  16. Click-coated, heparinized, decellularized vascular grafts.

    Science.gov (United States)

    Dimitrievska, Sashka; Cai, Chao; Weyers, Amanda; Balestrini, Jenna L; Lin, Tylee; Sundaram, Sumati; Hatachi, Go; Spiegel, David A; Kyriakides, Themis R; Miao, Jianjun; Li, Guoyun; Niklason, Laura E; Linhardt, Robert J

    2015-02-01

    A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels. Copyright © 2014 Acta Materialia Inc. All rights reserved.

  17. Nonecholocating fruit bats produce biosonar clicks with their wings.

    Science.gov (United States)

    Boonman, Arjan; Bumrungsri, Sara; Yovel, Yossi

    2014-12-15

    Because evolution mostly acts over millions of years, the intermediate steps leading to a functional sensory system remain enigmatic. Accordingly, there is an ongoing debate regarding the evolution of bat echolocation. In search of the origin of bat echolocation, we studied how Old World fruit bats, which have always been classified as nonecholocating, orient in complete darkness. We found that two of these nonecholocating species used click-like sounds to detect and discriminate objects in complete darkness. However, we discovered that this click-based echo sensing is rudimentary and does not allow these bats to estimate distance accurately as all other echolocating bats can. Moreover, unlike all other echolocating bats, which generate pulses using the larynx or the tongue, these bats generated clicks with their wings. We provide evidence suggesting that all Old World fruit bats can click with their wings. Although this click-based echo sensing used by Old World fruit bats may not represent the ancestral form of current (laryngeal) bat echolocation, we argue that clicking fruit bats could be considered behavioral fossils, opening a window to study the evolution of echolocation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Geographic variation in Risso's dolphin echolocation click spectra.

    Science.gov (United States)

    Soldevilla, Melissa S; Baumann-Pickering, Simone; Cholewiak, Danielle; Hodge, Lynne E W; Oleson, Erin M; Rankin, Shannon

    2017-08-01

    Discrimination of bioacoustic signals to the species or population level is critical for using passive acoustic monitoring to study cetacean ecology. Risso's dolphins off southern California have distinctive peaks and notches in their echolocation clicks, but it was unknown whether Risso's dolphins from other geographic areas have similarly distinctive click spectra and whether populations are acoustically distinct. This study investigates using clicks for species and population identification by characterizing the spectral structure of Risso's dolphin echolocation clicks recorded over wide-ranging geographic regions including the U.S. waters of the North Atlantic Ocean, Gulf of Mexico, and North Pacific Ocean; and international waters of the Eastern Tropical Pacific. All recordings with Risso's dolphin clicks exhibited the spectral peak and notch pattern described off southern California, indicating the presence of peak banding patterns is useful for species discrimination. Geographic regions were a significant explanatory factor for variability in the frequencies of click spectral peaks, with relatively higher frequency peaks and notches found off Hawaii compared to California waters and off the southeast U.S. compared to the Gulf of Mexico. In the North Atlantic Ocean, a latitudinal cline in frequencies was evident. Potential causes of acoustic variation within and among acoustic encounters are evaluated.

  19. Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis.

    Science.gov (United States)

    Aransay, Ana; Rodríguez-López, Claudia; García-Amado, María; Clascá, Francisco; Prensa, Lucía

    2015-01-01

    Pathways arising from the ventral tegmental area (VTA) release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VTA projections is well-known, the actual axonal wiring of individual VTA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VTA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VTA cells with iontophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VTA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells), and neurons with multibranched axons targeting both the forebrain and the brainstem (F + BSPN cells). Dopaminergic phenotype was observed in FPN cells. Moreover, four "subtypes" could be distinguished among the FPN cells based on their projection targets: (1) "Mesocorticolimbic" FPN projecting to both neocortex and basal forebrain; (2) "Mesocortical" FPN innervating the neocortex almost exclusively; (3) "Mesolimbic" FPN projecting to the basal forebrain, accumbens and caudateputamen; and (4) "Mesostriatal" FPN targeting only the caudateputamen. While the F + BSPN cells were scattered within VTA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VTA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.

  20. Radiation-induced DNA single-strand scission and its rejoining in spermatogonia and spermatozoa of mouse

    International Nuclear Information System (INIS)

    Ono, T.; Okada, S.

    1977-01-01

    Gamma-ray-induced DNA single-strand scissions and the ability to repair the scissions in spermatogonia from young mice and in spermatozoa from adult mice were studied quantitatively by an alkaline sucrose density-gradient centrifugation method. The average size of DNAs in non-irradiated spermatogonia was 2.6-3.0xx10 8 daltons, similar to those of a spermatid-rich population, and the size of DNA in non-irradiated spermatozoa was 1.2x10 8 daltons. In spermatogonia, the radiosensitivity of DNA was 0.42 single-strand breaks/10 12 daltons of DNA/rad in oxic conditions and only 0.24 under anoxic conditions. In spermatozoa the break efficiency of DNA was 0.22 single-strand breaks/10 12 daltons of DNA/rad under oxic conditions and altered little under anoxic irradiation. The DNA scissions were efficiently repaired in spermatogonia within 10 min, whereas the breaks in spermatozoa were not rejoined at all even after two days of post-irradiation time. The radiosensitivities of DNA, repair capability and non- and/or slowreparable DNA scissions were compared in spermatogonium-rich, spermatid-rich and spermatozoanrich populations

  1. A novel mouse model for non-invasive single marker tracking of mammary stem cells in vivo reveals stem cell dynamics throughout pregnancy.

    Directory of Open Access Journals (Sweden)

    Benjamin J Tiede

    Full Text Available Mammary stem cells (MaSCs play essential roles for the development of the mammary gland and its remodeling during pregnancy. However, the precise localization of MaSCs in the mammary gland and their regulation during pregnancy is unknown. Here we report a transgenic mouse model for luciferase-based single marker detection of MaSCs in vivo that we used to address these issues. Single transgene expressing mammary epithelial cells were shown to reconstitute mammary glands in vivo while immunohistochemical staining identified MaSCs in basal and luminal locations, with preponderance towards the basal position. By quantifying luciferase expression using bioluminescent imaging, we were able to track MaSCs non-invasively in individual mice over time. Using this model to monitor MaSC dynamics throughout pregnancy, we found that MaSCs expand in both total number and percentage during pregnancy and then drop down to or below baseline levels after weaning. However, in a second round of pregnancy, this expansion was not as extensive. These findings validate a powerful system for the analysis of MaSC dynamics in vivo, which will facilitate future characterization of MaSCs during mammary gland development and breast cancer.

  2. Quantitative evaluation of a single-distance phase-retrieval method applied on in-line phase-contrast images of a mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Mohammadi, Sara, E-mail: sara.mohammadi@elettra.trieste.it [The Abdus Salam International Centre for Theoretical Physics, Trieste (Italy); Synchrotron Light Source ‘Elettra’ Trieste, Strada Statale 14, km 163.5 in AREA Science Park, Basovizza 34149 (Italy); Larsson, Emanuel [Synchrotron Light Source ‘Elettra’ Trieste, Strada Statale 14, km 163.5 in AREA Science Park, Basovizza 34149 (Italy); Linköping University, SE-581 83 (Sweden); University of Trieste, Trieste (Italy); Alves, Frauke [University Hospital Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Dal Monego, Simeone [Cluster in Biomedicine s.c.r.l., AREA Science Park, Strada Statale 14, km 163.5, Basovizza, 34149 Trieste (Italy); Biffi, Stefania; Garrovo, Chiara [IRCCS Burlo Garofolo, via dell’Istria 65/1, 34137 Trieste (Italy); Lorenzon, Andrea [Cluster in Biomedicine s.c.r.l., AREA Science Park, Strada Statale 14, km 163.5, Basovizza, 34149 Trieste (Italy); Tromba, Giuliana [Synchrotron Light Source ‘Elettra’ Trieste, Strada Statale 14, km 163.5 in AREA Science Park, Basovizza 34149 (Italy); Dullin, Christian, E-mail: sara.mohammadi@elettra.trieste.it [University Hospital Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany)

    2014-05-16

    Quantitative analysis concerning the application of a single-distance phase-retrieval algorithm on in-line phase-contrast images of a mouse lung at different sample-to-detector distances is presented. Propagation-based X-ray phase-contrast computed tomography (PBI) has already proven its potential in a great variety of soft-tissue-related applications including lung imaging. However, the strong edge enhancement, caused by the phase effects, often hampers image segmentation and therefore the quantitative analysis of data sets. Here, the benefits of applying single-distance phase retrieval prior to the three-dimensional reconstruction (PhR) are discussed and quantified compared with three-dimensional reconstructions of conventional PBI data sets in terms of contrast-to-noise ratio (CNR) and preservation of image features. The PhR data sets show more than a tenfold higher CNR and only minor blurring of the edges when compared with PBI in a predominately absorption-based set-up. Accordingly, phase retrieval increases the sensitivity and provides more functionality in computed tomography imaging.

  3. Quantitative evaluation of a single-distance phase-retrieval method applied on in-line phase-contrast images of a mouse lung

    International Nuclear Information System (INIS)

    Mohammadi, Sara; Larsson, Emanuel; Alves, Frauke; Dal Monego, Simeone; Biffi, Stefania; Garrovo, Chiara; Lorenzon, Andrea; Tromba, Giuliana; Dullin, Christian

    2014-01-01

    Quantitative analysis concerning the application of a single-distance phase-retrieval algorithm on in-line phase-contrast images of a mouse lung at different sample-to-detector distances is presented. Propagation-based X-ray phase-contrast computed tomography (PBI) has already proven its potential in a great variety of soft-tissue-related applications including lung imaging. However, the strong edge enhancement, caused by the phase effects, often hampers image segmentation and therefore the quantitative analysis of data sets. Here, the benefits of applying single-distance phase retrieval prior to the three-dimensional reconstruction (PhR) are discussed and quantified compared with three-dimensional reconstructions of conventional PBI data sets in terms of contrast-to-noise ratio (CNR) and preservation of image features. The PhR data sets show more than a tenfold higher CNR and only minor blurring of the edges when compared with PBI in a predominately absorption-based set-up. Accordingly, phase retrieval increases the sensitivity and provides more functionality in computed tomography imaging

  4. Single and combined effects of Δ9-tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

    Science.gov (United States)

    King, Kirsten M; Myers, Alyssa M; Soroka-Monzo, Ariele J; Tuma, Ronald F; Tallarida, Ronald J; Walker, Ellen A; Ward, Sara Jane

    2017-09-01

    The non-psychoactive phytocannabinoid cannabidiol (CBD) can affect the pharmacological effects of Δ 9 -tetrahydrocannabinol (THC). We tested the possible synergy between CBD and THC in decreasing mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain. We also tested the effects of CBD on oxaliplatin- and vincristine-induced mechanical sensitivity. Paclitaxel-treated mice (8.0 mg·kg -1 i.p., days 1, 3, 5 and 7) were pretreated with CBD (0.625-20.0 mg·kg -1 i.p.), THC (0.625-20.0 mg·kg -1 i.p.) or CBD + THC (0.04 + 0.04-20.0 + 20.0 mg·kg -1 i.p.), and mechanical sensitivity was assessed on days 9, 14 and 21. Oxaliplatin-treated (6.0 mg·kg -1 i.p., day 1) or vincristine-treated mice (0.1 mg·kg -1 i.p. days 1-7) were pretreated with CBD (1.25-10.0 mg·kg -1 i.p.), THC (10.0 mg·kg -1 i.p.) or THC + CBD (0.16 mg·kg -1 THC + 0.16 mg·kg -1 CBD i.p.). Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity. CBD may be potent and effective at preventing the development of chemotherapy-induced peripheral neuropathy, and its clinical use may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of cannabis-based pharmacotherapies. © 2017 The British Pharmacological Society.

  5. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  6. CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo.

    Science.gov (United States)

    Kalebic, Nereo; Taverna, Elena; Tavano, Stefania; Wong, Fong Kuan; Suchold, Dana; Winkler, Sylke; Huttner, Wieland B; Sarov, Mihail

    2016-03-01

    We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h. Furthermore, by using microinjection of the Cas9 protein/gRNA complex into neural stem cells in organotypic slice culture, we obtained disruption of GFP expression within a single cell cycle. Finally, we used either Cas9 plasmid in utero electroporation or Cas9 protein complex microinjection to disrupt the expression of Eomes/Tbr2, a gene fundamental for neocortical neurogenesis. This resulted in a reduction in basal progenitors and an increase in neuronal differentiation. Thus, the present in vivo application of the CRISPR/Cas9 system in neural stem cells provides a rapid, efficient and enduring disruption of expression of specific genes to dissect their role in mammalian brain development. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  7. Single cell electroporation for longitudinal imaging of synaptic structure and function in the adult mouse neocortex in vivo

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2015-04-01

    Full Text Available Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation and germline transgenesis. Single cell electroporation has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of single cell electroporation to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.

  8. Ukufundisa izicuku zeziqhakancu emagameni (Teaching click clusters in words

    Directory of Open Access Journals (Sweden)

    Gxowa-Dlayedwa, Ntombizodwa Cynthia

    2015-12-01

    Full Text Available Some teachers find it uninteresting and difficult to teach isiXhosa phonemes and syllables to grade one to three learners. This has a negative impact as the literacy results are low because learners’ reading and writing skills are poor. The linguistics terms featuring in the title, namely; consonants, vowels and syllables as found in words facilitate reading, and thus improve literacy standards in every language. IsiXhosa is one of the eleven official languages in South Africa. Phonemes include clicks and/or click cluster and vowels. On the other hand, there are people who are interested in learning to speak isiXhosa, but the difficulties encountered during the pronunciation of clicks discourage many of them. This study believes that the knowledge of phonemes and syllables will boost the literacy standard in isiXhosa. Therefore, the purposes of this study are to show that clicks and click clusters are found in major word categories which are in life circles. Secondly, if words are divided into segments, it becomes easy to produce them in print and reading skills. Thirdly, reading is possible in every language, and most importantly, skills are transferable. The current study therefore, argues that the knowledge of phonemes and syllables facilitates reading and creative writing skills. The data used in this study were taken from a novel written by Sidlayi (2009. Few examples have been given by the researchers themselves with an objective to clarify some ideas.

  9. Discriminating features of echolocation clicks of melon-headed whales (Peponocephala electra), bottlenose dolphins (Tursiops truncatus), and Gray's spinner dolphins (Stenella longirostris longirostris).

    Science.gov (United States)

    Baumann-Pickering, Simone; Wiggins, Sean M; Hildebrand, John A; Roch, Marie A; Schnitzler, Hans-Ulrich

    2010-10-01

    Spectral parameters were used to discriminate between echolocation clicks produced by three dolphin species at Palmyra Atoll: melon-headed whales (Peponocephala electra), bottlenose dolphins (Tursiops truncatus) and Gray's spinner dolphins (Stenella longirostris longirostris). Single species acoustic behavior during daytime observations was recorded with a towed hydrophone array sampling at 192 and 480 kHz. Additionally, an autonomous, bottom moored High-frequency Acoustic Recording Package (HARP) collected acoustic data with a sampling rate of 200 kHz. Melon-headed whale echolocation clicks had the lowest peak and center frequencies, spinner dolphins had the highest frequencies and bottlenose dolphins were nested in between these two species. Frequency differences were significant. Temporal parameters were not well suited for classification. Feature differences were enhanced by reducing variability within a set of single clicks by calculating mean spectra for groups of clicks. Median peak frequencies of averaged clicks (group size 50) of melon-headed whales ranged between 24.4 and 29.7 kHz, of bottlenose dolphins between 26.7 and 36.7 kHz, and of spinner dolphins between 33.8 and 36.0 kHz. Discriminant function analysis showed the ability to correctly discriminate between 93% of melon-headed whales, 75% of spinner dolphins and 54% of bottlenose dolphins.

  10. Medclic: the Mediterranean in one click

    Science.gov (United States)

    Troupin, Charles; Frontera, Biel; Sebastián, Kristian; Pau Beltran, Joan; Krietemeyer, Andreas; Gómara, Sonia; Gomila, Mikel; Escudier, Romain; Juza, Mélanie; Mourre, Baptiste; Garau, Angels; Cañellas, Tomeu; Tintoré, Joaquín

    2016-04-01

    "Medclic: the Mediterranean in one click" is a research and dissemination project focused on the scientific, technological and societal approaches of the Balearic Islands Coastal Observing and Forecasting System ({SOCIB}{www.socib.es}) in a collaboration with "la Caixa" Foundation. SOCIB aims at research excellence and the development of technology which enables progress toward the sustainable management of coastal and marine environments, providing solutions to meet the needs of society. Medclic goes one step forward and has two main goals: at the scientific level, to advance in establishing and understanding the mesoscale variability at the regional scale and its interaction, and thus improving the characterisation of the "oceanic weather" in the Mediterranean; at the outreach level: to bring SOCIB and the new paradigm of multi-platform observation in real time closer to society, through scientific outreach. SOCIB Data Centre is the core of the new multi-platform and real time oceanography and is responsible for directing the different stages of data management, ranging from data acquisition to its distribution and visualization through web applications. The system implemented relies on open source solutions and provides data in line with international standards and conventions (INSPIRE, netCDF Climate and Forecast, ldots). In addition, the Data Centre has implemented a REST web service, called Data Discovery. This service allows data generated by SOCIB to be integrated into applications developed by the Data Centre itself or by third parties, as it is the case with Medclic. Relying on this data distribution, the new web Medclic, www.medclic.es, constitutes an interactive scientific and educational area of communication that contributes to the rapprochement of the general public with the new marine and coastal observing technologies. Thanks to the Medclic web, data coming from new observing technologies in oceanography are available in real time and in one clic

  11. Take care of your mouse!

    CERN Multimedia

    IT Department

    2011-01-01

    “Stop --- Think --- Click" is the basic recommendation for securely browsing the Internet and for securely reading e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. We would like to thank all those who donated their mouse to the CERN Animal Shelter for Computer Mice (http://cern.ch/c-a-s). For those who still use a mouse, please stay vigilant and  alert: do not click on links whose origin you do not trust or which look like gibberish. Do not install untrusted software or plug-ins, since software from untrusted sources may infect or compromise your computer, or violate copyrights. Finally, take particular care with e-mails: Do not open unexpected or suspicious e-mails or attachments. Delete them if they do not concern you or if they appear strange. If in doubt, or if you have questions, please do not hesitate to contact Computer.Security@cern.ch

  12. Single-Molecule Spectroscopy

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 2. Single-Molecule Spectroscopy: Every Molecule is Different! Kankan Bhattacharyya. General Article Volume 20 Issue 2 February 2015 pp 151-164. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Identification of factors promoting ex vivo maintenance of mouse hematopoietic stem cells by long-term single-cell quantification.

    Science.gov (United States)

    Kokkaliaris, Konstantinos D; Drew, Erin; Endele, Max; Loeffler, Dirk; Hoppe, Philipp S; Hilsenbeck, Oliver; Schauberger, Bernhard; Hinzen, Christoph; Skylaki, Stavroula; Theodorou, Marina; Kieslinger, Matthias; Lemischka, Ihor; Moore, Kateri; Schroeder, Timm

    2016-09-01

    The maintenance of hematopoietic stem cells (HSCs) during ex vivo culture is an important prerequisite for their therapeutic manipulation. However, despite intense research, culture conditions for robust maintenance of HSCs are still missing. Cultured HSCs are quickly lost, preventing their improved analysis and manipulation. Identification of novel factors supporting HSC ex vivo maintenance is therefore necessary. Coculture with the AFT024 stroma cell line is capable of maintaining HSCs ex vivo long-term, but the responsible molecular players remain unknown. Here, we use continuous long-term single-cell observation to identify the HSC behavioral signature under supportive or nonsupportive stroma cocultures. We report early HSC survival as a major characteristic of HSC-maintaining conditions. Behavioral screening after manipulation of candidate molecules revealed that the extracellular matrix protein dermatopontin (Dpt) is involved in HSC maintenance. DPT knockdown in supportive stroma impaired HSC survival, whereas ectopic expression of the Dpt gene or protein in nonsupportive conditions restored HSC survival. Supplementing defined stroma- and serum-free culture conditions with recombinant DPT protein improved HSC clonogenicity. These findings illustrate a previously uncharacterized role of Dpt in maintaining HSCs ex vivo. © 2016 by The American Society of Hematology.

  14. Hearing sensation levels of emitted biosonar clicks in an echolocating Atlantic bottlenose dolphin.

    Directory of Open Access Journals (Sweden)

    Songhai Li

    Full Text Available Emitted biosonar clicks and auditory evoked potential (AEP responses triggered by the clicks were synchronously recorded during echolocation in an Atlantic bottlenose dolphin (Tursiops truncatus trained to wear suction-cup EEG electrodes and to detect targets by echolocation. Three targets with target strengths of -34, -28, and -22 dB were used at distances of 2 to 6.5 m for each target. The AEP responses were sorted according to the corresponding emitted click source levels in 5-dB bins and averaged within each bin to extract biosonar click-related AEPs from noise. The AEP amplitudes were measured peak-to-peak and plotted as a function of click source levels for each target type, distance, and target-present or target-absent condition. Hearing sensation levels of the biosonar clicks were evaluated by comparing the functions of the biosonar click-related AEP amplitude-versus-click source level to a function of external (in free field click-related AEP amplitude-versus-click sound pressure level. The results indicated that the dolphin's hearing sensation levels to her own biosonar clicks were equal to that of external clicks with sound pressure levels 16 to 36 dB lower than the biosonar click source levels, varying with target type, distance, and condition. These data may be assumed to indicate that the bottlenose dolphin possesses effective protection mechanisms to isolate the self-produced intense biosonar beam from the animal's ears during echolocation.

  15. Complex Surface Concentration Gradients by Stenciled "Electro Click Chemistry"

    DEFF Research Database (Denmark)

    Hansen, Thomas Steen; Lind, Johan Ulrik; Daugaard, Anders Egede

    2010-01-01

    Complex one- or two-dimensional concentration gradients of alkynated molecules are produced on azidized conducting polymer substrates by stenciled "electro click chemistry". The latter describes the local electrochemical generation of catalytically active Cu(I) required to complete a "click...... reaction" between alkynes and azides at room temperature. A stencil on the counter electrode defines the shape and multiplicity of the gradient(s) on the conducting polymer substrate, while the specific reaction conditions control gradient steepness and the maximum concentration deposited. Biologically...

  16. Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

    Directory of Open Access Journals (Sweden)

    Schem Christian

    2013-01-01

    Full Text Available Abstract Background A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether Sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases. Method Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density. Results Preventive dosing administration of Sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with Sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels. Conclusions The findings suggest that Sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.

  17. Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq.

    Science.gov (United States)

    Chen, Lihe; Lee, Jae Wook; Chou, Chung-Lin; Nair, Anil V; Battistone, Maria A; Păunescu, Teodor G; Merkulova, Maria; Breton, Sylvie; Verlander, Jill W; Wall, Susan M; Brown, Dennis; Burg, Maurice B; Knepper, Mark A

    2017-11-14

    Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit. Single-cell RNA-seq using the IC- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs, and PCs. The data were used to create a freely accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters, and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing aquaporin-2 and anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., Notch2 chiefly in PCs vs. Jag1 chiefly in ICs), suggesting signaling cross-talk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.

  18. Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome.

    Science.gov (United States)

    Kadota, M; Nishigaki, R; Wang, C C; Toda, T; Shirayoshi, Y; Inoue, T; Gojobori, T; Ikeo, K; Rogers, M S; Oshimura, M

    2004-01-01

    Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed to result in apparent neuropathological abnormalities and to contribute to the phenotypic characteristics of mental retardation and premature development of Alzheimer disease. In order to identify the aberrant and specific genes involved in the early differentiation of DS neurons, we have utilized an in vitro neuronal differentiation system of mouse ES cells containing a single human chromosome 21 (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal differentiation were subjected to two-dimensional polyacrylamide gel electrophoresis protein separation followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to identify the proteins differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a novel set of specific gene products altered in early differentiating DS neuronal cells, which differs from that identified in adult or fetal brain with DS. The aberrant protein expression in early differentiating neurons, due to the hChr21 gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth, proliferation and differentiation, producing developmental abnormalities in neural patterning, which eventually leads to formation of a suboptimal functioning neuronal network in DS.

  19. Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

    Science.gov (United States)

    Liu, Yu-Yu; Brandt, Michael P; Shen, Daniel H; Kloos, Richard T; Zhang, Xiaoli; Jhiang, Sissy M

    2014-01-01

    Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T3)-supplemented mice was much less than that in mice received neither bTSH nor T3 (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model. PMID:20943721

  20. DNA barcoding of Japanese click beetles (Coleoptera, Elateridae).

    Science.gov (United States)

    Oba, Yuichi; Ôhira, Hitoo; Murase, Yukio; Moriyama, Akihiko; Kumazawa, Yoshinori

    2015-01-01

    Click beetles (Coleoptera: Elateridae) represent one of the largest groups of beetle insects. Some click beetles in larval form, known as wireworms, are destructive agricultural pests. Morphological identification of click beetles is generally difficult and requires taxonomic expertise. This study reports on the DNA barcoding of Japanese click beetles to enable their rapid and accurate identification. We collected and assembled 762 cytochrome oxidase subunit I barcode sequences from 275 species, which cover approximately 75% of the common species found on the Japanese main island, Honshu. This barcode library also contains 20 out of the 21 potential pest species recorded in Japan. Our analysis shows that most morphologically identified species form distinct phylogenetic clusters separated from each other by large molecular distances. This supports the general usefulness of the DNA barcoding approach for quick and reliable identification of Japanese elaterid species for environmental impact assessment, agricultural pest control, and biodiversity analysis. On the other hand, the taxonomic boundary in dozens of species did not agree with the boundary of barcode index numbers (a criterion for sequence-based species delimitation). These findings urge taxonomic reinvestigation of these mismatched taxa.

  1. DNA barcoding of Japanese click beetles (Coleoptera, Elateridae.

    Directory of Open Access Journals (Sweden)

    Yuichi Oba

    Full Text Available Click beetles (Coleoptera: Elateridae represent one of the largest groups of beetle insects. Some click beetles in larval form, known as wireworms, are destructive agricultural pests. Morphological identification of click beetles is generally difficult and requires taxonomic expertise. This study reports on the DNA barcoding of Japanese click beetles to enable their rapid and accurate identification. We collected and assembled 762 cytochrome oxidase subunit I barcode sequences from 275 species, which cover approximately 75% of the common species found on the Japanese main island, Honshu. This barcode library also contains 20 out of the 21 potential pest species recorded in Japan. Our analysis shows that most morphologically identified species form distinct phylogenetic clusters separated from each other by large molecular distances. This supports the general usefulness of the DNA barcoding approach for quick and reliable identification of Japanese elaterid species for environmental impact assessment, agricultural pest control, and biodiversity analysis. On the other hand, the taxonomic boundary in dozens of species did not agree with the boundary of barcode index numbers (a criterion for sequence-based species delimitation. These findings urge taxonomic reinvestigation of these mismatched taxa.

  2. Phonetic reduction of clicks – Evidence from Nǀuu

    DEFF Research Database (Denmark)

    Marquard, Carina; Niebuhr, Oliver; Witzlack-Makarevich, Alena

    2015-01-01

    Based on spontaneous speech data of the Tuu language Nǀuu, we used the cross-linguistically established domain-initial strengthening concept in order to examine, if and in which way clicks are subject to speech reduction (lenition) in relation to a reference sample of plosives. Results of combine...

  3. Synthesis of the Multinuclear Cobaloxime Complexes via Click ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 127; Issue 9. Synthesis of the Multinuclear Cobaloxime Complexes via Click Chemistry as Catalysts for the Formation of Cyclic Carbonates from Carbon Dioxide and Epoxides. Ahmet Kilic Armagan Keles Emine Aytar Mustafa Durgun Mahmut Ulusoy. Volume 127 ...

  4. The impact of summaries: What makes a user click?

    NARCIS (Netherlands)

    Fachry, K.N.; Kamps, J.; Zhang, J.

    2010-01-01

    Modern retrieval systems are in fact two-tier systems in which a user first views summaries of the results in a hit-list, and only when she decides to "click," the full result document is consulted. Standard information retrieval evaluation ignores the crucial summary step, and directly evaluates in

  5. Sensory biology: echolocation from click to call, mouth to wing.

    Science.gov (United States)

    Fenton, M Brock; Ratcliffe, John M

    2014-12-15

    Echolocators use echoes of sounds they produce, clicks or calls, to detect objects. Usually, these signals originate from the head. New work reveals that three species of bats use their wings to generate echolocation signals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Microwave assisted click chemistry on a conductive polymer film

    DEFF Research Database (Denmark)

    Daugaard, Anders Egede; Hansen, Thomas S.; Larsen, Niels Bent

    2011-01-01

    Microwave (MW) irradiation has been used to accelerate the functionalization of an azide functional poly(3,4-ethylenedioxythiophene) film by click chemistry. The absorption of MW energy by the conductive polymer has been exploited for localized activation of the reaction on the polymer surface...

  7. N-PEG´ylation of chitosan via "click chemistry" reactions

    Czech Academy of Sciences Publication Activity Database

    Kulbokaite, R.; Ciuta, G.; Netopilík, Miloš; Makuška, R.

    2009-01-01

    Roč. 69, č. 10 (2009), s. 771-778 ISSN 1381-5148 R&D Projects: GA ČR GA203/07/0659 Institutional research plan: CEZ:AV0Z40500505 Keywords : chitosan * poly(ethylene glycol) * click chemistry Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.461, year: 2009

  8. Modified condylotomy versus conventional conservative treatment in painful reciprocal clicking

    DEFF Research Database (Denmark)

    Bakke, Merete; Eriksson, Lars; Thorsen, Niels Max

    2008-01-01

    patients, 19-44 years of age, with severe painful reciprocal clicking. Before and after treatment, assessments were performed by subjective reports, clinical recordings, and blinded evaluations of radiography and magnetic resonance imaging (MRI). Based on the clinical evaluations before treatment, all...

  9. Compact Web browsing profiles for click-through rate prediction

    DEFF Research Database (Denmark)

    Fruergaard, Bjarne Ørum; Hansen, Lars Kai

    2014-01-01

    In real time advertising we are interested in finding features that improve click-through rate prediction. One source of available information is the bipartite graph of websites previously engaged by identifiable users. In this work, we investigate three different decompositions of such a graph...

  10. DNA Barcoding of Japanese Click Beetles (Coleoptera, Elateridae)

    Science.gov (United States)

    Oba, Yuichi; Ôhira, Hitoo; Murase, Yukio; Moriyama, Akihiko; Kumazawa, Yoshinori

    2015-01-01

    Click beetles (Coleoptera: Elateridae) represent one of the largest groups of beetle insects. Some click beetles in larval form, known as wireworms, are destructive agricultural pests. Morphological identification of click beetles is generally difficult and requires taxonomic expertise. This study reports on the DNA barcoding of Japanese click beetles to enable their rapid and accurate identification. We collected and assembled 762 cytochrome oxidase subunit I barcode sequences from 275 species, which cover approximately 75% of the common species found on the Japanese main island, Honshu. This barcode library also contains 20 out of the 21 potential pest species recorded in Japan. Our analysis shows that most morphologically identified species form distinct phylogenetic clusters separated from each other by large molecular distances. This supports the general usefulness of the DNA barcoding approach for quick and reliable identification of Japanese elaterid species for environmental impact assessment, agricultural pest control, and biodiversity analysis. On the other hand, the taxonomic boundary in dozens of species did not agree with the boundary of barcode index numbers (a criterion for sequence-based species delimitation). These findings urge taxonomic reinvestigation of these mismatched taxa. PMID:25636000

  11. Qualitative sensing of mechanical damage by a fluorogenic "click" reaction.

    Science.gov (United States)

    Döhler, Diana; Rana, Sravendra; Rupp, Harald; Bergmann, Henrik; Behzadi, Shahed; Crespy, Daniel; Binder, Wolfgang H

    2016-09-25

    A simple and unique damage-sensing tool mediated by a Cu(i)-catalyzed [3+2] cycloaddition reaction is reported, where a fluorogenic "click"-reaction highlights physical damage by a strong fluorescence increase accompanied by in situ monitoring of localized self-healing.

  12. "Clicking" Gene Therapeutics: A Successful Union of Chemistry and Biomedicine for New Solutions

    DEFF Research Database (Denmark)

    Astakhova, Kira; Ray, Roslyn; Taskova, Maria

    2018-01-01

    cells. One approach that holds much promise is the utilization of "click chemistry" to conjugate receptor or cell specific targeting molecules directly to the effector oligonucleotides. We discuss here the applications of the breakthrough technology of CuAAC click chemistry and the immense potential...... in utilizing "click chemistry" in the development of new age targeted oligonucleotide therapeutics....

  13. Nanofabrication Yields. Hybridization and Click-Fixation of Polycyclic DNA Nanoassemblies

    KAUST Repository

    Lundberg, Erik P.

    2011-09-27

    We demonstrate the stepwise assembly of a fully addressable polycyclic DNA hexagon nanonetwork for the preparation of a four-ring system, one of the biggest networks yet constructed from tripodal building blocks. We find that the yield exhibits a distinct upper level <100%, a fundamental problem of thermodynamic DNA assembly that appears to have been overlooked in the DNA nanotechnology literature. A simplistic model based on a single step-yield parameter y can quantitatively describe the total yield of DNA assemblies in one-pot reactions as Y = yduplex n, with n the number of hybridization steps. Experimental errors introducing deviations from perfect stoichiometry and the thermodynamics of hybridization equilibria contribute to decreasing the value of yduplex (on average y = 0.96 for our 10 base pair hybridization). For the four-ring system (n = 31), the total yield is thus less than 30%, which is clearly unsatisfactory if bigger nanoconstructs of this class are to be designed. Therefore, we introduced site-specific click chemistry for making and purifying robust building blocks for future modular constructs of larger assemblies. Although the present yield of this robust module was only about 10%, it demonstrates a first step toward a general fabrication approach. Interestingly, we find that the click yields follow quantitatively a binomial distribution, the predictability of which indicates the usefulness of preparing pools of pure and robust building blocks in this way. The binomial behavior indicates that there is no interference between the six simultaneous click reactions but that step-yield limiting factors such as topological constraints and Cu(I) catalyst concentration are local and independent. © 2011 American Chemical Society.

  14. ClickDiary: Online Tracking of Health Behaviors and Mood.

    Science.gov (United States)

    Chan, Ta-Chien; Yen, Tso-Jung; Fu, Yang-Chih; Hwang, Jing-Shiang

    2015-06-15

    Traditional studies of health behaviors are typically conducted using one-shot, cross-sectional surveys. Thus, participants' recall bias may undermine the reliability and validity of the data. To capture mood changes and health behaviors in everyday life, we designed an online survey platform, ClickDiary, which helped collect more complete information for comprehensive data analyses. We aim to understand whether daily mood changes are related to one's personal characteristics, demographic factors, and daily health behaviors. The ClickDiary program uses a Web-based platform to collect data on participants' health behaviors and their social-contact networks. The name ClickDiary comes from the platform's interface, which is designed to allow the users to respond to most of the survey questions simply by clicking on the options provided. Participants were recruited from the general population and came from various backgrounds. To keep the participants motivated and interested, the ClickDiary program included a random drawing for rewards. We used descriptive statistics and the multilevel proportional-odds mixed model for our analysis. We selected 130 participants who had completed at least 30 days of ClickDiary entries from May 1 to October 31, 2014 as our sample for the study. According to the results of the multilevel proportional-odds mixed model, a person tended to be in a better mood on a given day if he or she ate more fruits and vegetables, took in more sugary drinks, ate more fried foods, showed no cold symptoms, slept better, exercised longer, and traveled farther away from home. In addition, participants were generally in a better mood during the weekend than on weekdays. Sleeping well, eating more fruits and vegetables, and exercising longer each day all appear to put one in a better mood. With the online ClickDiary survey, which reduces the recall biases that are common in traditional one-shot surveys, we were able to collect and analyze the daily variations

  15. Automated classification of dolphin echolocation click types from the Gulf of Mexico.

    Science.gov (United States)

    Frasier, Kaitlin E; Roch, Marie A; Soldevilla, Melissa S; Wiggins, Sean M; Garrison, Lance P; Hildebrand, John A

    2017-12-01

    Delphinids produce large numbers of short duration, broadband echolocation clicks which may be useful for species classification in passive acoustic monitoring efforts. A challenge in echolocation click classification is to overcome the many sources of variability to recognize underlying patterns across many detections. An automated unsupervised network-based classification method was developed to simulate the approach a human analyst uses when categorizing click types: Clusters of similar clicks were identified by incorporating multiple click characteristics (spectral shape and inter-click interval distributions) to distinguish within-type from between-type variation, and identify distinct, persistent click types. Once click types were established, an algorithm for classifying novel detections using existing clusters was tested. The automated classification method was applied to a dataset of 52 million clicks detected across five monitoring sites over two years in the Gulf of Mexico (GOM). Seven distinct click types were identified, one of which is known to be associated with an acoustically identifiable delphinid (Risso's dolphin) and six of which are not yet identified. All types occurred at multiple monitoring locations, but the relative occurrence of types varied, particularly between continental shelf and slope locations. Automatically-identified click types from autonomous seafloor recorders without verifiable species identification were compared with clicks detected on sea-surface towed hydrophone arrays in the presence of visually identified delphinid species. These comparisons suggest potential species identities for the animals producing some echolocation click types. The network-based classification method presented here is effective for rapid, unsupervised delphinid click classification across large datasets in which the click types may not be known a priori.

  16. Optimization of helical acquisition parameters to preserve uniformity of mouse whole body using multipinhole collimator in single-photon emission computed tomography

    Directory of Open Access Journals (Sweden)

    Naoyuki Ukon

    Full Text Available Focusing on whole-body uniformity in small-animal single-photon emission computed tomography (SPECT, we examined the optimal helical acquisition parameters using five-pinhole collimators for mouse imaging. SPECT images of an 80-mm-long cylindrical phantom with 99mTc solution were acquired using an Inveon multimodality imaging platform. The bed travels used in this study were 0, 30, 60, 90 and 120 mm, and the numbers of revolutions traversed during the SPECT scan were 1.0, 2.0, 3.0, 4.0, 5.0 and 7.0, respectively. Artifacts that degrade uniformity in reconstructed images were conspicuous when the bed travel was smaller than the object length. Regarding the distal-to-center ratio (DCR of SPECT values in the object’s axial direction, the DCR nearest to the ideal ratio of 1.00 was 1.02 in the optimal uniformity with 4.0 revolutions and a bed travel of 120 mm. Moreover, the helical acquisition using these parameters suppressed the formation of artifacts. We proposed the optimal parameters in whole-body helical SPECT; the bed travel was sufficiently larger than the object length; the 4.0 or more revolutions were required for a pitch of approximately 30 mm/revolution. The optimal acquisition parameters in SPECT to preserve uniformity would contribute to the accurate quantification of whole-body biodistribution. Keywords: Helical acquisition, Multipinhole collimator, Computed tomography, SPECT

  17. A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse.

    Science.gov (United States)

    Wei, Ran; Li, Qi; Lam, Sylvia; Leung, Jana; Cheung, Charlton; Zhang, Xiaofan; Sham, Pak Chung; Chua, Siew Eng; McAlonan, Grainne Mary

    2016-11-01

    Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the 'survivors' of a toxic insult. Low dose or late gestation exposure has not been widely studied. We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse. We also examined postnatal levels of glutamic acid decarboxylase (GAD65 and GAD67) as markers for GABA neurons, because GABA pathology and subsequent excitatory/inhibitory imbalance is strongly implicated in ASD. Pregnant C57BL/6N mice received a single subcutaneous injection of 100 or 200mg/kg on gestation day 17. The control group received a saline injection on the same day. The offspring were tested in a battery of behavioral tests in adolescence and adulthood. Six brain regions were harvested and GAD65 and GAD67 were measured by western blotting. Compared to saline-exposed controls, adult mice exposed to prenatal VPA had impaired novel object exploration and fear conditioning anomalies. GAD67 was decreased in midbrain, olfactory bulb, prefrontal cortex and increased in cerebellum, hippocampus and striatum; GAD65 was decreased in all 6 regions. Our results suggest that a low dose of VPA in late pregnancy has persistent effects on brain development, and in particular the GABA system, which may be relevant to ASD. Further attention to the impact of gestation time and dose of exposure in VPA-induced ASD models is encouraged. Copyright © 2016. Published by Elsevier B.V.

  18. Screening for single-chain variable fragment antibodies against multiple Cry1 toxins from an immunized mouse phage display antibody library.

    Science.gov (United States)

    Dong, Sa; Bo, Zongyi; Zhang, Cunzheng; Feng, Jianguo; Liu, Xianjin

    2018-04-01

    Single-chain variable fragment (scFv) is a kind of antibody that possess only one chain of the complete antibody while maintaining the antigen-specific binding abilities and can be expressed in prokaryotic system. In this study, scFvs against Cry1 toxins were screened out from an immunized mouse phage displayed antibody library, which was successfully constructed with capacity of 6.25 × 10 7  CFU/mL. Using the mixed and alternative antigen coating strategy and after four rounds of affinity screening, seven positive phage-scFvs against Cry1 toxins were selected and characterized. Among them, clone scFv-3H9 (MG214869) showing relative stable and high binding abilities to six Cry1 toxins was selected for expression and purification. SDS-PAGE indicated that the scFv-3H9 fragments approximately 27 kDa were successfully expressed in Escherichia coli HB2151 strain. The purified scFv-3H9 was used to establish the double antibody sandwich enzyme-linked immunosorbent assay method (DAS-ELISA) for detecting six Cry1 toxins, of which the lowest detectable limits (LOD) and the lowest quantitative limits (LOQ) were 3.14-11.07 and 8.22-39.44 ng mL -1 , respectively, with the correlation coefficient higher than 0.997. The average recoveries of Cry1 toxins from spiked rice leaf samples were ranged from 84 to 95%, with coefficient of variation (CV) less than 8.2%, showing good accuracy for the multi-residue determination of six Cry1 toxins in agricultural samples. This research suggested that the constructed phage display antibody library based on the animal which was immunized with the mixture of several antigens under the same category can be used for the quick and effective screening of generic antibodies.

  19. Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse

    Directory of Open Access Journals (Sweden)

    Vandewauw Ine

    2013-02-01

    Full Text Available Abstract Background Somatosensory nerve fibres arising from cell bodies within the trigeminal ganglia (TG in the head and from a string of dorsal root ganglia (DRG located lateral to the spinal cord convey endogenous and environmental stimuli to the central nervous system. Although several members of the transient receptor potential (TRP superfamily of cation channels have been implicated in somatosensation, the expression levels of TRP channel genes in the individual sensory ganglia have never been systematically studied. Results Here, we used quantitative real-time PCR to analyse and compare mRNA expression of all TRP channels in TG and individual DRGs from 27 anatomically defined segments of the spinal cord of the mouse. At the mRNA level, 17 of the 28 TRP channel genes, TRPA1, TRPC1, TRPC3, TRPC4, TRPC5, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPML1 and TRPP2, were detectable in every tested ganglion. Notably, four TRP channels, TRPC4, TRPM4, TRPM8 and TRPV1, showed statistically significant variation in mRNA levels between DRGs from different segments, suggesting ganglion-specific regulation of TRP channel gene expression. These ganglion-to-ganglion differences in TRP channel transcript levels may contribute to the variability in sensory responses in functional studies. Conclusions We developed, compared and refined techniques to quantitatively analyse the relative mRNA expression of all TRP channel genes at the single ganglion level. This study also provides for the first time a comparative mRNA distribution profile in TG and DRG along the entire vertebral column for the mammalian TRP channel family.

  20. Carbohydrate CuAAC click chemistry for therapy and diagnosis.

    Science.gov (United States)

    He, Xiao-Peng; Zeng, Ya-Li; Zang, Yi; Li, Jia; Field, Robert A; Chen, Guo-Rong

    2016-06-24

    Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Estimating Ads’ Click through Rate with Recurrent Neural Network

    Directory of Open Access Journals (Sweden)

    Chen Qiao-Hong

    2016-01-01

    Full Text Available With the development of the Internet, online advertising spreads across every corner of the world, the ads' click through rate (CTR estimation is an important method to improve the online advertising revenue. Compared with the linear model, the nonlinear models can study much more complex relationships between a large number of nonlinear characteristics, so as to improve the accuracy of the estimation of the ads’ CTR. The recurrent neural network (RNN based on Long-Short Term Memory (LSTM is an improved model of the feedback neural network with ring structure. The model overcomes the problem of the gradient of the general RNN. Experiments show that the RNN based on LSTM exceeds the linear models, and it can effectively improve the estimation effect of the ads’ click through rate.

  2. Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II-ethylenediamine precatalyst

    Directory of Open Access Journals (Sweden)

    Redouane Beniazza

    2015-10-01

    Full Text Available The search for copper catalysts able to perform effectively click reactions in water in the absence of sodium ascorbate is an active area of current research with strong potential for applications in bioconjugation. The water-soluble and photoreducible copper(II–EDA (EDA = ethylenediamine complex 1, which has two 4-benzoylbenzoates acting as both counterion and photosensitizer, has been synthesized and characterized by different techniques including single crystal X-ray diffraction. Highly efficient photoreduction was demonstrated when solutions of 1 in hydrogen atom donating solvents, such as THF or MeOH, were exposed to UVA radiation (350–400 nm provided by a low pressure mercury lamp (type TLC = thin-layer chromatography, 365 nm, or by a 23 W fluorescent bulb, or by ambient/sunlight. In water, a much poorer hydrogen atom donating solvent, the photoreduction of 1 proved inefficient. Interestingly, EPR studies revealed that complex 1 could nonetheless be effectively photoreduced in water when alkynes were present in solution. The catalytic activity of 1 for click reactions involving a range of water-soluble alkynes and azides, in particular saccharides, was tested under various illumination conditions. Complex 1 was found to exhibit a photolatent character, the photogenerated copper(I being very reactive. On irradiating aqueous reaction mixtures containing 1 mol % of 1 at 365 nm (TLC lamp for 1 h, click reactions were shown to proceed to full conversion.

  3. "Click" saccharide/beta-lactam hybrids for lectin inhibition.

    Science.gov (United States)

    Palomo, Claudio; Aizpurua, Jesus M; Balentová, Eva; Azcune, Itxaso; Santos, J Ignacio; Jiménez-Barbero, Jesús; Cañada, Javier; Miranda, José Ignacio

    2008-06-05

    Hybrid glycopeptide beta-lactam mimetics designed to bind lectins or carbohydrate recognition domains in selectins have been prepared according to a "shape-modulating linker" design. This approach was implemented using the azide-alkyne "click" cycloaddition reaction, and as shown by NMR/MD experiments, binding of the resulting mimetics to Ulex Europaeus Lectin-1 (UEL-1) occurred after a "bent-to-extended" conformational change around a partially rotatable triazolylmethylene moiety.

  4. A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor.

    Directory of Open Access Journals (Sweden)

    Clémence Bernard

    2016-05-01

    Full Text Available During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells. In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these "transfer" sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.

  5. Treatment Effects of Maxillary Flat Occlusal Splints for Painful Clicking of the Temporomandibular Joint

    Directory of Open Access Journals (Sweden)

    Sung-Wen Chang

    2010-06-01

    Full Text Available Existing therapies for symptoms related to painful clicking of the temporomandibular joint (TMJ have rarely met with complete success and predicting prognosis remains difficult. Few studies have reported the efficacy of maxillary flat occlusal splints (MFOSs for the treatment of painful clicking of the TMJ, and few studies have evaluated the predisposing factors that influence the clinical outcomes of MFOSs. The aim of this study was to investigate the treatment efficacy of MFOSs for painful clicking of the TMJ, and to determine the factors influencing TMJ therapy with MFOSs. We conducted a retrospective study of 109 patients suffering from unilateral clicking concurrent with preauricular area pain for at least 2 months between 2004 and 2008. Seventy-five patients were treated with an MFOS, while 34 patients did not receive MFOS therapy. Clicking score, pain-free maximal mouth opening, pain score, duration of the clicking sounds, age and bruxism were recorded during treatment and involved into the reviews. The degree of joint clicking was determined by a stethoscope placed in the anterolateral area of the external auditory canal and was divided into four grades. Data were analyzed using a Mann-Whitney U test, Fisher's exact test, and Student's t test. Results showed statistically significant differences in treatment outcomes between the MFOS-treated and control groups in clicking index, maximal mouth opening, pain and complete remission rates of symptoms within 1 year. Furthermore, for patients treated with MFOS, there were statistically significant differences in the clinical outcomes between those with a high clicking index and those with a low index before treatment. Factors significantly correlated with successful outcomes of MFOS included nocturnal bruxism, patient age and duration of clicking. MFOSs can be used to treat patients with painful clicking of the TMJ and related symptoms. The severity of clicking, bruxism, age and duration of

  6. Circular DNA by "Bis-Click" Ligation: Template-Independent Intramolecular Circularization of Oligonucleotides with Terminal Alkynyl Groups Utilizing Bifunctional Azides.

    Science.gov (United States)

    Yang, Haozhe; Seela, Frank

    2016-01-22

    A highly effective and convenient "bis-click" strategy was developed for the template-independent circularization of single-stranded oligonucleotides by employing copper(I)-assisted azide-alkyne cycloaddition. Terminal triple bonds were incorporated at both ends of linear oligonucleotides. Alkynylated 7-deaza-2'-deoxyadenosine and 2'-deoxyuridine residues with different side chains were used in solid-phase synthesis with phosphoramidite chemistry. The bis-click ligation of linear 9- to 36-mer oligonucleotides with 1,4-bis(azidomethyl)benzene afforded circular DNA in a simple and selective way; azido modification of the oligonucleotide was not necessary. Short ethynyl side chains were compatible with the circularization of longer oligonucleotides, whereas octadiynyl residues were used for short 9-mers. Compared with linear duplexes, circular bis-click constructs exhibit a significantly increased duplex stability over their linear counterparts. The intramolecular bis-click ligation protocol is not limited to DNA, but may also be suitable for the construction of other macrocycles, such as circular RNAs, peptides, or polysaccharides. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Immunostimulatory mouse granuloma protein.

    Science.gov (United States)

    Fontan, E; Fauve, R M; Hevin, B; Jusforgues, H

    1983-10-01

    Earlier studies have shown that from subcutaneous talc-induced granuloma in mice, a fraction could be extracted that fully protected mice against Listeria monocytogenes. Using standard biochemical procedures--i.e., ammonium sulfate fractionation, preparative electrophoresis, gel filtration chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis--we have now purified an active factor to homogeneity. A single band was obtained in NaDodSO4/polyacrylamide gel with an apparent Mr of 55,000. It migrated with alpha 1-globulins and the isoelectric point was 5 +/- 0.1. The biological activity was destroyed with Pronase but not with trypsin and a monospecific polyclonal rabbit antiserum was obtained. The intravenous injection of 5 micrograms of this "mouse granuloma protein" fully protects mice against a lethal inoculum of L. monocytogenes. Moreover, after their incubation with 10 nM mouse granuloma protein, mouse peritoneal cells became cytostatic against Lewis carcinoma cells.

  8. Superstructures of fluorescent cyclodextrin via click-reaction

    Directory of Open Access Journals (Sweden)

    Arkadius Maciollek

    2013-04-01

    Full Text Available Mono-(6-azido-6-deoxy-β-cyclodextrin (CD was covalently attached to an alkyne-modified 5-methyl-2-(pyridin-2-ylthiazol-4-ol yielding a fluorophore containing CD in a click-type reaction. Intermolecular complexes were formed by poly(host–guest-interactions. The supramolecular structures were characterized by 1H NMR-ROESY spectroscopy, dynamic light scattering, UV–vis spectroscopy, fluorescence spectroscopy, and asymmetric flow field-flow fractionation. By adding potassium adamantane-1-carboxylate, the thiazol dye is displaced from the CD-cavity and the elongated noncovalent polymeric structures collapse.

  9. Click Reactions and Boronic Acids: Applications, Issues, and Potential Solutions

    Directory of Open Access Journals (Sweden)

    Chaofeng Dai

    2010-08-01

    Full Text Available Boronic acids have been widely used in a wide range of organic reactions, in the preparation of sensors for carbohydrates, and as potential pharmaceutical agents. With the growing importance of click reactions, inevitably they are also applied to the synthesis of compounds containing the boronic acid moiety. However, such applications have unique problems. Chief among them is the issue of copper-mediated boronic acid degradation in copper-assisted [2,3]-cycloadditions involving an alkyne and an azido compound as the starting materials. This review summarizes recent developments, analyzes potential issues, and discusses known as well as possible solutions.

  10. Functionalization of PEDOT by Click Chemistry and ATRP

    DEFF Research Database (Denmark)

    Hoffmann, Christian; Daugaard, Anders Egede

    Poly(3,4‐ethylenedioxythiophene) (PEDOT) is a conductive polymer which has received increasing attention and many developments have been investigated. PEDOT has been applied in many different areas such as biosensors or polymer solar cells. This work presents a modification of PEDOT films through...... Click Chemistry with alkynes followed by activator regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to develop PEDOT films with anti‐fouling properties through application of a model system based on a crosslinked surface of polystyrene PS‐N3....

  11. Click chemistry with polymers, dendrimers, and hydrogels for drug delivery.

    Science.gov (United States)

    Lallana, Enrique; Fernandez-Trillo, Francisco; Sousa-Herves, Ana; Riguera, Ricardo; Fernandez-Megia, Eduardo

    2012-04-01

    During the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery.

  12. Grafting of Polycaprolactone on Oxidized Nanocelluloses by Click Chemistry

    Directory of Open Access Journals (Sweden)

    Claude Daneault

    2013-03-01

    Full Text Available The main objective of this work is the grafting of polycaprolactone diol (PCL on the surface of oxidized nanocelluloses (ONC in order to enhance the compatibility between the hydrophilic cellulose nanofibres and the hydrophobic polymer matrix. This grafting was successfully realized with a new strategy known as click chemistry. In this context, the oxidized nanocelluloses bearing alkyl groups (ONC-PR were prepared by reacting amino groups of propargylamine (PR with carboxyl groups of ONC. In parallel, PCL was converted into azido-polycaprolactone (PCL-N3 in two steps: (i tosylation of polycaprolactone (PCL-OTs and (ii conversion of PCL-OTs into PCL-N3 by nucleophilic displacement using sodium azide. Finally, ONC-PR was reacted with PCL-N3 in heterogeneous conditions through click chemistry in order to prepare polycaprolactone grafted oxidized nanocellulose (ONC-g-PCL, which could be suitable for improving the interfacial adhesion in the composite materials. The grafted samples were characterized by transmission electron microscopy and by Fourier transform infrared spectroscopy (FTIR, X-ray photoelectron spectroscopy (XPS and Carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR spectroscopic techniques.

  13. Grafting of Polycaprolactone on Oxidized Nanocelluloses by Click Chemistry

    Science.gov (United States)

    Benkaddour, Abdelhaq; Jradi, Khalil; Robert, Sylvain; Daneault, Claude

    2013-01-01

    The main objective of this work is the grafting of polycaprolactone diol (PCL) on the surface of oxidized nanocelluloses (ONC) in order to enhance the compatibility between the hydrophilic cellulose nanofibres and the hydrophobic polymer matrix. This grafting was successfully realized with a new strategy known as click chemistry. In this context, the oxidized nanocelluloses bearing alkyl groups (ONC-PR) were prepared by reacting amino groups of propargylamine (PR) with carboxyl groups of ONC. In parallel, PCL was converted into azido-polycaprolactone (PCL-N3) in two steps: (i) tosylation of polycaprolactone (PCL-OTs) and (ii) conversion of PCL-OTs into PCL-N3 by nucleophilic displacement using sodium azide. Finally, ONC-PR was reacted with PCL-N3 in heterogeneous conditions through click chemistry in order to prepare polycaprolactone grafted oxidized nanocellulose (ONC-g-PCL), which could be suitable for improving the interfacial adhesion in the composite materials. The grafted samples were characterized by transmission electron microscopy and by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and Carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR) spectroscopic techniques. PMID:28348327

  14. On-Surface Synthesis by Click Chemistry Investigated by STM and XPS

    DEFF Research Database (Denmark)

    Vadapoo, Sundar Raja

    2014-01-01

    such as molecular electronics and surface functionalization. In this thesis, a well-defined click chemistry approach is followed, with the study of azide-alkyne cycloaddition on Cu(111) surface in UHV environment. A successful achievement of the click reaction product via on-surface synthesis has been shown, which...

  15. An API-based search system for one click access to information

    NARCIS (Netherlands)

    Ionita, Dan; Tax, Niek; Hiemstra, Djoerd

    This paper proposes a prototype One Click access system, based on previous work in the field and the related 1CLICK-2@NTCIR10 task. The proposed solution integrates methods from into a three tier algorithm: query categorization, information extraction and output generation and offers suggestions on

  16. Improving Web Page Retrieval using Search Context from Clicked Domain Names

    NARCIS (Netherlands)

    Li, R.

    Search context is a crucial factor that helps to understand a user’s information need in ad-hoc Web page retrieval. A query log of a search engine contains rich information on issued queries and their corresponding clicked Web pages. The clicked data implies its relevance to the query and can be

  17. The Evolution of Click-n-Mortar E-tailing in Denmark

    DEFF Research Database (Denmark)

    Bøge Sørensen, Lars; Holst, Lisa L.

    2003-01-01

    The paper at hand presents an extension and application of Kotzab & Madlbergers (Kotzab &Madlberger, 2001) original clicks-and-mortar web-scan framework, which is here used to reexaminethe click-and-mortar activities of the top 100 Danish retailers and compare with resultsfrom the identical study...

  18. An Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin and Fulvestrant (Falsodex, as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts.

    Directory of Open Access Journals (Sweden)

    Qing Chen

    Full Text Available To investigate the effects of trastuzumab (herceptin and fulvestrant (falsodex either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue.Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied. The distribution and abundance of the proteins p-Akt and p-Erk expressed in these cells in response to single agents or combinatorial treatment were also investigated. In addition, the effects of trastuzumab and fulvestrant, either as single agents or in combination on tumor growth as well as on expression of the protein p-MED1 expressed in in vivo mouse xenograft models was also examined.Cell proliferation was increasingly inhibited by trastuzumab or fulvestrant or both, with a CI1 in both human cell lines. The rate of apoptosis increased only in the BT-474 cell line and not in the ZR-75-1 cell line upon treatment with fulvestrant and not trastuzumab as a single agent (P0.05. Cell accumulation in the G1 phase of cell cycle was investigated in all treatment groups (P<0.05, and the combination of trastuzumab and fulvestrant reversed the effects of fulvestrant alone on p-Akt and p-Erk protein expression levels. Using ZR-75-1 or BT-474 to generate in vivo tumor xenografts in BALB/c athymic mouse models, we showed that a combination of both drugs resulted in a stronger inhibition of tumor growth (P<0.05 and a greater decrease in the levels of activated MED1 (p-MED1 expressed in tumor issues compared with the use of either drug as a single agent.We demonstrate that the administration of trastuzumab and fulvestrant in combination results in positive synergistic effects on both, ZR-75-1 and BT-474 cell lines. This combinatorial approach is

  19. Clicking in a killer whale habitat: narrow-band, high-frequency biosonar clicks of harbour porpoise (Phocoena phocoena and Dall's porpoise (Phocoenoides dalli.

    Directory of Open Access Journals (Sweden)

    Line A Kyhn

    Full Text Available Odontocetes produce a range of different echolocation clicks but four groups in different families have converged on producing the same stereotyped narrow band high frequency (NBHF click. In microchiropteran bats, sympatric species have evolved the use of different acoustic niches and subtly different echolocation signals to avoid competition among species. In this study, we examined whether similar adaptations are at play among sympatric porpoise species that use NBHF echolocation clicks. We used a six-element hydrophone array to record harbour and Dall's porpoises in British Columbia (BC, Canada, and harbour porpoises in Denmark. The click source properties of all porpoise groups were remarkably similar and had an average directivity index of 25 dB. Yet there was a small, but consistent and significant 4 kHz difference in centroid frequency between sympatric Dall's (137±3 kHz and Canadian harbour porpoises (141±2 kHz. Danish harbour porpoise clicks (136±3 kHz were more similar to Dall's porpoise than to their conspecifics in Canada. We suggest that the spectral differences in echolocation clicks between the sympatric porpoises are consistent with evolution of a prezygotic isolating barrier (i.e., character displacement to avoid hybridization of sympatric species. In practical terms, these spectral differences have immediate application to passive acoustic monitoring.

  20. Effectiveness of mouse interferon alpha/beta compared to single-agent chemotherapy in increasing survival time of mice after intravenous inoculation of Friend erythroleukemia cells.

    Science.gov (United States)

    Gresser, I; Maury, C; Belardelli, F; Maunoury, M T; Machover, D

    1988-03-16

    DBA/2 mice received an iv injection of 2 X 10(6) Friend erythroleukemia cells (FLCs; approximately equal to 4 X 10(5) lethal dose50), which multiplied rapidly in the liver and spleen and killed all untreated or control treated mice between 7 and 12 days. Daily interferon (IFN) treatment resulted in a very marked increase in survival time and apparent cure of 4 of 22 tumor-inoculated mice. In contrast, treatment of tumor-injected (iv) mice with cyclophosphamide, 5-fluorouracil, and methotrexate increased survival time by only a few days; and treatment of mice with cisplatin, vincristine, doxorubicin, bleomycin, or etoposide was ineffective. However, when FLCs were injected ip, both cytostatic drugs and IFN exerted an antitumor effect. We conclude that IFN alpha/beta was particularly effective in inhibiting the development of liver and spleen metastases and in increasing mouse survival time after iv inoculation of FLCs.

  1. Click-based echolocation in bats: not so primitive after all.

    Science.gov (United States)

    Yovel, Yossi; Geva-Sagiv, Maya; Ulanovsky, Nachum

    2011-05-01

    Echolocating bats of the genus Rousettus produce click sonar signals, using their tongue (lingual echolocation). These signals are often considered rudimentary and are believed to enable only crude performance. However, the main argument supporting this belief, namely the click's reported long duration, was recently shown to be an artifact. In fact, the sonar clicks of Rousettus bats are extremely short, ~50-100 μs, similar to dolphin vocalizations. Here, we present a comparison between the sonar systems of the 'model species' of laryngeal echolocation, the big brown bat (Eptesicus fuscus), and that of lingual echolocation, the Egyptian fruit bat (Rousettus aegyptiacus). We show experimentally that in tasks, such as accurate landing or detection of medium-sized objects, click-based echolocation enables performance similar to laryngeal echolocators. Further, we describe a sophisticated behavioral strategy for biosonar beam steering in clicking bats. Finally, theoretical analyses of the signal design--focusing on their autocorrelations and wideband ambiguity functions--predict that in some aspects, such as target ranging and Doppler-tolerance, click-based echolocation might outperform laryngeal echolocation. Therefore, we suggest that click-based echolocation in bats should be regarded as a viable echolocation strategy, which is in fact similar to the biosonar used by most echolocating animals, including whales and dolphins.

  2. Temporal suppression of the click-evoked otoacoustic emission level-curve

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2011-01-01

    The click-evoked otoacoustic emission (CEOAE) level-curve grows linearly for clicks below 40–60 dB and saturates for higher inputs. This study investigates dynamic (i.e., time-dependent) features of the CEOAE level-curve by presenting a suppressor-click less than 8 ms before the test-click. An al......The click-evoked otoacoustic emission (CEOAE) level-curve grows linearly for clicks below 40–60 dB and saturates for higher inputs. This study investigates dynamic (i.e., time-dependent) features of the CEOAE level-curve by presenting a suppressor-click less than 8 ms before the test...... for the short- (i.e., 6–18 ms) and long-latency (i.e., 24–36 ms) regions of the CEOAE, indicating that temporal suppression similarly affects synchronized spontaneous otoacoustic emissions (SSOAEs) and purely evoked CEOAE components. Overall, this study demonstrates that temporal suppression of the CEOAE level...

  3. An acoustic study of contrasting plosives and click accompaniments in Xhosa.

    Science.gov (United States)

    Jessen, Michael

    2002-01-01

    The phonetic manifestation of distinctive plosive types and click accompaniments in Xhosa was investigated with measurements of voice onset time (VOT), closure duration, voicing during closure, and burst amplitude. There is a high degree of interspeaker as well as token-to-token variability in the voiceless unaspirated plosives and clicks concerning their pronunciation with or without audible ejection. The plosives are much more frequently ejective than the corresponding clicks. If present, ejection is manifested by increased VOT, burst amplitude, or both. Duration of voicing during closure is substantial only in the implosive, but not in the 'voiced' plosives and clicks. After nasals the percentage of voicing during closure is high in 'voiced' plosives due to the very short closure duration found in that context; in the post-nasal 'voiced' clicks closure is mostly reduced to zero. Aspirated plosives and clicks in Xhosa show VOT values that are on average relatively long when compared to other languages. Closure duration tends to be shorter in aspirated plosives and clicks than in other categories. Copyright 2002 S. Karger AG, Basel

  4. Assessing segmentation processes by click detection: online measure of statistical learning, or simple interference?

    Science.gov (United States)

    Franco, Ana; Gaillard, Vinciane; Cleeremans, Axel; Destrebecqz, Arnaud

    2015-12-01

    Statistical learning can be used to extract the words from continuous speech. Gómez, Bion, and Mehler (Language and Cognitive Processes, 26, 212-223, 2011) proposed an online measure of statistical learning: They superimposed auditory clicks on a continuous artificial speech stream made up of a random succession of trisyllabic nonwords. Participants were instructed to detect these clicks, which could be located either within or between words. The results showed that, over the length of exposure, reaction times (RTs) increased more for within-word than for between-word clicks. This result has been accounted for by means of statistical learning of the between-word boundaries. However, even though statistical learning occurs without an intention to learn, it nevertheless requires attentional resources. Therefore, this process could be affected by a concurrent task such as click detection. In the present study, we evaluated the extent to which the click detection task indeed reflects successful statistical learning. Our results suggest that the emergence of RT differences between within- and between-word click detection is neither systematic nor related to the successful segmentation of the artificial language. Therefore, instead of being an online measure of learning, the click detection task seems to interfere with the extraction of statistical regularities.

  5. Comparison of echolocation clicks from geographically sympatric killer whales and long-finned pilot whales

    DEFF Research Database (Denmark)

    Eskesen, Ida; Wahlberg, Magnus; Simon, Malene

    2010-01-01

    The source characteristics of biosonar signals from sympatric killer whales and long-finned pilot whales in a Norwegian fjord were compared. A total of 137 pilot whale and more than 2000 killer whale echolocation clicks were recorded using a linear four-hydrophone array. Of these, 20 pilot whale...... clicks and 28 killer whale clicks were categorized as being recorded on-axis. The clicks of pilot whales had a mean apparent source level of 196 dB re 1 lPa pp and those of killer whales 203 dB re 1 lPa pp. The duration of pilot whale clicks was significantly shorter (23 ls, S.E.¼1.3) and the centroid...... frequency significantly higher (55 kHz, S.E.¼2.1) than killer whale clicks (duration: 41 ls, S.E.¼2.6; centroid frequency: 32 kHz, S.E.¼1.5). The rate of increase in the accumulated energy as a function of time also differed between clicks from the two species. The differences in duration, frequency...

  6. Synthesis and applications of biomedical and pharmaceutical polymers via click chemistry methodologies.

    Science.gov (United States)

    van Dijk, Maarten; Rijkers, Dirk T S; Liskamp, Rob M J; van Nostrum, Cornelus F; Hennink, Wim E

    2009-11-01

    In this review, the synthesis and application of biomedical and pharmaceutical polymers synthesized via the copper(I)-catalyzed alkyne-azide cycloaddition, the thiol-ene reaction, or a combination of both click reactions are discussed. Since the introduction of both "click" methods, numerous articles have disclosed new approaches for the synthesis of polymers with different architectures, e.g., block and graft copolymers, dendrimers, and hydrogels, for pharmaceutical and biomedical applications. By describing selected examples, an overview is given of the possibilities and limitations that these two "click" methods may offer.

  7. Directionality of sperm whale sonar clicks and its relation to piston radiation theory

    DEFF Research Database (Denmark)

    Beedholm, K.; Møhl, Bertel

    2006-01-01

    This paper investigates the applicability to sperm whales of the theory of sound radiating from a piston. The theory is applied to a physical model and to a series of sperm whale clicks. Results show that wave forms of off-axis signals can be reproduced by convolving an on-axis signal...... with the spatial impulse response of a piston. The angle of a recorded click can be estimated as the angle producing the spatial impulse response that gives the best match with the observation when convolved with the on-axis wave form. It is concluded that piston theory applies to sperm whale sonar click emission....

  8. Effective click construction of bridged- and spiro-multicyclic polymer topologies with tailored cyclic prepolymers (kyklo-telechelics).

    Science.gov (United States)

    Sugai, Naoto; Heguri, Hiroyuki; Ohta, Kengo; Meng, Qingyuan; Yamamoto, Takuya; Tezuka, Yasuyuki

    2010-10-27

    An alkyne-azide addition, i.e., click, reaction in conjunction with an electrostatic self-assembly and covalent fixation (ESA-CF) process has been demonstrated to effectively construct a variety of unprecedented multicyclic polymer topologies. A series of single cyclic poly(tetrahydrofuran), poly(THF), precursors having an alkyne group (Ia), an azide group (Ib), two alkyne groups at the opposite positions (Ic), and an alkyne group and an azide group at the opposite positions (Id) have been prepared by the ESA-CF process. Moreover, a bicyclic 8-shaped precursor having two alkyne groups at the opposite positions (Ie) was synthesized. The subsequent click reaction of Ia with linear (IIa) and three-armed star (IIb) telechelic precursors having azide groups has been performed to construct bridged-type two-way (IIIa) and three-way (IIIb) paddle-shaped polymer topologies, respectively. Likewise, spiro-type tandem tricyclic (IVa) and tetracyclic (IVb) topologies resulted from Ib/Ic and Ib/Ie, respectively. Furthermore, three types of multicyclic topologies that are composed of repeating ring (Va), alternating ring/linear (Vb), and alternating ring/star (Vc) units have been synthesized from Id, Ic/IIa, and Ic/IIb, respectively.

  9. Ultrasensitive detection of DNA and RNA based on enzyme-free click chemical ligation chain reaction on dispersed gold nanoparticles.

    Science.gov (United States)

    Kato, Daiki; Oishi, Motoi

    2014-10-28

    An ultrasensitive colorimetric DNA and RNA assay using a combination of enzyme-free click chemical ligation chain reaction (CCLCR) on dispersed gold nanoparticles (GNPs) and a magnetic separation process has been developed. The click chemical ligation between an azide-containing probe DNA-modified GNP and a dibenzocyclooctyne-containing probe biotinyl DNA occurred through hybridization with target DNA (RNA) to form the biotinyl-ligated GNPs (ligated products). Eventually, both the biotinyl-ligated GNPs and target DNA (RNA) were amplified exponentially using thermal cycling. After separation of the biotinyl-ligated GNPs using streptavidin-modified magnetic beads, the change in intensity of the surface plasmon band at 525 nm in the supernatants was observed by UV/vis measurement and was also evident visually. The CCLCR assay provides ultrasensitive detection (50 zM: several copies) of target DNA that is comparable to PCR-based approaches. Note that target RNA could also be detected with similar sensitivity without the need for reverse transcription to the corresponding cDNA. The amplification efficiency of the CCLCR assay was as high as 82% due to the pseudohomogeneous reaction behavior of CCLCR on dispersed GNPs. In addition, the CCLCR assay was able to discriminate differences in single-base mismatches and to specifically detect target DNA and target RNA from the cell lysate.

  10. In situ visualization of newly synthesized proteins in environmental microbes using amino acid tagging and click chemistry

    Science.gov (United States)

    Hatzenpichler, Roland; Scheller, Silvan; Tavormina, Patricia L; Babin, Brett M; Tirrell, David A; Orphan, Victoria J

    2014-01-01

    Here we describe the application of a new click chemistry method for fluorescent tracking of protein synthesis in individual microorganisms within environmental samples. This technique, termed bioorthogonal non-canonical amino acid tagging (BONCAT), is based on the in vivo incorporation of the non-canonical amino acid L-azidohomoalanine (AHA), a surrogate for l-methionine, followed by fluorescent labelling of AHA-containing cellular proteins by azide-alkyne click chemistry. BONCAT was evaluated with a range of phylogenetically and physiologically diverse archaeal and bacterial pure cultures and enrichments, and used to visualize translationally active cells within complex environmental samples including an oral biofilm, freshwater and anoxic sediment. We also developed combined assays that couple BONCAT with ribosomal RNA (rRNA)-targeted fluorescence in situ hybridization (FISH), enabling a direct link between taxonomic identity and translational activity. Using a methanotrophic enrichment culture incubated under different conditions, we demonstrate the potential of BONCAT-FISH to study microbial physiology in situ. A direct comparison of anabolic activity using BONCAT and stable isotope labelling by nano-scale secondary ion mass spectrometry (15NH3 assimilation) for individual cells within a sediment-sourced enrichment culture showed concordance between AHA-positive cells and 15N enrichment. BONCAT-FISH offers a fast, inexpensive and straightforward fluorescence microscopy method for studying the in situ activity of environmental microbes on a single-cell level. PMID:24571640

  11. Effects of single and split doses of cobalt-60 gamma rays and 14 MeV neutrons on mouse stem cell spermatogonia.

    Science.gov (United States)

    Hacker-Klom, U B; Köhnlein, W; Göhde, W

    2000-12-01

    The long-term effects of ionizing radiation on male gonads may be the result of damage to spermatogonial stem cells. Doses of 10 cGy to 15 Gy (60)Co gamma rays or 10 cGy to 7 Gy 14 MeV neutrons were given to NMRI mice as single or split doses separated by a 24-h interval. The ratios of haploid spermatids/2c cells and the coefficients of variation of DNA histogram peaks as measures of both the cytocidal and the clastogenic actions of radiation were analyzed by DNA flow cytometry after DAPI staining. The coefficient of variation is not only a statistical examination of the data but is also used here as a measure of residual damage to DNA (i.e. a biological dosimeter). Testicular histology was examined in parallel. At 70 days after irradiation, the relative biological effectiveness for neutrons at 50% survival of spermatogonial stem cells was 3.6 for single doses and 2.8 for split doses. The average coefficient of variation of unirradiated controls of elongated spermatids was doubled when stem cells were irradiated with single doses of approximately 14 Gy (60)Co gamma rays or 3 Gy neutrons and observed 70 days later. Split doses of (60)Co gamma rays were more effective than single doses, doubling DNA dispersion at 7 Gy. No fractionation effect was found with neutrons with coefficients of variation.

  12. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  13. Evaluation of the May 2005 Click It or Ticket mobilization to increase seat belt use

    Science.gov (United States)

    2007-05-01

    Click It or Ticket (CIOT) is an intense, short-duration, seat belt publicity and enforcement program. The CIOT May 2005 Mobilization involved approximately $33 million of purchased media. Law enforcement agencies across the Nation reported issuing mo...

  14. Source parameter estimates of echolocation clicks from wild pygmy killer whales (Feresa attenuata) (L)

    Science.gov (United States)

    Madsen, P. T.; Kerr, I.; Payne, R.

    2004-10-01

    Pods of the little known pygmy killer whale (Feresa attenuata) in the northern Indian Ocean were recorded with a vertical hydrophone array connected to a digital recorder sampling at 320 kHz. Recorded clicks were directional, short (25 μs) transients with estimated source levels between 197 and 223 dB re. 1 μPa (pp). Spectra of clicks recorded close to or on the acoustic axis were bimodal with peak frequencies between 45 and 117 kHz, and with centroid frequencies between 70 and 85 kHz. The clicks share characteristics of echolocation clicks from similar sized, whistling delphinids, and have properties suited for the detection and classification of prey targeted by this odontocete. .

  15. Recording and quantification of ultrasonic echolocation clicks from free-ranging toothed whales

    DEFF Research Database (Denmark)

    Madsen, Peter Teglberg; Wahlberg, Magnus

    2007-01-01

    Toothed whales produce short, ultrasonic clicks of high directionality and source level to probe their environment acoustically. This process, termed echolocation, is to a large part governed by the properties of the emitted clicks. Therefore derivation of click source parameters from free......-ranging animals is of increasing importance to understand both how toothed whales use echolocation in the wild and how they may be monitored acoustically. This paper addresses how source parameters can be derived from free-ranging toothed whales in the wild using calibrated multi-hydrophone arrays and digital...... recorders. We outline the properties required of hydrophones, amplifiers and analog to digital converters, and discuss the problems of recording echolocation clicks on the axis of a directional sound beam. For accurate localization the hydrophone array apertures must be adapted and scaled to the behavior of...

  16. Navigation To and From a Page: Which Links Get Clicked From Where

    Science.gov (United States)

    Use Google Analytics navigation summary data to find out what page users most frequently click your Contact Us link from (Previous Page Path), or which links on your homepage are popular or unpopular (Next Page Path).

  17. Parallel search engine optimisation and pay-per-click campaigns: A comparison of cost per acquisition

    Directory of Open Access Journals (Sweden)

    Wouter T. Kritzinger

    2017-07-01

    Full Text Available Background: It is imperative that commercial websites should rank highly in search engine result pages because these provide the main entry point to paying customers. There are two main methods to achieve high rankings: search engine optimisation (SEO and pay-per-click (PPC systems. Both require a financial investment – SEO mainly at the beginning, and PPC spread over time in regular amounts. If marketing budgets are applied in the wrong area, this could lead to losses and possibly financial ruin. Objectives: The objective of this research was to investigate, using three real-world case studies, the actual expenditure on and income from both SEO and PPC systems. These figures were then compared, and specifically, the cost per acquisition (CPA was used to decide which system yielded the best results. Methodology: Three diverse websites were chosen, and analytics data for all three were compared over a 3-month period. Calculations were performed to reduce the figures to single ratios, to make comparisons between them possible. Results: Some of the resultant ratios varied widely between websites. However, the CPA was shown to be on average 52.1 times lower for SEO than for PPC systems. Conclusion: It was concluded that SEO should be the marketing system of preference for e-commerce-based websites. However, there are cases where PPC would yield better results – when instant traffic is required, and when a large initial expenditure is not possible.

  18. Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

    Directory of Open Access Journals (Sweden)

    Nattawut Yotapan

    2014-09-01

    Full Text Available DNA or its analogues with an environment-sensitive fluorescent label are potentially useful as a probe for studying the structure and dynamics of nucleic acids. In this work, pyrrolidinyl peptide nucleic acid (acpcPNA was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV–vis and fluorescence spectroscopy in the absence and in the presence of DNA. In contrast to the usual quenching observed in Nile red-labeled DNA, the hybridization with DNA resulted in blue shifting and an enhanced fluorescence regardless of the neighboring bases. More pronounced blue shifts and fluorescence enhancements were observed when the DNA target carried a base insertion in close proximity to the Nile red label. The results indicate that the Nile red label is located in a more hydrophobic environment in acpcPNA–DNA duplexes than in the single-stranded acpcPNA. The different fluorescence properties of the acpcPNA hybrids of complementary DNA and DNA carrying a base insertion are suggestive of different interactions between the Nile red label and the duplexes.

  19. Surface Modification of Nanoporous 1,2-Polybutadiene by Atom Transfer Radical Polymerization or Click Chemistry

    DEFF Research Database (Denmark)

    Guo, Fengxiao; Jankova Atanasova, Katja; Schulte, Lars

    2010-01-01

    Surface-initiated atom transfer radical polymerization (ATRP) and click chemistry were used to obtain functional nanoporous polymers based oil nanoporous 1,2-polybutadiene (PB) with gyroid morphology. The ATRP monolith initiator was prepared by immobilizing bromoester initiators onto the pore walls...... ATRP-grafting of hydrophilic polyacrylates and click of MPEG, the originally hydrophobic samples transformed into hydrophilic nanoporous materials. The successful modification was confirmed by infrared spectroscopy, contact angle measurements and measurements of spontaneous water uptake, while...

  20. Low fouling polysulfone ultrafiltration membrane via click chemistry

    KAUST Repository

    Xie, Yihui

    2014-10-13

    Hydrophilic surfaces are known to be less prone to fouling. Ultrafiltration membranes are frequently prepared from rather hydrophobic polymers like polysulfone (PSU). Strategies to keep the good pore forming characteristics of PSU, but with improved hydrophilicity are proposed here. PSU functionalized with 1,2,3-triazole ring substituents containing OH groups was successfully synthesized through click chemistry reaction. The structures of the polymers were confirmed using NMR spectroscopy and Fourier transform infrared spectroscopy (FTIR). High thermal stability (>280°C) was observed by thermal gravimetric analysis. Elemental analysis showed the presence of nitrogen containing triazole group with different degrees of functionalization (23%, 49%, 56%, and 94%). The glass transition temperature shifted with the introduction of triazole pendant groups from 190°C (unmodified) to 171°C. Ultrafiltration membranes were prepared via phase inversion by immersion in different coagulation baths (NMP/water mixtures with volume ratios from 0/100 to 40/60). The morphologies of these membranes were studied by field emission scanning electron microscopy (FESEM). The optimized PSU bearing triazole functions membranes exhibited water permeability up to 187 L m-2 h-1 bar-1, which is 23 times higher than those prepared under the same conditions but with unmodified polysulfone (PSU; 8 L m-2 h-1 bar-1). Results of bovine serum albumin protein rejection test indicated that susceptibility to fouling decreased with the modification, due to the increased hydrophilicity, while keeping high protein rejection ratio (>99%).

  1. Surface Eroding, Semicrystalline Polyanhydrides via Thiol-Ene "Click" Photopolymerization.

    Science.gov (United States)

    Poetz, Katie L; Mohammed, Halimatu S; Shipp, Devon A

    2015-05-11

    Surface eroding and semicrystalline polyanhydrides, with tunable erosion times and drug delivery pharmacokinetics largely dictated by erosion, are produced easily with thiol-ene "click" polymerization. This strategy yields both linear and cross-linked network polyanhydrides that are readily and fully cured within minutes using photoinitiation, can contain up to 60% crystallinity, and have tensile moduli up to 25 MPa for the compositions studied. Since they readily undergo hydrolysis and exhibit the oft-preferred surface erosion mechanism, they may be particularly useful in drug delivery applications. The polyanhydrides were degraded under pseudophysiological conditions and cylindrical samples (10 mm diameter × 5 mm height) were completely degraded within ∼10 days, with the mass-time profile being linear for much of this time after a ∼24 h induction period. Drug release studies, using lidocaine as a model, showed pharmacokinetics that displayed a muted burst release in the early stages of erosion, but then a delayed release profile that is closely correlated to the erosion kinetics. Furthermore, cytotoxicity studies of the linear and cross-linked semicrystalline polyanhydrides, and degradation products, against fibroblast cells indicate that the materials have good cytocompatibility. Overall, cells treated with up to 2500 mg/L of the semicrystalline polyanhydrides and degradation products show >90% human dermal fibroblast adult (HDFa) cell viability indicative of good cytocompatibility.

  2. Vocal reporting of echolocation targets: dolphins often report before click trains end.

    Science.gov (United States)

    Ridgway, S H; Elsberry, W R; Blackwood, D J; Kamolnick, T; Todd, M; Carder, D A; Chaplin, Monica; Cranford, T W

    2012-01-01

    Bottlenose dolphins (Tursiops truncatus) wore opaque suction cups over their eyes while stationing behind an acoustically opaque door. This put the dolphins in a known position and orientation. When the door opened, the dolphin clicked to detect targets. Trainers specified that Dolphin S emit a whistle if the target was a 7.5 cm water filled sphere, or a pulse burst if the target was a rock. S remained quiet if there was no target. Dolphin B whistled for the sphere. She remained quiet for rock and for no target. Thus, S had to choose between three different responses, whistle, pulse burst, or remain quiet. B had to choose between two different responses, whistle or remain quiet. S gave correct vocal responses averaging 114 ms after her last echolocation click (range 182 ms before and 219 ms after the last click). Average response for B was 21 ms before her last echolocation click (range 250 ms before and 95 ms after the last click in the train). More often than not, B began her whistle response before her echolocation train ended. The findings suggest separate neural pathways for generation of response vocalizations as opposed to echolocation clicks. © 2012 Acoustical Society of America.

  3. A directly patternable click-active polymer film via initiated chemical vapor deposition (iCVD)

    International Nuclear Information System (INIS)

    Im, Sung Gap; Kim, Byeong-Su; Tenhaeff, Wyatt E.; Hammond, Paula T.; Gleason, Karen K.

    2009-01-01

    A new 'click chemistry' active functional polymer film was directly obtained from a commercially available monomer of propargyl acrylate (PA) via easy, one-step process of initiated chemical vapor deposition (iCVD). Fourier transform infrared (FTIR) spectra confirmed that significant amount of the click-active acetylene functional group was retained after the iCVD process. The degree of crosslinking could be controlled by intentionally adding crosslinker, such as ethylene glycol diacrylate (EGDA) that was polymerized with PA to form click-active, completely insoluble copolymer. The formed iCVD polymers could also be grafted on various inorganic substrates with silane coupling agents. These crosslinking and grafting techniques give iCVD polymers chemical and mechanical stability, which allows iCVD polymers applicable to various click chemistry without any modification of reaction conditions. Pre-patterned iCVD polymer could be obtained via photolithography and an azido-functionalized dye molecule was also successfully attached on iCVD polymer via click chemistry. Moreover, pPA film demonstrated sensitivity to e-beam irradiation, which enabled clickable substrates having nanometer scale patterns without requiring the use of an additional e-beam resist. Direct e-beam exposure of this multifunctional iCVD layer, a 200 nm pattern, and QD particles were selectively conjugated on the substrates via click chemistry. Thus, iCVD pPA has shown dual functionality as of 'clickable' e-beam sensitive material.

  4. "Click" analytics for "click" chemistry - A simple method for calibration-free evaluation of online NMR spectra.

    Science.gov (United States)

    Michalik-Onichimowska, Aleksandra; Kern, Simon; Riedel, Jens; Panne, Ulrich; King, Rudibert; Maiwald, Michael

    2017-04-01

    Driven mostly by the search for chemical syntheses under biocompatible conditions, so called "click" chemistry rapidly became a growing field of research. The resulting simple one-pot reactions are so far only scarcely accompanied by an adequate optimization via comparably straightforward and robust analysis techniques possessing short set-up times. Here, we report on a fast and reliable calibration-free online NMR monitoring approach for technical mixtures. It combines a versatile fluidic system, continuous-flow measurement of 1 H spectra with a time interval of 20s per spectrum, and a robust, fully automated algorithm to interpret the obtained data. As a proof-of-concept, the thiol-ene coupling between N-boc cysteine methyl ester and allyl alcohol was conducted in a variety of non-deuterated solvents while its time-resolved behaviour was characterized with step tracer experiments. Overlapping signals in online spectra during thiol-ene coupling could be deconvoluted with a spectral model using indirect hard modeling and were subsequently converted to either molar ratios (using a calibration-free approach) or absolute concentrations (using 1-point calibration). For various solvents the kinetic constant k for pseudo-first order reaction was estimated to be 3.9h -1 at 25°C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Regional brain blood flow in mouse: quantitative measurement using a single-pass radio-tracer method and a mathematical algorithm.

    Science.gov (United States)

    Xu, K; Radhakrishnan, K; Serhal, A; Allen, F; Lamanna, J C; Puchowicz, M A

    2011-01-01

    We have developed a reliable experimental method for measuring local regional cerebral blood flows in anesthetized mice. This method is an extension of the well-established single-pass dual-label indicator method for simultaneously measuring blood flow and glucose influx in rat brains. C57BL6J mice (n = 10) were anesthetized and regional blood flows (ml/min/g) were measured using the radio-tracer method. To test the sensitivity of this method we used a mathematical algorithm to predict the blood flows and compared the two sets of results.Measured regional blood flows between 0.7 and 1.7 ml/min/g were similar to those we have previously reported in the rat. The predicted blood flows using an assumed linearly increasing arterial tracer concentration-versus-time profile (that is, a ramp) were similar to the values measured in the physiological experiments (R(2) 0.99; slope 0.91). Thus,measurements of local regional cerebral blood flow in anesthetized mice using a single-pass radio-tracer method appear to be reliable.

  6. Immunogenicity and efficacy of single antigen Gp63, polytope and polytopeHSP70 DNA vaccines against visceral Leishmaniasis in experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Rakhee Sachdeva

    2009-12-01

    Full Text Available Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA, polytope (Poly/pcDNA and Polytope fused with hsp70 (Poly/hsp/pcDNA against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-gamma over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis.

  7. Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion.

    Science.gov (United States)

    Kent, David G; Li, Juan; Tanna, Hinal; Fink, Juergen; Kirschner, Kristina; Pask, Dean C; Silber, Yvonne; Hamilton, Tina L; Sneade, Rachel; Simons, Benjamin D; Green, Anthony R

    2013-01-01

    Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F

  8. Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.

    Science.gov (United States)

    Ifrim, Marius F; Williams, Kathryn R; Bassell, Gary J

    2015-05-06

    Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. Copyright © 2015 the authors 0270-6474/15/357116-15$15.00/0.

  9. Detection of activated platelets in a mouse model of carotid artery thrombosis with 18 F-labeled single-chain antibodies.

    Science.gov (United States)

    Ardipradja, Katie; Yeoh, Shinn Dee; Alt, Karen; O'Keefe, Graeme; Rigopoulos, Angela; Howells, David W; Scott, Andrew M; Peter, Karlheinz; Ackerman, Uwe; Hagemeyer, Christoph E

    2014-03-01

    Activated platelets are key players in thrombosis and inflammation. We previously generated single-chain antibodies (scFv) against ligand-induced binding sites (LIBS) on the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. The aim of this study was the construction and characterisation of a novel (18)F PET radiotracer based on this antibody. ScFv(anti-LIBS) and control antibody mut-scFv were reacted with N-succinimidyl-4-[(18)F]fluorobenzoate (S[(18)F]FB). Radiolabeled scFv was incubated with in vitro formed platelet clots and injected into mice with FeCl(3) induced thrombus in the left carotid artery. Clots were imaged in the PET scanner and amount of radioactivity measured using an ionization chamber and image analysis. Assessment of vessel injury as well as the biodistribution of the radiolabeled scFv was studied. After incubation with increasing concentrations of (18)F-scFv(anti-LIBS) clots had retained significantly higher amounts of radioactivity compared to clots incubated with radiolabeled (18)F-mut-scFv (13.3 ± 3.8 vs. 3.6 ± 1 KBq, p tracer in the injured vessel compared with the non-injured vessel, with 12.6 ± 4.7% injected dose per gram (ID/g) uptake in the injured vessel and 3.7 ± 0.9% ID/g in the non-injured vessel 5 minutes after injection (p < 0.05, n = 6). Our results show that the novel antibody radiotracer (18)F-scFv(anti-LIBS) is useful for the sensitive detection of activated platelets and thrombosis. We describe the first (18)F variant of a scFv(anti-LIBS) against activated platelets. This diagnostic agent could provide a powerful tool for the assessment of acute thrombosis and inflammation in patients in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering.

    Science.gov (United States)

    Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan

    2014-06-01

    Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Detection of activated platelets in a mouse model of carotid artery thrombosis with 18F-labeled single-chain antibodies

    International Nuclear Information System (INIS)

    Ardipradja, Katie; Yeoh, Shinn Dee; Alt, Karen; O’Keefe, Graeme; Rigopoulos, Angela; Howells, David W.; Scott, Andrew M.; Peter, Karlheinz; Ackerman, Uwe; Hagemeyer, Christoph E.

    2014-01-01

    Introduction: Activated platelets are key players in thrombosis and inflammation. We previously generated single-chain antibodies (scFv) against ligand-induced binding sites (LIBS) on the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. The aim of this study was the construction and characterisation of a novel 18 F PET radiotracer based on this antibody. Methods: ScFv anti-LIBS and control antibody mut-scFv were reacted with N-succinimidyl-4-[ 18 F]fluorobenzoate (S[ 18 F]FB). Radiolabeled scFv was incubated with in vitro formed platelet clots and injected into mice with FeCl 3 induced thrombus in the left carotid artery. Clots were imaged in the PET scanner and amount of radioactivity measured using an ionization chamber and image analysis. Assessment of vessel injury as well as the biodistribution of the radiolabeled scFv was studied. Results: After incubation with increasing concentrations of 18 F-scFv anti-LIBS clots had retained significantly higher amounts of radioactivity compared to clots incubated with radiolabeled 18 F-mut-scFv (13.3 ± 3.8 vs. 3.6 ± 1 KBq, p < 0.05, n = 9, decay corrected). In the in vivo experiments we found an high uptake of the tracer in the injured vessel compared with the non-injured vessel, with 12.6 ± 4.7% injected dose per gram (ID/g) uptake in the injured vessel and 3.7 ± 0.9% ID/g in the non-injured vessel 5 minutes after injection (p < 0.05, n = 6). Conclusions: Our results show that the novel antibody radiotracer 18 F-scFv anti-LIBS is useful for the sensitive detection of activated platelets and thrombosis. Advances in knowledge and implications for patient care: We describe the first 18 F variant of a scFv anti-LIBS against activated platelets. This diagnostic agent could provide a powerful tool for the assessment of acute thrombosis and inflammation in patients in the future

  12. Efficient functionalization of carbon nanotubes with porphyrin dendrons via click chemistry.

    Science.gov (United States)

    Palacin, Thomas; Khanh, Hung Le; Jousselme, Bruno; Jegou, Pascale; Filoramo, Arianna; Ehli, Christian; Guldi, Dirk M; Campidelli, Stéphane

    2009-10-28

    The attempt to decorate carbon nanotubes with organic molecules as a powerful means to form new functional materials has attracted broad attention in the scientific community. Here, we report the functionalization of single-walled carbon nanotubes (SWNTs) with zinc porphyrins (ZnP) using very mild conditions to afford a series of SWNTs-ZnP (1 and 2) electron donor-acceptor conjugates. Owing to the presence of either one or two ZnP, introduced via "click chemistry", different absorption cross sections were realized. Important in this context is that the covalent linkages between SWNT and ZnP were corroborated by monitoring the diagnostic signature of the nitrogen atoms as part of the formed triazole ring by X-ray photoelectron spectroscopy (XPS). The resulting SWNTs-ZnP 1 and 2 were fully characterized. This characterization was complemented by a full-fledged investigation of their electrochemical and photophysical properties. In particular, appreciably strong electronic coupling between the photo- and electroactive constituents (i.e., SWNT and ZnP) led to rapid excited-state deactivation of ZnP via charge transfer to the nanotubes. Here, the different absorption cross sections throughout the visible part of the solar spectrum turned out to be valuable in enhancing the overall light-harvesting features. Upon photoexcitation, for both SWNTs-ZnP 1 and 2, radical ion pair states (i.e., reduced SWNT and oxidized ZnP) are formed. The charge-separated states decay to regenerate the singlet ground state with lifetimes of 820 and 200 ps for 1 and 2, respectively.

  13. A Decade of Click Chemistry in Protein Palmitoylation: Impact on Discovery and New Biology.

    Science.gov (United States)

    Gao, Xinxin; Hannoush, Rami N

    2018-03-15

    Protein palmitoylation plays diverse roles in regulating the trafficking, stability, and activity of cellular proteins. The advent of click chemistry has propelled the field of protein palmitoylation forward by providing specific, sensitive, rapid, and easy-to-handle methods for studying protein palmitoylation. This year marks the 10th anniversary since the first click chemistry-based fatty acid probes for detecting protein lipid modifications were reported. The goal of this review is to highlight key biological advancements in the field of protein palmitoylation during the past 10 years. In particular, we discuss the impact of click chemistry on enabling protein palmitoylation proteomics methods, uncovering novel lipid modifications on proteins and elucidating their functions, as well as the development of non-radioactive biochemical and enzymatic assays. In addition, this review provides context for building and exploring new research avenues in protein palmitoylation through the use of clickable fatty acid probes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Pure Play vs. Bricks-and-Clicks: Who Reaps the Benefits of Virtual Retailing?

    OpenAIRE

    Youlong Zhuang; Albert L. Lederer

    2006-01-01

    Pure play and bricks-and-clicks represent today’s two major retailing models. The current study answers four questions comparing the two models in terms of the e-commerce benefits achieved and information systems management practices used to achieve them. It applies a Web-based survey to compare 69 pure plays to 348 bricks-and-clicks retailers in terms of the market expansion, customer service, back-end efficiency, inventory management, and cost reduction benefits reaped, as well as in term...

  15. Temporal suppression of long-latency click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2007-01-01

    A comprehensive set of results from double click suppression experiments on otoacoustic emissions (OAEs) have been presented by Hine and Thornton (2002) and Kapadia and Lutman (2000). They found that suppression of a click-evoked otoacoustic emission (CEOAE) varied with the timing and level...... subjects showed that the nonlinear suppression effect remained on the long-latency CEOAE, indicating that both SOAEs and CEOAEs originate from the same cochlear nonlinearities, as earlier suggested by Kemp and Chum (1980). The apparent similar origin of both types of emissions implies that the same...

  16. CuAAC click reactions for the design of multifunctional luminescent ruthenium complexes.

    Science.gov (United States)

    Zabarska, Natalia; Stumper, Anne; Rau, Sven

    2016-02-14

    CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed.

  17. The function of male sperm whale slow clicks in a high latitude habitat: communication, echolocation, or prey debilitation?

    Science.gov (United States)

    Oliveira, Cláudia; Wahlberg, Magnus; Johnson, Mark; Miller, Patrick J O; Madsen, Peter T

    2013-05-01

    Sperm whales produce different click types for echolocation and communication. Usual clicks and buzzes appear to be used primarily in foraging while codas are thought to function in social communication. The function of slow clicks is less clear, but they appear to be produced by males at higher latitudes, where they primarily forage solitarily, and on the breeding grounds, where they roam between groups of females. Here the behavioral context in which these vocalizations are produced and the function they may serve was investigated. Ninety-nine hours of acoustic and diving data were analyzed from sound recording tags on six male sperm whales in Northern Norway. The 755 slow clicks detected were produced by tagged animals at the surface (52%), ascending from a dive (37%), and during the bottom phase (11%), but never during the descent. Slow clicks were not associated with the production of buzzes, other echolocation clicks, or fast maneuvering that would indicate foraging. Some slow clicks were emitted in seemingly repetitive temporal patterns supporting the hypothesis that the function for slow clicks on the feeding grounds is long range communication between males, possibly relaying information about individual identity or behavioral states.

  18. Proof of Concept Analysis of Using Photo-Click Chemistry on Ionic Liquid Monomers with Propargyl Functionality

    Science.gov (United States)

    Kattekola, Samhita

    Click chemistry refers to a specific set of organic chemistry reactions that proceed under mild conditions, are high yielding, and are extremely selective. Due to their orthogonality, these types of reactions have opened doors for the fabrication of materials of many kinds. This work explores the applicability of click chemistry used in conjunction with ionic liquids. The kinetics of light initiated click chemistry reactions of CuAAC and thiol-yne on ionic liquids functionalized with alkyne are examined, setting up the foundation for many applications including but not limited to ion-containing membranes, adhesives, and organic catalysts. Photo-click chemistry is a recent discovery and all its facets have not been explored yet. While it is evident that photo-click reactions have made the already friendly click reactions even more amicable, there is a vast gap in the literature on the fundamentals of this reaction. It was observed that the cationic structure of the ionic liquid monomer and the presence of the anion significantly affect the kinetics of the click reactions. For the CuAAC reaction, the fastest kinetics were produced by a weakly coordinating anion and aromatic structure cation combination and it was deduced that anions which strongly interact with Cu(I) inhibit the reaction. Additionally, it was discovered that the polarity of the thiol monomer has an effect on the thiol-yne click reaction. A more polar thiol in thiol-yne reactions with ionic liquids appears to facilitate the reaction to proceed to full conversion.

  19. Gyroscope-Driven Mouse Pointer with an EMOTIV? EEG Headset and Data Analysis Based on Empirical Mode Decomposition

    OpenAIRE

    Rosas-Cholula, Gerardo; Ramirez-Cortes, Juan Manuel; Alarcon-Aquino, Vicente; Gomez-Gil, Pilar; Rangel-Magdaleno, Jose de Jesus; Reyes-Garcia, Carlos

    2013-01-01

    This paper presents a project on the development of a cursor control emulating the typical operations of a computer-mouse, using gyroscope and eye-blinking electromyographic signals which are obtained through a commercial 16-electrode wireless headset, recently released by Emotiv. The cursor position is controlled using information from a gyroscope included in the headset. The clicks are generated through the user’s blinking with an adequate detection procedure based on the spectral-like tech...

  20. What speeds up the internal clock? Effects of clicks and flicker on duration judgements and reaction time.

    Science.gov (United States)

    Wearden, J H; Williams, Emily A; Jones, Luke A

    2017-03-01

    Four experiments investigated the effect of pre-stimulus events on judgements of the subjective duration of tones that they preceded. Experiments 1 to 4 used click trains, flickering squares, expanding circles, and white noise as pre-stimulus events and showed that (a) periodic clicks appeared to "speed up" the pacemaker of an internal clock but that the effect wore off over a click-free delay, (b) aperiodic click trains, and visual stimuli in the form of flickering squares and expanding circles, also produced similar increases in estimated tone duration, as did white noise, although its effect was weaker. A fifth experiment examined the effects of periodic flicker on reaction time and showed that, as with periodic clicks in a previous experiment, reaction times were shorter when preceded by flicker than without.

  1. Centralized mouse repositories.

    Science.gov (United States)

    Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

    2012-10-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

  2. A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates-Bioinspired Sulfoxidation Catalysts

    Czech Academy of Sciences Publication Activity Database

    Tomanová, P.; Šturala, J.; Buděšínský, Miloš; Cibulka, R.

    2015-01-01

    Roč. 20, č. 11 (2015), s. 19837-19848 ISSN 1420-3049 Institutional support: RVO:61388963 Keywords : click chemistry * cyclodextrin * flavin * monooxygenase * oxidation * sulfoxides * green chemistry Subject RIV: CC - Organic Chemistry Impact factor: 2.465, year: 2015 http://www.mdpi.com/1420-3049/20/11/19667/htm

  3. Freedom of Contract in Click Wrap Agreements in Malaysia and the United States of America

    Directory of Open Access Journals (Sweden)

    Maryam Rafiei

    2011-06-01

    Full Text Available Technological advancement in the communications industry, particularly over the last decade, has given rise to consumers and commercial providers who want to form their own business or contractual agreements via the Internet. The mark of such technology can be seen in a new form of contract called “click wrap.”

  4. Copper-free 'click' : 1,3-dipolar cycloaddition of azides and arynes

    NARCIS (Netherlands)

    Campbell-Verduyn, Lachlan; Elsinga, Philip H.; Mirfeizi, Leila; Dierckx, Rudi A.; Feringa, Ben L.

    2008-01-01

    Arynes formed through fluoride-promoted ortho-elimination of o-(trimethylsilyl)aryl triflates can undergo [3 + 2] cycloaddition with various azides to form substituted benzotriazoles. The rapid reaction times and mild conditions make this an attractive variation of the classical 'click' reaction of

  5. C,N-Chelated Organotin(IV) Azides: Synthesis, Structure and Use within the Click Chemistry.

    Czech Academy of Sciences Publication Activity Database

    Švec, P.; Bartoš, K.; Růžičková, Z.; Cuřínová, Petra; Dušek, L.; Turek, J.; de Proft, F.; Růžička, A.

    2016-01-01

    Roč. 40, č. 7 (2016), s. 5808-5817 ISSN 1144-0546 Grant - others:FWO(BE) 12T6615N Institutional support: RVO:67985858 Keywords : organotin(IV) azides * click chemistry * chelation Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2016

  6. All-in-One azides: empowered click reaction for in vivo labeling and imaging of biomolecules.

    Science.gov (United States)

    Su, Yaning; Li, Li; Wang, Haibin; Wang, Xiaochen; Zhang, Zhiyuan

    2016-02-04

    We designed and synthesized All-in-One (AIO) reactive azide reagents for bioorthogonal reactions with highly efficient Cu(I) ligand moieties, an azido group, and functional tags for imaging or purification. The AIO reagents displayed fast and efficient click ligation and can be applied in a wide range of in vivo systems.

  7. Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

    DEFF Research Database (Denmark)

    Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

    2017-01-01

    were synthesized by solid phase click chemistry to develop novel, potent, selective MC4R agonists. Using cAMP measurements and a transcriptional reporter assay, we observed that several constrained agonists generated by a cycloaddition reaction displayed high selectivity (223- to 467-fold) toward MC4R...

  8. CLICK: Arts Education and Critical Social Dialogue within Global Youth Work Practice

    Science.gov (United States)

    Aubrey, Meg

    2015-01-01

    This article discusses CLICK, a collaborative theatre project between the Mess Up The Mess Theatre Company in Wales, the Hong Kong Academy for Performing Arts, the Australian Theatre for Young People, and Inspired Productions in New Zealand. This case study demonstrates the value of using arts education to bring together young people from multiple…

  9. Multi-channel services for click and mortars : Development of a design method

    NARCIS (Netherlands)

    Simons, L.P.A.

    2006-01-01

    The rise of Internet commerce led to multiple predictions of disintermediation and the decline of physical shopping. However, a "click and mortar" approach, which combines online, offline and telephone contact, has added value for customers and for supplier profitability, as recent research

  10. The acquisition of clicks by non-mother-tongue speakers | Lewis ...

    African Journals Online (AJOL)

    The clicks, once regarded as "clacks" by the early missionaries of the Cape in the 1820's (Shepherd, 1940: 57), are exceptional as well as unusual sounds in that they not only occur as interjections or non-linguistic gestures in some languages, but they also occur in the consonant inventory of a limited number of languages ...

  11. EXCTRA - EXploiting the Click-TRAil : Assessing the benefits of Learning Analytics

    NARCIS (Netherlands)

    Conijn, Rianne; Snijders, Chris; Matzat, Uwe; Kleingeld, Ad; Nij Bijvank, Wouter

    2016-01-01

    Currently, Learning Management Systems (LMS) are being used in the majority of educational institutions to provide learning materials online. As a by-product of these systems—every click is recorded—one gets a rich amount of data about students’ online behaviour. Recently many researchers have

  12. Click synthesis of 1, 4-disubstituted-1, 2, 3-triazoles catalysed by ...

    Indian Academy of Sciences (India)

    Abstract. A CuO-CeO2 nanocomposite in the presence of amberlite-supported azide has been used for the click synthesis of 1,4-disubstituted-1,2,3-triazoles in good yields. This catalyst can be reused several times without any significant decrease in the catalytic activity.

  13. Effect of Sound Conditioning on Click Auditory Brainstem Response Threshold Shifts in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Masoud Motalebi Kashani

    2012-10-01

    Full Text Available Background and Aim: Sound conditioning is exposure to a non-traumatic, moderate level of sound which increases inner ear resistance against further severe noise. In this study, we aimed to survey the effect of sound conditioning on auditory brainstem response (ABR threshold shifts using click stimulus, and the effect of the frequency of conditioning on hearing protection.Methods: Fifteen guinea pigs were randomly divided into 3 groups. Two conditioned groups were exposed to 1 kHz, and 4 kHz octave band noise at 85 dB SPL, 6 hours per day for 5 days, respectively.On the sixth day, the animals were exposed to 4 kHz octave band noise at 105 dB SPL, for 4 hours.The control group was exposed to intense noise, 4 kHz at 105 Db SPL for 4 hours (withoutconditioning. After exposure, ABR thresholds using click were recorded an hour, and 7 days after noise exposure.Results: The results of the ABR with click stimulus showed less thresold shifts in conditioned groups than control (p≤0.001. Comparison of the results of conditioned groups, showed less threshold shift by 4 kHz conditioning, however, this difference was not statistically significant (p>0.05.Conclusion: Electrophysiological data of our study showed that sound conditioning has a protective effect against subsequent intensive noise exposure, and the frequency of conditioning does not havesignificant effect on ABR threshold shifts when using click stimulus.

  14. "Just Clicks": An Interpretive Phenomenological Analysis of Professional Dancers' Experience of Flow

    Science.gov (United States)

    Hefferon, Kate M.; Ollis, Stewart

    2006-01-01

    The subjective experience of flow in professional dancers was analyzed using interpretive phenomenological analysis (IPA). Flow is believed to be a psychological state in which the mind and body "just click", creating optimal performance. Unfortunately, sport and performance research have severely neglected reviewing the flow experience in…

  15. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

    Directory of Open Access Journals (Sweden)

    Marina Bantzi

    2015-04-01

    Full Text Available In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  16. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more.

    Science.gov (United States)

    Bantzi, Marina; Rigol, Stephan; Giannis, Athanassios

    2015-01-01

    In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  17. Electronic health record innovations: Helping physicians - One less click at a time.

    Science.gov (United States)

    Guo, Uta; Chen, Lu; Mehta, Parag H

    2017-09-01

    Physician burnout is becoming an epidemic, due to the pressures of being productive, an imperfect electronic health record (EHR) system, and limited face-to-face time with patients. Poor usability in EHR-user interface can force users to go through more steps (i.e. more clicks on the computer) in accomplishing a task. This increased 'click burden' is a source of frustration for physicians. In the light of increased click burden and time due to meaningful use requirements, there is a need to improve the physician's experience by creating innovations in EHR. This case study describes an attempt by physicians at NewYork-Presbyterian Brooklyn Methodist Hospital to enhance the EHR experience with more efficient methods of documentation, chart review, ordering and patient safety. The EHR innovations trialled in this study were: a mobile documentation application; abnormal test results auto-populated into an EHR patient summary; physician alerts to reduce inappropriate test ordering; and a system of safety alerts on a dashboard. These innovations led to decreased click burden and allowed physicians to spend less time on the computer and more time with patients. Physician-driven changes to EHR systems have the potential to streamline virtual workflows and the management of health information and to improve patient safety, reduce physician burnout and increase physician job satisfaction.

  18. New 1,2,3-Triazole Iminosugars Derivatives Using Click Chemistry

    Directory of Open Access Journals (Sweden)

    Chahrazed Benhaoua

    2012-01-01

    Full Text Available The click concept refers ease, efficient, and the selective chemicals transformations. In this study, a novel regiospecific copper (I-catalyzed 1, 3-dipolar of terminal alkynes to azide provided a practicable synthetic pathway of triazole iminosugars derivatives. A series of new triazole-pyrrolidinols are reported in good yield.

  19. Transistors-From Point Contact to Single Electron

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 12. Transistors – From Point Contact to Single Electron. D N Bose. General Article Volume 2 Issue 12 December 1997 pp 39-54. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/12/0039-0054 ...

  20. Weighing Designs to Detect a Single Counterfeit Coin

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 21; Issue 2. Weighing Designs to Detect a Single Counterfeit Coin. Jyotirmoy Sarkar Bikas K Sinha. General Article Volume 21 Issue 2 February 2016 pp 125-150. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. CrazyEgg Reports for Single Page Analysis

    Science.gov (United States)

    CrazyEgg provides an in depth look at visitor behavior on one page. While you can use GA to do trend analysis of your web area, CrazyEgg helps diagnose the design of a single Web page by visually displaying all visitor clicks during a specified time.

  2. Non-invasive stem cell tracking in hindlimb ischemia animal model using bio-orthogonal copper-free click chemistry.

    Science.gov (United States)

    Lee, Si Yeon; Lee, Sangmin; Lee, Jangwook; Yhee, Ji Young; Yoon, Hwa In; Park, Soon-Jung; Koo, Heebeom; Moon, Sung-Hwan; Lee, Hyukjin; Cho, Yong Woo; Kang, Sun Woong; Lee, Sang-Yup; Kim, Kwangmeyung

    2016-10-28

    Labeling of stem cells aims to distinguish transplanted cells from host cells, understand in vivo fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the in vivo evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated N-azidoacetyl-d-mannosamine (Ac 4 ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated in vitro. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track in vivo fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. How to Do Things with Mouse Clicks: Applying Austin's Speech Act Theory to Explain Learning in Virtual Worlds

    Science.gov (United States)

    Loke, Swee-Kin; Golding, Clinton

    2016-01-01

    This article addresses learning in desktop virtual worlds where students role play for professional education. When students role play in such virtual worlds, they can learn some knowledge and skills that are useful in the physical world. However, existing learning theories do not provide a plausible explanation of how performing non-verbal…

  4. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...... pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  5. Probability effects in anticipation investigated with online behavioural measures (mouse tracking)

    DEFF Research Database (Denmark)

    Bruhn, Pernille; Bærentsen, Klaus B.

    degrees of probability depending on context and preceding events. It is therefore of fundamental importance to investigate how knowledge of probability modulates anticipatory processes. Previous studies found effects of stimulus probability on RT and accuracy, but these are only indirect and post......-hoc behavioural measures of the anticipatory processes involved. Methods: The present study investigates how knowledge of probability affects real-time anticipatory processes. Behaviour is monitored online by tracking the computer mouse trajectory leading to a required response (mouse-click on Target......). The paradigm implements a probability structure that allows the participant to gain knowledge about the relative probability of the occurrence of two alternative events (target occurring at left or right side). Results: Preliminary results indicate that knowledge of probability affects both RT and mouse...

  6. CuAAC-Based Click Chemistry in Self-Healing Polymers.

    Science.gov (United States)

    Döhler, Diana; Michael, Philipp; Binder, Wolfgang H

    2017-10-17

    Click chemistry has emerged as a significant tool for materials science, organic chemistry, and bioscience. Based on the initial concept of Barry Sharpless in 2001, the copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC) reaction has triggered a plethora of chemical concepts for linking molecules and building blocks under ambient conditions, forming the basis for applications in autonomous cross-linking materials. Self-healing systems on the other hand are often based on mild cross-linking chemistries that are able to react either autonomously or upon an external trigger. In the ideal case, self-healing takes place efficiently at low temperatures, independent of the substrate(s) used, by forming strong and stable networks, binding to the newly generated (cracked) interfaces to restore the original material properties. The use of the CuAAC in self-healing systems, most of all the careful design of copper-based catalysts linked to additives as well as the chemical diversity of substrates, has led to an enormous potential of applications of this singular reaction. The implementation of click-based strategies in self-healing systems therefore is highly attractive, as here chemical (and physical) concepts of molecular reactivity, molecular design, and even metal catalysis are connected to aspects of materials science. In this Account, we will show how CuAAC reactions of multivalent components can be used as a tool for self-healing materials, achieving cross-linking at low temperatures (exploiting concepts of autocatalysis or internal chelation within the bulk CuAAC and systematic optimization of the efficiency of the used Cu(I) catalysts). Encapsulation strategies to separate the click components by micro- and nanoencapsulation are required in this context. Consequently, the examples reported here describe chemical concepts to realize more efficient and faster click reactions in self-healing polymeric materials. Thus, enhanced chain diffusion in (hyper

  7. Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

    2010-01-01

    Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

  8. Recensão crítica : "The click moment: seizing opportunity in an unpredictable world”

    OpenAIRE

    Sousa, Ivo Dias de

    2015-01-01

    Recensão crítica à obra de Frans Johansson, “The click moment : seizing opportunity in an unpredictable world", 2012 “The Click Moment” is one the best two book about success that I read in the last two or three years – the other one is “Smartcuts: How Hackers, Innovators, and Icons Accelerate Success” by Shane Snow. In a nutshell, what is “The Click Moment” about? Fundamentally, the book revolves around two main points: Firstly that success is in great part, the result of randomness. Seco...

  9. Hearing impairment in children with congenital cytomegalovirus (CMV) infection based on distortion product otoacoustic emissions (DPOAE) and brain evoked response audiometry stimulus click (BERA Click) examinations

    Science.gov (United States)

    Airlangga, T. J.; Mangunatmadja, I.; Prihartono, J.; Zizlavsky, S.

    2017-08-01

    Congenital cytomegalovirus (congenital CMV) infection is a leading factor of nongenetic sensorineural hearing loss in children. Hearing loss caused by CMV infection does not have a pathognomonic configuration hence further research is needed. The development of knowledge on hearing loss caused by congenital CMV infection is progressing in many countries. Due to a lack of research in the context of Indonesia, this study assesses hearing impairment in children with congenital CMV infection in Indonesia, more specifically in the Cipto Mangunkusumo Hospital. Our objective was to profile hearing impairment in children 0-5 years of age with congenital CMV infection using Distortion Product Otoacoustic Emissions (DPOAE) and Brain Evoked Response Audiometry Stimulus Click (BERA Click) examinations. This cross-sectional study was conducted in the Cipto Mangunkusum Hospital from November, 2015 to May 2016 with 27 children 0-5 years of age with congenital CMV infection. Of individual ears studied, 58.0% exhibited sensorineural hearing loss. There was a significant relationship between developmental delay and incidence of sensorineural hearing loss. Subjects with a developmental delay were 6.57 times more likely (CI 95%; 1.88-22.87) to experience sensorineural hearing loss. Congenital CMV infection has an important role in causing sensorineural hearing loss in children.

  10. A New Modular Approach to Nanoassembly: Stable and Addressable DNA Nanoconstructs via Orthogonal Click Chemistries

    KAUST Repository

    Gerrard, Simon R.

    2012-10-23

    Thermodynamic instability is a problem when assembling and purifying complex DNA nanostructures formed by hybridization alone. To address this issue, we have used photochemical fixation and orthogonal copper-free, ring-strain-promoted, click chemistry for the synthesis of dimeric, trimeric, and oligomeric modular DNA scaffolds from cyclic, double-stranded, 80-mer DNA nanoconstructs. This particular combination of orthogonal click reactions was more effective for nanoassembly than others explored. The complex nanostructures are stable to heat and denaturation agents and can therefore be purified and characterized. They are addressable in a sequence-specific manner by triplex formation, and they can be reversibly and selectively deconstructed. Nanostructures utilizing this orthogonal, chemical fixation methodology can be used as building blocks for nanomachines and functional DNA nanoarchitectures. © 2012 American Chemical Society.

  11. Synthesis and Characterization of Multiwalled Carbon Nanotubes/Poly(HEMA-co-MMA) by Utilizing Click Chemistry.

    Science.gov (United States)

    Bach, Long Giang; Cao, Xuan Thang; Islam, Md Rafiqul; Jeong, Yeon Tae; Kim, Jong Su; Lim, Kwon Taek

    2016-03-01

    The hybrid material consisting of multi walled carbon nanotubes (MWNTs) and poly(2-hydroxyethylmethacrylate-co-methylmethacrylate) [poly(HEMA-co-MMA)] was synthesized by a combination of RAFT and Click chemistry. In the primary stage, the copolymer poly(HEMA-co-MMA) was prepared by applying RAFT technique. Alkynyl side groups were incorporated onto the poly(HEMA-co-MMA) backbone by esterification reaction. Then, MWNTs-N3 was prepared by treating MWNTs with 4-azidobutylamine. The click coupling reaction between azide-functionalized MWNTs (MWNTs-N3) and the alkyne-functionalized random copolymer ((HEMA-co-MMA)-Alkyne) with the Cu(I)-catalyzed [3+2] Huisgen cycloaddition afforded the hybrid compound. The structure and properties of poly(MMA-co-HEMA)-g-MWNTs were investigated by FT-IR, EDX and TGA measurements. The copolymer brushes were observed to be immobilized onto the functionalized MWNTs by SEM and TEM analysis.

  12. Thiol-ene click chemistry: a biocompatible way for orthogonal bioconjugation of colloidal nanoparticles.

    Science.gov (United States)

    Liu, Yuan; Hou, Weijia; Sun, Hao; Cui, Cheng; Zhang, Liqin; Jiang, Ying; Wu, Yongxiang; Wang, Yanyue; Li, Juan; Sumerlin, Brent S; Liu, Qiaoling; Tan, Weihong

    2017-09-01

    Bioconjugation based on crosslinking primary amines to carboxylic acid groups has found broad applications in protein modification, drug development, and nanomaterial functionalization. However, proteins, which are made up of amino acids, typically give nonselective bioconjugation when using primary amine-based crosslinking. In order to control protein orientation and activity after conjugation, selective bioconjugation is desirable. We herein report an efficient and cysteine-selective thiol-ene click reaction-based bioconjugation strategy using colloidal nanoparticles. The resulting thiol-ene based aptamer and enzyme nanoconjugates demonstrated excellent target binding ability and enzymatic activity, respectively. Thus, thiol-ene click chemistry can provide a stable and robust crosslinker in a biocompatible manner for bioconjugation of any thiol-containing biomolecule with nanomaterials. This will open more opportunities for applications of thiol-ene reactions and functional colloidal nanoparticles in chemical biology.

  13. Click polymerization and characterization of TiO2 nanoparticles to one-dimensional nanochains

    Science.gov (United States)

    Xia, Ru; Ruan, Zheng; Zhang, Yujiao; Zhu, Hui; Cao, Ming; Chen, Peng; Miao, Jibin; Qian, Jiasheng

    2017-11-01

    In this paper, one-dimensional TiO2 nanochains were prepared by polymerization of azide-alkyne click reactions. As a first step, the TiO2 nanoparticles (NPs) were esterified with 2-bromopropionic bromide, grafted by atom transfer radical polymerization (ATRP) of styrene, followed by azidation (TiO2sbnd PSsbnd N3). Second, another part of the TiO2 NPs were modified by propargyl bromide (TiO2sbnd Ctbnd CH). By azide-alkyne click reactions between the azide and alkyne-terminated TiO2 NPs, one-dimensional TiO2 nanochains linked by polystyrene (PS) was successfully synthesized. The chemical structure of the product was characterized using FTIR, TGA and TEM.

  14. Intense ultrasonic clicks from echolocating toothed whales do not elicit anti-predator responses or debilitate the squid Loligo pealeii

    DEFF Research Database (Denmark)

    Wilson, Maria; Hanlon, R.T.; Tyack, P.L.

    2007-01-01

    an evolutionary selection pressure on cephalopods to develop a mechanism for detecting and evading sound-emitting toothed whale predators. Ultrasonic detection has evolved in some insects to avoid echolocating bats, and it can be hypothesized that cephalopods might have evolved similar ultrasound detection......Toothed whales use intense ultrasonic clicks to echolocate prey and it has been hypothesized that they also acoustically debilitate their prey with these intense sound pulses to facilitate capture. Cephalopods are an important food source for toothed whales, and there has probably been...... as an anti-predation measure. We test this hypothesis in the squid Loligo pealeii in a playback experiment using intense echolocation clicks from two squid-eating toothed whale species. Twelve squid were exposed to clicks at two repetition rates (16 and 125 clicks per second) with received sound pressure...

  15. Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

    NARCIS (Netherlands)

    van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

    2007-01-01

    Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

  16. Magnetic poly(N-propargylacrylamide) microspheres: preparation by precipitation polymerization and use in model click reactions

    Czech Academy of Sciences Publication Activity Database

    Macková, Hana; Proks, Vladimír; Horák, Daniel; Kučka, Jan; Trchová, Miroslava

    2011-01-01

    Roč. 49, č. 22 (2011), s. 4820-4829 ISSN 0887-624X R&D Projects: GA AV ČR KJB400500904; GA AV ČR(CZ) KAN401220801; GA ČR GAP503/10/0664 Institutional research plan: CEZ:AV0Z40500505 Keywords : click chemistry * magnetic * microspheres Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.919, year: 2011

  17. Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry

    DEFF Research Database (Denmark)

    Bak, Martin; Jølck, Rasmus Irming; Eliasen, Rasmus

    2016-01-01

    be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry.......2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces....

  18. Auditory Cortex Responses to Clicks and Sensory Modulation Difficulties in Children with Autism Spectrum Disorders (ASD)

    OpenAIRE

    Orekhova, Elena V.; Tsetlin, Marina M.; Butorina, Anna V.; Novikova, Svetlana I.; Gratchev, Vitaliy V.; Sokolov, Pavel A.; Elam, Mikael; Stroganova, Tatiana A.

    2012-01-01

    Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and ma...

  19. Click & seed” approach to the biomimetic modification of material surfaces

    Czech Academy of Sciences Publication Activity Database

    Proks, Vladimír; Jaroš, J.; Pop-Georgievski, Ognen; Kučka, Jan; Popelka, Štěpán; Dvořák, P.; Hampl, A.; Rypáček, František

    2012-01-01

    Roč. 12, č. 9 (2012), s. 1232-1242 ISSN 1616-5187 R&D Projects: GA AV ČR KJB400500904; GA ČR GAP108/11/1857; GA MŠk 1M0538 Institutional research plan: CEZ:AV0Z40500505 Keywords : biomimetic modifications * click chemistry * peptide radiolabeling Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.742, year: 2012

  20. Comparison of the auditory systems of heterosexuals and homosexuals: Click-evoked otoacoustic emissions

    OpenAIRE

    McFadden, Dennis; Pasanen, Edward G.

    1998-01-01

    Click-evoked otoacoustic emissions (CEOAEs) are echo-like waveforms emitted by normal-hearing cochleas in response to a brief transient. CEOAEs are known to be stronger in females than in males. In this experiment, the CEOAEs of homosexual and bisexual females were found to be intermediate to those of heterosexual females and heterosexual males. A parsimonious explanation is that the auditory systems of homosexual and bisexual females, and the brain structures responsible for their sexual ori...

  1. A New Approach for Mobile Advertising Click-Through Rate Estimation Based on Deep Belief Nets

    OpenAIRE

    Chen, Jie-Hao; Zhao, Zi-Qian; Shi, Ji-Yun; Zhao, Chong

    2017-01-01

    In recent years, with the rapid development of mobile Internet and its business applications, mobile advertising Click-Through Rate (CTR) estimation has become a hot research direction in the field of computational advertising, which is used to achieve accurate advertisement delivery for the best benefits in the three-side game between media, advertisers, and audiences. Current research on the estimation of CTR mainly uses the methods and models of machine learning, such as linear model or re...

  2. Dental malocclusion is not related to temporomandibular joint clicking: a logistic regression analysis in a patient population.

    Science.gov (United States)

    Manfredini, Daniele; Perinetti, Giuseppe; Guarda-Nardini, Luca

    2014-03-01

    To assess the association of several dental malocclusion features with temporomandibular joint (TMJ) click sounds in a population of temporomandibular disorder (TMD) patients. Four hundred forty-two TMD patients (72% female; 32.2 ± 5.7 years, range 25-44 years) were divided into a TMJ clicking and a no-TMJ clicking group, based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) assessment. Seven occlusal features were recorded for each patient: (1) posterior crossbite, (2) overbite, (3) open bite, (4) overjet, (5) mediotrusive and (6) laterotrusive interferences and (7) retruded contact position to maximum intercuspation (RCP-MI) slide length. A logistic regression model was created to estimate the association of occlusal features with TMJ clicking. The difference between the groups as for the prevalence of the various occlusal features was generally not statistically significant, with minor exceptions. Mediotrusive interferences (P  =  .015) and RCP-MI slide ≥2 mm (P  =  .001) were the two occlusal features that were associated with the probability of having TMJ clicking, even if the adjusted odds ratios for TMJ clicking were low for both variables (1.63 and 1.89, respectively). Moreover, the amount of variance in the prevalence of TMJ clicking that was predicted by the final model was as low as 4.5% (R(2)  =  0.045). Findings from the present investigation suggested that in a population of TMD patients, the contribution of dental malocclusion features to predict TMJ click sounds is minimal with no clinical relevance.

  3. Fast and flexible selection with a single switch.

    Directory of Open Access Journals (Sweden)

    Tamara Broderick

    Full Text Available Selection methods that require only a single-switch input, such as a button click or blink, are potentially useful for individuals with motor impairments, mobile technology users, and individuals wishing to transmit information securely. We present a single-switch selection method, "Nomon," that is general and efficient. Existing single-switch selection methods require selectable options to be arranged in ways that limit potential applications. By contrast, traditional operating systems, web browsers, and free-form applications (such as drawing place options at arbitrary points on the screen. Nomon, however, has the flexibility to select any point on a screen. Nomon adapts automatically to an individual's clicking ability; it allows a person who clicks precisely to make a selection quickly and allows a person who clicks imprecisely more time to make a selection without error. Nomon reaps gains in information rate by allowing the specification of beliefs (priors about option selection probabilities and by avoiding tree-based selection schemes in favor of direct (posterior inference. We have developed both a Nomon-based writing application and a drawing application. To evaluate Nomon's performance, we compared the writing application with a popular existing method for single-switch writing (row-column scanning. Novice users wrote 35% faster with the Nomon interface than with the scanning interface. An experienced user (author TB, with 10 hours practice wrote at speeds of 9.3 words per minute with Nomon, using 1.2 clicks per character and making no errors in the final text.

  4. Clicks, whistles and pulses: Passive and active signal use in dolphin communication

    Science.gov (United States)

    Herzing, Denise L.

    2014-12-01

    The search for signals out of noise is a problem not only with radio signals from the sky but in the study of animal communication. Dolphins use multiple modalities to communicate including body postures, touch, vision, and most elaborately sound. Like SETI radio signal searches, dolphin sound analysis includes the detection, recognition, analysis, and interpretation of signals. Dolphins use both passive listening and active production to communicate. Dolphins use three main types of acoustic signals: frequency modulated whistles (narrowband with harmonics), echolocation (broadband clicks) and burst pulsed sounds (packets of closely spaced broadband clicks). Dolphin sound analysis has focused on frequency-modulated whistles, yet the most commonly used signals are burst-pulsed sounds which, due to their graded and overlapping nature and bimodal inter-click interval (ICI) rates are hard to categorize. We will look at: 1) the mechanism of sound production and categories of sound types, 2) sound analysis techniques and information content, and 3) examples of lessons learned in the study of dolphin acoustics. The goal of this paper is to provide perspective on how animal communication studies might provide insight to both passive and active SETI in the larger context of searching for life signatures.

  5. LS CE-Chirp® vs. Click in the neuroaudiological diagnosis by ABR.

    Science.gov (United States)

    Cargnelutti, Michelle; Cóser, Pedro Luis; Biaggio, Eliara Pinto Vieira

    The chirp stimulus was developed seeking to counterbalance the delay of the sound wave on its journey through the cochlea, allowing the hair cells to depolarize at the same time. The result is a simultaneous stimulation providing better neural synchrony and, consequently, the recording of responses with greater amplitudes. To compare the absolute latency of waves I, III and V, the interpeak intervals I-III, III-V and I-V, amplitude values of wave V and its association with the amplitude of wave I, and the interaural difference V-V in the auditory brainstem response (ABR) using Click and LS CE-Chirp ® stimuli to determine whether the responses evoked by LS CE-Chirp ® could be applied to neuroaudiological diagnosis. Cross-sectional study with 30 normal-hearing individuals. The parameters used were: intensity of 85dBnHL, alternating polarity; 17.1 stimuli/s and 100-3000Hz filters. The absolute latencies of waves I, III and V observed with LS CE-Chirp ® and click did not show significant differences. Significantly higher amplitudes of wave V were observed with the LS CE-Chirp ® . The interaural difference between the wave V latencies between stimuli showed no significant difference. The LS CE-Chirp ® stimulus was shown to be as efficient as the click to capture ABR at high levels of stimulation, with the advantage of producing greater-amplitude V waves. Copyright © 2016. Published by Elsevier Editora Ltda.

  6. Irreversible bonding of polyimide and polydimethylsiloxane (PDMS) based on a thiol-epoxy click reaction

    International Nuclear Information System (INIS)

    Hoang, Michelle V; Chung, Hyun-Joong; Elias, Anastasia L

    2016-01-01

    Polyimide is one of the most popular substrate materials for the microfabrication of flexible electronics, while polydimethylsiloxane (PDMS) is the most widely used stretchable substrate/encapsulant material. These two polymers are essential in fabricating devices for microfluidics, bioelectronics, and the internet of things; bonding these materials together is a crucial challenge. In this work, we employ click chemistry at room temperature to irreversibly bond polyimide and PDMS through thiol-epoxy bonds using two different methods. In the first method, we functionalize the surfaces of the PDMS and polyimide substrates with mercaptosilanes and epoxysilanes, respectively, for the formation of a thiol-epoxy bond in the click reaction. In the second method, we functionalize one or both surfaces with mercaptosilane and introduce an epoxy adhesive layer between the two surfaces. When the surfaces are bonded using the epoxy adhesive without any surface functionalization, an extremely small peel strength (<0.01 N mm −1 ) is measured with a peel test, and adhesive failure occurs at the PDMS surface. With surface functionalization, however, remarkably higher peel strengths of ∼0.2 N mm −1 (method 1) and  >0.3 N mm −1 (method 2) are observed, and failure occurs by tearing of the PDMS layer. We envision that the novel processing route employing click chemistry can be utilized in various cases of stretchable and flexible device fabrication. (paper)

  7. Source parameters of echolocation clicks from wild bottlenose dolphins (Tursiops aduncus and Tursiops truncatus).

    Science.gov (United States)

    Wahlberg, Magnus; Jensen, Frants H; Soto, Natacha Aguilar; Beedholm, Kristian; Bejder, Lars; Oliveira, Cláudia; Rasmussen, Marianne; Simon, Malene; Villadsgaard, Anne; Madsen, Peter T

    2011-10-01

    The Indian Ocean and Atlantic bottlenose dolphins (Tursiops aduncus and Tursiops truncatus) are among the best studied echolocating toothed whales. However, almost all echolocation studies on bottlenose dolphins have been made with captive animals, and the echolocation signals of free-ranging animals have not been quantified. Here, biosonar source parameters from wild T. aduncus and T. truncatus were measured with linear three- and four-hydrophone arrays in four geographic locations. The two species had similar source parameters, with source levels of 177-228 dB re 1 μPa peak to peak, click durations of 8-72 μs, centroid frequencies of 33-109 kHz and rms bandwidths between 23 and 54 kHz. T. aduncus clicks had a higher frequency emphasis than T. truncatus. The transmission directionality index was up to 3 dB higher for T. aduncus (29 dB) as compared to T. truncatus (26 dB). The high directionality of T. aduncus does not appear to be only a physical consequence of a higher frequency emphasis in clicks, but may also be caused by differences in the internal properties of the sound production system. © 2011 Acoustical Society of America

  8. Dumbbells, trikes and quads: organic-inorganic hybrid nanoarchitectures based on "clicked" gold nanoparticles.

    Science.gov (United States)

    Sander, Fabian; Fluch, Ulrike; Hermes, Jens Peter; Mayor, Marcel

    2014-01-29

    The controlled assembly of gold nanoparticles in terms of the spatial arrangement and number of particles is essential for many future applications like electronic devices, sensors and labeling. Here an approach is presented to build up oligomers of mono functionalized gold nanoparticles by the use of 1,3-bipolar azide alkyne cycloaddition click chemistry. The gold nanoparticles of 1.3 nm diameter are stabilized by one dendritic thioether ligand comprising an alkyne function. Together with di-, tri- and tetra-azide linker molecules the gold nanoparticle can be covalently coupled by a wet chemical protocol. The reaction is tracked with IR and UV-vis spectroscopy and the yielded organic-inorganic hybrid structures are analyzed by transmission electron microscopy. To evaluate the success of this click chemistry reaction statistical analysis of the formed oligomers is performed. The geometric and spatial arrangements of the found oligomers match perfectly the calculated values for the used linker molecules. Dimers, trimers and tetramers could be identified after the reaction with the corresponding linker molecule. The results of this model reaction suggest that the used click chemistry protocol is working well with mono functionalized gold nanoparticles. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Modular "click" chemistry for electrochemically and photoelectrochemically active molecular interfaces to tin oxide surfaces.

    Science.gov (United States)

    Benson, Michelle C; Ruther, Rose E; Gerken, James B; Rigsby, Matthew L; Bishop, Lee M; Tan, Yizheng; Stahl, Shannon S; Hamers, Robert J

    2011-08-01

    We demonstrate the use of "click" chemistry to form electrochemically and photoelectrochemically active molecular interfaces to SnO(2) nanoparticle thin films. By using photochemical grafting to link a short-chain alcohol to the surface followed by conversion to a surface azide group, we enable use of the Cu(I)-catalyzed azide-alkyne [3 + 2] cycloaddition (CuAAC) reaction, a form of "click" chemistry, on metal oxide surfaces. Results are shown with three model compounds to test the surface chemistry and subsequent ability to achieve electrochemical and photoelectrochemical charge transfer. Surface-tethered ferrocene groups exhibit good electron-transfer characteristics with thermal rates estimated at >1000 s(-1). Time-resolved surface photovoltage measurements using a ruthenium terpyridyl coordination compound demonstrate photoelectron charge transfer on time scales of nanoseconds or less, limited by the laser pulse width. The results demonstrate that the CuAAC "click" reaction can be used to form electrochemically and photoelectrochemically active molecular interfaces to SnO(2) and other metal oxide semiconductors.

  10. Metal Free Azide-Alkyne Click Reaction: Role of Substituents and Heavy Atom Tunneling.

    Science.gov (United States)

    Karmakar, Sharmistha; Datta, Ayan

    2015-09-03

    Metal free click reactions provide an excellent noninvasive tool to modify and understand the processes in biological systems. Release of ring strain in cyclooctynes on reaction with azides on the formation of triazoles results in small activation energies for various intermolecular Huisgen reactions (1-9). Substitution of difluoro groups at the α, α' position of the cyclooctyne ring enhances the rates of cycloadditions by 10 and 20 times for methyl azide and benzyl azide respectively at room temperature. The computed rate enhancement on difluoro substitution using direct dynamical calculations using the canonical variational transition state theory (CVT/CAG) with small curvature tunneling (SCT) corrections are in excellent agreement with the experimental results. For the intramolecular click reaction (10) notwithstanding its much higher activation energy, quantum mechanical tunneling (QMT) enhances the rate of cycloaddition significantly and increases the N(14)/N(15) primary kinetic isotope effect at 298 K. QMT is shown to be rather efficient in 10 due to a thin barrier of ∼2.4 Å. The present study shows that tunneling effects can be significant for intramolecular click reactions.

  11. Click-crosslinkable and photodegradable gelatin hydrogels for cytocompatible optical cell manipulation in natural environment

    Science.gov (United States)

    Tamura, Masato; Yanagawa, Fumiki; Sugiura, Shinji; Takagi, Toshiyuki; Sumaru, Kimio; Kanamori, Toshiyuki

    2015-01-01

    This paper describes the generation of “click-crosslinkable“ and “photodegaradable“ gelatin hydrogels from the reaction between dibenzocycloctyl-terminated photoclevable tetra-arm polyethylene glycol and azide-modified gelatin. The hydrogels were formed in 30 min through the click-crosslinking reaction. The micropatterned features in the hydrogels were created by micropatterned light irradiation; the minimum resolution of micropatterning was 10-μm widths for line patterns and 20-μm diameters for circle patterns. Cells were successfully encapsulated in the hydrogels without any loss of viability across a wide concentration range of crosslinker. In contrast, an activated-ester-type photocleavable crosslinker, which we previously used to prepare photodegradable gelatin hydrogels, induced a decrease in cell viability at crosslinker concentrations greater than 1.8 mM. We also observed morphology alteration and better growth of cancer cells in the click-crosslinked photodegradable gelatin hydrogels that included matrigel than in the absence of matrigel. We also demonstrated micropatterning of the hydrogels encapsulating cells and optical cell separation. Both of the cells that remained in the non-irradiated area and the cells collected from the irradiated area maintained their viability. PMID:26450015

  12. Protein addressing on patterned microchip by coupling chitosan electrodeposition and 'electro-click' chemistry.

    Science.gov (United States)

    Shi, Xiao-Wen; Qiu, Ling; Nie, Zhen; Xiao, Ling; Payne, Gregory F; Du, Yumin

    2013-12-01

    Many applications in proteomics and lab-on-chip analysis require methods that guide proteins to assemble at surfaces with high spatial and temporal control. Electrical inputs are particularly convenient to control, and there has been considerable effort to discover simple and generic mechanisms that allow electrical inputs to trigger protein assembly on-demand. Here, we report the electroaddressing of a protein to a patterned surface by coupling two generic electroaddressing mechanisms. First, we electrodeposit the stimuli-responsive film-forming aminopolysaccharide chitosan to form a hydrogel matrix at the electrode surface. After deposition, the matrix is chemically functionalized with alkyne groups. Second, we ''electro-click' an azide-tagged protein to the functionalized matrix using electrical signals to trigger conjugation by Huisgen 1,3-dipolar cycloadditions. Specifically, a cathodic potential is applied to the matrix-coated electrode to reduce Cu(II) to Cu(I) which is required for the click reaction. Using fluorescently-labeled bovine serum albumin as our model, we demonstrate that protein conjugation can be controlled spatially and temporally. We anticipate that the coupling of polysaccharide electrodeposition and electro-click chemistry will provide a simple and generic approach to electroaddress proteins within compatible hydrogel matrices.

  13. In situ click chemistry: from small molecule discovery to synthetic antibodies

    Science.gov (United States)

    Agnew, Heather D.; Lai, Bert; Lee, Su Seong; Lim, Jaehong; Nag, Arundhati; Pitram, Suresh; Rohde, Rosemary; Heath, James R.

    2013-01-01

    Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents. PMID:22836343

  14. The energy ratio mapping algorithm: a tool to improve the energy-based detection of odontocete echolocation clicks.

    Science.gov (United States)

    Klinck, Holger; Mellinger, David K

    2011-04-01

    The energy ratio mapping algorithm (ERMA) was developed to improve the performance of energy-based detection of odontocete echolocation clicks, especially for application in environments with limited computational power and energy such as acoustic gliders. ERMA systematically evaluates many frequency bands for energy ratio-based detection of echolocation clicks produced by a target species in the presence of the species mix in a given geographic area. To evaluate the performance of ERMA, a Teager-Kaiser energy operator was applied to the series of energy ratios as derived by ERMA. A noise-adaptive threshold was then applied to the Teager-Kaiser function to identify clicks in data sets. The method was tested for detecting clicks of Blainville's beaked whales while rejecting echolocation clicks of Risso's dolphins and pilot whales. Results showed that the ERMA-based detector correctly identified 81.6% of the beaked whale clicks in an extended evaluation data set. Average false-positive detection rate was 6.3% (3.4% for Risso's dolphins and 2.9% for pilot whales).

  15. Genetic Code Expansion- and Click Chemistry-Based Site-Specific Protein Labeling for Intracellular DNA-PAINT Imaging.

    Science.gov (United States)

    Nikić-Spiegel, Ivana

    2018-01-01

    Super-resolution microscopy allows imaging of cellular structures at nanometer resolution. This comes with a demand for small labels which can be attached directly to the structures of interest. In the context of protein labeling, one way to achieve this is by using genetic code expansion (GCE) and click chemistry. With GCE, small labeling handles in the form of noncanonical amino acids (ncAAs) are site-specifically introduced into a target protein. In a subsequent step, these amino acids can be directly labeled with small organic dyes by click chemistry reactions. Click chemistry labeling can also be combined with other methods, such as DNA-PAINT in which a "clickable" oligonucleotide is first attached to the ncAA-bearing target protein and then labeled with complementary fluorescent oligonucleotides. This protocol will cover both aspects: I describe (1) how to encode ncAAs and perform intracellular click chemistry-based labeling with an improved GCE system for eukaryotic cells and (2) how to combine click chemistry-based labeling with DNA-PAINT super-resolution imaging. As an example, I show click-PAINT imaging of vimentin and low-abundance nuclear protein, nucleoporin 153.

  16. The Knockout Mouse Project

    Science.gov (United States)

    Austin, Christopher P; Battey, James F; Bradley, Allan; Bucan, Maja; Capecchi, Mario; Collins, Francis S; Dove, William F; Duyk, Geoffrey; Dymecki, Susan; Eppig, Janan T; Grieder, Franziska B; Heintz, Nathaniel; Hicks, Geoff; Insel, Thomas R; Joyner, Alexandra; Koller, Beverly H; Lloyd, K C Kent; Magnuson, Terry; Moore, Mark W; Nagy, Andras; Pollock, Jonathan D; Roses, Allen D; Sands, Arthur T; Seed, Brian; Skarnes, William C; Snoddy, Jay; Soriano, Philippe; Stewart, David J; Stewart, Francis; Stillman, Bruce; Varmus, Harold; Varticovski, Lyuba; Verma, Inder M; Vogt, Thomas F; von Melchner, Harald; Witkowski, Jan; Woychik, Richard P; Wurst, Wolfgang; Yancopoulos, George D; Young, Stephen G; Zambrowicz, Brian

    2009-01-01

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. PMID:15340423

  17. Genetically engineered mouse models of prostate cancer

    NARCIS (Netherlands)

    Nawijn, Martijn C.; Bergman, Andreas M.; van der Poel, Henk G.

    Objectives: Mouse models of prostate cancer are used to test the contribution of individual genes to the transformation process, evaluate the collaboration between multiple genetic lesions observed in a single tumour, and perform preclinical intervention studies in prostate cancer research. Methods:

  18. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  19. Spontaneous Movements of a Computer Mouse Reveal Egoism and In-group Favoritism.

    Science.gov (United States)

    Maliszewski, Norbert; Wojciechowski, Łukasz; Suszek, Hubert

    2017-01-01

    The purpose of the project was to assess whether the first spontaneous movements of a computer mouse, when making an assessment on a scale presented on the screen, may express a respondent's implicit attitudes. In Study 1, the altruistic behaviors of 66 students were assessed. The students were led to believe that the task they were performing was also being performed by another person and they were asked to distribute earnings between themselves and the partner. The participants performed the tasks under conditions with and without distractors. With the distractors, in the first few seconds spontaneous mouse movements on the scale expressed a selfish distribution of money, while later the movements gravitated toward more altruism. In Study 2, 77 Polish students evaluated a painting by a Polish/Jewish painter on a scale. They evaluated it under conditions of full or distracted cognitive abilities. Spontaneous movements of the mouse on the scale were analyzed. In addition, implicit attitudes toward both Poles and Jews were measured with the Implicit Association Test (IAT). A significant association between implicit attitudes (IAT) and spontaneous evaluation of images using a computer mouse was observed in the group with the distractor. The participants with strong implicit in-group favoritism of Poles revealed stronger preference for the Polish painter's work in the first few seconds of mouse movement. Taken together, these results suggest that spontaneous mouse movements may reveal egoism (in-group favoritism), i.e., processes that were not observed in the participants' final decisions (clicking on the scale).

  20. A dynamic duo: pairing click chemistry and postpolymerization modification to design complex surfaces.

    Science.gov (United States)

    Arnold, Rachelle M; Patton, Derek L; Popik, Vladimir V; Locklin, Jason

    2014-10-21

    Advances in key 21st century technologies such as biosensors, biomedical implants, and organic light-emitting diodes rely heavily on our ability to imagine, design, and understand spatially complex interfaces. Polymer-based thin films provide many advantages in this regard, but the direct synthesis of polymers with incompatible functional groups is extremely difficult. Using postpolymerization modification in conjunction with click chemistry can circumvent this limitation and result in multicomponent surfaces that are otherwise unattainable. The two methods used to form polymer thin films include physisorption and chemisorption. Physisorbed polymers suffer from instability because of the weak intermolecular forces between the film and the substrate, which can lead to dewetting, delamination, desorption, or displacement. Covalent immobilization of polymers to surfaces through either a "grafting to" or "grafting from" approach provides thin films that are more robust and less prone to degradation. The grafting to technique consists of adsorbing a polymer containing at least one reactive group along the backbone to form a covalent bond with a complementary surface functionality. Grafting from involves polymerization directly from the surface, in which the polymer chains deviate from their native conformation in solution and stretch away from the surface because of the high density of chains. Postpolymerization modification (PPM) is a strategy used by our groups over the past several years to immobilize two or more different chemical functionalities onto substrates that contain covalently grafted polymer films. PPM exploits monomers with reactive pendant groups that are stable under the polymerization conditions but are readily modified via covalent attachment of the desired functionality. "Click-like" reactions are the most common type of reactions used for PPM because they are orthogonal, high-yielding, and rapid. Some of these reactions include thiol-based additions

  1. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze po...

  2. Discrimination of fast click-series produced by tagged Risso's dolphins (Grampus griseus) for echolocation or communication.

    Science.gov (United States)

    Arranz, P; DeRuiter, S L; Stimpert, A K; Neves, S; Friedlaender, A S; Goldbogen, J A; Visser, F; Calambokidis, J; Southall, B L; Tyack, P L

    2016-09-15

    Early studies that categorized odontocete pulsed sounds had few means of discriminating signals used for biosonar-based foraging from those used for communication. This capability to identify the function of sounds is important for understanding and interpreting behavior; it is also essential for monitoring and mitigating potential disturbance from human activities. Archival tags were placed on free-ranging Grampus griseus to quantify and discriminate between pulsed sounds used for echolocation-based foraging and those used for communication. Two types of rapid click-series pulsed sounds, buzzes and burst pulses, were identified as produced by the tagged dolphins and classified using a Gaussian mixture model based on their duration, association with jerk (i.e. rapid change of acceleration) and temporal association with click trains. Buzzes followed regular echolocation clicks and coincided with a strong jerk signal from accelerometers on the tag. They consisted of series averaging 359±210 clicks (mean±s.d.) with an increasing repetition rate and relatively low amplitude. Burst pulses consisted of relatively short click series averaging 45±54 clicks with decreasing repetition rate and longer inter-click interval that were less likely to be associated with regular echolocation and the jerk signal. These results suggest that the longer, relatively lower amplitude, jerk-associated buzzes are used in this species to capture prey, mostly during the bottom phase of foraging dives, as seen in other odontocetes. In contrast, the shorter, isolated burst pulses that are generally emitted by the dolphins while at or near the surface are used outside of a direct, known foraging context. © 2016. Published by The Company of Biologists Ltd.

  3. Auditory brainstem responses for click and CE-chirp stimuli in individuals with and without occupational noise exposure

    Directory of Open Access Journals (Sweden)

    Zeena Venkatacheluvaiah Pushpalatha

    2016-01-01

    Full Text Available Introduction: Encoding of CE-chirp and click stimuli in auditory system was studied using auditory brainstem responses (ABRs among individuals with and without noise exposure. Materials and Methods: The study consisted of two groups. Group 1 (experimental group consisted of 20 (40 ears individuals exposed to occupational noise with hearing thresholds within 25 dB HL. They were further divided into three subgroups based on duration of noise exposure (0–5 years of exposure-T1, 5–10 years of exposure-T2, and >10 years of exposure-T3. Group 2 (control group consisted of 20 individuals (40 ears. Absolute latency and amplitude of waves I, III, and V were compared between the two groups for both click and CE-chirp stimuli. T1, T2, and T3 groups were compared for the same parameters to see the effect of noise exposure duration on CE-chirp and click ABR. Result: In Click ABR, while both the parameters for wave III were significantly poorer for the experimental group, wave V showed a significant decline in terms of amplitude only. There was no significant difference obtained for any of the parameters for wave I. In CE-Chirp ABR, the latencies for all three waves were significantly prolonged in the experimental group. However, there was a significant decrease in terms of amplitude in only wave V for the same group. Discussion: Compared to click evoked ABR, CE-Chirp ABR was found to be more sensitive in comparison of latency parameters in individuals with occupational noise exposure. Monitoring of early pathological changes at the brainstem level can be studied effectively by using CE-Chirp stimulus in comparison to click stimulus. Conclusion: This study indicates that ABR’s obtained with CE-chirp stimuli serves as an effective tool to identify the early pathological changes due to occupational noise exposure when compared to click evoked ABR.

  4. The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, (99m)Tc) radiopharmaceuticals.

    Science.gov (United States)

    Ganguly, Tanushree; Kasten, Benjamin B; Bučar, Dejan-Krešimir; MacGillivray, Leonard R; Berkman, Clifford E; Benny, Paul D

    2011-12-28

    Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)(3) (M = Re, (99m)Tc) based radiopharmaceuticals. Both 'click, then chelate' and 'prelabel, then click' synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy. This journal is © The Royal Society of Chemistry 2011

  5. Modification of chemical and conformational properties of natural organic matter by click chemistry as revealed by ESI-Orbitrap mass spectrometry.

    Science.gov (United States)

    Nebbioso, Antonio; Piccolo, Alessandro

    2015-11-01

    A click reaction is reported here for the first time as a useful technique to control the conformational stability of natural organic matter (NOM) suprastructures. Click conjugates were successfully formed between a previously butynylated NOM hydrophobic fraction and a hydrophilic polyethylene glycol (PEG)-amino chain. The click products were shown by size exclusion chromatography (HPSEC) hyphenated with Orbitrap mass spectrometry (MS) in electrospray ionization (ESI) (+), while precursors were visible in ESI (-). Despite their increase in molecular weight, HPSEC elution of click conjugates occurred after that of precursors, thus showing their departure from the NOM supramolecular association. This indicates that the click-conjugated NOM molecules were varied in their hydrophilic and cationic character and lost the capacity to accommodate in the original hydrophobic suprastructures. The most abundant product had the C16H30O5N4 formula, a click conjugate of butanoic acid, while other products were short-chained (C4-C8) linear unsaturated and hydroxylated carboxylic acids. Tandem MS revealed formation of triazole rings in clicked conjugates and their two fragmentations at the ester and the C-N alkyl-aryl bonds. The behavior of NOM molecules modified by click chemistry confirms that hydrophobicity and ionic charge of humic molecules play a pivotal role in stabilizing intermolecular forces in NOM. Moreover, the versatility of the click reaction may become useful to decorate NOM molecules with a variety of substrates, in order to alter NOM conformational and chemical properties and diversify its applications in the environment.

  6. Evaluating and Optimizing Online Advertising: Forget the Click, but There Are Good Proxies.

    Science.gov (United States)

    Dalessandro, Brian; Hook, Rod; Perlich, Claudia; Provost, Foster

    2015-06-01

    Online systems promise to improve advertisement targeting via the massive and detailed data available. However, there often is too few data on exactly the outcome of interest, such as purchases, for accurate campaign evaluation and optimization (due to low conversion rates, cold start periods, lack of instrumentation of offline purchases, and long purchase cycles). This paper presents a detailed treatment of proxy modeling, which is based on the identification of a suitable alternative (proxy) target variable when data on the true objective is in short supply (or even completely nonexistent). The paper has a two-fold contribution. First, the potential of proxy modeling is demonstrated clearly, based on a massive-scale experiment across 58 real online advertising campaigns. Second, we assess the value of different specific proxies for evaluating and optimizing online display advertising, showing striking results. The results include bad news and good news. The most commonly cited and used proxy is a click on an ad. The bad news is that across a large number of campaigns, clicks are not good proxies for evaluation or for optimization: clickers do not resemble buyers. The good news is that an alternative sort of proxy performs remarkably well: observed visits to the brand's website. Specifically, predictive models built based on brand site visits-which are much more common than purchases-do a remarkably good job of predicting which browsers will make a purchase. The practical bottom line: evaluating and optimizing campaigns using clicks seems wrongheaded; however, there is an easy and attractive alternative-use a well-chosen site-visit proxy instead.

  7. Hydrophobic Coatings by Thiol-Ene Click Functionalization of Silsesquioxanes with Tunable Architecture.

    Science.gov (United States)

    Dirè, Sandra; Bottone, Davide; Callone, Emanuela; Maniglio, Devid; Génois, Isabelle; Ribot, François

    2017-08-08

    The hydrolysis-condensation of trialkoxysilanes under strictly controlled conditions allows the production of silsesquioxanes (SSQs) with tunable size and architecture ranging from ladder to cage-like structures. These nano-objects can serve as building blocks for the preparation of hybrid organic/inorganic materials with selected properties. The SSQs growth can be tuned by simply controlling the reaction duration in the in situ water production route (ISWP), where the kinetics of the esterification reaction between carboxylic acids and alcohols rules out the extent of organosilane hydrolysis-condensation. Tunable SSQs with thiol functionalities (SH-NBBs) are suitable for further modification by exploiting the simple thiol-ene click reaction, thus allowing for modifying the wettability properties of derived coatings. In this paper, coatings were prepared from SH-NBBs with different architecture onto cotton fabrics and paper, and further functionalized with long alkyl chains by means of initiator-free UV-induced thiol-ene coupling with 1-decene (C10) and 1-tetradecene (C14). The coatings appeared to homogeneously cover the natural fibers and imparted a multi-scale roughness that was not affected by the click functionalization step. The two-step functionalization of cotton and paper warrants a stable highly hydrophobic character to the surface of natural materials that, in perspective, suggests a possible application in filtration devices for oil-water separation. Furthermore, the purification of SH-NBBs from ISWP by-products was possible during the coating process, and this step allowed for the fast, initiator-free, click-coupling of purified NBBs with C10 and C14 in solution with a nearly quantitative yield. Therefore, this approach is an alternative route to get sol-gel-derived, ladder-like, and cage-like SSQs functionalized with long alkyl chains.

  8. Gyroscope-Driven Mouse Pointer with an EMOTIV® EEG Headset and Data Analysis Based on Empirical Mode Decomposition

    Science.gov (United States)

    Rosas-Cholula, Gerardo; Ramirez-Cortes, Juan Manuel; Alarcon-Aquino, Vicente; Gomez-Gil, Pilar; Rangel-Magdaleno, Jose de Jesus; Reyes-Garcia, Carlos

    2013-01-01

    This paper presents a project on the development of a cursor control emulating the typical operations of a computer-mouse, using gyroscope and eye-blinking electromyographic signals which are obtained through a commercial 16-electrode wireless headset, recently released by Emotiv. The cursor position is controlled using information from a gyroscope included in the headset. The clicks are generated through the user's blinking with an adequate detection procedure based on the spectral-like technique called Empirical Mode Decomposition (EMD). EMD is proposed as a simple and quick computational tool, yet effective, aimed to artifact reduction from head movements as well as a method to detect blinking signals for mouse control. Kalman filter is used as state estimator for mouse position control and jitter removal. The detection rate obtained in average was 94.9%. Experimental setup and some obtained results are presented. PMID:23948873

  9. VIRTUAL MOUSE MENGGUNAKAN ALGORITMA HAARCASCADE DAN HOUGH TRANSFORM SEBAGAI MEDIA INTERAKSI MANUSIA DENGAN KOMPUTER BAGI PENYANDANG DISABILITAS

    Directory of Open Access Journals (Sweden)

    Fandy Setyo Utomo

    2015-02-01

    Full Text Available Komputer adalah salah satu media untuk pencarian informasi. Dalam mengoperasikan komputer seseorang harus dapat menggerakkan pointer pada layar komputer dengan mouse. Hal ini menjadi sulit untuk dilakukan bagi penderita disabilitas gerak tangan. Penelitian yang dilakukan bertujuan untuk membuat aplikasi virtual mouse yang dapat digunakan sebagai media interaksi antara penyandang disabilitas dengan komputer. Proses penjejakan wajah untuk mengendalikan pointer menggunakan algoritma Haarcascade Classifier, sedangkan untuk operasi click event mouse menggunakan deteksi kedipan mata dengan algoritma Hough Transform. Penelitian dilakukan dalam beberapa tahap yaitu melakukan analisis kebutuhan fungsional, membuat desain aplikasi, implementasi, dan pengujian aplikasi. Pengujian dilakukan terhadap kecepatan aplikasi dalam mendeteksi wajah berdasarkan sudut kemiringan wajah tertentu. Selain itu, pengujian dilakukan pula terhadap kecepatan aplikasi dalam mendeteksi iris mata berdasarkan nilai threshold tertentu. Berdasarkan hasil pengujian aplikasi dapat disimpulkan bahwa nilai pergeseran memiliki toleransi 10o hingga 25o untuk pendeteksian wajah, sedangkan nilai threshold yang baik untuk pendeteksian iris mata berkisar antara 90 sampai dengan 100.

  10. Gyroscope-driven mouse pointer with an EMOTIV® EEG headset and data analysis based on Empirical Mode Decomposition.

    Science.gov (United States)

    Rosas-Cholula, Gerardo; Ramirez-Cortes, Juan Manuel; Alarcon-Aquino, Vicente; Gomez-Gil, Pilar; Rangel-Magdaleno, Jose de Jesus; Reyes-Garcia, Carlos

    2013-08-14

    This paper presents a project on the development of a cursor control emulating the typical operations of a computer-mouse, using gyroscope and eye-blinking electromyographic signals which are obtained through a commercial 16-electrode wireless headset, recently released by Emotiv. The cursor position is controlled using information from a gyroscope included in the headset. The clicks are generated through the user's blinking with an adequate detection procedure based on the spectral-like technique called Empirical Mode Decomposition (EMD). EMD is proposed as a simple and quick computational tool, yet effective, aimed to artifact reduction from head movements as well as a method to detect blinking signals for mouse control. Kalman filter is used as state estimator for mouse position control and jitter removal. The detection rate obtained in average was 94.9%. Experimental setup and some obtained results are presented.

  11. Gyroscope-Driven Mouse Pointer with an EMOTIV® EEG Headset and Data Analysis Based on Empirical Mode Decomposition

    Directory of Open Access Journals (Sweden)

    Carlos Reyes-Garcia

    2013-08-01

    Full Text Available This paper presents a project on the development of a cursor control emulating the typical operations of a computer-mouse, using gyroscope and eye-blinking electromyographic signals which are obtained through a commercial 16-electrode wireless headset, recently released by Emotiv. The cursor position is controlled using information from a gyroscope included in the headset. The clicks are generated through the user’s blinking with an adequate detection procedure based on the spectral-like technique called Empirical Mode Decomposition (EMD. EMD is proposed as a simple and quick computational tool, yet effective, aimed to artifact reduction from head movements as well as a method to detect blinking signals for mouse control. Kalman filter is used as state estimator for mouse position control and jitter removal. The detection rate obtained in average was 94.9%. Experimental setup and some obtained results are presented.

  12. The Source Parameters of Echolocation Clicks from Captive and Free-Ranging Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaeorientalis).

    Science.gov (United States)

    Fang, Liang; Wang, Ding; Li, Yongtao; Cheng, Zhaolong; Pine, Matthew K; Wang, Kexiong; Li, Songhai

    2015-01-01

    The clicks of Yangtze finless porpoises (Neophocaena asiaeorientalis asiaeorientalis) from 7 individuals in the tank of Baiji aquarium, 2 individuals in a netted pen at Shishou Tian-e-zhou Reserve and 4 free-ranging individuals at Tianxingzhou were recorded using a broadband digital recording system with four element hydrophones. The peak-to-peak apparent source level (ASL_pp) of clicks from individuals at the Baiji aquarium was 167 dB re 1 μPa with mean center frequency of 133 kHz, -3dB bandwidth of 18 kHz and -10 dB duration of 58 μs. The ASL_pp of clicks from individuals at the Shishou Tian-e-zhou Reserve was 180 dB re 1 μPa with mean center frequency of 128 kHz, -3dB bandwidth of 20 kHz and -10 dB duration of 39 μs. The ASL_pp of clicks from individuals at Tianxingzhou was 176 dB re 1 μPa with mean center frequency of 129 kHz, -3dB bandwidth of 15 kHz and -10 dB duration of 48 μs. Differences between the source parameters of clicks among the three groups of finless porpoises suggest these animals adapt to their echolocation signals depending on their surroundings.

  13. Super-resolution optical DNA Mapping via DNA methyltransferase-directed click chemistry

    DEFF Research Database (Denmark)

    Vranken, Charlotte; Deen, Jochem; Dirix, Lieve

    2014-01-01

    to the DNA. We achieve a labelling efficiency of ∼70% with an average labelling density approaching one site every 500 bp. Such labelling density bridges the gap between the output of a typical DNA sequencing experiment and the long-range information derived from traditional optical DNA mapping. We lay...... the foundations for a wider-scale adoption of DNA mapping by screening 11 methyltransferases for their ability to direct sequence-specific DNA transalkylation; the first step of the DNA labelling process and by optimizing reaction conditions for fluorophore coupling via a click reaction. Three of 11 enzymes...

  14. Click grafting of seaweed polysaccharides onto PVC surfaces using an ionic liquid as solvent and catalyst.

    Science.gov (United States)

    Bigot, Sandra; Louarn, Guy; Kébir, Nasreddine; Burel, Fabrice

    2013-11-06

    Seaweed antibacterial polysaccharides were grafted onto poly(vinylchloride) (PVC) surfaces using an original click chemistry pathway. PVC isothiocyanate surfaces (PVC-NCS) were first prepared by nucleophilic substitution of the chloride groups by isothiocyanate groups in DMSO/water medium. Then, unmodified Ulvan, Fucan, Laminarin or Zosterin was directly grafted onto the PVC-NCS surface using 1-ethyl-3-methyl imidazolium phosphate, an ionic liquid, as solvent and catalyst. To attest the grafting effectiveness, the new PVC surfaces were well characterized by AFM, XPS and contact angle measurements. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Click chemistry based biomolecular conjugation monitoring using surface-enhanced Raman spectroscopy mapping

    DEFF Research Database (Denmark)

    Palla, Mirko; Kumar, Shiv; Li, Zengmin

    2016-01-01

    We describe here a novel surface-enhanced Raman spectroscopy (SERS) based technique for monitoring the conjugation of small molecules by the well-known click reaction between an alkyne and azido moiety on the partner molecules. The monitoring principle is based on the loss of the characteristic...... such as bioconjugation, material science or drug discovery. Additionally, as an attractive advantage of this technique, no significant background signal is expected during the measurements, since these signals reside in a Raman silent region of 2000–2300 cm−1, where virtually all biological molecules are transparent....

  16. Fast, Cell-compatible Click Chemistry with Copper-chelating Azides for Biomolecular Labeling**

    Science.gov (United States)

    Uttamapinant, Chayasith; Tangpeerachaikul, Anupong; Grecian, Scott; Clarke, Scott; Singh, Upinder; Slade, Peter; Gee, Kyle R.; Ting, Alice. Y.

    2012-01-01

    We report that azides capable of copper-chelation undergo much faster “Click chemistry” (copper-accelerated azide-alkyne cycloaddition, or CuAAC) than nonchelating azides under a variety of biocompatible conditions. This kinetic enhancement allowed us to perform site-specific protein labeling on the surface of living cells with only 10–40 µM CuI/II and much higher signal than could be obtained using the best previously-reported live-cell compatible CuAAC labeling conditions. Detection sensitivity was also increased for CuAAC detection of alkyne-modified proteins and RNA labeled by metabolic feeding. PMID:22555882

  17. Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

    DEFF Research Database (Denmark)

    Ebbesen, Morten F; Schaffert, D.H.; Crowley, Michael L

    2013-01-01

    This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well-defined, reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N-(3......-azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA-co-AzMA) copolymers with high control of molecular weight (∼10–54 kDa) and polydispersity (≤1.06). The utility of the side-chain azide functionality by Cu(I)-catalyzed azide...

  18. Towards enhancing click-draw based graphical passwords using multi-touch behaviours on smartphones

    DEFF Research Database (Denmark)

    Meng, Weizhi; Li, Wenjuan; Kwok, Lam For

    2017-01-01

    Graphical passwords (GPs) are recognised as one of the potential alternatives in addressing the limitations in conventional text-based password authentication. With the rapid development of mobile devices (i.e., the increase of computing power), GP-based systems have already been implemented...... and its impact on graphical password creation is an important topic in the literature. In this paper, our interest is to investigate the influence of multi-touch behaviours on users’ habit in creating graphical passwords, especially on click-draw based GPs (shortly CD-GPS) on mobile devices...

  19. Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

    DEFF Research Database (Denmark)

    Nåbo, Lina J.; Madsen, Charlotte S.; Jensen, Knud J.

    2015-01-01

    Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...

  20. Quantitation of Protein Translation Rate In Vivo with Bioorthogonal Click-Chemistry.

    Science.gov (United States)

    Belda-Palazón, Borja; Ferrando, Alejandro; Farràs, Rosa

    2016-01-01

    The development of novel bioorthogonal reactives that can be used to tag biomolecules in vivo has revolutionized the studies of cellular and molecular biology. Among those novel reactive substances, amino acid analogs can be used to label nascent proteins, thus opening new avenues for measuring protein translation rates in vivo with a limited manipulation of the sample. Here, we describe the use of Click-chemistry to tag and separate newly synthesized proteins in mammalian cells that can be used, coupled with western analysis, to estimate the translation rate of any protein of interest.

  1. The digital laser: on-demand laser modes with the click of a button

    CSIR Research Space (South Africa)

    Forbes, A

    2014-02-01

    Full Text Available stream_source_info Forbes_2014_ABSTRACT ONLY.pdf.txt stream_content_type text/plain stream_size 729 Content-Encoding UTF-8 stream_name Forbes_2014_ABSTRACT ONLY.pdf.txt Content-Type text/plain; charset=UTF-8 The digital... laser: on-demand laser modes with the click of a button Forbes A, Ngcobo S, Burger L and Litvin IA ABSTRACT In this paper we will outline our recent advances in all-digital control of light. Importantly, we will outline how to create a so...

  2. One-pot synthesis of Au@SiO2 catalysts: A click chemistry approach

    KAUST Repository

    Solovyeva, Vera A.

    2014-10-13

    Using the copper-catalyzed azide-alkyne cycloaddition "click" reaction, a library of triazole amphiphiles with a variety of functional polar "heads" and hydrophobic or superhydrophobic "tails" was synthesized. The amphiphiles were evaluated for their ability to stabilize small Au nanoparticles, and, at the same time, serve as templates for nanocasting porous SiO2. One of the Au@SiO2 materials thus prepared was found to be a highly active catalyst for the Au nanoparticle-catalyzed regioselective hydroamination of alkynes.

  3. Synthesis of Donor-Acceptor Conjugated Polymers by "CLICK" Polymerization for OPV applications

    DEFF Research Database (Denmark)

    Brandt, Rasmus Guldbæk; Yu, Donghong

    The intent of this study was to utilize the Copper(I)-catalyzed Azide Alkyne Cycloaddition (CuAAC) as a polymerization technique (“Click” Polymerization) for synthesizing novel π-conjugated low band gap polymers for organic photovoltaic applications (OPV). The chosen approach was to synthesize...... an alternating electron donating (donor, D) and electron withdrawing (acceptor, A) co-polymer. The chosen monomers were well known units, and the novelty lies in using the monomer units with the click methodology. An insoluble alternating copolymer consisting of 2,7-diazido-9,9-dioctyl-9Hflourene and 1...

  4. An Efficient and Straightforward Method for Radiolabeling of Nanoparticles with {sup 64}Cu via Click Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Eun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Kwangmeyung [Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Park, Sang Hyun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Department of Radiobiotechnology and Applied Radioisotope Science, Korea University of Science and Technology, Deajeon 305-350 (Korea, Republic of)

    2015-07-01

    Recently, nanoparticles have received a great deal of interest in diagnosis and therapy applications. Since nanoparticles possess intrinsic features that are often required for a drug delivery system and diagnosis, they have potential to be used as platforms for integrating imaging and therapeutic functions, simultaneously. Intrinsic issues that are associated with theranostic nanoparticles, particularly in cancer treatment, include an efficient and straightforward radiolabeling method for understanding the in vivo biodistribution of nanoparticles to reach the tumor region, and monitoring therapeutic responses. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled nanoparticles with {sup 64}Cu via a strain-promoted azide, i.e., an alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated into glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the pre-radiolabeled alkyne complex with {sup 64}Cu radionuclide. Following incubation with the {sup 64}Cu-radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-{sup 64}Cu with high specific activity, 18.5 GBq/μ mol), the azide-functionalized CNPs were radiolabeled successfully with {sup 64}Cu, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper-free click chemistry was accomplished within 30 min, with great efficiency in aqueous conditions. After {sup 64}Cu-CNPs were intravenously administered to tumor-bearing mice, the real time, in vivo biodistribution and tumor-targeting ability of {sup 64}Cu-CNPs were quantitatively evaluated by micro-PET images of tumor-bearing mice. These results

  5. Synthesis of Janus nanoparticles via a combination of the reversible click reaction and "grafting to" strategies.

    Science.gov (United States)

    Li, Junting; Wang, Lei; Benicewicz, Brian C

    2013-09-17

    A critical challenge in nanoparticle functionalization has been the preparation of polymer-grafted asymmetric (Janus) nanoparticles (diameter reversible click reaction and "grafting to" strategies to synthesize such nanoparticles. Mechanochemistry was used in a protection-deprotection process to separate nanoparticles cleanly that were anchored to larger particles, and the recovered azide-functionalized larger particles could be recycled as face-blocking moieties. With this combination of strategies, we prepared 15 nm silica nanoparticles that were partially functionalized with poly(methyl methacrylate). Additionally, the unique self-assembly behaviors of the resultant Janus nanoparticles were investigated in different solvents at different concentrations.

  6. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  7. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  8. Recent Trends in Bioorthogonal Click-Radiolabeling Reactions Using Fluorine-18

    Directory of Open Access Journals (Sweden)

    Doreen Pietzsch

    2013-07-01

    Full Text Available The increasing application of positron emission tomography (PET in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile bioorthogonal conjugation techniques especially for the radiolabeling of biologically active high molecular weight compounds like peptides, proteins or antibodies. Taking into consideration that the introduction of fluorine-18 (t1/2 = 109.8 min proceeds under harsh conditions, radiolabeling of these biologically active molecules represents an outstanding challenge and is of enormous interest. Special attention has to be paid to the method of 18F-introduction. It should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. For these reasons and due to the high number of functional groups found in these compounds, a specific labeling procedure has to be developed for every bioactive macromolecule. Bioorthogonal strategies including the Cu-assisted Huisgen cycloaddition and its copper-free click variant, both Staudinger Ligations or the tetrazine-click reaction have been successfully applied and represent valuable alternatives for the selective introduction of fluorine-18 to overcome the afore mentioned obstacles. This comprehensive review deals with the progress and illustrates the latest developments in the field of bioorthogonal labeling with the focus on the preparation of radiofluorinated building blocks and tracers for molecular imaging.

  9. Topology independent comparison of RNA 3D structures using the CLICK algorithm.

    Science.gov (United States)

    Nguyen, Minh N; Sim, Adelene Y L; Wan, Yue; Madhusudhan, M S; Verma, Chandra

    2017-01-09

    RNA molecules are attractive therapeutic targets because non-coding RNA molecules have increasingly been found to play key regulatory roles in the cell. Comparing and classifying RNA 3D structures yields unique insights into RNA evolution and function. With the rapid increase in the number of atomic-resolution RNA structures, it is crucial to have effective tools to classify RNA structures and to investigate them for structural similarities at different resolutions. We previously developed the algorithm CLICK to superimpose a pair of protein 3D structures by clique matching and 3D least squares fitting. In this study, we extend and optimize the CLICK algorithm to superimpose pairs of RNA 3D structures and RNA-protein complexes, independent of the associated topologies. Benchmarking Rclick on four different datasets showed that it is either comparable to or better than other structural alignment methods in terms of the extent of structural overlaps. Rclick also recognizes conformational changes between RNA structures and produces complementary alignments to maximize the extent of detectable similarity. Applying Rclick to study Ribonuclease III protein correctly aligned the RNA binding sites of RNAse III with its substrate. Rclick can be further extended to identify ligand-binding pockets in RNA. A web server is developed at http://mspc.bii.a-star.edu.sg/minhn/rclick.html. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Music, clicks, and their imaginations favor differently the event-based timing component for rhythmic movements.

    Science.gov (United States)

    Bravi, Riccardo; Quarta, Eros; Del Tongo, Claudia; Carbonaro, Nicola; Tognetti, Alessandro; Minciacchi, Diego

    2015-06-01

    The involvement or noninvolvement of a clock-like neural process, an effector-independent representation of the time intervals to produce, is described as the essential difference between event-based and emergent timing. In a previous work (Bravi et al. in Exp Brain Res 232:1663-1675, 2014a. doi: 10.1007/s00221-014-3845-9 ), we studied repetitive isochronous wrist's flexion-extensions (IWFEs), performed while minimizing visual and tactile information, to clarify whether non-temporal and temporal characteristics of paced auditory stimuli affect the precision and accuracy of the rhythmic motor performance. Here, with the inclusion of new recordings, we expand the examination of the dataset described in our previous study to investigate whether simple and complex paced auditory stimuli (clicks and music) and their imaginations influence in a different way the timing mechanisms for repetitive IWFEs. Sets of IWFEs were analyzed by the windowed (lag one) autocorrelation-wγ(1), a statistical method recently introduced for the distinction between event-based and emergent timing. Our findings provide evidence that paced auditory information and its imagination favor the engagement of a clock-like neural process, and specifically that music, unlike clicks, lacks the power to elicit event-based timing, not counteracting the natural shift of wγ(1) toward positive values as frequency of movements increase.

  11. Sequential nucleophilic substitutions permit orthogonal click functionalization of multicomponent PEG brushes.

    Science.gov (United States)

    Sha, Jin; Lippmann, Ethan S; McNulty, Jason; Ma, Yulu; Ashton, Randolph S

    2013-09-09

    Multicomponent poly(ethylene glycol) (PEG) brushes (i.e., ≥ 2 adjacent PEG brushes) can be used to engineer culture substrates with microscale, nonfouling regions decorated with covalently immobilized ligands that mediate biospecific interactions. However, synthesizing such brushes with orthogonal immobilization chemistries to permit differential biofunctionalization is nontrivial and often requires synthesis of PEG-co-polymers. To simplify synthesis and enhance the versatility of such substrates, we developed a protocol for generating orthogonal click-functionalized multicomponent PEG brushes using sequential nucleophilic substitutions by sodium azide, ethanolamine, and propargylamine. The novel application of propargylamine-mediated substitution functionalizes PEG brushes with acetylene groups, and for the first time, ethanolamine-mediated substitution is shown to be sufficient for passivating the "living" polymer chain ends between brush synthesis steps. Thus, our multicomponent PEG brushes present dual orthogonal chemistries (i.e., azido and acetylene groups) for ligand immobilization via versatile copper-free click reactions, which are useful for in situ surface modifications during cell culture.

  12. Click chemistry approach to conventional vegetable tanning process: accelerated method with improved organoleptic properties.

    Science.gov (United States)

    Krishnamoorthy, Ganesan; Ramamurthy, Govindaswamy; Sadulla, Sayeed; Sastry, Thotapalli Parvathaleswara; Mandal, Asit Baran

    2014-09-01

    Click chemistry approaches are tailored to generate molecular building blocks quickly and reliably by joining small units together selectively and covalently, stably and irreversibly. The vegetable tannins such as hydrolyzable and condensed tannins are capable to produce rather stable radicals or inhibit the progress of radicals and are prone to oxidations such as photo and auto-oxidation, and their anti-oxidant nature is well known. A lot remains to be done to understand the extent of the variation of leather stability, color variation (lightening and darkening reaction of leather), and poor resistance to water uptake for prolonged periods. In the present study, we have reported click chemistry approaches to accelerated vegetable tanning processes based on periodates catalyzed formation of oxidized hydrolysable and condensed tannins for high exhaustion with improved properties. The distribution of oxidized vegetable tannin, the thermal stability such as shrinkage temperature (T s) and denaturation temperature (T d), resistance to collagenolytic activities, and organoleptic properties of tanned leather as well as the evaluations of eco-friendly characteristics were investigated. Scanning electron microscopic analysis indicates the cross section of tightness of the leather. Differential scanning calorimetric analysis shows that the T d of leather is more than that of vegetable tanned or equal to aldehyde tanned one. The leathers exhibited fullness, softness, good color, and general appearance when compared to non-oxidized vegetable tannin. The developed process benefits from significant reduction in total solids and better biodegradability in the effluent, compared to non-oxidized vegetable tannins.

  13. A versatile method for functionalization and grafting of 2-hydroxyethyl cellulose (HEC) via Click chemistry.

    Science.gov (United States)

    Eissa, Ahmed M; Khosravi, Ezat; Cimecioglu, A Levent

    2012-10-01

    This article describes a versatile method for the modification of 2-hydroxyethyl cellulose (HEC) involving azide-alkyne cycloaddition reaction to impart neutral (ester) and ionic (carboxylic acid and 1(ry) amine) functionalities. The synthetic approach involved, first the introduction of the azide functionality to HEC and then followed by its cycloaddition reaction with several alkyne terminated compounds: namely ethyl propiolate, 5-hexynoic acid and propargyl amine. Sequential Click reactions were also demonstrated to be feasible by the successful synthesis of polydimethylsiloxane (PDMS) grafted HEC containing neutral (ester) and ionic (carboxylic acid and 1(ry) amine) functionalities. The Click chemistry was then further utilized similarly to graft poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) segments to HEC to access its hydrophobic and hydrophilic analogs, respectively. AFM analysis revealed that while HEC itself formed uniform oval features, the PLA grafted HEC exhibited a brushlike architecture. The formation of these brushlike structures suggested that the HEC backbone exhibits an extended conformation with the side chains stretched out. The resulting polymeric materials were characterized by solution and solid state (13)C NMR and FTIR spectroscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Assembly of a biocompatible triazole-linked gene by one-pot click-DNA ligation

    Science.gov (United States)

    Kukwikila, Mikiembo; Gale, Nittaya; El-Sagheer, Afaf H.; Brown, Tom; Tavassoli, Ali

    2017-11-01

    The chemical synthesis of oligonucleotides and their enzyme-mediated assembly into genes and genomes has significantly advanced multiple scientific disciplines. However, these approaches are not without their shortcomings; enzymatic amplification and ligation of oligonucleotides into genes and genomes makes automation challenging, and site-specific incorporation of epigenetic information and/or modified bases into large constructs is not feasible. Here we present a fully chemical one-pot method for the assembly of oligonucleotides into a gene by click-DNA ligation. We synthesize the 335 base-pair gene that encodes the green fluorescent protein iLOV from ten functionalized oligonucleotides that contain 5ʹ-azide and 3ʹ-alkyne units. The resulting click-linked iLOV gene contains eight triazoles at the sites of chemical ligation, and yet is fully biocompatible; it is replicated by DNA polymerases in vitro and encodes a functional iLOV protein in Escherichia coli. We demonstrate the power and potential of our one-pot gene-assembly method by preparing an epigenetically modified variant of the iLOV gene.

  15. An Organometallic Cu20Nanocluster: Synthesis, Characterization, Immobilization on Silica, and "Click" Chemistry.

    Science.gov (United States)

    Cook, Andrew W; Jones, Zachary R; Wu, Guang; Scott, Susannah L; Hayton, Trevor W

    2018-01-10

    The development of atomically precise nanoclusters (APNCs) protected by organometallic ligands, such as acetylides and hydrides, is an emerging area of nanoscience. In principle, these organometallic APNCs should not require harsh pretreatment for activation toward catalysis, such as calcination, which can lead to sintering. Herein, we report the synthesis of the mixed-valent organometallic copper APNC, [Cu 20 (CCPh) 12 (OAc) 6 )] (1), via reduction of Cu(OAc) with Ph 2 SiH 2 in the presence of phenylacetylene. This cluster is a rare example of a two-electron copper superatom, and the first to feature a tetrahedral [Cu 4 ] 2+ core, which is a unique "kernel" for a Cu-only superatom. Complex 1 can be readily immobilized on dry, partially dehydroxylated silica, a process that cleanly results in release of 1 equiv of phenylacetylene per Cu 20 cluster. Cu K-edge EXAFS confirms that the immobilized cluster 2 is structurally similar to 1. In addition, both 1 and 2 are effective catalysts for [3+2] cycloaddition reactions between alkynes and azides (i.e., "Click" reactions) at room temperature. Significantly, neither cluster requires any pretreatment for activation toward catalysis. Moreover, EXAFS analysis of 2 after catalysis demonstrates that the cluster undergoes no major structural or nuclearity changes during the reaction, consistent with our observation that supported cluster 2 is more stable than unsupported cluster 1 under "Click" reaction conditions.

  16. The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals†

    Science.gov (United States)

    Ganguly, Tanushree; Kasten, Benjamin B.; Bučar, Dejan-Krešimir; MacGillivray, Leonard R.; Berkman, Clifford E.

    2011-01-01

    Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)3 (M = Re, 99mTc) based radiopharmaceuticals. Both ‘click, then chelate’ and ‘prelabel, then click’ synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy. PMID:22044929

  17. The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals†

    OpenAIRE

    Ganguly, Tanushree; Kasten, Benjamin B.; Bučar, Dejan-Krešimir; MacGillivray, Leonard R.; Berkman, Clifford E.; Benny, Paul D.

    2011-01-01

    Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)3 (M = Re, 99mTc) based radiopharmaceuticals. Both ‘click, then chelate’ and ‘prelabel, then click’ synthetic routes produced identical products in high yields and lacked metal-hydrazide/-hydrazone interactions, highlighting the potential of this click strategy.

  18. Just Click It: Undergraduate Procedures for the Copper(I)-Catalyzed Formation of 1,2,3-Triazoles from Azides and Terminal Acetylenes

    Science.gov (United States)

    Sharpless, William D.; Peng Wu; Hansen, Trond Vidar; Lindberg, James G.

    2005-01-01

    The click chemistry uses only the most reliable reactions to build complex molecules from olefins, electrophiles and heteroatom linkers. A variation on Huisgen's azide-alkyne 1,2,3-triazole synthesis, the addition of the copper (I), the premium example of the click reaction, catalyst strongly activates terminal acetylenes towards the 1,3-dipole in…

  19. FANTOM5 CAGE profiles of human and mouse samples

    NARCIS (Netherlands)

    Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Kojima, Miki; Kubosaki, Atsutaka; Manabe, Ri-ichiroh; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A; Babina, Magda; Baillie, J Kenneth; Barnett, Timothy C; Beckhouse, Anthony G; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J; Clevers, Hans C; Davis, Carrie A; Detmar, Michael; Dohi, Taeko; Edge, Albert S B; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Farach-Carson, Mary C; Faulkner, Geoffrey J; Ferrai, Carmelo; Fisher, Malcolm E; Forrester, Lesley M; Fujita, Rie; Furusawa, Jun-ichi; Geijtenbeek, Teunis B; Gingeras, Thomas; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Hitchens, Kelly J; Hume, David A; Ikawa, Tomokatsu; Ishizu, Yuri; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I; Kempfle, Judith S; Kenna, Tony J; Kere, Juha; Khachigian, Levon M; Kitamura, Toshio; Klein, Sarah; Klinken, S Peter; Knox, Alan J; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Mackay-Sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J; Motohashi, Hozumi; Mummery, Christine L; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Schulze-Tanzil, Gundula G; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A; Winteringham, Louise N; Wolvetang, Ernst; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide

    2017-01-01

    In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples,

  20. Click-assembling triazole membrane on copper surface via one-step or two-steps and their corrosion inhibition performance

    Science.gov (United States)

    Wang, Yizhen; Yu, Yinzhe; Zhang, Jie; Gao, Lixin; Feng, Likui; Zhang, Daquan

    2018-01-01

    Triazole membrane was prepared on copper surface via one-step or two-steps click chemistry reaction of azide and alkyne compounds. Fourier transforms infrared spectroscopy (FT-IR) suggests the formation of triazole membrane on copper surface through both of one-step and two-steps click-assembling. The electrochemical results indicate that the protection efficiency of triazole click-assembling membrane forming via one-step is better than that for two-steps. The surface film on copper via one-step click-assembling is mainly composed of the triazole membrane. As for two-steps click-assembling, the triazole membrane is mainly produced in the defect of the alkyne inhibition film.

  1. Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review.

    Science.gov (United States)

    Hosseinnejad, Tayebeh; Fattahi, Bahareh; Heravi, Majid M

    2015-10-01

    Recently, the experimental and computational chemists have been attracted widely to the click synthesis of 1,2,3 triazoles and their derivatives, mainly due to the fact that they are interesting from structural and mechanistic points of view. Moreover, catalyzed click have been well established as a successful strategy showing high regioselectivity and high yield for the synthesis of 1,2,3-triazoles. In this review, we try to highlight the recently reported computational assessments on the origins and predection of regioselectivity in the catalyzed click synthesis of triazoles from the mechanistic and thermodynamical points of view. In this light, density functional theory (DFT) calculations on the free energy profiles of azide-alkyne cycloaddition reactions have been underscored. The stereoelectronic features for the role of copper, ruthenium, and iridium as catalyst on regioselectivity of click reactions have also be discussed. Graphical Abstract Computational origins for the regioselective behavior of 1,2,3 triazoles click synthesis.

  2. mouseTube

    Science.gov (United States)

    Torquet, Nicolas; de Chaumont, Fabrice; Faure, Philippe; Bourgeron, Thomas; Ey, Elodie

    2016-01-01

    Ultrasonic vocalisation is a broadly used proxy to evaluate social communication in mouse models of neuropsychiatric disorders. The efficacy and robustness of testing these models suffer from limited knowledge of the structure and functions of these vocalisations as well as of the way to analyse the data. We created mouseTube , an open database with a web interface, to facilitate sharing and comparison of ultrasonic vocalisations data and metadata attached to a recording file. Metadata describe 1) the acquisition procedure, e.g ., hardware, software, sampling frequency, bit depth; 2) the biological protocol used to elicit ultrasonic vocalisations; 3) the characteristics of the individual emitting ultrasonic vocalisations ( e.g. , strain, sex, age). To promote open science and enable reproducibility, data are made freely available. The website provides searching functions to facilitate the retrieval of recording files of interest. It is designed to enable comparisons of ultrasonic vocalisation emission between strains, protocols or laboratories, as well as to test different analysis algorithms and to search for protocols established to elicit mouse ultrasonic vocalisations. Over the long term, users will be able to download and compare different analysis results for each data file. Such application will boost the knowledge on mouse ultrasonic communication and stimulate sharing and comparison of automatic analysis methods to refine phenotyping techniques in mouse models of neuropsychiatric disorders.

  3. Mouth-clicks used by blind expert human echolocators - signal description and model based signal synthesis.

    Directory of Open Access Journals (Sweden)

    Lore Thaler

    2017-08-01

    Full Text Available Echolocation is the ability to use sound-echoes to infer spatial information about the environment. Some blind people have developed extraordinary proficiency in echolocation using mouth-clicks. The first step of human biosonar is the transmission (mouth click and subsequent reception of the resultant sound through the ear. Existing head-related transfer function (HRTF data bases provide descriptions of reception of the resultant sound. For the current report, we collected a large database of click emissions with three blind people expertly trained in echolocation, which allowed us to perform unprecedented analyses. Specifically, the current report provides the first ever description of the spatial distribution (i.e. beam pattern of human expert echolocation transmissions, as well as spectro-temporal descriptions at a level of detail not available before. Our data show that transmission levels are fairly constant within a 60° cone emanating from the mouth, but levels drop gradually at further angles, more than for speech. In terms of spectro-temporal features, our data show that emissions are consistently very brief (~3ms duration with peak frequencies 2-4kHz, but with energy also at 10kHz. This differs from previous reports of durations 3-15ms and peak frequencies 2-8kHz, which were based on less detailed measurements. Based on our measurements we propose to model transmissions as sum of monotones modulated by a decaying exponential, with angular attenuation by a modified cardioid. We provide model parameters for each echolocator. These results are a step towards developing computational models of human biosonar. For example, in bats, spatial and spectro-temporal features of emissions have been used to derive and test model based hypotheses about behaviour. The data we present here suggest similar research opportunities within the context of human echolocation. Relatedly, the data are a basis to develop synthetic models of human echolocation

  4. Catalyst-Free Conjugation and In Situ Quantification of Nanoparticle Ligand Surface Density Using Fluorogenic Cu-Free Click Chemistry

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming; Sun, Honghao; Berg, Rolf Henrik

    2011-01-01

    A highly efficient method for functionalizing nanoparticles and directly quantifying conjugation efficiency and ligand surface density has been developed. Attachment of 3-azido-modifed RGD-peptides to PEGylated liposomes was achieved by using Cu-free click conditions. Upon coupling a fluorophore ...

  5. Click synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by CuO ...

    Indian Academy of Sciences (India)

    Click synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by. CuO–CeO2 nanocomposite in the presence of amberlite-supported azide. JALAL ALBADIa,∗, JAFAR ABBASI SHIRANb and AZAM MANSOURNEZHADc. aBehbahan Khatam Alanbia University of Technology, Behbahan 6361647189, Iran. bFaculty of Science ...

  6. Mixed-methods analytic approach for determining potential impacts of vessel noise on sperm whale click behavior.

    Science.gov (United States)

    Azzara, Alyson J; von Zharen, Wyndylyn M; Newcomb, Joal J

    2013-12-01

    The Gulf of Mexico is a center of marine activities from seismic exploration to shipping, drilling, platform installation, lightering, and construction, among others. This analysis explored whether sperm whales respond to the passage of vessels using changes in total number of clicks during vessel passages as a proxy for potential variation in behavior. The data for this analysis were collected in 2001 as part of a larger Littoral Acoustic Demonstration Center project using the Environmental Acoustics Recording System buoys. These buoys were bottom moored, autonomous, and self-recording systems consisting of an omni-directional hydrophone and instrument package. Data from 36 days of continuous acoustic monitoring were recorded at a sampling rate of 11.725 kHz, and produced reliable recordings from 5 Hz to ∼5.8 kHz. Multiple preparatory steps were executed including calibration of an automatic click detector. Results indicate a significant decrease (32%) in the number of clicks detected as a ship approached an area. There were also significantly fewer clicks detected after the vessel passed than before (23%).

  7. Are occlusal characteristics, headache, parafunctional habits and clicking sounds associated with the signs and symptoms of temporomandibular disorder in adolescents?

    Science.gov (United States)

    Lauriti, Leandro; Motta, Lara Jansiski; Silva, Paula Fernanda da Costa; Leal de Godoy, Camila Haddad; Alfaya, Thays Almeida; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil

    2013-10-01

    [Purpose] To assess the association between the oclusal characteristics, headache, parafunctional habits and clicking sounds and signs/symptoms of TMD in adolescents. [Subjects] Adolescents between 14 and 18 years of age. [Methods] The participants were evaluated using the Helkimo Index and a clinical examination to track clicking sounds, parafunctional habits and other signs/symptoms of temporomandibular disorder (TMD). Subjects were classified according to the presence or absence of headache, type of occlusion, facial pattern and type of bite. In statistical analyse we used the chi-square test and Fisher's exact test, with a level of significance of 5%. [Results] The sample was made up of 81 adolescents with a mean age of 15.64 years; 51.9% were male. The prevalence of signals/symptoms of TMD was 74.1%, predominantly affecting females. Signals/symptoms of TMD were significantly associated with clicking sounds, headache and nail biting. No associations were found between signals/symptoms of TMD and angle classification, type of bite and facial pattern. [Conclusion] Headache is one of the most closely associated symptoms of TMD. Clicking sounds were found in the majority of cases. Therefore, the sum of two or more factors may be necessary for the onset and perpetuation of TMD.

  8. How Users Take Advantage of Different Forms of Interactivity on Online News Sites: Clicking, E-Mailing, and Commenting

    Science.gov (United States)

    Boczkowski, Pablo J.; Mitchelstein, Eugenia

    2012-01-01

    This study examines the uptake of multiple interactive features on news sites. It looks at the thematic composition of the most clicked, most e-mailed, and most commented stories during periods of heightened and routine political activity. Results show that (a) during the former period, the most commented stories were more likely to be focused on…

  9. Target and identify: triazene linker helps identify azidation sites of labelled proteins via click and cleave strategy.

    Science.gov (United States)

    Lohse, Jonas; Schindl, Alexandra; Danda, Natasha; Williams, Chris P; Kramer, Karl; Kuster, Bernhard; Witte, Martin D; Médard, Guillaume

    2017-10-31

    A method for identifying probe modification of proteins via tandem mass spectrometry was developed. Azide bearing molecules are immobilized on functionalised sepharose beads via copper catalysed Huisgen-type click chemistry and selectively released under acidic conditions by chemical cleavage of the triazene linkage. We applied this method to identify the modification site of targeted-diazotransfer on BirA.

  10. Copper-Free Click Biofunctionalization of Silicon Nitride Surfaces via Strain-Promoted Alkyne-Azide Cycloaddition Reactions

    NARCIS (Netherlands)

    Manova, R.K.; Pujari, S.P.; Weijers, C.A.G.M.; Zuilhof, H.; Beek, van T.A.

    2012-01-01

    Cu-free "click" chemistry is explored on silicon nitride (Si3N4) surfaces as an effective way for oriented immobilization of biomolecules. An omega-unsaturated ester was grafted onto Si3N4 using UV irradiation. Hydrolysis followed by carbodiimide-mediated activation yielded surface-bound active

  11. Integrating the Visual Arts Back into the Classroom with Mobile Applications: Teaching beyond the "Click and View" Approach

    Science.gov (United States)

    Katz-Buonincontro, Jen; Foster, Aroutis

    2013-01-01

    Teachers can use mobile applications to integrate the visual arts back into the classroom, but how? This article generates recommendations for selecting and using well-designed mobile applications in the visual arts beyond a "click and view " approach. Using quantitative content analysis, the results show the extent to which a sample of…

  12. Azidomethyl-ruthenocene: facile synthesis of a useful metallocene derivative and its application in the 'click' labelling of biomolecules.

    Science.gov (United States)

    Patra, Malay; Metzler-Nolte, Nils

    2011-11-07

    A convenient synthesis of azidomethyl-ruthenocene and its use in the covalent labelling of amino acids, peptides and a peptide nucleic acid (PNA) monomer derivative by Cu(I) catalyzed azide-alkyne coupling (Cu-AAC, "click chemistry") are described. This journal is © The Royal Society of Chemistry 2011

  13. Click chemistry as a powerful and chemoselective tool for the attachment of targeting ligands to polymer drug carriers

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Braunová, Alena; Laga, Richard; Pechar, Michal; Ulbrich, Karel

    2014-01-01

    Roč. 5, č. 4 (2014), s. 1340-1350 ISSN 1759-9954 Grant - others:AV ČR(CZ) AP0802 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:61389013 Keywords : click chemistry * RAFT polymerization * hydrophilic polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.520, year: 2014

  14. Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking

    Czech Academy of Sciences Publication Activity Database

    Daďová, Jitka; Vrábel, Milan; Adámik, Matěj; Brázdová, Marie; Pohl, Radek; Fojta, Miroslav; Hocek, Michal

    2015-01-01

    Roč. 21, č. 45 (2015), s. 16091-16102 ISSN 0947-6539 R&D Projects: GA ČR GBP206/12/G151 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : biotransformations * click chemistry * conjugation * nucleic acids * proteins Subject RIV: CC - Organic Chemistry Impact factor: 5.771, year: 2015

  15. Facile synthesis of 4-vinyl- and 4-fluorovinyl-1,2,3-triazoles via bifunctional “click-olefination” reagents

    Science.gov (United States)

    Kumar, Rakesh; Pradhan, Padmanava; Zajc, Barbara

    2011-01-01

    Modular synthesis of vinyl and fluorovinyl triazoles can be achieved from bifunctional propargyl and fluoropropargyl sulfones by Cu-catalyzed azide-alkyne ligation and Julia-Kocienski olefination. Competitive click reactions of the protio and fluoropropargyl sulfones show higher reactivity of the latter, and a preliminary DFT analysis was performed. PMID:21336351

  16. Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles

    Czech Academy of Sciences Publication Activity Database

    Smyslová, P.; Popa, I.; Lyčka, A.; Tejral, Gracian; Havlač, J.

    2015-01-01

    Roč. 10, č. 2 (2015), e0144613 E-ISSN 1932-6203 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:68378041 Keywords : copper-free click * alkyne cycloaddition * chemistry Subject RIV: CC - Organic Chemistry Impact factor: 3.057, year: 2015

  17. Fused Tetrazoles as Azide Surrogates in Click Reaction: Efficient Synthesis of N-Heterocycle-substituted 1,2,3-Triazoles

    Science.gov (United States)

    Chattopadhyay, Buddhadeb; Rivera Vera, Claudia I.; Chuprakov, Stepan; Gevorgyan, Vladimir

    2010-01-01

    It has been shown that various pyrido-, quinolino-, pyrazino- and qunoxalinotetrazoles can efficienly be used as azide components in the Cu-catalyzed click reaction with alkynes. This method allows for efficient synthesis of a wide variety of N-heterocyclic derivatives of 1,2,3-triazoles. PMID:20380424

  18. Do User (Browse and Click) Sessions Relate to Their Questions in a Domain-specific Collection?

    DEFF Research Database (Denmark)

    Steinhauer, Jeremy; Delcambre, Lois M.L.; Lykke, Marianne

    2013-01-01

    We seek to improve information retrieval in a domain-specific col-lection by clustering user sessions as recorded in a click log and then classifying later user sessions in real-time. As a preliminary step, we explore, the main as-sumption of this approach: whether user sessions in such a site...... relate to the question that they are answering. The contribution of this paper is the evalua-tion of the suitability of common machine learning metrics (measuring the dis-tance between two sessions) to distinguish sessions of users searching for the answer to same or different questions. We found...... that sessions for people an-swering the same question are significantly different that those answering dif-ferent questions, but results are dependent on the distance metric used. We ex-plain why some distance metrics performed better than others....

  19. Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery.

    Directory of Open Access Journals (Sweden)

    Ming Wang

    Full Text Available Exosomes are small, cell-secreted vesicles that transfer proteins and genetic information between cells. This intercellular transmission regulates many physiological and pathological processes. Therefore, exosomes have emerged as novel biomarkers for disease diagnosis and as nanocarriers for drug delivery. Here, we report an easy-to-adapt and highly versatile methodology to modulate exosome composition and conjugate exosomes for intracellular delivery. Our strategy combines the metabolic labeling of newly synthesized proteins or glycan/glycoproteins of exosome-secreting cells with active azides and bioorthogonal click conjugation to modify and functionalize the exosomes. The azide-integrated can be conjugated to a variety of small molecules and proteins and can efficiently deliver conjugates into cells. The metabolic engineering of exosomes diversifies the chemistry of exosomes and expands the functions that can be introduced into exosomes, providing novel, powerful tools to study the roles of exosomes in biology and expand the biomedical potential of exosomes.

  20. Copper-chelating azides for efficient click conjugation reactions in complex media.

    Science.gov (United States)

    Bevilacqua, Valentina; King, Mathias; Chaumontet, Manon; Nothisen, Marc; Gabillet, Sandra; Buisson, David; Puente, Céline; Wagner, Alain; Taran, Frédéric

    2014-06-02

    The concept of chelation-assisted copper catalysis was employed for the development of new azides that display unprecedented reactivity in the copper(I)-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction. Azides that bear strong copper-chelating moieties were synthesized; these functional groups allow the formation of azide copper complexes that react almost instantaneously with alkynes under diluted conditions. Efficient ligation occurred at low concentration and in complex media with only one equivalent of copper, which improves the biocompatibility of the CuAAC reaction. Furthermore, such a click reaction allowed the localization of a bioactive compound inside living cells by fluorescence measurements. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Sugar microarray via click chemistry: molecular recognition with lectins and amyloid β (1–42

    Directory of Open Access Journals (Sweden)

    Erino Matsumoto, Takahiro Yamauchi, Tomohiro Fukuda and Yoshiko Miura

    2009-01-01

    Full Text Available Sugar microarrays were fabricated on various substrates via click chemistry. Acetylene-terminated substrates were prepared by forming self-assembled monolayers (SAMs on a gold substrate with alkyl-disulfide and on silicon, quartz and glass substrates with a silane-coupling reagent. The gold substrates were subjected to surface plasmon resonance measurements, and the quartz and glass substrates were subjected to spectroscopy measurements and optical microscopy observation. The saccharide-immobilized substrate on the gold substrate showed specific interaction with the corresponding lectin, and the saccharides showed inert surface properties to other proteins with a high signal-to-noise ratio. We also focused on the saccharide–protein interaction on protein amyloidosis of Alzheimer amyloid β. Amyloid β peptide showed conformation transition on the saccharide-immobilization substrate into a β-sheet, and fibril formation and amyloid aggregates were found on the specific saccharides.

  2. "Click" synthesis of fatty acid derivatives as fast-degrading polyanhydride precursors.

    Science.gov (United States)

    Lluch, Cristina; Lligadas, Gerard; Ronda, Joan C; Galià, Marina; Cadiz, Virginia

    2011-09-01

    Fast-degrading linear and branched polyanhydrides are obtained by melt-condensation of novel di- and tri-carboxylic acid monomers based on oleic and undecylenic acid synthesized using photoinitiated thiol-ene click chemistry. (1)H NMR spectroscopy, size exclusion chromatography, differential scanning calorimetry, thermogravimetric analysis, and FT-IR spectroscopy have been used to fully characterize these polymers. The hydrolytic degradation of these polymers was studied by means of weight loss, anhydride bond loss, and changes in molecular weight, showing fast degrading properties. Drug release studies from the synthesized polyanhydrides have also been conducted, using rhodamine B as a hydrophobic model drug, to evaluate the potential of these polymers in biomedical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Synthesis of amphiphilic aminated inulin via 'click chemistry' and evaluation for its antibacterial activity.

    Science.gov (United States)

    Dong, Fang; Zhang, Jun; Yu, Chunwei; Li, Qing; Ren, Jianming; Wang, Gang; Gu, Guodong; Guo, Zhanyong

    2014-09-15

    Inulins are a group of abundant, water-soluble, renewable polysaccharides, which exhibit attractive bioactivities and natural properties. Improvement such as chemical modification of inulin is often performed prior to further utilization. We hereby presented a method to modify inulin at its primary hydroxyls to synthesize amphiphilic aminated inulin via 'click chemistry' to facilitate its chemical manipulation. Additionally, its antibacterial property against Staphylococcus aureus (S. aureus) was also evaluated and the best inhibitory index against S. aureus was 58% at 1mg/mL. As the amphiphilic aminated inulin is easy to prepare and exhibits improved bioactivity, this material may represent as an attractive new platform for chemical modifications of inulin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Preparation of photochromic silk fabrics based on thiol-halogen click chemistry

    Science.gov (United States)

    Fan, Ji; Wang, Wei; Yu, Dan

    2018-02-01

    In this study, we have synthesized a photochromic compound 9‧-(2-bromo-2-methylethoxycarbonyl)-1,3,3-trimethyl-spiro[2H-indole-2,3‧-[3H]naphtha[2,1-b] [1,4]oxazine] and applied it to the silk fabric to acquire photochromic properties. First, tris (2-carboxyethyl) phosphine (TCEP) was used as a reducing agent to produce thiol groups on the surface of silk fabric. Then, these thiol groups will react with -Br groups of the spirooxazine via thiol-halogen click chemistry. The spirooxazine was characterized by FTIR and UV. And the color change properties of the as-prepared silk fabrics were evaluated by the color measurement methods. The results indicated that treated silk fabric has excellent photochromic properties.

  5. Extremely efficient catalysis of carbon-carbon bond formation using "click" dendrimer-stabilized palladium nanoparticles.

    Science.gov (United States)

    Astruc, Didier; Ornelas, Cátia; Diallo, Abdou K; Ruiz, Jaime

    2010-07-20

    This article is an account of the work carried out in the authors' laboratory illustrating the usefulness of dendrimer design for nanoparticle palladium catalysis. The "click" synthesis of dendrimers constructed generation by generation by 1-->3 C connectivity, introduces 1,2,3-triazolyl ligands insides the dendrimers at each generation. Complexation of the ligands by Pd(II) followed by reduction to Pd(0) forms dendrimer-stabilized Pd nanoparticles (PdNPs) that are extremely reactive in the catalysis of olefin hydrogenation and C-C bond coupling reactions. The stabilization can be outer-dendritic for the small zeroth-generation dendrimer or intra-dendritic for the larger first- and second-generation dendrimers. The example of the Miyaura-Suzuki reaction that can be catalyzed by down to 1 ppm of PdNPs with a "homeopathic" mechanism (the less, the better) is illustrated here, including catalysis in aqueous solvents.

  6. Synthesis of Polyethers Containing Triazole Units in the Backbone by Click Chemistry in a Tricomponent Reaction

    Directory of Open Access Journals (Sweden)

    Moslem Mansour Lakouraj

    2013-01-01

    Full Text Available A series of linear aromatic polyethers containing triazole units were synthesized via the direct click reaction of dibromide and bisethynyl compounds in the presence of sodium azide as one pot reaction. The structures of polymers were approved by using IR and 1H NMR techniques. The solubility experiments showed that polymers have good solubility in polar aprotic solvents such as DMSO, DMF, and NMP at higher temperatures. Thermal stability of the polymers was measured using thermogravimetric analysis (TGA and differential scanning calorimetry (DSC which indicated that they possessed good thermal stability ( up to 558°C and high (191.7–260°C under N2 atmosphere. All the polymers were amorphous according to the DSC and X-ray diffraction. These polymers exhibited strong UV-vis absorption maxima near to 400 nm and up to 500 nm in DMSO solution.

  7. Advertisement Click-Through Rate Prediction Based on the Weighted-ELM and Adaboost Algorithm

    Directory of Open Access Journals (Sweden)

    Sen Zhang

    2017-01-01

    Full Text Available Accurate click-through rate (CTR prediction can not only improve the advertisement company’s reputation and revenue, but also help the advertisers to optimize the advertising performance. There are two main unsolved problems of the CTR prediction: low prediction accuracy due to the imbalanced distribution of the advertising data and the lack of the real-time advertisement bidding implementation. In this paper, we will develop a novel online CTR prediction approach by incorporating the real-time bidding (RTB advertising by the following strategies: user profile system is constructed from the historical data of the RTB advertising to describe the user features, the historical CTR features, the ID features, and the other numerical features. A novel CTR prediction approach is presented to address the imbalanced learning sample distribution by integrating the Weighted-ELM (WELM and the Adaboost algorithm. Compared to the commonly used algorithms, the proposed approach can improve the CTR significantly.

  8. Click-evoked otoacoustic emissions in children and adolescents with gender identity disorder.

    Science.gov (United States)

    Burke, Sarah M; Menks, Willeke M; Cohen-Kettenis, Peggy T; Klink, Daniel T; Bakker, Julie

    2014-11-01

    Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds that are produced by the inner ear in response to click-stimuli. CEOAEs generally have a higher amplitude in women compared to men and neonates already show a similar sex difference in CEOAEs. Weaker responses in males are proposed to originate from elevated levels of testosterone during perinatal sexual differentiation. Therefore, CEOAEs may be used as a retrospective indicator of someone's perinatal androgen environment. Individuals diagnosed with Gender Identity Disorder (GID), according to DSM-IV-TR, are characterized by a strong identification with the other gender and discomfort about their natal sex. Although the etiology of GID is far from established, it is hypothesized that atypical levels of sex steroids during a critical period of sexual differentiation of the brain might play a role. In the present study, we compared CEOAEs in treatment-naïve children and adolescents with early-onset GID (24 natal boys, 23 natal girls) and control subjects (65 boys, 62 girls). We replicated the sex difference in CEOAE response amplitude in the control group. This sex difference, however, was not present in the GID groups. Boys with GID showed stronger, more female-typical CEOAEs whereas girls with GID did not differ in emission strength compared to control girls. Based on the assumption that CEOAE amplitude can be seen as an index of relative androgen exposure, our results provide some evidence for the idea that boys with GID may have been exposed to lower amounts of androgen during early development in comparison to control boys.

  9. Immunologic analyses of mouse cystathionase in normal and leukemic cells

    International Nuclear Information System (INIS)

    Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.

    1978-01-01

    Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

  10. Molecular pharmacology and ligand docking studies reveal a single amino acid difference between mouse and human serotonin 5-HT2A receptors that impacts behavioral translation of novel 4-phenyl-2-dimethylaminotetralin ligands.

    Science.gov (United States)

    Canal, Clinton E; Cordova-Sintjago, Tania; Liu, Yue; Kim, Myong S; Morgan, Drake; Booth, Raymond G

    2013-12-01

    During translational studies to develop 4-phenyl-2-dimethylaminotetralin (PAT) compounds for neuropsychiatric disorders, the (2R,4S)-trans-(+)- and (2S,4R)-trans-(-)-enantiomers of the analog 6-hydroxy-7-chloro-PAT (6-OH-7-Cl-PAT) demonstrated unusual pharmacology at serotonin (5-HT) 5-HT2 G protein-coupled receptors (GPCRs). The enantiomers had similar affinities (Ki) at human (h) 5-HT2A receptors (≈ 70 nM). In an in vivo mouse model of 5-HT2A receptor activation [(±)-(2,5)-dimethoxy-4-iodoamphetamine (DOI)-elicited head twitch], however, (-)-6-OH-7-Cl-PAT was about 5-fold more potent than the (+)-enantiomer at attenuating the DOI-elicited response. It was discovered that (+)-6-OH-7-Cl-PAT (only) had ≈ 40-fold-lower affinity at mouse (m) compared with h5-HT2A receptors. Molecular modeling and computational ligand docking studies indicated that the 6-OH moiety of (+)- but not (-)-6-OH-7-Cl-PAT could form a hydrogen bond with serine residue 5.46 of the h5-HT2A receptor. The m5-HT2A as well as m5-HT2B, h5-HT2B, m5-HT2C, and h5-HT2C receptors have alanine at position 5.46, obviating this interaction; (+)-6-OH-7-Cl-PAT also showed ≈ 50-fold lower affinity than (-)-6-OH-7-Cl-PAT at m5-HT2C and h5-HT2C receptors. Mutagenesis studies confirmed that 5-HT2A S5.46 is critical for (+)- but not (-)-6-OH-7-Cl-PAT binding, as well as function. The (+)-6-OH-7-Cl-PAT enantiomer showed partial agonist effects at h5-HT2A wild-type (WT) and m5-HT2A A5.46S point-mutated receptors but did not activate m5-HT2A WT and h5-HT2A S5.46A point-mutated receptors, or h5-HT2B, h5-HT2C, and m5-HT2C receptors; (-)-6-OH-7-Cl-PAT did not activate any of the 5-HT2 receptors. Experiments also included the (2R,4S)-trans-(+)- and (2S,4R)-trans-(-)-enantiomers of 6-methoxy-7-chloro-PAT to validate hydrogen bonding interactions proposed for the corresponding 6-OH analogs. Results indicate that PAT ligand three-dimensional structure impacts target receptor binding and translational outcomes

  11. Mouse models of cataract

    Indian Academy of Sciences (India)

    2009-12-31

    Dec 31, 2009 ... Mutations affecting the mouse lens can be identified easily by visual inspection, and a remarkable number of mutant lines ..... out mutants do not show an ocular phenotype, the two Bfsp genes are important for lens ... The more severe mutants have in addition to the ocular symptoms some more clinical ...

  12. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  13. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  14. Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus.

    Directory of Open Access Journals (Sweden)

    Elizabeth Jaworski

    2017-05-01

    Full Text Available Defective-Interfering RNAs (DI-RNAs have long been known to play an important role in virus replication and transmission. DI-RNAs emerge during virus passaging in both cell-culture and their hosts as a result of non-homologous RNA recombination. However, the principles of DI-RNA emergence and their subsequent evolution have remained elusive. Using a combination of long- and short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. For short-read RNAseq, we employed 'ClickSeq' due to its ability to sensitively and confidently detect RNA recombination events with nucleotide resolution. In parallel, we used the Oxford Nanopore Technologies's (ONT MinION to resolve full-length defective and wild-type viral genomes. Together, these accurately resolve both rare and common RNA recombination events, determine the correlation between recombination events, and quantifies the relative abundance of different DI-RNAs throughout passaging. We observe the formation of a diverse pool of defective RNAs at each stage of viral passaging. However, many of these 'intermediate' species, while present in early stages of passaging, do not accumulate. After approximately 9 days of passaging we observe the rapid accumulation of DI-RNAs with a correlated reduction in specific infectivity and with the Nanopore data find that DI-RNAs are characterized by multiple RNA recombination events. This suggests that intermediate DI-RNA species are not competitive and that multiple recombination events interact epistatically to confer 'mature' DI-RNAs with their selective advantage allowing for their rapid accumulation. Alternatively, it is possible that mature DI-RNA species are generated in a single event involving multiple RNA rearrangements. These insights have

  15. Establishment of mouse expanded potential stem cells.

    Science.gov (United States)

    Yang, Jian; Ryan, David J; Wang, Wei; Tsang, Jason Cheuk-Ho; Lan, Guocheng; Masaki, Hideki; Gao, Xuefei; Antunes, Liliana; Yu, Yong; Zhu, Zhexin; Wang, Juexuan; Kolodziejczyk, Aleksandra A; Campos, Lia S; Wang, Cui; Yang, Fengtang; Zhong, Zhen; Fu, Beiyuan; Eckersley-Maslin, Melanie A; Woods, Michael; Tanaka, Yosuke; Chen, Xi; Wilkinson, Adam C; Bussell, James; White, Jacqui; Ramirez-Solis, Ramiro; Reik, Wolf; Göttgens, Berthold; Teichmann, Sarah A; Tam, Patrick P L; Nakauchi, Hiromitsu; Zou, Xiangang; Lu, Liming; Liu, Pentao

    2017-10-19

    Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.

  16. Tandem diazonium salt electroreduction and click chemistry as a novel, efficient route for grafting macromolecules to gold surface

    Science.gov (United States)

    Mahouche, Samia; Mekni, Nejib; Abbassi, Leila; Lang, Philippe; Perruchot, Christian; Jouini, Mohamed; Mammeri, Fayna; Turmine, Mireille; Romdhane, Hatem Ben; Chehimi, Mohamed M.

    2009-11-01

    Bis-alkynylated oligoethyleneglycol (OEG) and a monopropargyl-functionalized perfluorinated ethylene glycol (FEG) were clicked to azide-functionalized gold surface (Au-N 3) at room temperature via the well known 1,3 cycloaddition click chemical reaction. The Au-N 3 substrate was obtained by nucleophilic attack of NaN 3 on gold substrates modified by the electrochemical reduction of the BF4-, +N 2-C 6H 4-CH 2Br diazonium salt. This electrochemical process yields aryl layer-modified gold of the type Au-C 6H 4-CH 2Br (hereafter Au-Br). The untreated and modified gold plates were examined by XPS, PMIRRAS and contact angle measurements. XPS brought evidence for electrografting aryl layers by the detection of Br3d; azide functionalization by the increase of the N/Br atomic ratio; and click reaction of OEG with Au-N 3 by the increase of O/N ratio. In addition, the perfluorinated plate (Au-FEG) exhibited F1s and characteristic C1s peaks from -(CF 2) 7- chain and terminal CF 3. Infra red spectroscopy (PMIRRAS) evidenced (i) grafting N 3 to Au-Br; (ii) characteristic stretching bands, from ethylene glycol units, C-O-C (1100-1300 cm -1); CF 2 (1000-1100 cm -1) and CF 3 (1100-1350 cm -1) from FEG grafts; and (iii) suppression of alkynyl bands from OEG and FEG after surface click chemistry. More importantly, PMIRRAS results support an important bridging of the bispropargyl oligoethylene glycol at the gold surface. Water drop contact angles were found to be 48.7° and 83.0° for Au-OEG and Au-FEG, respectively, therefore highlighting the control over the hydrophilic/hydrophobic character of the clicked substrate. This work shows that clicking macromolecules to grafted, diazonium salt-derived aryl layers is a novel, simple and valuable approach for designing robust, functional surface organic coatings.

  17. Characteristics of the mouse genomic histamine H1 receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others

    1996-08-15

    We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

  18. Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

    Directory of Open Access Journals (Sweden)

    Jacqueline Morris

    2017-12-01

    Full Text Available Summary: A number of mitochondrial diseases arise from single-nucleotide variant (SNV accumulation in multiple mitochondria. Here, we present a method for identification of variants present at the single-mitochondrion level in individual mouse and human neuronal cells, allowing for extremely high-resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high-confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single-mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations, resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single-mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds. : Morris et al. use independent sequencing of multiple individual mitochondria from mouse and human brain cells to show high pervasiveness of mutations. The mutations are heteroplasmic within single mitochondria and within and between cells. These findings suggest mechanisms by which mutations accumulate over time, resulting in mitochondrial dysfunction and disease. Keywords: single mitochondrion, single cell, human neuron, mouse neuron, single-nucleotide variation

  19. RIKEN mouse genome encyclopedia.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  20. Au-Cu core-shell nanocube-catalyzed click reactions for efficient synthesis of diverse triazoles.

    Science.gov (United States)

    Madasu, Mahesh; Hsia, Chi-Fu; Huang, Michael H

    2017-06-01

    Au-Cu core-shell nanocubes and octahedra synthesized in aqueous solution were employed to catalyze a 1,3-dipolar cycloaddition reaction between phenylacetylene and benzyl azide in water at 50 °C for 3 h. Interestingly, the nanocubes were far more efficient in catalyzing this reaction, giving 91% yield of a regioselective 1,4-triazole product, while octahedra only recorded 46% yield. The Au-Cu nanocubes were subsequently employed to catalyze the click reaction between benzyl azide and a broad range of aromatic and aliphatic alkynes. The product yields ranged from 78 to 99%. Clearly the Au-Cu cubes exposing {100} surfaces are an excellent and green catalyst for click reactions.

  1. Capacitive facial movement detection for human-computer interaction to click by frowning and lifting eyebrows: assistive technology.

    Science.gov (United States)

    Rantanen, Ville; Niemenlehto, Pekka-Henrik; Verho, Jarmo; Lekkala, Jukka

    2010-01-01

    A capacitive facial movement detection method designed for human-computer interaction is presented. Some point-and-click interfaces use facial electromyography for clicking. The presented method provides a contactless alternative. Electrodes with no galvanic coupling to the face are used to form electric fields. Changes in the electric fields due to facial movements are detected by measuring capacitances between the electrodes. A prototype device for measuring a capacitance signal affected by frowning and lifting eyebrows was constructed. A commercial integrated circuit for capacitive touch sensors is used in the measurement. The applied movement detection algorithm uses an adaptive approach to provide operation capability in noisy and dynamic environments. Experimentation with 10 test subjects proved that, under controlled circumstances, the movements are detected with good efficiency, but characterizing the movements into frowns and eyebrow lifts is more problematic. Integration with a two-dimensional (2D) pointing solution and further experiments are still required.

  2. General method for labeling siRNA by click chemistry with fluorine-18 for the purpose of PET imaging.

    Science.gov (United States)

    Mercier, Frédéric; Paris, Jérôme; Kaisin, Geoffroy; Thonon, David; Flagothier, Jessica; Teller, Nathalie; Lemaire, Christian; Luxen, André

    2011-01-19

    The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction, was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An alkyne solid support CPG for the preparation of monostranded oligonucleotides functionalized with alkyne has been developed. Two complementary azide labeling agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3-[(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical yields (decay-corrected), respectively. After annealing with the complementary strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and purity.

  3. [Functional harmony of the sonar clicks and whistles in the acoustic emissions of the Amazonian dolphin Sotalis fluviatilis Gervais and Deville].

    Science.gov (United States)

    Alcuri, G; Busnel, R G

    1989-01-01

    By analyzing acoustic signals recorded from Sotalia in the Amazon River, its appears that phonation system use the same mechanism to produce click and monochromatic whistling, with a regular evolution between them.

  4. Ex vivo gene editing of the dystrophin gene in muscle stem cells mediated by peptide nucleic acid single stranded oligodeoxynucleotides induces stable expression of dystrophin in a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Nik-Ahd, Farnoosh; Bertoni, Carmen

    2014-07-01

    Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutations in the dystrophin gene, which result in the complete absence of dystrophin protein throughout the body. Gene correction strategies hold promise to treating DMD. Our laboratory has previously demonstrated the ability of peptide nucleic acid single-stranded oligodeoxynucleotides (PNA-ssODNs) to permanently correct single-point mutations at the genomic level. In this study, we show that PNA-ssODNs can target and correct muscle satellite cells (SCs), a population of stem cells capable of self-renewing and differentiating into muscle fibers. When transplanted into skeletal muscles, SCs transfected with correcting PNA-ssODNs were able to engraft and to restore dystrophin expression. The number of dystrophin-positive fibers was shown to significantly increase over time. Expression was confirmed to be the result of the activation of a subpopulation of SCs that had undergone repair as demonstrated by immunofluorescence analyses of engrafted muscles using antibodies specific to full-length dystrophin transcripts and by genomic DNA analysis of dystrophin-positive fibers. Furthermore, the increase in dystrophin expression detected over time resulted in a significant improvement in muscle morphology. The ability of transplanted cells to return into quiescence and to activate upon demand was confirmed in all engrafted muscles following injury. These results demonstrate the feasibility of using gene editing strategies to target and correct SCs and further establish the therapeutic potential of this approach to permanently restore dystrophin expression into muscle of DMD patients. © 2014 AlphaMed Press.

  5. Click Addition of a DNA Thread to the N-Termini of Peptides for Their Translocation through Solid-State Nanopores.

    Science.gov (United States)

    Biswas, Sudipta; Song, Weisi; Borges, Chad; Lindsay, Stuart; Zhang, Peiming

    2015-10-27

    Foremost among the challenges facing single molecule sequencing of proteins by nanopores is the lack of a universal method for driving proteins or peptides into nanopores. In contrast to nucleic acids, the backbones of which are uniformly negatively charged nucleotides, proteins carry positive, negative and neutral side chains that are randomly distributed. Recombinant proteins carrying a negatively charged oligonucleotide or polypeptide at the C-termini can be translocated through a α-hemolysin (α-HL) nanopore, but the required genetic engineering limits the generality of these approaches. In this present study, we have developed a chemical approach for addition of a charged oligomer to peptides so that they can be translocated through nanopores. As an example, an oligonucleotide PolyT20 was tethered to peptides through first selectively functionalizing their N-termini with azide followed by a click reaction. The data show that the peptide-PolyT20 conjugates translocated through nanopores, whereas the unmodified peptides did not. Surprisingly, the conjugates with their peptides tethered at the 5'-end of PolyT20 passed the nanopores more rapidly than the PolyT20 alone. The PolyT20 also yielded a wider distribution of blockade currents. The same broad distribution was found for a conjugate with its peptide tethered at the 3'-end of PolyT20, suggesting that the larger blockades (and longer translocation times) are associated with events in which the 5'-end of the PolyT20 enters the pore first.

  6. Bio-orthogonal "click-and-release" donation of caged carbonyl sulfide (COS) and hydrogen sulfide (H2S).

    Science.gov (United States)

    Steiger, Andrea K; Yang, Yang; Royzen, Maksim; Pluth, Michael D

    2017-01-24

    Hydrogen sulfide (H 2 S) is an important biomolecule with high therapeutic potential. Here we leverage the inverse-electron demand Diels-Alder (IEDDA) click reaction between a thiocarbamate-functionalized trans-cyclooctene and a tetrazine to deliver carbonyl sulfide (COS), which is quickly converted to H 2 S by the uniquitous enzyme carbonic anhydrase (CA), thus providing a new strategy for bio-orthogonal COS/H 2 S donation.

  7. Clicking in shallow rivers: short-range echolocation of Irrawaddy and Ganges River dolphins in a shallow, acoustically complex habitat.

    Directory of Open Access Journals (Sweden)

    Frants H Jensen

    Full Text Available Toothed whales (Cetacea, odontoceti use biosonar to navigate their environment and to find and catch prey. All studied toothed whale species have evolved highly directional, high-amplitude ultrasonic clicks suited for long-range echolocation of prey in open water. Little is known about the biosonar signals of toothed whale species inhabiting freshwater habitats such as endangered river dolphins. To address the evolutionary pressures shaping the echolocation signal parameters of non-marine toothed whales, we investigated the biosonar source parameters of Ganges river dolphins (Platanista gangetica gangetica and Irrawaddy dolphins (Orcaella brevirostris within the river systems of the Sundarban mangrove forest. Both Ganges and Irrawaddy dolphins produced echolocation clicks with a high repetition rate and low source level compared to marine species. Irrawaddy dolphins, inhabiting coastal and riverine habitats, produced a mean source level of 195 dB (max 203 dB re 1 µPapp whereas Ganges river dolphins, living exclusively upriver, produced a mean source level of 184 dB (max 191 re 1 µPapp. These source levels are 1-2 orders of magnitude lower than those of similar sized marine delphinids and may reflect an adaptation to a shallow, acoustically complex freshwater habitat with high reverberation and acoustic clutter. The centroid frequency of Ganges river dolphin clicks are an octave lower than predicted from scaling, but with an estimated beamwidth comparable to that of porpoises. The unique bony maxillary crests found in the Platanista forehead may help achieve a higher directionality than expected using clicks nearly an octave lower than similar sized odontocetes.

  8. Effectiveness of a Randomized Controlled Lifestyle Intervention to Prevent Obesity among Chinese Primary School Students: CLICK-Obesity Study

    OpenAIRE

    Xu, Fei; Ware, Robert S.; Leslie, Eva; Tse, Lap Ah; Wang, Zhiyong; Li, Jiequan; Wang, Youfa

    2015-01-01

    Background Childhood obesity has been increasing rapidly worldwide. There is limited evidence for effective lifestyle interventions to prevent childhood obesity worldwide, especially in developing countries like China. The objective of this study was to assess the effectiveness of a school-based multi-component lifestyle childhood obesity prevention program (the CLICK-Obesity study) in Mainland China. Methods A cluster randomized controlled trial was developed among grade 4 students from 8 ur...

  9. Clicking in shallow rivers: short-range echolocation of Irrawaddy and Ganges River dolphins in a shallow, acoustically complex habitat.

    Science.gov (United States)

    Jensen, Frants H; Rocco, Alice; Mansur, Rubaiyat M; Smith, Brian D; Janik, Vincent M; Madsen, Peter T

    2013-01-01

    Toothed whales (Cetacea, odontoceti) use biosonar to navigate their environment and to find and catch prey. All studied toothed whale species have evolved highly directional, high-amplitude ultrasonic clicks suited for long-range echolocation of prey in open water. Little is known about the biosonar signals of toothed whale species inhabiting freshwater habitats such as endangered river dolphins. To address the evolutionary pressures shaping the echolocation signal parameters of non-marine toothed whales, we investigated the biosonar source parameters of Ganges river dolphins (Platanista gangetica gangetica) and Irrawaddy dolphins (Orcaella brevirostris) within the river systems of the Sundarban mangrove forest. Both Ganges and Irrawaddy dolphins produced echolocation clicks with a high repetition rate and low source level compared to marine species. Irrawaddy dolphins, inhabiting coastal and riverine habitats, produced a mean source level of 195 dB (max 203 dB) re 1 µPapp whereas Ganges river dolphins, living exclusively upriver, produced a mean source level of 184 dB (max 191) re 1 µPapp. These source levels are 1-2 orders of magnitude lower than those of similar sized marine delphinids and may reflect an adaptation to a shallow, acoustically complex freshwater habitat with high reverberation and acoustic clutter. The centroid frequency of Ganges river dolphin clicks are an octave lower than predicted from scaling, but with an estimated beamwidth comparable to that of porpoises. The unique bony maxillary crests found in the Platanista forehead may help achieve a higher directionality than expected using clicks nearly an octave lower than similar sized odontocetes.

  10. Chemical surface reactions by click chemistry: coumarin dye modification of 11-bromoundecyltrichlorosilane monolayers

    International Nuclear Information System (INIS)

    Haensch, Claudia; Hoeppener, Stephanie; Schubert, Ulrich S

    2008-01-01

    The functionalization of surfaces and the ability to tailor their properties with desired physico-chemical functions is an important field of research with a broad spectrum of applications. These applications range from the modification of wetting properties, over the alteration of optical properties, to the fabrication of molecular electronic devices. In each of these fields, it is of specific importance to be able to control the quality of the layers with high precision. The present study demonstrates an approach that utilizes the 1,3-dipolar cycloaddition of terminal acetylenes to prepare triazole-terminated monolayers on different substrates. The characterization of the precursor monolayers, the optimization of the chemical surface reactions as well as the clicking of a fluorescent dye molecule on such azide-terminated monolayers was carried out. A coumarin 343 derivative was utilized to discuss the aspects of the functionalization approach. Based on this approach, a number of potential surface reactions, facilitated via the acetylene-substituted functional molecules, for a broad range of applications is at hand, thus leading to numerous possibilities where surface modifications are concerned. These modifications can be applied on non-structured surfaces of silicon or glass or can be used on structured surfaces. Various possibilities are discussed

  11. Multiple shape memory polymers based on laminates formed from thiol-click chemistry based polymerizations.

    Science.gov (United States)

    Podgórski, M; Wang, C; Bowman, C N

    2015-09-14

    This investigation details the formation of polymer network trilayer laminates formed by thiol-X click chemistries, and their subsequent implementation and evaluation for quadruple shape memory behavior. Thiol-Michael addition and thiol-isocyanate-based crosslinking reactions were employed to fabricate each of the laminate's layers with independent control of the chemistry and properties of each layer and outstanding interlayer adhesion and stability. The characteristic features of step-growth thiol-X reactions, such as excellent network uniformity and narrow thermal transitions as well as their stoichiometric nature, enabled fabrication of trilayer laminates with three distinctly different glass transition temperatures grouped within a narrow range of 100 °C. Through variations in the layer thicknesses, a step-wise modulus drop as a function of temperature was achieved. This behavior allowed multi-step programming and the demonstration and quantification of quadruple shape memory performance. As is critical for this performance, the interface connecting the layers was evaluated in stoichiometric as well as off-stoichiometric systems. It was shown that the laminated structures exhibit strong interfacial binding and hardly suffer any delamination during cyclic material testing and deformation.

  12. Synthesis of new triazole arotinoids analogues via "Click Chemistry" with potential anticancer activity

    Directory of Open Access Journals (Sweden)

    Mariana A. A. Aleixo

    2012-06-01

    Full Text Available Retinoids are  a  class  of  natural  and  synthetic  vitamin A analogues structurally related to all-trans-retinoic acid (ATRA. This class of compounds can inhibit cell proliferation and induce differentiation and apoptosis of cells, and several are used in cancer therapy. Using the concept of bioisosterism, new triazole analogues were designed from the molecular modification of the potent derivative arotinoid AM580. This compound has an amide grouping which is a bioisostere of 1,2,3-triazole ring. Through "Click Chemistry” approach, triazole analogues were obtained by reaction of Huisgen 1,3-dipolar cycloaddition between aryl azides and terminal acetylene, previously synthesized. The reagents used were CuI, triethylamine and mixture of ethanol:water. The first compound synthesized showed anticancer activity, while the second proved to be inactive. The molecular docking results showed that both compounds have high affinity for the retinoid RARα receptor (related to anticancer activity, but probably the second compound has antagonist activity on this receptor.

  13. Auditory cortex responses to clicks and sensory modulation difficulties in children with autism spectrum disorders (ASD.

    Directory of Open Access Journals (Sweden)

    Elena V Orekhova

    Full Text Available Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH. The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.

  14. Auditory cortex responses to clicks and sensory modulation difficulties in children with autism spectrum disorders (ASD).

    Science.gov (United States)

    Orekhova, Elena V; Tsetlin, Marina M; Butorina, Anna V; Novikova, Svetlana I; Gratchev, Vitaliy V; Sokolov, Pavel A; Elam, Mikael; Stroganova, Tatiana A

    2012-01-01

    Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.

  15. A New Approach for Mobile Advertising Click-Through Rate Estimation Based on Deep Belief Nets.

    Science.gov (United States)

    Chen, Jie-Hao; Zhao, Zi-Qian; Shi, Ji-Yun; Zhao, Chong

    2017-01-01

    In recent years, with the rapid development of mobile Internet and its business applications, mobile advertising Click-Through Rate (CTR) estimation has become a hot research direction in the field of computational advertising, which is used to achieve accurate advertisement delivery for the best benefits in the three-side game between media, advertisers, and audiences. Current research on the estimation of CTR mainly uses the methods and models of machine learning, such as linear model or recommendation algorithms. However, most of these methods are insufficient to extract the data features and cannot reflect the nonlinear relationship between different features. In order to solve these problems, we propose a new model based on Deep Belief Nets to predict the CTR of mobile advertising, which combines together the powerful data representation and feature extraction capability of Deep Belief Nets, with the advantage of simplicity of traditional Logistic Regression models. Based on the training dataset with the information of over 40 million mobile advertisements during a period of 10 days, our experiments show that our new model has better estimation accuracy than the classic Logistic Regression (LR) model by 5.57% and Support Vector Regression (SVR) model by 5.80%.

  16. A New Approach for Mobile Advertising Click-Through Rate Estimation Based on Deep Belief Nets

    Directory of Open Access Journals (Sweden)

    Jie-Hao Chen

    2017-01-01

    Full Text Available In recent years, with the rapid development of mobile Internet and its business applications, mobile advertising Click-Through Rate (CTR estimation has become a hot research direction in the field of computational advertising, which is used to achieve accurate advertisement delivery for the best benefits in the three-side game between media, advertisers, and audiences. Current research on the estimation of CTR mainly uses the methods and models of machine learning, such as linear model or recommendation algorithms. However, most of these methods are insufficient to extract the data features and cannot reflect the nonlinear relationship between different features. In order to solve these problems, we propose a new model based on Deep Belief Nets to predict the CTR of mobile advertising, which combines together the powerful data representation and feature extraction capability of Deep Belief Nets, with the advantage of simplicity of traditional Logistic Regression models. Based on the training dataset with the information of over 40 million mobile advertisements during a period of 10 days, our experiments show that our new model has better estimation accuracy than the classic Logistic Regression (LR model by 5.57% and Support Vector Regression (SVR model by 5.80%.

  17. Power ultrasound in metal-assisted synthesis: From classical Barbier-like reactions to click chemistry.

    Science.gov (United States)

    Cintas, Pedro; Palmisano, Giovanni; Cravotto, Giancarlo

    2011-07-01

    The search for more efficient and greener synthetic procedures to obtain highly functionalized chemical structures has always found in metal-assisted reactions a noteworthy strategy. All these reactions fall in the main domain of sonochemistry; in fact few techniques can compete with power ultrasound in so efficiently activating a metal surface, thus enhancing and accelerating its subsequent reaction with an organic substrate. Young researchers will certainly benefit from the rich literature and past experience of several pioneers who have, since the early eighties, laid the foundations of modern sonochemical synthetic protocols. Herein we provide a concise overview that describes how ultrasound acts in such a way as to make it a fundamental tool in improving the classical one-step coupling promoted by zero-valent metal species, usually referred to as Barbier-like reactions. From early hallmarks to recent accomplishments, especially the latest Cu-catalyzed alkyne-azide reaction (the so-called Click reaction), intended to be a universal ligation in chemistry and biology; we highlight the role and crucial effects of sonication on these processes. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Sustainable thermoplastic elastomers derived from cellulose, fatty acid and furfural via ATRP and click chemistry.

    Science.gov (United States)

    Yu, Juan; Lu, Chuanwei; Wang, Chunpeng; Wang, Jifu; Fan, Yimin; Chu, Fuxiang

    2017-11-15

    Cellulose-based thermoplastic elastomers (TPEs) have attracted considerable attention because of their rigid backbone, good mechanical properties, renewable nature and abundance. In the present study, sustainable TPEs based on ethyl cellulose (EC), fatty acid and furfural were generated by the combination of ATRP and "click chemistry". To fabricate sustainable TPEs with higher toughness, a range of polymers, including mono random-copolymer poly(tetrahydrofurfuryl methacrylate-co-lauryl methacrylate) (P(THFMA-co-LMA), dual polymer side chains PTHFMA and PLMA, and mono-block copolymer PTHFMA-b-PLMA, were designed as side chains to fabricate EC brush copolymers with random, dual or block side chain architectures using the "grafting from" and "grafting onto" methods. The multi-armed structures, chemical compositions and phase separation of these EC brush copolymers were confirmed by FT-IR, 1 H NMR, GPC, DSC, TEM and SEM. Overall, three types of EC brush copolymers all exhibited the desired mechanical properties of TPEs. In addition, the EC brush copolymers with dual/block side chain architectures showed higher tensile strength than that of the random polymers with similar compositions. Copyright © 2017. Published by Elsevier Ltd.

  19. Rice straw modified by click reaction for selective extraction of noble metal ions.

    Science.gov (United States)

    Wang, Jingjing; Wei, Jun; Li, Juan

    2015-02-01

    Rice straw was modified by azide-alkyne click reaction in order to realize selective extraction of noble metal ions. The ability of the modified straw to adsorb Pd(2+) and Pt(4+) was assessed using a batch adsorption technique. It was found that the sorption equilibrium could be reached within 1h and the adsorption capacity increased with temperature for both Pd(2+) and Pt(4+). The maximum sorption capacities for Pd(2+) and Pt(4+) were respectively attained in 1.0 and 0.1 mol/L HCl. The modified straw showed excellent selectivity for noble metal ions in comparison to the pristine straw. In addition, the modified straw was examined as a column packing material for extraction of noble metal ions. It was indicated that 1.0 mL/min was the best flow rate for Pd(2+) and Pt(4+). The modified straw could be repeatedly used for 10 times without any significant loss in the initial binding affinity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Synthesis of novel pyrazoline based bis (1,2,3-triazole scaffolds via click chemistry

    Directory of Open Access Journals (Sweden)

    Kiran Kothuri

    2017-01-01

    Full Text Available A series of novel bis(1,2,3-triazoles derivatives 7a–m were synthesized by the 1,3-dipolar cycloaddition (click-reaction of 1-methyl-3,5-bis(2- -(prop-2-yn-1-yloxyphenyl-4,5-dihydro-1H-pyrazole (5 with various aralkyl azides 6a–m in the presence of sodium ascorbate and copper sulphate with good yields. The required precursor 5 was synthesized by reacting (E-1,3- -bis(2-hydroxyphenylprop-2-en-1-one (3 with methylhydrazine hydrate via 2,2′-(1-methyl-4,5-dihydro-1H-pyrazole-3,5-diyldiphenol 4, followed by reaction with propargyl bromide. The homogeneity of all the newly synthesized compounds was checked by TLC. The IR, NMR, mass spectral data and elemental analysis were in accord with the assigned structure. The title compounds were evaluated for their antibacterial activity against various bacterial strains, i.e., Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis; compounds 7f–7h and 7j were found to be moderately active against the bacteria, when compared with that of the standard drug. Furthermore, the same library of compounds was evaluated for their antioxidant activity using the nitric oxide radical scavenging activity. The results of the study showed that compounds 7e–7h and 7k–7m showed good radical scavenging activity.

  1. Development of a female attractant for the click beetle pest Agriotes brevis.

    Science.gov (United States)

    Vuts, József; Furlan, Lorenzo; Csonka, Éva Bálintné; Woodcock, Christine M; Caulfield, John C; Mayon, Patrick; Pickett, John A; Birkett, Michael A; Tóth, Miklós

    2014-04-01

    Traps suitable for catching female Agriotes click beetles may provide better reconnaissance than pheromone-baited traps which catch only males, thereby contributing to more efficient crop protection. The basis for this study came from (i) observations of female Agriotes brevis (Candeze) aggregating beneath foliage of Medicago sativa (L.) and Lolium italicum (A. Br.) placed on plastic sheets on bare soil, and (ii) field tests demonstrating attraction of females to traps baited with foliage from these plants. The aim was to identify and field test volatile compounds from M. sativa and L. italicum leaves. A number of electrophysiologically active chemicals were identified from headspace extracts of M. sativa and L. italicum. Three different synthetic blends of the identified compounds, comprising four, seven and nine components, were field tested. The four- and nine-component blends caught more female A. brevis than unbaited traps, with the proportion of females not differing between blends. The plant-derived blends were shown to catch female A. brevis under field conditions when applied in traps. Of these, the four-component blend, given its relatively simple composition [(Z)-3-hexenyl acetate:methyl benzoate:(Z)-3-hexen-1-ol:methyl salicylate 300:5:30:30 mg bait(-1)], may be a suitable 'standard' blend for bait optimisation. © 2013 Society of Chemical Industry.

  2. Blind consent? A social psychological investigation of non-readership of click-through agreements.

    Science.gov (United States)

    Plaut, Victoria C; Bartlett, Robert P

    2012-08-01

    Across two studies we aimed to measure empirically the extent of non-readership of click-through agreements (CTAs), identify the dominant beliefs about CTAs contributing to non-readership, and experimentally manipulate these beliefs to decrease automatic non-reading behavior and enhance contract efficiency. In our initial questionnaire study (Study 1), as predicted, the vast majority of participants reported not reading CTAs and the most prevalent beliefs about CTAs contributing to non-readership included: they are too long and time-consuming, they are all the same, they give one no choice but to agree, they are irrelevant, and vendors are generally reputable. Manipulating these beliefs on a simulated music website (Study 2) revealed an increase in readership. In addition, CTA comprehension and CTA rejection rates were both increased significantly by manipulating the length of the CTA. These results demonstrate support for the influence of widely held beliefs about CTAs on contract readership, provide evidence against the common "limited cognition" perspective on non-readership, and suggest that presenting CTAs in a short, readable format can increase CTA readership and comprehension as well as shopping of CTA terms. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  3. A New Approach for Mobile Advertising Click-Through Rate Estimation Based on Deep Belief Nets

    Science.gov (United States)

    Zhao, Zi-Qian; Shi, Ji-Yun; Zhao, Chong

    2017-01-01

    In recent years, with the rapid development of mobile Internet and its business applications, mobile advertising Click-Through Rate (CTR) estimation has become a hot research direction in the field of computational advertising, which is used to achieve accurate advertisement delivery for the best benefits in the three-side game between media, advertisers, and audiences. Current research on the estimation of CTR mainly uses the methods and models of machine learning, such as linear model or recommendation algorithms. However, most of these methods are insufficient to extract the data features and cannot reflect the nonlinear relationship between different features. In order to solve these problems, we propose a new model based on Deep Belief Nets to predict the CTR of mobile advertising, which combines together the powerful data representation and feature extraction capability of Deep Belief Nets, with the advantage of simplicity of traditional Logistic Regression models. Based on the training dataset with the information of over 40 million mobile advertisements during a period of 10 days, our experiments show that our new model has better estimation accuracy than the classic Logistic Regression (LR) model by 5.57% and Support Vector Regression (SVR) model by 5.80%. PMID:29209363

  4. Relationship between overbite/overjet and clicking or crepitus of the temporomandibular joint.

    Science.gov (United States)

    Hirsch, Christian; John, Mike T; Drangsholt, Mark T; Mancl, Lloyd A

    2005-01-01

    Since occlusal variables such as overbite and overjet have been thought to be associated with temporomandibular disorders (TMD), and joint sounds are some of the most prevalent signs of TMD, the aim of this study was to determine whether overbite and overjet are risk factors for temporomandibular joint (TMJ) sounds. A population-based cross-sectional study of 3,033 subjects (age range, 10 to 75 years; 53% female) was conducted in Germany. Overbite/overjet, reproducible reciprocal clicking (RRC) during open-close jaw movements that did not occur in the protrusive jaw position, and joint crepitus were assessed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). When age and gender were controlled for, high or low values of overbite and overjet were not associated with a greater risk of RRC and crepitus as compared to a reference category of a normal overbite and overjet of 2 to 3 mm (multiple logistic regression; odds ratios 0.7 to 1.3; P > .05 for all). This study showed that higher or lower overbite or overjet jaw relationships, even extreme values, are not risk factors for TMJ sounds as assessed by clinical examination.

  5. Fluorometric method for inorganic pyrophosphatase activity detection and inhibitor screening based on click chemistry.

    Science.gov (United States)

    Xu, Kefeng; Chen, Zhonghui; Zhou, Ling; Zheng, Ou; Wu, Xiaoping; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

    2015-01-06

    A fluorometric method for pyrophosphatase (PPase) activity detection was developed based on click chemistry. Cu(II) can coordinate with pyrophosphate (PPi), the addition of pyrophosphatase (PPase) into the above system can destroy the coordinate compound because PPase catalyzes the hydrolysis of PPi into inorganic phosphate and produces free Cu(II), and free Cu(II) can be reduced by sodium ascorbate (SA) to form Cu(I), which in turn initiates the ligating reaction between nonfluorescent 3-azidocoumarins and terminal alkynes to produce a highly fluorescent triazole complex, based on which, a simple and sensitive turn on fluorometric method for PPase can be developed. The fluorescence intensity of the system has a linear relationship with the logarithm of the PPase concentration in the range of 0.5 and 10 mU with a detection limit down to 0.2 mU (S/N = 3). This method is cost-effective and convenient without any labels or complicated operations. The proposed system was applied to screen the potential PPase inhibitor with high efficiency. The proposed method can be applied to diagnosis of PPase-related diseases.

  6. Label-free electrochemical DNA sensor using "click"-functionalized PEDOT electrodes.

    Science.gov (United States)

    Galán, Teresa; Prieto-Simón, Beatriz; Alvira, Margarita; Eritja, Ramón; Götz, Günther; Bäuerle, Peter; Samitier, Josep

    2015-12-15

    Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected by differential pulse voltammetry, evaluating the changes in the electrochemical properties of the polymer produced by the recognition event. A limit of detection of 0.13 nM was achieved using this highly selective PEDOT-based genosensor, without the need for labeling techniques or microelectrode fabrication processes. These results are promising for the development of label-free and reagentless DNA hybridization sensors based on conducting polymeric substrates. Biosensors can be easily prepared using any DNA sequence containing an alkyne moiety. The data presented here reveal the potential of this DNA sensor for diagnostic applications in the screening of diseases, such as "Hepatitis C", and genetic mutations. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics.

    Science.gov (United States)

    Pokorny, Jan; Borkova, Lucie; Urban, Milan

    2018-02-13

    Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry

    Directory of Open Access Journals (Sweden)

    Ye Tian

    2016-06-01

    Full Text Available In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a–e, 11a–e, 12a–e, 13a–e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29 under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05–125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a–e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.

  9. Click functionalization of phenyl-capped bithiophene on azide-terminated self-assembled monolayers

    International Nuclear Information System (INIS)

    Zheng, Yijun; Cui, Jiaxi; Ikeda, Taichi

    2015-01-01

    Graphical abstract: - Highlights: • Electrochemically-active self-assembled monolayers with phenyl-capped bithiophene were prepared. • Post-functionalization method based on click chemistry solved the solubility issue of phenyl-capped thiophene alkanethiol. • The capture and release of the counter anions during the redox reaction were detectable by E-QCM. - Abstract: We immobilized tetra(ethylene glycol)-substituted phenyl-capped bithiophene with alkyne terminals (Ph2TPh-alkyne) on azide-terminated self-assembled monolayers (N 3 -SAMs) by Cu-catalyzed azide-alkyne cycloaddition reaction. Ph2TPh-functionalized SAMs on a gold substrate showed reversible electrochemical response. The surface densities of the azide groups in N 3 -SAMs and Ph2TPh units in Ph2TPh-functionalized SAMs were estimated to be 7.3 ± 0.3 × 10 −10 mol cm −2 and 4.6 ± 0.3 × 10 −10 mol cm −2 , respectively, by quartz crystal microbalance (QCM). Most of Ph2TPh-alkynes are considered to be anchored on N 3 -SAMs via both terminal groups. Ph2TPh-functionalized SAMs exhibited reversible redox peaks in cyclic voltammetry (CV). In redox reaction, reversible capture and release of the counter anion could be monitored by electrochemical QCM (E-QCM).

  10. Click functionalization of phenyl-capped bithiophene on azide-terminated self-assembled monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yijun; Cui, Jiaxi [Max Planck Institute for Polymer Research (MPIP), Ackermannweg 10, Mainz 55128 (Germany); Ikeda, Taichi, E-mail: IKEDA.Taichi@nims.go.jp [Max Planck Institute for Polymer Research (MPIP), Ackermannweg 10, Mainz 55128 (Germany); Polymer Materials Unit, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044 (Japan)

    2015-11-15

    Graphical abstract: - Highlights: • Electrochemically-active self-assembled monolayers with phenyl-capped bithiophene were prepared. • Post-functionalization method based on click chemistry solved the solubility issue of phenyl-capped thiophene alkanethiol. • The capture and release of the counter anions during the redox reaction were detectable by E-QCM. - Abstract: We immobilized tetra(ethylene glycol)-substituted phenyl-capped bithiophene with alkyne terminals (Ph2TPh-alkyne) on azide-terminated self-assembled monolayers (N{sub 3}-SAMs) by Cu-catalyzed azide-alkyne cycloaddition reaction. Ph2TPh-functionalized SAMs on a gold substrate showed reversible electrochemical response. The surface densities of the azide groups in N{sub 3}-SAMs and Ph2TPh units in Ph2TPh-functionalized SAMs were estimated to be 7.3 ± 0.3 × 10{sup −10} mol cm{sup −2} and 4.6 ± 0.3 × 10{sup −10} mol cm{sup −2}, respectively, by quartz crystal microbalance (QCM). Most of Ph2TPh-alkynes are considered to be anchored on N{sub 3}-SAMs via both terminal groups. Ph2TPh-functionalized SAMs exhibited reversible redox peaks in cyclic voltammetry (CV). In redox reaction, reversible capture and release of the counter anion could be monitored by electrochemical QCM (E-QCM).

  11. Design of functionalized cellulosic honeycomb films: site-specific biomolecule modification via "click chemistry".

    Science.gov (United States)

    Xu, William Z; Zhang, Xinyue; Kadla, John F

    2012-02-13

    Value-added materials from naturally abundant polymers such as cellulose are of significant importance. In particular, cellulosic open-framework structures with controlled chemical functionality of the internal surface have great potential in many biosensor applications. Although various cellulose derivatives can form porous honeycomb structured materials, solubility issues and problems with film formation exist. To address this, we have generated robust cellulosic open-framework structures that can be post-functionalized through site-specific modification. Regioselectively modified amphiphilic cellulose azides, 3-O-azidopropoxypoly(ethylene glycol)-2,6-di-O-thexyldimethylsilyl cellulosics, were synthesized, and honeycomb-patterned films were readily produced by the simple breath figures method. Changing the degree of polymerization (DP) of the pendent ethylene glycol (EG(DP)) groups from 22 to 4 increased the corresponding honeycomb film pore diameters from ~1.2 to ~2.6 μm, enabling the potential tuning of pore size. Moreover, these novel azido-functionalized honeycomb films were easily functionalized using Cu(I)-catalyzed alkyne-azide [2 + 3] cycloaddition reaction; biotin was "clicked" onto the azide functionalized cellulosic honeycomb films without any effect to the film structure. These results indicate this system may serve as a platform for the design and development of biosensors.

  12. The application of click chemistry in the synthesis of agents with anticancer activity

    Directory of Open Access Journals (Sweden)

    Ma N

    2015-03-01

    Full Text Available Nan Ma,1–3 Ying Wang,3 Bing-Xin Zhao,3 Wen-Cai Ye,1,3 Sheng Jiang2 1Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 2Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 3Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China Abstract: The copper(I-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. Keywords: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, antimicrotubule agents

  13. "Click" chemistry mildly stabilizes bifunctional gold nanoparticles for sensing and catalysis.

    Science.gov (United States)

    Li, Na; Zhao, Pengxiang; Liu, Na; Echeverria, María; Moya, Sergio; Salmon, Lionel; Ruiz, Jaime; Astruc, Didier

    2014-07-01

    A large family of bifunctional 1,2,3-triazole derivatives that contain both a polyethylene glycol (PEG) chain and another functional fragment (e.g., a polymer, dendron, alcohol, carboxylic acid, allyl, fluorescence dye, redox-robust metal complex, or a β-cyclodextrin unit) has been synthesized by facile "click" chemistry and mildly coordinated to nanogold particles, thus providing stable water-soluble gold nanoparticles (AuNPs) in the size range 3.0-11.2 nm with various properties and applications. In particular, the sensing properties of these AuNPs are illustrated through the detection of an analogue of a warfare agent (i.e., sulfur mustard) by means of a fluorescence "turn-on" assay, and the catalytic activity of the smallest triazole-AuNPs (core of 3.0 nm) is excellent for the reduction of 4-nitrophenol in water. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. In situ photopolymerization of biomaterials by thiol-yne click chemistry.

    Science.gov (United States)

    Lomba, Miguel; Oriol, Luis; Alcalá, Rafael; Sánchez, Carlos; Moros, María; Grazú, Valeria; Serrano, José Luis; De la Fuente, Jesús M

    2011-11-10

    The thiol-yne click chemistry reaction has been used for the in situ photocrosslinking of an aliphatic hyperbranched polyester. The biocompatibility of the resulting networks has been studied and marked cytotoxicity was not found for HeLa (human cervical carcinoma) tumoral cells and COS7 fibroblasts. The photoinduced thiol-yne process allows the generation of patterned structures with different geometries in films by DLW and these materials can be used as substrates for cell adhesion. The influence of the substrate geometry on cell adhesion has been studied by culturing cells onto these substrates and a preference for the photopatterned polymeric material can be seen in some of the structures by contrast phase microscopy. Actin and vinculin fluorescent staining revealed different adhesion behavior for HeLa cells and COS7 fibroblasts and this could be assigned to the different motility of cells. The thiol-yne photoreaction has proven to be an attractive approach for the preparation of micropatterned biomaterials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Amphiphilic self-assembled polymeric copper catalyst to parts per million levels: click chemistry.

    Science.gov (United States)

    Yamada, Yoichi M A; Sarkar, Shaheen M; Uozumi, Yasuhiro

    2012-06-06

    Self-assembly of copper sulfate and a poly(imidazole-acrylamide) amphiphile provided a highly active, reusable, globular, solid-phase catalyst for click chemistry. The self-assembled polymeric Cu catalyst was readily prepared from poly(N-isopropylacrylamide-co-N-vinylimidazole) and CuSO(4) via coordinative convolution. The surface of the catalyst was covered with globular particles tens of nanometers in diameter, and those sheetlike composites were layered to build an aggregated structure. Moreover, the imidazole units in the polymeric ligand coordinate to CuSO(4) to give a self-assembled, layered, polymeric copper complex. The insoluble amphiphilic polymeric imidazole Cu catalyst with even 4.5-45 mol ppm drove the Huisgen 1,3-dipolar cycloaddition of a variety of alkynes and organic azides, including the three-component cyclization of a variety of alkynes, organic halides, and sodium azide. The catalytic turnover number and frequency were up to 209000 and 6740 h(-1), respectively. The catalyst was readily reused without loss of catalytic activity to give the corresponding triazoles quantitatively.

  16. Click chemistry for [{sup 99m}Tc(CO){sub 3}] labeling of Lys{sup 3}-bombesin

    Energy Technology Data Exchange (ETDEWEB)

    Ferro-Flores, G., E-mail: ferro_flores@yahoo.com.m [Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, Estado de Mexico, C.P. 52750 (Mexico); Rivero, I.A. [Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, Estado de Mexico, C.P. 52750 (Mexico); Instituto Tecnologico de Tijuana, Baja California (Mexico); Santos-Cuevas, C.L. [Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, Estado de Mexico, C.P. 52750 (Mexico); Universidad Autonoma del Estado de Mexico (Mexico); Sarmiento, J.I. [Instituto Tecnologico de Tijuana, Baja California (Mexico); Arteaga de Murphy, C. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Mexico); Ocampo-Garcia, B.E. [Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N, La Marquesa, Ocoyoacac, Estado de Mexico, C.P. 52750 (Mexico); Garcia-Becerra, R.; Ordaz-Rosado, D. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Mexico)

    2010-12-15

    {sup 99m}Tc-HYNIC labeled Lys{sup 3}-bombesin has shown specific binding to gastrin-releasing peptide receptors (GRP-r) over-expressed in cancer cells. Click chemistry offers an innovative functionalization strategy for biomolecules such as bombesin. The aim of this research was to apply a click chemistry approach for [{sup 99m}Tc(CO){sub 3}] labeling of Lys{sup 3}-bombesin and to compare the in vitro MCF7 breast cancer cell uptake and biodistribution profile in mice with that of {sup 99m}Tc-EDDA/HYNIC-Lys{sup 3}-bombesin. The results suggest a higher lipophilicity for {sup 99m}Tc(CO){sub 3}-triazole-Lys{sup 3}-bombesin which explains its higher in vivo hepatobiliary elimination. Pancreas-to-blood ratio for {sup 99m}Tc(CO){sub 3}-triazole-Lys{sup 3}-bombesin was 4.46 at 3 h and both bombesin radiopharmaceuticals showed specific recognition for GRP receptors in MCF7 cancer cells. Click chemistry is a reliable approach for [{sup 99m}Tc(CO){sub 3}] labeling of Lys{sup 3}-bombesin.

  17. The effects of temporo mandibular joint disorder with clicking symptom on children mastication performance in Deutero Malay race children aged 12-15 years

    Directory of Open Access Journals (Sweden)

    Henri Hartman

    2014-11-01

    Full Text Available Temporo Mandibular Joint Disorder (TMD could be caused by forward head posture. Articular sound/TMJ clicking is the most often sign and symptom for TMD that could happen in human being. The presence of TMD such as TMJ clicking would cause an imbalance masticatory system. The purpose of this research is to investigate TMJ clicking effects to masticatory performance. This research was cross-sectional study with a type of epidemiology survey. Subject were children aged 12-15 years old Deutero-Malay sub-races Live in Bandung and was taken using multi-stage random sampling technique. Subject; consisted of 24 children as control group and 28 children as TMJ clicking group. Both group were then checked for masticatory performance using multiple sieve method and 20x chewing of artificial test food. Mastication performance value represented by median particle size (MPS particle distribution (b for each group. MPS from TMJ clicking group (3.0571,SD=0.9990 showed higher value than control group (2.28958,SD=0.66838. Statistic analysis with t-test showed that there’s a significant result in both of group (pvalue=0,0024, α = 0,05. Conclussion, temporo mandibular joint clicking subject has lower masticatory performance.

  18. Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain

    International Nuclear Information System (INIS)

    Ishiwata, K.; Senda, M.; Saitoh, T.; Taguchi, K.; Toda, J.; Sano, T.; Koyanagi, Y.

    2001-01-01

    We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [ 11 C]raclopride to striatal dopamine D 2 receptors in mice. The binding of [ 11 C]raclopride, but not of [ 11 C]N-methylspiperone or [ 11 C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [ 11 C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [ 11 C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [ 11 C]raclopride to dopamine D 2 receptors, but did not induce degeneration of the receptors. (author)

  19. Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis screen

    Energy Technology Data Exchange (ETDEWEB)

    Kermany, Mohammad [St. Jude Children' s Research Hospital; Parker, Lisan [St. Jude Children' s Research Hospital; Guo, Yun-Kai [St. Jude Children' s Research Hospital; Miller, Darla R [ORNL; Swanson, Douglas J [ORNL; Yoo, Tai-June [Neuroscience Institute, Memphis, TN; Goldowitz, Daniel [University of Tennessee Health Science Center, Memphis; Zuo, Jian [St. Jude Children' s Research Hospital

    2006-01-01

    The Tennessee Mouse Genome Consortium (TMGC) employed an N-ethyl-N-nitrosourea (ENU)-mutagenesis scheme to identify mouse recessive mutants with hearing phenotypes. We employed auditory brainstem responses (ABR) to click and 8, 16, and 32 kHz stimuli and screened 285 pedigrees (1819 mice of 8-11 weeks old in various mixed genetic backgrounds) each bred to carry a homozygous ENU-induced mutation. To define mutant pedigrees, we measured P12 mice per pedigree in P2 generations and used a criterion where the mean ABR threshold per pedigree was two standard deviations above the mean of all offspring from the same parental strain. We thus identified 17 mutant pedigrees (6%), all exhibiting hearing loss at high frequencies (P16 kHz) with an average threshold elevation of 30-35 dB SPL. Interestingly, four mutants showed sex-biased hearing loss and six mutants displayed wide range frequency hearing loss. Temporal bone histology revealed that six of the first nine mutants displayed cochlear morphological defects: degeneration of spiral ganglia, spiral ligament fibrocytes or inner hair cells (but not outer hair cells) mostly in basal turns. In contrast to other ENU-mutagenesis auditory screens, our screen identified high-frequency, mild and sex-biased hearing defects. Further characterization of these 17 mouse models will advance our understanding of presbycusis and noise-induced hearing loss in humans.

  20. Digenic Inheritance in Cystinuria Mouse Model

    Science.gov (United States)

    Espino, Meritxell; Font-Llitjós, Mariona; Vilches, Clara; Salido, Eduardo; Prat, Esther; López de Heredia, Miguel; Palacín, Manuel; Nunes, Virginia

    2015-01-01

    Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients. PMID:26359869

  1. Digenic Inheritance in Cystinuria Mouse Model.

    Directory of Open Access Journals (Sweden)

    Meritxell Espino

    Full Text Available Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months and late stage (8-months of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/- present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/- and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients.

  2. The Mouse Limb Anatomy Atlas: An interactive 3D tool for studying embryonic limb patterning

    Directory of Open Access Journals (Sweden)

    DeLaurier April

    2008-09-01

    Full Text Available Abstract Background The developing mouse limb is widely used as a model system for studying tissue patterning. Despite this, few references are available that can be used for the correct identification of developing limb structures, such as muscles and tendons. Existing textual references consist of two-dimensional (2D illustrations of the adult rat or mouse limb that can be difficult to apply when attempting to describe the complex three-dimensional (3D relationship between tissues. Results To improve the resources available in the mouse model, we have generated a free, web-based, interactive reference of limb muscle, tendon, and skeletal structures at embryonic day (E 14.5 http://www.nimr.mrc.ac.uk/3dlimb/. The Atlas was generated using mouse forelimb and hindlimb specimens stained using immunohistochemistry to detect muscle and tendon. Limbs were scanned using Optical Projection Tomography (OPT, reconstructed to make 3D models and annotated using computer-assisted segmentation tools in Amira 3D Visualisation software. The annotated dataset is visualised using Java, JAtlasView software. Users click on the names of structures and view their shape, position and relationship with other structures within the 3D model and also in 2D virtual sections. Conclusion The Mouse Limb Anatomy Atlas provides a novel and valuable tool for researchers studying limb development and can be applied to a range of research areas, including the identification of abnormal limb patterning in transgenic lines and studies of models of congenital limb abnormalities. By using the Atlas for "virtual" dissection, this resource offers an alternative to animal dissection. The techniques we have developed and employed are also applicable to many other model systems and anatomical structures.

  3. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third......-degree burn injury was induced with a hot-air blower. The third-degree burn was confirmed histologically. At 48 h, a decline in the concentration of peripheral blood leucocytes was observed in the group of mice with burn wound. The reduction was ascribed to the decline in concentration of polymorphonuclear...... neutrophil leucocytes and monocytes. When infecting the skin with Pseudomonas aeruginosa, a dissemination of bacteria was observed only in the burn wound group. Histological characterization of the skin showed an increased polymorphonuclear neutrophil granulocytes dominated inflammation in the group of mice...

  4. Immobilization of alkynyl functionalized manganese phthalocyanine via click electrochemistry for electrocatalytic oxygen evolution reaction.

    Science.gov (United States)

    Öztaş, B; Akyüz, D; Koca, A

    2017-10-04

    Peripherally and non-peripherally terminal alkynyl substituted manganese phthalocyanines (MnPc) were synthesized and characterized and then used as functional materials in modified electrodes. MnPcs were substituted with alkynyl groups, which are reactive moieties in click electrochemistry (CEC) reactions. Mn(iii) cations were incorporated into the cavity of the Pc ring in order to increase the redox activity of the complexes. Electrochemical characterizations of the complexes were determined by voltammetric and in situ spectroelectrochemical measurements in order to determine their possible technological applications. MnPc complexes illustrated five redox couples and these redox couples were assigned as [Cl-Mn III Pc 2- ]/[Cl-Mn II Pc 2- ] 1- , [Cl-Mn II Pc 2- ] 1- /[Cl-Mn I Pc 2- ] 2- , [Cl-Mn I Pc 2- ] 2- /[ Cl-Mn I Pc 3- ] 3- , and [Cl-Mn III Pc 2- ]/[Cl-Mn III Pc 1- ] 1+ redox processes. The position of the substituents affected the mechanism of the redox reactions and influenced the tendency to react with the molecular oxygen. Moreover, changing the position of the substituents slightly influenced the peak potentials and reversibility of the redox processes. For the applications, modified electrodes (ITO/PANI-N 3 -MnPc and GCE/PANI-N 3 -MnPc) were constructed with CEC reaction between azido functionalized polyaniline (PANI-N 3 ) and terminally alkynyl substituted MnPcs and these electrodes. Voltammetric characterizations of the modified electrodes illustrated suitable redox activity and conductivity for the practical applications. Finally, the GCE/PANI-N 3 -MnPc electrode was tested as a potential electrocatalyst for water splitting reaction. Although the GCE/PANI-N 3 -MnPc electrode did not catalyze the hydrogen evolution reaction (HER), it significantly catalyzed the oxygen evolution reaction (OER) in aqueous solution.

  5. Library of Antifouling Surfaces Derived From Natural Amino Acids by Click Reaction.

    Science.gov (United States)

    Xu, Chen; Hu, Xin; Wang, Jie; Zhang, Ye-Min; Liu, Xiao-Jiu; Xie, Bin-Bin; Yao, Chen; Li, Yi; Li, Xin-Song

    2015-08-12

    Biofouling is of great concern in numerous applications ranging from ophthalmological implants to catheters, and from bioseparation to biosensors. In this report, a general and facile strategy to combat surface fouling is developed by grafting of amino acids onto polymer substrates to form zwitterionic structure through amino groups induced epoxy ring opening click reaction. First of all, a library of poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) hydrogels with zwitterionic surfaces were prepared, resulting in the formation of pairs of carboxyl anions and protonated secondary amino cations. The analysis of attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the successful immobilization of amino acids on the hydrogel surfaces. After that, the contact angle and equilibrium water content of the modified hydrogels showed that the hydrogels exhibited improved hydrophilicity compared with the parent hydrogel. Furthermore, the protein deposition was evaluated by bicinchoninic acid assay using bovine serum albumin (BSA) and lysozyme as models. The results indicated that the performance of the hydrogels was determined by the nature of incorporated amino acid: the hydrogels incorporated with neutral amino acids had nonspecific antiadsorption capability to both BSA and lysozyme; the hydrogels incorporated with charged amino acids showed antiadsorption behaviors against protein with same charge and enhanced adsorption to the protein with opposite charge; the optimal antiadsorption performance was observed on the hydrogels incorporated with polar amino acids with a hydroxyl residual. The improvement of antiprotein fouling of the neutral amino acids grafted hydrogels can be ascribed to the formation of zwitterionic surfaces. Finally, a couple of soft contact lenses grafted with amino acids were fabricated having improved antifouling property and hydrophilicity. The result demonstrated the success of

  6. Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

    Science.gov (United States)

    Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

    2014-02-17

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.

  7. Neutron issues in the JANUS mouse program

    International Nuclear Information System (INIS)

    Carnes, B.A.; Grahn, D.

    1990-01-01

    Over the last 25 years, the JANUS program in the Biological and Medical Research Division at Argonne National Laboratory (ANL) has compiled a database on the response of both sexes of an F 1 hybrid mouse, the B6CF 1 (C57BL/6 x BALB/c), to external whole- body irradiation by 60 Co γ-rays and fission neutrons. Three basic patterns of exposure for both neutrons and γ-rays have been investigated: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. All irradiations were terminated at predetermined total doses, with dose calculated in centigrays at the midline of the mouse. Three endpoints will be discussed in this paper: (1) life shortening, (2) a point estimate for cumulative mortality, and (3) the hazard function. Life shortening is used as an analysis endpoint because it summarizes, in a single index, the integrated effect of all injuries accumulated by an organism. Histopathological analyses of the mice used in the ANL studies have indicated that 85% of the deaths were caused by neoplasms. Connective tissue tumors were the dominant tumor in the B6CF 1 mouse, with tumors of lymphoreticular origin accounting for approximately 80% of this class. The latter two endpoints will therefore be used to describe the life table experience of mice dying from the lymphoreticular class of tumors. Dose-response models will be applied to the three endpoints in order to describe the response function for neutron exposures, evaluate the effect of dose range and pattern of exposure on the response function for neutrons, and provide a set of neutron relative biological effectiveness (RBE) values of the ANL database. 25 refs

  8. More than just a mouse click: research into work practices behind the assignment of medical trust marks on the World Wide Web.

    Science.gov (United States)

    Adams, Samantha A; de Bont, Antoinette A

    2007-06-01

    Hyperlinked web trust marks have been a popular topic of discussion during the past 10 years. However, the discussion has focused mostly on what these trust marks are not doing in terms of helping patients (or other lay end users) find reliable medical information on the web. In this paper, we discuss how this focus on patients and their actions with respect to trust marks, has overshadowed, if not rendered invisible, what trust marks are doing to educate medical site/information providers. We draw on data from ethnographic research conducted at the Health on the Net Foundation in 2002 and 2003 in order to explore an alternate definition of what it means to be a 'user' of a trust mark and the importance of the review process in educating site providers. We argue that understanding the work involved in the process of assigning a seal is crucial to understanding the role that the seal plays as part of the medical internet.

  9. Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals

    Directory of Open Access Journals (Sweden)

    Dabelsteen Torben

    2008-11-01

    Full Text Available Abstract Background Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. Results A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. Conclusion The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1 body size, (2 age and (3 presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals.

  10. Ribosome-templated azide–alkyne cycloadditions: synthesis of potent macrolide antibiotics by in situ click chemistry

    Science.gov (United States)

    Glassford, Ian; Teijaro, Christiana N.; Daher, Samer S.; Weil, Amy; Small, Meagan C.; Redhu, Shiv K.; Colussi, Dennis J.; Jacobson, Marlene A.; Childers, Wayne E.; Buttaro, Bettina; Nicholson, Allen W.; MacKerell, Alexander D.; Cooperman, Barry S.; Andrade, Rodrigo B.

    2016-01-01

    Over half of all antibiotics target the bacterial ribosome—Nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semi-synthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolidefunctionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome-templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a sixteen-component reaction (i.e., azide 2 and fifteen alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the Site-Identification by Ligand Competitive Saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogs with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1). PMID:26878192

  11. Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by In Situ Click Chemistry.

    Science.gov (United States)

    Glassford, Ian; Teijaro, Christiana N; Daher, Samer S; Weil, Amy; Small, Meagan C; Redhu, Shiv K; Colussi, Dennis J; Jacobson, Marlene A; Childers, Wayne E; Buttaro, Bettina; Nicholson, Allen W; MacKerell, Alexander D; Cooperman, Barry S; Andrade, Rodrigo B

    2016-03-09

    Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolide-functionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome-templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a 16-component reaction (i.e., azide 2 and 15 alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the site-identification by ligand competitive saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogues with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1).

  12. A comparison of conventional and click labeling approaches to the synthesis of F-18 labeled glucopyranosyl triazole

    International Nuclear Information System (INIS)

    Kim, D. H.; Choi, Y. S.; Lee, K. H.; Choi, J. Y.; Choi, Y.; Kim, B. T.

    2007-01-01

    Radiolabeled glucose analogs are attractive targets for in vivo imaging of glucose metabolism. In the present study, F-18 labeled glucopyranosyl triazole was synthesized using conventional and click labeling approaches, and their results were compared in terms of radiochemical yield, specific activity, and synthesis time. 4-[(2-Fluoroethyl)-1-(-D-glucopyranosyl)]-1H-1, 2, 3-triazole (1) was synthesized by the Cu(I)-catalyzed 1, 3-cycloaddition of tetraacetyl glucopyranosyl azide and 3-butyn-1-ol, hydroxy group fluorination, tetraacetyl group deprotection, and subsequent neutralization. [F-18]1 was synthesized using two conventional radiofluorination of tetraacetyl triazole tosylate precursor, followed by tetraacetyl group deprotection and Cu(I)-catalyzed 1, 3-cycloaddition of F-18 labeled butyne and glucopyranosyl azide. The radiotracer was purified by reverse phase HPLC and co-injected with 1 into a HPLC system to confirm its identity. Non-radiolabeled standard 1 was synthesized in overall 33% yield. In the synthesis of [F-18]1, the click labeling approach was superior to the conventional approach, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mol vs. 23.5 GBq/mol), and shorter synthesis time (75-80 min vs. 95-100 min). In addition, protection of the hydroxy groups of glucopyranosyl azide was not required in the former method. The radiotracer was identified by co-elution with 1 on HPLC. These results demonstrate that click labeling approach is a rapid and efficient method which does not require the protection of functional groups, and that it can readily be applied to the preparation of other radiotracers

  13. Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles.

    Directory of Open Access Journals (Sweden)

    Petra Smyslova

    Full Text Available Copper-free click reactions between a dibenzoazocine derivative and azides derived from 5-methyluridine were investigated. The non-catalyzed reaction yielded both regioisomers in an approximately equivalent ratio. The NMR spectra of each regioisomer revealed conformational isomery. The ratio of isomers was dependent on the type of regioisomer and the type of solvent. The synthesis of various analogs, a detailed NMR study and computational modeling provided evidence that the isomery was dependent on the interaction of the azocine and pyrimidine parts.

  14. "Clicked" sugar-curcumin conjugate: modulator of amyloid-β and tau peptide aggregation at ultralow concentrations.

    Science.gov (United States)

    Dolai, Sukanta; Shi, Wei; Corbo, Christopher; Sun, Chong; Averick, Saadyah; Obeysekera, Dinali; Farid, Mina; Alonso, Alejandra; Banerjee, Probal; Raja, Krishnaswami

    2011-12-21

    The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of curcumin with amplified bioefficacy in modulating amyloid-β and tau peptide aggregation is presented. Curcumin inhibits amyloid-β and tau peptide aggregation at micromolar concentrations; the sugar-curcumin conjugate inhibits Aβ and tau peptide aggregation at concentrations as low as 8 nM and 0.1 nM, respectively. In comparison to curcumin, this conveniently synthesized Alzheimer's drug candidate is a more powerful antioxidant.

  15. Click construction of spiro- and bridged-quatrefoil polymer topologies with kyklo-telechelics having an azide group.

    Science.gov (United States)

    Ko, Yee Song; Yamamoto, Takuya; Tezuka, Yasuyuki

    2014-02-01

    Unprecedented tetracyclic polymer topologies with spiro- and a bridged-type quatrefoil forms are effectively constructed through an alkyne-azide, click-linking reaction by employing a kyklo-telechelic poly(tetrahydrofuran), poly(THF), precursor having an azide group, obtained through an electrostatic self-assembly and covalent fixation (ESA-CF) process, and complementary tetrafunctional alkyne reagents of either a pentaerythritol derivative or a four-armed star telechelic polymer precursor. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Synthesis of New 3-(2-Chloroquinolin-3-yl)-5-Phenylisoxazole Derivatives via Click-Chemistry Approach

    International Nuclear Information System (INIS)

    Fernández-Galleguillos, Carlos; Saavedra, Luis A.; Gutierrez, Margarita

    2014-01-01

    Herein, we report the synthesis of new substituted 3-(2-chloroquinolin-3-yl)-5-phenylisoxazole (3a-j) by click chemistry in good to moderate yields. This approach is based on the regioselective copper(I)-catalyzed cycloaddition between different nitrile oxides derived from 2-chloroquinoline- 3-carbaldehyde (2a-j) and phenylacetylene. Finally these derivatives were screened for their antibacterial evaluation in vitro against three Gram-negative clinical bacteria: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii using standard methods. (author)

  17. Synthesis of New 3-(2-Chloroquinolin-3-yl)-5-Phenylisoxazole Derivatives via Click-Chemistry Approach

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Galleguillos, Carlos; Saavedra, Luis A.; Gutierrez, Margarita [Laboratorio de Sintesis Organica, Instituto de Quimica de Recursos Naturales, Universidad de Talca (Chile)

    2014-02-15

    Herein, we report the synthesis of new substituted 3-(2-chloroquinolin-3-yl)-5-phenylisoxazole (3a-j) by click chemistry in good to moderate yields. This approach is based on the regioselective copper(I)-catalyzed cycloaddition between different nitrile oxides derived from 2-chloroquinoline- 3-carbaldehyde (2a-j) and phenylacetylene. Finally these derivatives were screened for their antibacterial evaluation in vitro against three Gram-negative clinical bacteria: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii using standard methods. (author)

  18. Brainstem auditory evoked potentials with the use of acoustic clicks and complex verbal sounds in young adults with learning disabilities.

    Science.gov (United States)

    Kouni, Sophia N; Giannopoulos, Sotirios; Ziavra, Nausika; Koutsojannis, Constantinos

    2013-01-01

    Acoustic signals are transmitted through the external and middle ear mechanically to the cochlea where they are transduced into electrical impulse for further transmission via the auditory nerve. The auditory nerve encodes the acoustic sounds that are conveyed to the auditory brainstem. Multiple brainstem nuclei, the cochlea, the midbrain, the thalamus, and the cortex constitute the central auditory system. In clinical practice, auditory brainstem responses (ABRs) to simple stimuli such as click or tones are widely used. Recently, complex stimuli or complex auditory brain responses (cABRs), such as monosyllabic speech stimuli and music, are being used as a tool to study the brainstem processing of speech sounds. We have used the classic 'click' as well as, for the first time, the artificial successive complex stimuli 'ba', which constitutes the Greek word 'baba' corresponding to the English 'daddy'. Twenty young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) comprised the diseased group. Twenty sex-, age-, education-, hearing sensitivity-, and IQ-matched normal subjects comprised the control group. Measurements included the absolute latencies of waves I through V, the interpeak latencies elicited by the classical acoustic click, the negative peak latencies of A and C waves, as well as the interpeak latencies of A-C elicited by the verbal stimulus 'baba' created on a digital speech synthesizer. The absolute peak latencies of waves I, III, and V in response to monoaural rarefaction clicks as well as the interpeak latencies I-III, III-V, and I-V in the dyslexic subjects, although increased in comparison with normal subjects, did not reach the level of a significant difference (plearning disabilities' and who were characterized as with 'light' dyslexia according to dyslexia tests, no significant delays were found in peak latencies A and C and interpeak latencies A-C in comparison with the control group. Acoustic

  19. INBOUND AND OUTBOUND MARKETING TECHNIQUES: A COMPARISON BETWEEN ITALIAN AND ROMANIAN PURE PLAYERS AND CLICK AND MORTAR COMPANIES

    Directory of Open Access Journals (Sweden)

    Elisa Rancati

    2015-05-01

    Full Text Available Despite the large number of blog posts and articles regarding the use of Inbound and Outbound Marketing techniques, no research articles compares the propensity of companies towards these opposite types of marketing techniques among different countries. The present study is mainly focused on literature review of Inbound vs Outbound Marketing and acknowledge the academic community, interested in Content Marketing studies, about the availability of data sets regarding the implementation of these techniques at the level of Italian and Romanian pure players and click and mortar companies, which will be explored in the near future through appropriate statistical methods within the framework of a cross-cultural research.

  20. Analysis of Physical, Chemical and Microbiological Pollution in one Right Click

    International Nuclear Information System (INIS)

    Tabet, A.; Khoury, A.

    2011-01-01

    Current researches on the topic of indoor air pollution are moving towards expertise and prevention. Therefore it seems so critical to invest in the area of expertise and create a measuring device performing chemical, physical and bacteriological analysis in one click. Our choice of development towards this system of information management is oriented towards a modular system which can simultaneously transmit on real-time the analysis in the internet. Our production work has used several solutions and analyzed several possible methods such as microprocessor that has shown its reliability. The electronic system worked well even with some problems solved at the level of detection of particles α, β and γ. The solution NO-IP as for the transfer of data over the Internet has been successfully tested. In the same way we have been constrained to achieve measurement campaigns to verify the ability of the device to give consistent values. These campaigns were conducted on the Beaulieu of the University of Rennes 1, given the size of the site; it gives us a fairly comprehensive range of situations. These measurement campaigns extended for several months, with the purpose of comparing and analyzing the various results. These campaigns offer an opportunity of testing the operation of the aircraft and assessing the performance, knowing that all measures were compared to the device certified EN (Gasman). For the development of our device, we specify the direction and scope of the study area, analyze the existing level of detection performed and technical data manipulated, obtain a comprehensive description of the electronic system and reach a reasoned choice of a solution type of development. This allowed us to develop a multifunction prototype which objective is to control the quality of indoor air pollution in habitations. This device admits the same principle as product modem M2M (Machine to Machine). Through processes M2M, machinery (measuring instruments (device) and air

  1. Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review.

    Science.gov (United States)

    Talge, Nicole M; Tudor, Brooke M; Kileny, Paul R

    2018-03-30

    Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click-evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well-characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta-analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically-developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I-III, III-V, I-V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random-effects regressions to generate component-specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I-III (g = 0.7, 95% CI 0.2, 1.2), and I-V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium-to-large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co-occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Auditory brainstem responses (ABR) may be associated with ASD, but

  2. Curing of polymer thermosets via click reactions and on demand processes

    Science.gov (United States)

    Brei, Mark Richard

    In the first project, an azide functional resin and tetra propargyl aromatic diamines were fabricated for use as a composite matrix. These systems take already established epoxy/amine matrices and functionalize them with click moieties. This allows lower temperatures to be used in the production of a thermoset part. These new systems yield many better mechanical properties than their epoxy/amine derivatives, but their Tgs are low in comparison. The second project investigates the characterization of a linear system based off of the above azide functional resin and a difunctional alkyne. Through selectively choosing catalyst, the linear system can show regioselectivity to either a 1,4-disubstituted triazole, or a 1,5-disubstituted triazole. Without the addition of catalyst, the system produces both triazoles in almost an equal ratio. The differently catalyzed systems were cured and then analyzed by 1H and 13C NMR to better understand the structure of the material. The third project builds off of the utility of the aforementioned azide/alkyne system and introduces an on-demand aspect to the curing of the thermoset. With the inclusion of copper(II) within the azide/alkyne system, UV light is able to catalyze said reaction and cure the material. It has been shown that the copper(II) loading levels can be extremely small, which helps in reducing the copper's effect on mechanical properties The fourth project takes a look at polysulfide-based sealants. These sealants are normally cured via an oxidative reaction. This project took thiol-terminated polysulfides and fabricated alkene-terminated polysulfides for use as a thiol-ene cured material. By changing the mechanism for cure, the polysulfide can be cured via UV light with the use of a photoinitiator within the thiol/alkene polysulfide matrix. The final chapter will focus on a characterization technique, MALDI-TOF, which was used to help characterize the above materials as well as many others. By using MALDI-TOF, the

  3. Single motor unit firing behaviour in the right trapezius muscle during rapid movement of right or left index finger.

    Directory of Open Access Journals (Sweden)

    Karen eSøgaard

    2014-11-01

    Full Text Available Computer work is associated with low level sustained activity in the trapezius muscle that may cause myalgia. The activity may be attention related or part of a general multijoint motor program providing stabilization of the shoulder girdle for precise finger manipulation. This study examines single motor unit (MU firing pattern in the right trapezius muscle during fast movements of ipsi or contralateral index finger. Modulated firing rate would support a general multi joint motor program, while a generally increased and continuous firing rate would support attention related activation. 12 healthy female subjects were seated at a computer work place with elbows and forearms supported. Ten double clicks (DC were performed with right and left index finger on a computer mouse instrumented with a trigger.Surface EMG was recorded from right and left trapezius muscle. Intramuscular EMG was recorded with a quadripolar wire electrode in the right trapezius.Surface EMG was analysed as %MVE. The intramuscular EMG was decomposed into individual MU action potential trains. Instantaneous firing rate (IFR was calculated from inter-spike interval with ISI shorter than 20 ms defined as doublets. IFR was averaged across 10 DC to show IFR modulation.Surface EMG in both right and left trapezius was 1.8-2.5%MVE. During right hand DC a total of 32 MUs were identified. Four subjects showed no activity. Four showed MU activity with weak or no variations related to the timing of DC. Four subjects showed large modulation in IFR with temporal relation to DC. During left hand DC 15 MUs were identified in 4 subjects, for two of the subjects with IFR modulations related to DC. Doublets was found as an integrated part of MU activation in the trapezius muscle and for one subject temporarily related to DC. In conclusion, DC with ipsi- and contralateral fast movements of the index finger was found to evoke biomechanically as well as attention related activity pattern in the

  4. Successful mouse hepatocyte culture with sandwich collagen gel formation

    Science.gov (United States)

    Choi, Hyun Jung

    2013-01-01

    Purpose Primary mammalian hepatocytes largely retain their liver-specific functions when they are freshly derived from donors. However, long-term cultures of functional hepatocytes are difficult to establish. To increase the longevity and maintain the differentiated functions of hepatocytes in primary culture, cells can be cultured in a sandwich configuration of collagen. In such a configuration, hepatocytes can be cultured for longer periods compared with cultures on single layers of collagen. However, research regarding mouse hepatocytes in sandwich culture is lacking. Methods Primary mouse hepatocytes were sandwiched between two layers of collagen to maintain the stability of their liver-specific functions. After gelation, 2 mL of hepatocyte culture medium was applied. Results After 24 hours, 5, 10 days of culture, the collagen gel sandwich maintained the cellular border and numbers of bile canaliculi more efficiently than a single collagen coating in both high and low density culture dishes. Reverse transcription-polymerase chain reaction analysis of alpha-1-antitrypsin (AAT), hepatocyte nuclear factor 4 alpha (HNF4A), alphafetoprotein, albumin, tryptophan oxygenase (TO), the tyrosine aminotransferase gene, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase for mouse primary hepatocytes cultured on collagen coated dishes and collagen gels showed superior hepatocyte-related gene expression in cells grown using the collagen gel sandwich culture system. AAT, HNF4A, albumin, TO were found to be expressed in mouse hepatocytes cultured on collagen gels for 5 and 10 days. In contrast, mouse hepatocytes grown on collagen-coated dishes did not express these genes after 5 and 10 days of culture. Conclusion The collagen gel sandwich method is suitable for primary culture system of adult mouse hepatocytes. PMID:23577314

  5. A Study of Functional Polymer Colloids Prepared Using Thiol-Ene/Yne Click Chemistry

    Science.gov (United States)

    Durham, Olivia Z.

    This project demonstrates the first instance of thiol-ene chemistry as the polymerization method for the production of polymer colloids in two-phase heterogeneous suspensions, miniemulsions, and emulsions. This work was also expanded to thiol-yne chemistry for the production of polymer particles containing increased crosslinking density. The utility of thiol-ene and thiol-yne chemistries for polymerization and polymer modification is well established in bulk systems. These reactions are considered 'click' reactions, which can be defined as processes that are both facile and simple, offering high yields with nearly 100% conversion, no side products, easy product separation, compatibility with a diverse variety of commercially available starting materials, and orthogonality with other chemistries. In addition, thiol-ene and thiol-yne chemistry follow a step-growth mechanism for the development of highly uniform polymer networks, where polymer growth is dependent on the coupling of functional groups. These step-growth polymerization systems are in stark contrast to the chain-growth mechanisms of acrylic and styrenic monomers that have dominated the field of conventional heterogeneous polymerizations. Preliminary studies evaluated the mechanism of particle production in suspension and miniemulsion systems. Monomer droplets were compared to the final polymer particles to confirm that particle growth occurred through the polymerization of monomer droplets. Additional parameters examined include homogenization energy (mechanical mixing), diluent species and concentration, and monomer content. These reactions were conducted using photoinitiation to yield particles in a matter of minutes with diameters in the size range of several microns to hundreds of microns in suspensions or submicron particles in miniemulsions. Improved control over the particle size and size distribution was examined through variation of reaction parameters. In addition, a method of seeded suspension

  6. Optimised quantum hacking of superconducting nanowire single-photon detectors.

    Science.gov (United States)

    Tanner, Michael G; Makarov, Vadim; Hadfield, Robert H

    2014-03-24

    We explore bright-light control of superconducting nanowire single-photon detectors (SNSPDs) in the shunted configuration (a practical measure to avoid latching). In an experiment, we simulate an illumination pattern the SNSPD would receive in a typical quantum key distribution system under hacking attack. We show that it effectively blinds and controls the SNSPD. The transient blinding illumination lasts for a fraction of a microsecond and produces several deterministic fake clicks during this time. This attack does not lead to elevated timing jitter in the spoofed output pulse, and hence does not introduce significant errors. Five different SNSPD chip designs were tested. We consider possible countermeasures to this attack.

  7. Optimised quantum hacking of superconducting nanowire single-photon detectors

    Science.gov (United States)

    Tanner, Michael G.; Makarov, Vadim; Hadfield, Robert H.

    2014-03-01

    We explore bright-light control of superconducting nanowire single-photon detectors (SNSPDs) in the shunted configuration (a practical measure to avoid latching). In an experiment, we simulate an illumination pattern the SNSPD would receive in a typical quantum key distribution system under hacking attack. We show that it effectively blinds and controls the SNSPD. The transient blinding illumination lasts for a fraction of a microsecond and produces several deterministic fake clicks during this time. This attack does not lead to elevated timing jitter in the spoofed output pulse, and hence does not introduce significant errors. Five different SNSPD chip designs were tested. We consider possible countermeasures to this attack.

  8. A Comprehensive Atlas of the Adult Mouse Penis

    Science.gov (United States)

    Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.

    2016-01-01

    Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156

  9. Phylogenetic relationships of click beetles (Coleoptera: Elateridae) inferred from 28S ribosomal DNA: insights into the evolution of bioluminescence in Elateridae.

    Science.gov (United States)

    Sagegami-Oba, Reiko; Oba, Yuichi; Ohira, Hitoo

    2007-02-01

    Although the taxonomy of click beetles (family Elateridae) has been studied extensively, inconsistencies remain. We examine here the relationships between species of Elateridae based on partial sequences of nuclear 28S ribosomal DNA. Specimens were collected primarily from Japan, while luminous click beetles were also sampled from Central and South America to investigate the origins of bioluminescence in Elateridae. Neighbor-joining, maximum-parsimony, and maximum-likelihood analyses produced a consistent basal topology with high statistical support that is partially congruent with the results of previous investigations based on the morphological characteristics of larvae and adults. The most parsimonious reconstruction of the "luminous" and "nonluminous" states, based on the present molecular phylogeny, indicates that the ancestral state of Elateridae was nonluminous. This suggests that the bioluminescence in click beetle evolved independent of that of other luminous beetles, such as Lampyridae, despite their common mechanisms of bioluminescence.

  10. Click modification of helical amylose by poly(L-lysine) dendrons for non-viral gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Jia-Dong [PCFM Lab and GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen (Zhongshan) University, Guangzhou 510275 (China); Zhuang, Bao-Xiong [Second Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou 510102 (China); Mai, Kaijin [PCFM Lab and GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen (Zhongshan) University, Guangzhou 510275 (China); Chen, Ru-Fu [Second Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou 510102 (China); Wang, Jie, E-mail: sumsjw@163.com [Second Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou 510102 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [PCFM Lab and GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen (Zhongshan) University, Guangzhou 510275 (China)

    2015-04-01

    Although amylose as a naturally-occurring helical polysaccharide has been widely used for biomedical applications, few studies have dealt with its chemical modification for non-viral gene delivery. In this work, the click modification of amylose by poly(L-lysine) dendrons was carried out and then characterized by Fourier transform infrared spectroscopy, wide-angle X-ray diffraction and elemental analyses. Such a modified polysaccharide exhibited excellent ability to condense plasmid pMSCV-GFP-PARK2 into compact and spherical nanoparticles. Moreover, it displayed much lower cytotoxicity when compared to branched polyethylenimine (bPEI, 25 kDa), a commercially available gene vector. Similar to bPEI, it had a dose-dependent gene transfection activity in human embryonic kidney 293T cells, as observed by confocal laser scanning microscopy and flow cytometry. At each optimized N/P ratio, the percentage of transfected cells by this modified polysaccharide was found to be comparable to that by bPEI. Western blot and cell apoptosis analyses confirmed its effectiveness for the delivery of plasmid pMSCV-GFP-PARK2 to 293T cells. - Highlights: • The click modification of amylose by poly(L-lysine) dendrons was carried out. • This modified amylose could condense plasmid pMSCV-GFP-PARK2 into nanocomplexes. • This modified amylose exhibited much lower cytotoxicity than commercial polyethylenimine. • This modified amylose could delivery efficiently plasmid pMSCV-GFP-PARK2 to 293T cells.

  11. Improving Kinetics of “Click-Crosslinking” for Self-Healing Nanocomposites by Graphene-Supported Cu-Nanoparticles

    Directory of Open Access Journals (Sweden)

    Neda Kargarfard

    2017-12-01

    Full Text Available Investigation of the curing kinetics of crosslinking reactions and the development of optimized catalyst systems is of importance for the preparation of self-healing nanocomposites, able to significantly extend their service lifetimes. Here we study different modified low molecular weight multivalent azides for a capsule-based self-healing approach, where self-healing is mediated by graphene-supported copper-nanoparticles, able to trigger “click”-based crosslinking of trivalent azides and alkynes. When monitoring the reaction kinetics of the curing reaction via reactive dynamic scanning calorimetry (DSC, it was found that the “click-crosslinking” reactivity decreased with increasing chain length of the according azide. Additionally, we could show a remarkable “click” reactivity already at 0 °C, highlighting the potential of click-based self-healing approaches. Furthermore, we varied the reaction temperature during the preparation of our tailor-made graphene-based copper(I catalyst to further optimize its catalytic activity. With the most active catalyst prepared at 700 °C and the optimized set-up of reactants on hand, we prepared capsule-based self-healing epoxy nanocomposites.

  12. Efficient Homodifunctional Bimolecular Ring-Closure Method for Cyclic Polymers by Combining RAFT and Self-Accelerating Click Reaction.

    Science.gov (United States)

    Qu, Lin; Sun, Peng; Wu, Ying; Zhang, Ke; Liu, Zhengping

    2017-08-01

    An efficient metal-free homodifunctional bimolecular ring-closure method is developed for the formation of cyclic polymers by combining reversible addition-fragmentation chain transfer (RAFT) polymerization and self-accelerating click reaction. In this approach, α,ω-homodifunctional linear polymers with azide terminals are prepared by RAFT polymerization and postmodification of polymer chain end groups. By virtue of sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA) as small linkers, well-defined cyclic polymers are then prepared using the self-accelerating double strain-promoted azide-alkyne click (DSPAAC) reaction to ring-close the azide end-functionalized homodifunctional linear polymer precursors. Due to the self-accelerating property of DSPAAC ring-closing reaction, this novel method eliminates the requirement of equimolar amounts of telechelic polymers and small linkers in traditional bimolecular ring-closure methods. It facilitates this method to efficiently and conveniently produce varied pure cyclic polymers by employing an excess molar amount of DBA small linkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery

    Directory of Open Access Journals (Sweden)

    X. T. Cao

    2017-10-01

    Full Text Available A pH-triggered drug delivery system of degradable core cross-linked (CCL prodrug micelles was prepared by click chemistry. Doxorubicin conjugated block copolymers of azido functional poly(ethylene oxide-b-poly(glycidyl methacrylate were synthesized by the combination of RAFT polymerization, epoxide ring-opening reaction, and acid-cleavable hydrazone linkages. The CCL prodrug micelles were produced by the reaction of dipropargyl 3,3′-dithiodipropionate and dipropargyl adipate cross-linking agents with the azido groups of the micellar core via alkyne-azide click reaction, which were denoted as CCL/SS and CCL/noSS, respectively. The TEM images of CCL/SS prodrug micelles showed a spherical shape with the average diameter of 61.0 nm from water, and the shape was maintained with an increased diameter upon dilution with 5-fold DMF. The high DOX conjugation efficiency was 88.4%. In contrast to a very slow DOX release from CCL/SS prodrug micelles under the physiological condition (pH 7.4, the drug release is much faster (90% at pH 5.0 and 10 mM of GSH after 96 h. The cytotoxicity test and confocal laser scanning microscopy analysis revealed that CCL/SS prodrug micelles had much enhanced intracellular drug release capability in HepG2 cells than CCL/noSS prodrug micelles.

  14. Fluorescent porous film modified polymer optical fiber via "click" chemistry: stable dye dispersion and trace explosive detection.

    Science.gov (United States)

    Ma, Jiajun; Lv, Ling; Zou, Gang; Zhang, Qijin

    2015-01-14

    In this paper, we report a facile strategy to fabricate fluorescent porous thin film on the surface of U-bent poly(methyl methacrylate) optical fiber (U-bent POF) in situ via "click" polymerization for vapor phase sensing of explosives. Upon irradiation of evanescent UV light transmitting within the fiber under ambient condition, a porous film (POSS-thiol cross-linking film, PTCF) is synthesized on the side surface of the fiber by a thiol-ene "click" reaction of vinyl-functionalized polyhedral oligomeric silsesquioxanes (POSS-V8) and alkane dithiols. When vinyl-functionalized porphyrin, containing four allyl substituents at the periphery, is added into precursors for the polymerization, fluorescence porphyrin can be covalently bonded into the cross-linked network of PTCF. This "fastened" way reduces the aggregation-induced fluorescence self-quenching of porphyrin and enhances the physicochemical stability of the porous film on the surface of U-bent POF. Fluorescent signals of the PTCF/U-bent POF probe made by this method exhibit high fluorescence quenching toward trace TNT and DNT vapor and the highest fluorescence quenching efficiency is observed for 1, 6-hexanedimercaptan-based film. In addition, because of the presence of POSS-V8 with multi cross-linkable groups, PTCF exhibits well-organized pore network and stable dye dispersion, which not only causes fast and sensitive fluorescence quenching against vapors of nitroaromatic compounds, but also provides a repeatability of the probing performance.

  15. Click strategy using disodium salts of amino acids improves the water solubility of plinabulin and KPU-300.

    Science.gov (United States)

    Yakushiji, Fumika; Muguruma, Kyohei; Hayashi, Yoshiki; Shirasaka, Takuya; Kawamata, Ryosuke; Tanaka, Hironari; Yoshiwaka, Yushi; Taguchi, Akihiro; Takayama, Kentaro; Hayashi, Yoshio

    2017-07-15

    Plinabulin and KPU-300 are promising anti-microtubule agents; however, the low water solubility of these compounds (soluble derivatives of plinabulin and KPU-300 with a click strategy using disodium salts of amino acids. The mother skeleton, diketopiperazine (DKP), was transformed into a monolactim-type alkyne and a copper-catalyzed alkyne azide cycloaddition (CuAAC) combined azides that was derived from amino acids as a water-solubilizing moiety. The conversion of carboxyl groups into disodium salts greatly improved the water solubility by 0.8 million times compared to the solubility of the parent molecules. In addition, the α-amino acid side chains of the water-solubilizing moieties affected both the water solubility and the half-lives of the compounds during enzymatic hydrolysis. Our effort to develop a variety of water-soluble derivatives using the click strategy has revealed that the replaceable water-solubilizing moieties can alter molecular solubility and stability under enzymatic hydrolysis. With this flexibility, we are approaching to the in vivo study using water-soluble derivative. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Cyclodextrin-Triazole Derivative Functionalized on Ag-SiO{sub 2} Core-Shell Nanoparticles via Click Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Park, Gun Bae; Singu, Bal Sydulu; Hong, Sang Eun; Yoon, Kuk Ro [Hannam Univ., Daejeon (Korea, Republic of)

    2016-09-15

    Click chemistry has provided a versatile strategy for functionalization in solution chemistry under mild reaction conditions with a high degree of functional group compatibility. Initially, silver (Ag) nanoparticles were prepared by the chemical reduction method, followed by the synthesis of silver–silica (Ag–SiO{sub 2}) core–shell nanoparticles by the Stöber method. The Ag–SiO2 core shell nanoparticles were functionalized with the alkyne derivative. The cycloaddition reaction between the azide-functionalized cyclodextrin and the alkyne-functionalized Ag–SiO{sub 2} core–shell nanoparticles was carried out via the copper-catalyzed click reaction, leading to the formation of the cyclodextrin-triazole derivative on the Ag–SiO{sub 2} core–shell nanoparticles. The presence of the resulting cyclodextrin-triazole derivative on the silver–silica core–shell nanoparticles was confirmed by Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA).

  17. Hand gestures mouse cursor control

    Directory of Open Access Journals (Sweden)

    Marian-Avram Vincze

    2014-05-01

    Full Text Available The paper describes the implementation of a human-computer interface for controlling the mouse cursor. The test reveal the fact: a low-cost web camera some processing algorithms are quite enough to control the mouse cursor on computers. Even if the system is influenced by the illuminance level on the plane of the hand, the current study may represent a start point for some studies on the hand tracking and gesture recognition field.

  18. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

    Directory of Open Access Journals (Sweden)

    Zhan-Jiang Zheng

    2015-12-01

    Full Text Available The Cu(I-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted.

  19. Chemical Modification of Cyclodextrin and Amylose by Click Reaction and Its Application to the Synthesis of Poly-alkylamine-Modified Antibacterial Sugars.

    Science.gov (United States)

    Yamamura, Hatsuo

    2017-01-01

    Cyclodextrin (CD) can be chemically modified into desired and sophisticated functional molecules. However, poly-modification often produces complicated mixtures, resulting in a low yield of the desired product. As the most promising procedure to solve such problems and to achieve poly-modification of the CD molecule, we present here the Huisgen 1,3-dipolar cycloaddition, known as a click reaction. This review will describe the results of our microwave-assisted click reaction for the poly-modification of CD and amylose molecules, and its application to the study of synthetic membrane active antibacterial derivatives.

  20. The Mouse House: A brief history of the ORNL mouse-genetics program, 1947–2009

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Liane B.

    2013-10-01

    The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable

  1. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.

    Science.gov (United States)

    Russell, Liane B

    2013-01-01

    The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a

  2. Mouse Resource Browser--a database of mouse databases.

    Science.gov (United States)

    Zouberakis, Michael; Chandras, Christina; Swertz, Morris; Smedley, Damian; Gruenberger, Michael; Bard, Jonathan; Schughart, Klaus; Rosenthal, Nadia; Hancock, John M; Schofield, Paul N; Kollias, George; Aidinis, Vassilis

    2010-07-06

    The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the concomitant need for formalized experimental descriptions, data standardization, database interoperability and integration, a need that has yet to be met. We present here the Mouse Resource Browser (MRB), a database of mouse databases that indexes 217 publicly available mouse resources under 22 categories and uses a standardised database description framework (the CASIMIR DDF) to provide information on their controlled vocabularies (ontologies and minimum information standards), and technical information on programmatic access and data availability. Focusing on interoperability and integration, MRB offers automatic generation of downloadable and re-distributable SOAP application-programming interfaces for resources that provide direct database access. MRB aims to provide useful information to both bench scientists, who can easily navigate and find all mouse related resources in one place, and bioinformaticians, who will be provided with interoperable resources containing data which can be mined and integrated. Database URL: http://bioit.fleming.gr/mrb.

  3. Molecular analysis of heritable mouse mutations

    International Nuclear Information System (INIS)

    Rinchik, E.M.

    1987-01-01

    Germ-like mutations of the mouse have for years comprised one class of biological markers for mammalian reproductive and developmental toxicology. Understanding the molecular nature of mutations and the mechanisms by which mutations are translated into specific (and often complex) phenotypes, however, still looms as a major goal of mammalian biology. Molecular genetic analysis of heritable mouse mutations constitutes a significant, experimentally malleable strategy for relating genomic DNA structure to genic expression and function in mammals. The integrated use of recombinant DNA technology, which allows both the identification and analysis of expression of single genes, and classical genetic and cytogenetic analysis, which allow the important correlation between basic DNA defects and the organismic consequences of such defects, has been crucial to this strategy. Some of the approaches (e.g., specific-gene cloning, random-clone analysis of genomic regions, insertional mutagenesis) for studying the nature and effect of both mutations and their wild-type counterparts that have resulted from this integration of genetic analysis and molecular biology have been applied to many loci within the murine genome. Studies of the nature and effects of a complex set of radiation-induced mutations at the dilute-short ear (d-se) region of chromosome 9, a specific example of this type of integrated analysis, are discussed

  4. Immunostimulatory mouse granuloma protein.

    OpenAIRE

    Fontan, E; Fauve, R M; Hevin, B; Jusforgues, H

    1983-01-01

    Earlier studies have shown that from subcutaneous talc-induced granuloma in mice, a fraction could be extracted that fully protected mice against Listeria monocytogenes. Using standard biochemical procedures--i.e., ammonium sulfate fractionation, preparative electrophoresis, gel filtration chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis--we have now purified an active factor to homogeneity. A single band was obtained in NaDodSO4/polyacrylamide gel with...

  5. Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry : Fragment Linking and -Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

    NARCIS (Netherlands)

    Mondal, Milon; Unver, M. Yagiz; Pal, Asish; Bakker, Matthijs; Berrier, Stephan R.; Hirsch, Anna K H

    2016-01-01

    There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein-templated click chemistry is an efficient and powerful method that accelerates the hit-identification

  6. Site-SpecificCu Labeling of the Serine Protease, Active Site Inhibited Factor Seven Azide (FVIIai-N), Using Copper Free Click Chemistry

    DEFF Research Database (Denmark)

    Jeppesen, Troels E; Kristensen, Lotte K; Nielsen, Carsten H

    2018-01-01

    A method for site-specific radiolabeling of the serine protease active site inhibited factor seven (FVIIai) with64Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved in hemostasis, angiogenesis, proliferation, cell migrati...

  7. One-step fabrication of PEGylated fluorescent nanodiamonds through the thiol-ene click reaction and their potential for biological imaging

    Science.gov (United States)

    Huang, Hongye; Liu, Meiying; Tuo, Xun; Chen, Junyu; Mao, Liucheng; Wen, Yuanqing; Tian, Jianwen; Zhou, Naigen; Zhang, Xiaoyong; Wei, Yen

    2018-05-01

    Over the past years, fluorescent carbon nanoparticles have got growing interest for biological imaging. Fluorescent nanodiamonds (FNDs) are novel fluorescent carbon nanoparticles with multitudinous useful properties, including remarkable fluorescence properties, extremely low toxicity and high refractive index. However, facile preparation of FNDs with designable properties and functions from non-fluorescent detonation nanodiamonds (DNDs) has demonstrated to be challengeable. In this work, we reported for the first time that preparation of Polyethylene glycol (PEG) functionalized FNDs through a one-step thiol-ene click reaction using thiol containing PEG (PEG-SH) as the coating agent. Based on the characterization results, we demonstrated that PEG-SH could be efficiently introduced on DNDs to obtain FNDs through the thiol-ene click chemistry. The resultant FND-PEG composites showed high water dispersibility, strong fluorescence and low cytotoxicity. Moreover, FND-PEG composites could be internalized by cells and displayed good cell dyeing performance. All of these features implied that FND-PEG composites are of great potential for biological imaging. Taken together, a facile one-step strategy based on the one-step thiol-ene click reaction has been developed for efficient preparation of FND-PEG composites from non-fluorescent DNDs. The strategy should be also useful for fabrication of many other functional FNDs via using different thiol containing compounds for the universality of thiol-ene click reaction.

  8. Site-Directed Spin-Labeling of Nucleic Acids by Click Chemistry. Detection of Abasic Sites in Duplex DNA by EPR Spectroscopy

    DEFF Research Database (Denmark)

    Sigurdsson, Snorri; Vogel, Stefan; Shelke, Sandip

    2010-01-01

    This paper describes a spin label that can detect and identify local structural deformations in duplex DNA, in particular abasic sites. The spin label was incorporated into DNA by a new postsynthetic approach using click-chemistry on a solid support, which simplified both the synthesis...

  9. Development of Automated Whistle and Click Classifiers for Odontocete Species in the Western Atlantic Ocean and the Waters Surrounding the Hawaiian Islands

    Science.gov (United States)

    2015-09-30

    order to further explore the utility of click measurements for species classification, a Discriminant Function Analysis (DFA) was used to classify... localisation of cetaceans. Proceedings of the Institute of Acoustics, 30 Pt 5. United Kingdom. May-Collado, L.J., and D. Wartzok. 2008. A comparison of

  10. Feeding at a high pitch: Source parameters of narrow band,high-frequency clicks from echolocating off-shore hourglassdolphins and coastal Hector's dolphins

    DEFF Research Database (Denmark)

    Kyhn, Line Anker; Tougaard, Jakob; Jensen, Frants Havmand

    2009-01-01

    (Lagenorhynchus cruciger) and Hector's dolphins (Cephalorhynchus hectori ) were made in the Drake Passage between Tierra del Fuego and the Antarctic Peninsular and Banks Peninsular Akaroa Harbour, New Zealand with a four element hydrophone array. Analysis of source parameters shows that both species produce...... narrow band high-frequency (NBHF) echolocation clicks. Coastal Hector's dolphins produce clicks with a mean peak frequency of 129 kHz, 3 dB bandwidth of 20 kHz, 57 ys, 10 dB duration, and mean apparent source level (ASL) of 177 dB re 1 yPa (p.-p.). The oceanic hourglass dolphins produce clicks with mean...... peak frequency of 126 kHz, 3 dB bandwidth of 8 kHz, 116 ys, 10 dB duration, and a mean estimated ASL of 197 dB re 1 yPa (p.-p.). Thus, hourglass dolphins apparently produce clicks of higher source level, which should allow them to detect prey at more than twice the distance compared to Hector...

  11. Facile synthesis of linear-dendritic cholesteryl-poly(epsilon-caprolactone)-b-(L-lysine)(G2) by thiol-ene and azide-alkyne "click" reactions

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Binder, W.H.; Tanner, S.

    2010-01-01

    The construction of a linear-dendritic block copolymer consisting of terminal cholesteryl moiety, poly(epsilon-caprolactone), and a second generation L-lysine dendron has been accomplished by the combination of copper(I) catalyzed azide-alkyne and UV-triggered thiol-ene "click" reactions. Ring-op...

  12. Frequency of temporomandibular joint dysfunction with clicking symptom due to primary molar premature loss in children aged 6-12 years old

    Directory of Open Access Journals (Sweden)

    Riana Hestu Laksitowati

    2009-03-01

    Full Text Available Temporomandibular joint dysfunction with clicking symptom is sound “click” when open and close the mouth. The purpose of this study was to obtain the description of the frequency of temporomandibular joint dysfunction with clicking symptom caused by premature loss of primary molar teeth in children aged 6-12 years old at SDIT Imam Bukhari. The study was a descriptive survey, 136 students as samples were taken by purposive sampling technique. Premature loss of primary molar teeth examined by checking up the first and second primary molars upper and lower jaw using the hand mirror and explorer. Temporomandibular joint dysfunction examined by palpation and using a stethoscope. The result of this study showed that from 136 students having premature loss there are 49 students (36,03% had temporomandibular joint dysfunction with clicking symptom. The conclusion of this study indicates that more than one-fourth students at SDIT Imam Bukhari with premature loss of primary molar teeth had temporomandibular joint dysfunction with clicking symptom.

  13. TL transgenic mouse strains

    International Nuclear Information System (INIS)

    Obata, Y.; Matsudaira, Y.; Hasegawa, H.; Tamaki, H.; Takahashi, T.; Morita, A.; Kasai, K.

    1993-01-01

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4 - CD8 - double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tla a -3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3 b -TL gene from B6 mice and constructed a chimeric gene in which T3 b -TL is driven by the promoter of H-2K b . With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F 1 mice were rejected. In the mice which rejected the grafts, CD8 + TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F 1 mice rejected the skin expressing T3 b -TL antigen and induced CTL that killed TL + lymphomas of B6 origin revealed that TL antigen encoded by T3 b -TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  14. A cell surface clicked navigation system to direct specific bone targeting.

    Science.gov (United States)

    Kim, Young; Zhang, Zhe; Shim, Jae-Hyuck; Lee, Tae Sup; Tung, Ching-Hsuan

    2018-02-01

    Cell therapies are promising up-and-coming therapeutic strategies for many diseases. For maximal therapeutic benefits, injected cells have to navigate their way to a designated area, including organ and tissue; unfortunately, the majority of therapeutic cells are currently administered without a guide or homing device. To improve this serious shortcoming, a functionalization method was developed to equip cells with a homing signal. Its application was demonstrated by applying an Azadibenzocyclooctyne-bisphosphonate (ADIBO-BP) and azide paired bioorthogonal chemistry on cells for bone specific homing. Jurkat T cells and bone marrow derived stromal cells (BMSCs) were cultured with tetraacetylated N-azidoacetyl-d-mannosamine (Ac 4 ManNAz) to place unnatural azido groups onto the cell's surface; these azido groups were then reacted with ADIBO-BP. The tethered bisphosphonates were able to bring Jurkat cells to hydroxyapatite, the major component of bone, and mineralized SAOS-2 cells. The incorporated BP groups also enhanced the specific affinity of BMSCs to mouse femur bone fragments in vitro. The introduced navigation strategy is expected to have a broad application in cell therapy, because through the biocompatible ADIBO and azide reactive pair, various homing signals could be efficiently anchored onto therapeutic cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The preparation and physical properties of polysulfide-based elastomers through one-pot thiol-ene click reaction

    Directory of Open Access Journals (Sweden)

    Y. W. Quan

    2013-07-01

    Full Text Available In this paper, polysulfide-based elastomers were successfully prepared through a simple one-pot thiol-ene click reaction of the liquid polysulfide oligomer with bisphenol-A diacrylate resin. Real-time Fourier transform infrared spectroscopy (FTIR analysis showed that the molecular weight of the liquid polysulfide oligomer had no effect on mercaptan functional group conversion. The obtained elastomers continued to keep low temperature flexibility of polysulfide except Elastomer-LP3, which was due to higher content of bisphenol-A structure. All the samples had a tensile strength of over 0.7 MPa, which was comparable to that of polysulfide polymer cured by metal oxide. Moreover, the samples exhibited higher thermal stability than metal oxide cured polysulfide. This vulcanization methodology will provide a fast, efficient, and environmentally friendly approach (without metal oxides and plasticizers for preparing polysulfide elastomers.

  16. A click chemistry approach for the synthesis of mono and bis aryloxy linked coumarinyl triazoles as anti-tubercular agents.

    Science.gov (United States)

    Anand, Ashish; Naik, Reshma J; Revankar, Hrishikesh M; Kulkarni, Manohar V; Dixit, Sheshagiri R; Joshi, Shrinivas D

    2015-11-13

    A series of mono and bis-triazole coumarin hybrids 6a-u and 9a-f respectively have been synthesized using 4-(azidomethyl)-2H-chromen-2-ones 5a-i and aryl propargyl ethers 2a-c/8 employing Click chemistry modified protocol for Azide-Alkyne cycloadditions(CuAAC). Anti-tubercular screening showed moderate activity for mono aryloxy compounds 6a-u with MIC 50-100 μg/mL, whereas the bis compounds 9a-f were more effective with MICs between 0.2 and 12.5 μg/mL. Molecular modeling and 3D-QSAR measurements using CoMFA and Topomer CoMFA further supported the observed results. The bis compound 9b showed excellent activity with MIC value as low as 0.2 μg/mL. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Star Poly(N-isopropylacrylamide Tethered to Polyhedral Oligomeric Silsesquioxane (POSS Nanoparticles by a Combination of ATRP and Click Chemistry

    Directory of Open Access Journals (Sweden)

    Shiao-Wei Kuo

    2012-01-01

    Full Text Available New star poly(N-isopropylacrylamide-b-polyhedral oligomeric silsesquioxane (PNIPAm-b-POSS copolymers were synthesized from octa-azido functionalized POSS (N3-POSS and alkyne-PNIPAm, which was prepared using an alkyne-functionalized atom transfer radical polymerization (ATRP initiator (propargyl 2-bromo-2-methylpropionamide, via click chemistry. These star PNIPAm-b-POSS copolymers undergo a sharp coil-globule transition in water at above 32°C changing from a hydrophilic state below this temperature to a hydrophobic state above it, which is similar to linear PNIPAm homopolymers. More interestingly, we found that these star polymers exhibited strong blue photoluminescence in water above a lower critical solution temperature (LCST. This photoluminescence was likely due to the constrained geometric freedom and relatively rigid structure caused by intramolecular hydrogen bonding within the star PNIPAm polymers, which exhibit an intrinsic fluorescent behavior.

  18. 10. international mouse genome conference

    Energy Technology Data Exchange (ETDEWEB)

    Meisler, M.H.

    1996-12-31

    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  19. Imaging Mouse Models of Cancer.

    Science.gov (United States)

    Lyons, Scott Keith

    2015-01-01

    Mouse models of cancer have proven to be an indispensable resource in furthering both our basic knowledge of cancer biology and the translation of new cancer treatments and imaging approaches into the clinic. As mouse models have developed and improved in their ability to model many diverse aspects of the human disease, so too has the need for robust imaging approaches to measure key biological parameters noninvasively. The aim of this review is to provide a brief overview of the various imaging approaches available to researchers today for imaging preclinical cancer models, highlighting their relative strengths and weaknesses. The very nature of modeling cancer in the mouse is also changing, and brief mention will be made on how imaging can maximize the utility of these new, accurate, and genetically versatile models.

  20. Mouse models of Fanconi anemia

    International Nuclear Information System (INIS)

    Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J.

    2009-01-01

    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  1. Analysis in the joint time-frequency domain of the identifying signatures of submerged targets insonified by dolphin clicks

    Science.gov (United States)

    Strifors, Hans C.; Gaunaurd, Guillermo C.; Moore, Patrick W.

    1997-06-01

    We study the scattering interaction of dolphin-emitted acoustic pulses ('clicks') with various elastic shells located, underwater, in front of the animal in a large test site in Kaneohe Bay, Hawaii. A carefully instrumented analog- to-digital system continuously captured the emitted clicks and also the returned, backscattered echoes. Using standard conditioning techniques and food reinforcers, the dolphin is taught to push an underwater paddle when the 'correct' target -- the one he has been trained to identify -- is presented to him. He communicates to us his consistently correct identifying choices in this manner. By means of several time- frequency distributions (TFD) of the Wigner-type, or Cohen class, we examine echoes returned by three types of cylindrical shells. The time-frequency distributions we compare in this survey are the pseudo-Wigner distribution (PWD), the Choi-Williams distribution (CWD), the adaptive spectrogram (AS), the cone-shaped distribution (CSD), the Gabor spectrogram (GS), and the spectrogram (SPEC). To be satisfactory for target identification purposes, a time- frequency representation of the echoes should display a sufficient amount of distinguishing features, and still be robust enough to suppress the interference of noise contained in the received signals. Both these properties in a time- frequency distribution depend on the distribution's capability of concentrating the featuers in time and frequency and of handling cross-term interference. With some time-frequency distributions there is a trade-off between the concentration of features and the suppression of cross-term interference. The results of our investigation serve the twofold purposes of (1) advancing the understanding of the amazing target identification capability of dolphins, and (2) to assist in assessing the possibility of identifying submerged targets using active sonar and a classifier based on target signatures in the combined time-frequency domain.

  2. Facile preparation of organic-silica hybrid monolith for capillary hydrophilic liquid chromatography based on "thiol-ene" click chemistry.

    Science.gov (United States)

    Chen, Ming-Luan; Zhang, Jun; Zhang, Zheng; Yuan, Bi-Feng; Yu, Qiong-Wei; Feng, Yu-Qi

    2013-04-05

    In this work, a one-step approach to facile preparation of organic-inorganic hybrid monoliths was successfully developed. After vinyl-end organic monomers and azobisisobutyronitrile (AIBN) were mixed with hydrolyzed tetramethoxysilane (TMOS) and 3-mercaptopropyltrimethoxysilane (MPTMS), the homogeneous mixture was introduced into a fused-silica capillary for simultaneous polycondensation and "thiol-ene" click reaction to form the organic-silica hybrid monoliths. By employing this strategy, two types of organic-silica hybrid monoliths with positively charged quaternary ammonium and amide groups were prepared, respectively. The functional groups were successfully introduced onto the monoliths during the sol-gel process with "thiol-ene" click reaction, which was demonstrated by ζ-potential assessment, energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared (FT-IR) spectroscopy. The porous structure of the prepared monolithic columns was examined by scanning electron microscopy (SEM), nitrogen adsorption-desorption measurement, and mercury intrusion porosimetry. These results indicate the prepared organic-silica hybrid monoliths possess homogeneous column bed, large specific surface area, good mechanical stability, and excellent permeability. The prepared monolithic columns were then applied for anion-exchange/hydrophilic interaction liquid chromatography. Different types of analytes, including benzoic acids, inorganic ions, nucleosides, and nucleotides, were well separated with high column efficiency around 80,000-130,000 plates/m. Taken together, we present a facile and universal strategy to prepare organic-silica hybrid monoliths with a variety of organic monomers using one-step approach. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics.

    Science.gov (United States)

    Korogiannaki, Myrto; Zhang, Jianfeng; Sheardown, Heather

    2017-10-01

    Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2-hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during

  4. Nickel complexes with "click"-derived pyridyl-triazole ligands: weak intermolecular interactions and catalytic ethylene oligomerisation.

    Science.gov (United States)

    Schweinfurth, David; Su, Cheng-Yong; Wei, Shi-Chao; Braunstein, Pierre; Sarkar, Biprajit

    2012-11-07

    The ligands 1-(cyclohexyl)-4-(2-pyridyl)-1,2,3-triazole (1), 1-(2,6-diisopropylphenyl)-4-(2-pyridyl)-1,2,3-triazole (2), 1-(4-butoxyphenyl)-4-(2-pyridyl)-1,2,3-triazole (3) and 1-(methyl)-4-(2-pyridyl)-1,2,3-triazole (4) were synthesized by the Cu(I) catalyzed "Click" reaction between 2-pyridylacetylene and the corresponding azides. The ligands were then reacted with NiBr(2)·3H(2)O to generate the complexes (1)(2)NiBr(2) (1a), (2)(2)NiBr(2) (2a), (3)(2)NiBr(2) (3a) and (4)(2)NiBr(2) (4a). Structural characterization of 1a confirmed the mononuclear and distorted octahedral environment around the Ni(II) center, with the pyridyl-triazole ligands coordinating in a bis-chelating fashion. Bond length analysis inside the 1,2,3-triazole ring shows a short N=N double bond that is flanked by two longer C-N and N-N bonds pointing to the existence of "azo" character in the ring. The highly polar five-membered 1,2,3-triazole ring makes its C-H bond acidic, and these bonds participate in an extended weak intermolecular C-H···Br interactions with the Br-groups of neighboring molecules, resulting in a 3-D network. The nickel complexes with these "Click" ligands were tested as pre-catalysts for ethylene oligomerization, and the complexes showed moderate activity in that reaction with good selectivity towards C4 oligomers.

  5. Dual-Colored DNA Comb Polymers for Single Molecule Rheology

    Science.gov (United States)

    Mai, Danielle; Marciel, Amanda; Schroeder, Charles

    2014-03-01

    We report the synthesis and characterization of branched biopolymers for single molecule rheology. In our work, we utilize a hybrid enzymatic-synthetic approach to graft ``short'' DNA branches to ``long'' DNA backbones, thereby producing macromolecular DNA comb polymers. The branches and backbones are synthesized via polymerase chain reaction with chemically modified deoxyribonucleotides (dNTPs): ``short'' branches consist of Cy5-labeled dNTPs and a terminal azide group, and ``long'' backbones contain dibenzylcyclooctyne-modified (DBCO) dNTPs. In this way, we utilize strain-promoted, copper-free cycloaddition ``click'' reactions for facile grafting of azide-terminated branches at DBCO sites along backbones. Copper-free click reactions are bio-orthogonal and nearly quantitative when carried out under mild conditions. Moreover, comb polymers can be labeled with an intercalating dye (e.g., YOYO) for dual-color fluorescence imaging. We characterized these materials using gel electrophoresis, HPLC, and optical microscopy, with atomic force microscopy in progress. Overall, DNA combs are suitable for single molecule dynamics, and in this way, our work holds the potential to improve our understanding of topologically complex polymer melts and solutions.

  6. Mouse Resource Browser-a database of mouse databases

    NARCIS (Netherlands)

    Zouberakis, Michael; Chandras, Christina; Swertz, Morris; Smedley, Damian; Gruenberger, Michael; Bard, Jonathan; Schughart, Klaus; Rosenthal, Nadia; Hancock, John M.; Schofield, Paul N.; Kollias, George; Aidinis, Vassilis

    2010-01-01

    The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the

  7. Effects of some physiological conditions on the radiosensitivity of mouse skin, 2

    International Nuclear Information System (INIS)

    Masuda, Kouji

    1979-01-01

    Effects of anatomic site and positioning during irradiation on the response of mouse skin to single or 32-fractionated gamma rays with one-day interval were studied, using the hind legs of C3Hf/Bu mice, and early skin reaction as an end point. No significant difference in the response of skin to single exposure was observed between dorsal side and abdominal side of a leg. When mouse skin was mechanically stimulated by hair shaving one-day prior to irradiation, the response of the skin to single exposure was more severe on dorsal side, while that to 32 fractions more severe on abdominal side. These results indicate that the dorsal skin of a hind leg has more potentially reproductive stem cells which can be stimulated by hair shaving. The response of mouse skin irradiated in dorsal position was relatively less severe compared to that irradiated in abdominal position. (author)

  8. Pro single page application development using Backbone.js and ASP.NET

    CERN Document Server

    Fink, Gil

    2014-01-01

    One of the most important and exciting trends in web development in recent years is the move towards single page applications, or SPAs. Instead of clicking through hyperlinks and waiting for each page to load, the user loads a site once and all the interactivity is handled fluidly by a rich JavaScript front end. If you come from a background in ASP.NET development, you'll be used to handling most interactions on the server side. Pro Single Page Application Development will guide you through your transition to this powerful new application type.The book starts in Part I by laying the groundwork

  9. Diffusion of [2-14C]diazepam across hairless mouse skin and human skin

    International Nuclear Information System (INIS)

    Koch, R.L.; Palicharla, P.; Groves, M.J.

    1987-01-01

    The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber

  10. Copper-free click-chemistry platform to functionalize cisplatin prodrugs.

    Science.gov (United States)

    Pathak, Rakesh K; McNitt, Christopher D; Popik, Vladimir V; Dhar, Shanta

    2014-06-02

    The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Mouse Models of Rheumatoid Arthritis.

    Science.gov (United States)

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients. © The Author(s) 2015.

  12. Quantification of Brain Access of Exendin-4 in the C57BL Mouse Model by SPIM Fluorescence Imaging and the Allen Mouse Brain Reference Model

    DEFF Research Database (Denmark)

    Jensen, Casper Bo; Secher, Anna; Hecksher-Sørensen, Jacob

    2015-01-01

    With the recent advance in 3D microscopy such as Single Plane Illumination Microscopy (SPIM) it is possible to obtain high resolution image volumes of the entire mouse brain. These data can be used to study the access of several peptides such as the glucagon-like peptide-1 (GLP-1) analogue Exendi...

  13. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

    Science.gov (United States)

    Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

    2011-01-01

    Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

  14. High resolution melt analysis (HRMA; a viable alternative to agarose gel electrophoresis for mouse genotyping.

    Directory of Open Access Journals (Sweden)

    Nicole Thomsen

    Full Text Available Most mouse genetics laboratories maintain mouse strains that require genotyping in order to identify the genetically modified animals. The plethora of mutagenesis strategies and publicly available mouse alleles means that any one laboratory may maintain alleles with random or targeted insertions of orthologous or unrelated sequences as well as random or targeted deletions and point mutants. Many experiments require that different strains be cross bred conferring the need to genotype progeny at more than one locus. In contrast to the range of new technologies for mouse mutagenesis, genotyping methods have remained relatively static with alleles typically discriminated by agarose gel electrophoresis of PCR products. This requires a large amount of researcher time. Additionally it is susceptible to contamination of future genotyping experiments because it requires that tubes containing PCR products be opened for analysis. Progress has been made with the genotyping of mouse point mutants because a range of new high-throughput techniques have been developed for the detection of Single Nucleotide Polymorphisms. Some of these techniques are suitable for genotyping point mutants but do not detect insertion or deletion alleles. Ideally, mouse genetics laboratories would use a single, high-throughput platform that enables closed-tube analysis to genotype the entire range of possible insertion and deletion alleles and point mutants. Here we show that High Resolution Melt Analysis meets these criteria, it is suitable for closed-tube genotyping of all allele types and current genotyping assays can be converted to this technology with little or no effort.

  15. Late effects of irradiation in mouse jejunum

    International Nuclear Information System (INIS)

    Reynaud, A.; Travis, E.L.

    1984-01-01

    The response of mouse jejunum at intervals up to 1 year after single 'priming' doses of X-rays has been assessed by crypt survival after retreatment with single doses of X-rays and morphometric analysis of changes in the intestinal submucosa. The crypt dose-survival curves in mice re-irradiated at 2, 6, or 12 months after priming irradiation were displaced to higher doses in pre-treated than in non-pre-treated mice and were characterized by higher D 0 values. Misonidazole given before the test exposure reversed this effect so that the dose survival curve for crypts in pre-treated mice were superimposed on that for mice not previously irradiated, suggesting that the increase in isoeffect dose and the change in the D 0 in previously exposed mice was due to crypt hypoxia. Quantifications of the area of the submucosa showed that its area was increased at all three times after the priming doses and was a result of collagen deposition and oedema. Thus, the hypoxia in the crypts was probably secondary to these changes. Deaths began at 6-7 months after priming irradiation and were due to intestinal obstruction and stenosis. Thus, as in other tissues, two phases of injury can be assayed in the intestine of experimental animals. (author)

  16. The Mouse SAGE Site: database of public mouse SAGE libraries

    Czech Academy of Sciences Publication Activity Database

    Divina, Petr; Forejt, Jiří

    2004-01-01

    Roč. 32, - (2004), s. D482-D483 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant - others:HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse SAGE libraries * web -based database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

  17. Mouse ribosomal RNA genes contain multiple differentially regulated variants.

    Directory of Open Access Journals (Sweden)

    Hung Tseng

    2008-03-01

    Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.

  18. Mouse models of myeloproliferative neoplasms: JAK of all grades

    Directory of Open Access Journals (Sweden)

    Juan Li

    2011-05-01

    Full Text Available In 2005, several groups identified a single gain-of-function point mutation in the JAK2 kinase that was present in the majority of patients with myeloproliferative neoplasms (MPNs. Since this discovery, much effort has been dedicated to understanding the molecular consequences of the JAK2V617F mutation in the haematopoietic system. Three waves of mouse models have been produced recently (bone marrow transplantation, transgenic and targeted knock-in, which have facilitated the understanding of the molecular pathogenesis of JAK2V617F-positive MPNs, providing potential platforms for designing and validating novel therapies in humans. This Commentary briefly summarises the first two types of mouse models and then focuses on the more recently generated knock-in models.

  19. A dose-surviving fraction curve for mouse colonic mucosa

    International Nuclear Information System (INIS)

    Tucker, S.L.; Thames, H.D. Jr.; Withers, H.R.; Mason, K.A.

    1983-01-01

    A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137 Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimated of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum. (author)

  20. Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

    Science.gov (United States)

    Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

    2017-03-15

    As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from

  1. Pentafluorobenzene end-group as a versatile handle for para fluoro "click" functionalization of polythiophenes.

    Science.gov (United States)

    Boufflet, Pierre; Casey, Abby; Xia, Yiren; Stavrinou, Paul N; Heeney, Martin

    2017-03-01

    A convenient method of introducing pentafluorobenzene (PFB) as a single end-group in polythiophene derivatives is reported via in situ quenching of the polymerization. We demonstrate that the PFB-group is a particularly useful end-group due to its ability to undergo fast nucleophilic aromatic substitutions. Using this molecular handle, we are able to quantitatively tether a variety of common nucleophiles to the polythiophene backbone. The mild conditions required for the reaction allows sensitive functional moieties, such as biotin or a cross-linkable trimethoxysilane, to be introduced as end-groups. The high yield enabled the formation of a diblock rod-coil polymer from equimolar reactants under transition metal-free conditions at room temperature. We further demonstrate that water soluble polythiophenes end-capped with PFB can be prepared via the hydrolysis of an ester precursor, and that such polymers are amenable to functionalization under aqueous conditions.

  2. Predation by killer whales (Orcinus orca) and the evolution of whistle loss and narrow-band high frequency clicks in odontocetes.

    Science.gov (United States)

    Morisaka, T; Connor, R C

    2007-07-01

    A disparate selection of toothed whales (Odontoceti) share striking features of their acoustic repertoires including the absence of whistles and high frequency but weak (low peak-to-peak source level) clicks that have a relatively long duration and a narrow bandwidth. The non-whistling, high frequency click species include members of the family Phocoenidae, members of one genus of delphinids, Cephalorhynchus, the pygmy sperm whale, Kogia breviceps, and apparently the sole member of the family Pontoporiidae. Our review supports the 'acoustic crypsis' hypothesis that killer whale predation risk was the primary selective factor favouring an echolocation and communication system in cephalorhynchids, phocoenids and possibly Pontoporiidae and Kogiidae restricted to sounds that killer whales hear poorly or not at all ( 100 kHz).

  3. Study on radiolabeling of 1, 2, 3-triazole analogs with fac-[188Re(CO)3(H2O)3]+ via click chemistry

    International Nuclear Information System (INIS)

    Wang Cheng; Yin Jilin; Zhou Zheng; Zhou Wei; Zhang Lan

    2013-01-01

    Click chemistry was used to study on radiolabeling of 1, 2, 3-triazole analogs with. fac-[ 188 Re(CO) 3 (H 2 O) 3 ] + . CuSO 4 /L-sodium ascorbate was chosen as the catalyst system, three terminal alkynes were conjugated with two different azides respectively, and then the new prepared fac-[ 188 Re(CO) 3 (H 2 O) 3 ] + was coordinated to the six triazoles. The results showed that the radiochemical yields (RCY) of the conjugation of fac-[ 188 Re(CO) 3 ] + with six triazoles were over 90%, and the triazoles showed high stability in phosphate-buffered saline and new-born calf serum. The preliminary biological evaluation results showed that the new 188 Re-labeling method via click chemistry could have general application in labeling bioactive molecules in high radiochemical yield and high specific activity for further SPECT research. (authors)

  4. Ribonucleoprotein localization in mouse oocytes

    Czech Academy of Sciences Publication Activity Database

    Flemr, Matyáš; Svoboda, Petr

    2011-01-01

    Roč. 53, č. 2 (2011), s. 136-141 ISSN 1046-2023 R&D Projects: GA ČR GA204/09/0085; GA ČR GAP305/10/2215; GA MŠk ME09039 Institutional research plan: CEZ:AV0Z50520514 Keywords : mouse oocyte * in situ hybridization * immunofluorescence Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.011, year: 2011

  5. Preparation and Preliminary Dielectric Characterization of Structured C60-Thiol-Ene Polymer Nanocomposites Assembled Using the Thiol-Ene Click Reaction

    OpenAIRE

    Ahmed, Hanaa M.; Windham, Amber D.; Al-Ejji, Maryam M.; Al-Qahtani, Noora H.; Hassan, Mohammad K.; Mauritz, Kenneth A.; Buchanan, Randy K.; Buchanan, J. Paige

    2015-01-01

    Fullerene-containing materials have the ability to store and release electrical energy. Therefore, fullerenes may ultimately find use in high-voltage equipment devices or as super capacitors for high electric energy storage due to this ease of manipulating their excellent dielectric properties and their high volume resistivity. A series of structured fullerene (C60) polymer nanocomposites were assembled using the thiol-ene click reaction, between alkyl thiols and allyl functionalized C60 deri...

  6. Role Pay-per-Click internetové reklamní kampaně v marketingových aktivitách firmy

    OpenAIRE

    Černý, Jakub

    2009-01-01

    This paper is focused on analysis of internet advertising and its role in marketing communication. The paper determines general methods and instruments of internet marketing and describes internet advertisement in comparison with traditional advertising media. In more detail the paper is focused on description and explanation of effect of Pay-Per-Click advertisement campaigns. The options of their usage and recognized differences are explicated by practical instance of marketing strategies of...

  7. On doing two things at once: dolphin brain and nose coordinate sonar clicks, buzzes and emotional squeals with social sounds during fish capture.

    Science.gov (United States)

    Ridgway, Sam; Samuelson Dibble, Dianna; Van Alstyne, Kaitlin; Price, DruAnn

    2015-12-01

    Dolphins fishing alone in open waters may whistle without interrupting their sonar clicks as they find and eat or reject fish. Our study is the first to match sound and video from the dolphin with sound and video from near the fish. During search and capture of fish, free-swimming dolphins carried cameras to record video and sound. A hydrophone in the far field near the fish also recorded sound. From these two perspectives, we studied the time course of dolphin sound production during fish capture. Our observations identify the instant of fish capture. There are three consistent acoustic phases: sonar clicks locate the fish; about 0.4 s before capture, the dolphin clicks become more rapid to form a second phase, the terminal buzz; at or just before capture, the buzz turns to an emotional squeal (the victory squeal), which may last 0.2 to 20 s after capture. The squeals are pulse bursts that vary in duration, peak frequency and amplitude. The victory squeal may be a reflection of emotion triggered by brain dopamine release. It may also affect prey to ease capture and/or it may be a way to communicate the presence of food to other dolphins. Dolphins also use whistles as communication or social sounds. Whistling during sonar clicking suggests that dolphins may be adept at doing two things at once. We know that dolphin brain hemispheres may sleep independently. Our results suggest that the two dolphin brain hemispheres may also act independently in communication. © 2015. Published by The Company of Biologists Ltd.

  8. Development of Automated Whistle and Click Classifiers for Odontocete Species in the Northwest Atlantic Ocean and the Waters Surrounding the Hawaiian Islands

    Science.gov (United States)

    2014-09-30

    multiple reasons. Some species or populations are listed as threatened or endangered (ex. insular false killer whales in Hawaii) and thus it is...information regarding marine mammal occurrence, distribution and behavior in Naval exercise areas. However, it is not possible with current technology to...clicks of melon-headed whales (Peponocephala electra), bottlenose dolphins (Tursiops truncatus), and Grayʼs spinner dolphins (Stenella longirostris

  9. One pot Click chemistry: A three component reaction for the synthesis of 2-mercaptobenzimidazole linked coumarinyl triazoles as anti-tubercular agents.

    Science.gov (United States)

    Anand, Ashish; Kulkarni, Manohar V; Joshi, Shrinivas D; Dixit, Sheshagiri R

    2016-10-01

    2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Biopolymers from vegetable oils via catalyst- and solvent-free "click" chemistry: effects of cross-linking density.

    Science.gov (United States)

    Hong, Jian; Luo, Qiang; Wan, Xianmei; Petrović, Zoran S; Shah, Bipin K

    2012-01-09

    New monomers were prepared by introducing the azide groups in castor, canola, corn, soybean, and linseed oils. Polymerization of the azidated oils with alkynated soybean oil under thermal "click" chemistry conditions (without using a solvent or a catalyst) yielded fully cross-linked elastomers (1-5) of almost the same density (1.05 × 10(-3) kg/m(3)). The degree of cross-linking gradually increased from the castor-derived polymer (220 mol/m(3)) to the linseed-derived polymer (683 mol/m(3)). A systematic correlation between the degree of cross-linking and the thermal and mechanical properties was observed in these biopolymers. Tensile strength (0.62-3.39 MPa) and glass transition temperature (-5 to 16 °C) increased and the linear thermal expansion coefficient decreased in the series from the canola-derived polymer (2) to the linseed-derived polymer (5). The castor-derived polymer (1) that possesses an additional hydroxyl group per fatty acid chain behaved differently.

  11. Discrete complexes immobilized onto click-SBA-15 silica: controllable loadings and the impact of surface coverage on catalysis.

    Science.gov (United States)

    Nakazawa, Jun; Smith, Brian J; Stack, T Daniel P

    2012-02-08

    Azidopropyl functionalized mesoporous silica SBA-15 were prepared with variable azide loadings of 0.03-0.7 mmol g(-1) (~2-50% of maximal surface coverage) through a direct synthesis, co-condensation approach. These materials are functionalized selectively with ethynylated organic moieties through a copper-catalyzed azide alkyne cycloaddition (CuAAC) or "click" reaction. Specific loading within a material can be regulated by either the azide loading or limiting the alkyne reagent relative to the azide loading. The immobilization of ferrocene, pyrene, tris(pyridylmethyl)amine (TPA), and iron porphyrin (FeTPP) demonstrates the robust nature and reproducibility of this two-step synthetic attachment strategy. Loading-sensitive pyrene fluorescence correlates with a theoretically random surface distribution, rather than a uniform one; site-isolation of tethered moieties ~15 Å in length occurs at loadings less than 0.02 mmol g(-1). The effect of surface loading on reactivity is observed in the oxygenation of SBA-15-[Cu(I)(TPA)]. SBA-15-[Mn(II)(TPA)]-catalyzed epoxidation exhibits a systematic dependence on surface loading. A comparison of homogeneous, site-isolated and site-dense complexes provides insight into catalyst speciation and ligand activity.

  12. Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia

    Science.gov (United States)

    Kim, Wan Jung; Korthals, Keith A.; Li, Suhua; Le, Christine; Kalisiak, Jarosław; Sharpless, K. Barry; Fokin, Valery V.; Miyamoto, Yukiko

    2017-01-01

    ABSTRACT Giardia lamblia is an important and ubiquitous cause of diarrheal disease. The primary agents in the treatment of giardiasis are nitroheterocyclic drugs, particularly the imidazoles metronidazole and tinidazole and the thiazole nitazoxanide. Although these drugs are generally effective, treatment failures occur in up to 20% of cases, and resistance has been demonstrated in vivo and in vitro. Prior work had suggested that side chain modifications of the imidazole core can lead to new effective 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has not been systematically investigated as an antimicrobial drug scaffold. Click chemistry was employed to synthesize 442 novel nitroheterocyclic compounds with extensive side chain modifications. Screening of this library against representative G. lamblia strains showed a wide spectrum of in vitro activities, with many of the compounds exhibiting superior activity relative to reference drugs and several showing >100-fold increase in potency and the ability to overcome existing forms of metronidazole resistance. The majority of new compounds displayed no cytotoxicity against human cells, and several compounds were orally active against murine giardiasis in vivo. These findings provide additional impetus for the systematic development of nitroheterocyclic compounds with nonimidazole cores as alternative and improved agents for the treatment of giardiasis and potentially other infectious agents. PMID:28396548

  13. Hepatocyte-targeting gene delivery using a lipoplex composed of galactose-modified aromatic lipid synthesized with click chemistry.

    Science.gov (United States)

    Sakashita, Mizuha; Mochizuki, Shinichi; Sakurai, Kazuo

    2014-10-01

    Highly efficient drug carriers targeting hepatocyte is needed for treatment for liver diseases such as liver cirrhosis and virus infections. Galactose or N-acetylgalactosamine is known to be recognized and incorporated into the cells through asialoglycoprotein receptor (ASGPR) that is exclusively expressed on hepatocyte and hepatoma. In this study, we synthesized a galactose-modified lipid with aromatic ring with click chemistry. To make a complex with DNA, termed 'lipoplex', we prepared a binary micelle composed of cationic lipid; dioleoyltrimethylammoniumpropane (DOTAP) and galactose-modified lipid (D/Gal). We prepared lipoplex from plasmid DNA (pDNA) and D/Gal and examined the cell specificity and transfection efficiency. The lipoplex was able to interact with ASGPR immobilized on gold substrate in the quartz-crystal microbalance (QCM) sensor cell. The lipoplex induced high gene expression to HepG2 cells, a human hepatocellular carcinoma cell line, but not to A549 cells, a human alveolar adenocarcinoma cell line. The treatment with asialofetuin, which is a ligand for ASGPR and would work as a competitive inhibitor, before addition of the lipoplexes decreased the expression to HepG2 cells. These results indicate that D/Gal lipoplex was incorporated into HepG2 cells preferentially through ASGPR and the uptake was caused by galactose specific receptor. This delivery system to hepatocytes may overcome the problems for gene therapy and be used for treatment of hepatitis and hepatic cirrhosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. "Click chemistry" in tailor-made polymethacrylates bearing reactive furfuryl functionality: a new class of self-healing polymeric material.

    Science.gov (United States)

    Kavitha, A Amalin; Singha, Nikhil K

    2009-07-01

    This investigation reports the effective use of the Diels-Alder (DA) reaction, a "click reaction" in the preparation of thermally amendable and self-healing polymeric materials having reactive furfuryl functionality. In this case, the DA and retro-DA (rDA) reactions were carried out between the tailor-made homo- and copolymer of furfuryl methacrylate prepared by atom-transfer radical polymerization and a bismaleimide (BM). The kinetic studies of DA and rDA reactions were carried out using Fourier transform infrared spectroscopy. The DA polymers were insoluble in toluene at room temperature. When the DA polymers were heated at 100 degrees C in toluene, it was soluble. This is because of the cleavage between furfuryl functionality and BM. The chemical cross-link density was determined by the Flory-Rehner equation. The cross-linked polymer showed much greater adhesive strength at room temperature, but the adhesive strength was quite low at higher temperature. The self-healing capability was studied by using scanning electron microscopy analysis. The thermal and dynamic mechanical properties of the thermally amendable cross-linked materials were investigated by thermogravimetric analysis and dynamic mechanical analysis.

  15. Fabrication of cross-linked hydrazone covalent organic frameworks by click chemistry and application to solid phase microextraction.

    Science.gov (United States)

    Wu, Mingxue; Chen, Gang; Ma, Jiutong; Liu, Ping; Jia, Qiong

    2016-12-01

    Covalent organic frameworks (COFs) are an emerging class of porous organic frameworks with diverse promising applications. Herein, we presented the first example of cross-linked hydrazone COFs (cross-linked COFs) coating via thiol-ene click chemistry for solid phase microextraction (SPME). Strong covalent bonds and interlayer of the prepared networks ensured the adsorption capacity and durability of the novel SPME fiber. π-π conjugated structure existed because of abundant phenyl rings and -C=N groups in the cross-lined COFs. A series of characterizations indicated that the cross-linked COFs possessed large surface areas, high porosities and stabilities as well as hydrophobicities. The fiber was applied to SPME of pesticide residues coupled with gas chromatography with an electron capture detector (GC-ECD). Under the optimum experimental conditions, enhancement factors in the range of 2190-10,998 were obtained, illustrating that the cross-linked COFs possessed remarkable preconcentration ability. The low detection limits of 0.0003-0.0023ngkg -1 were achieved with relative standard deviations (RSDs) in the range of 3.4-7.6% (intra-batch) and 5.7-11.6% (inter-batch), respectively. Recovery values in the range of 78.2-107.0% were obtained when the SPME-GC method was applied to the analysis of pesticides in cucumber samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Protein valves prepared by click reaction grafting of poly(N-isopropylacrylamide) to electrospun poly(vinyl chloride) fibrous membranes

    Science.gov (United States)

    Guo, Jian-Wei; Lin, Zhen-Yu; Chang, Chi-Jung; Lu, Chien-Hsing; Chen, Jem-Kun

    2018-05-01

    In this study, poly(vinyl chloride) (PVC) was electrospun into fibrous membranes and then reacted with NaN3 to generate azido-terminated PVC fibrous membranes. A propargyl-terminated poly(N-isopropylacrylamide) (PNIPAAm) was also synthesized and then grafted, through click reactions, onto the azido-terminated PVC fiber surface. Protrusion-, scale-, and joint-like structures of the PNIPAAm grafts on the PVC fibers were formed upon increasing the molecular weight of the PNIPAAm grafts. The PNIPAAm-grafted PVC fibrous mats exhibited completely wetted surfaces at 25 °C because of their high roughness. The static water contact angle of the PNIPAAm-grafted PVC fibrous mats reached 140° when the temperature was increased to 45 °C. This thermoresponsive behavior was significantly greater than that of the PNIPAAm grafted on a flat surface. Temperature-responsive membranes were constructed having a pore size of 1.38 μm and applied as protein valves to block and release an antibody (fluorescein-conjugated AffiniPure goat anti-rabbit IgG). At 25 °C, the collection efficiency remained at 94% for antibody concentrations up to 60 ng/L. As the temperature increased to 45 °C, the collection efficiency decreased abruptly, to 4%, when the antibody concentration was greater than 20 ng/L. Accordingly, this system of PNIPAAm-grafted PVC fibers functioned as a protein valve allowing the capture and concentration of proteins.

  17. Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation.

    Science.gov (United States)

    Scrivano, Luca; Iacopetta, Domenico; Sinicropi, Maria Stefania; Saturnino, Carmela; Longo, Pasquale; Parisi, Ortensia Ilaria; Puoci, Francesco

    2017-11-01

    Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib-polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC 50 value against MCF-7 cells.

  18. Synthesis and characterization of poly(vinylchloride type macrophotoinitiator comprising side-chain thioxanthone via click chemistry

    Directory of Open Access Journals (Sweden)

    2011-04-01

    Full Text Available Nowadays, the use of macromolecular photoinitiators provides for a good compatibility of the initiator in the formulation. Moreover, the migration of the initiator to the surface of the material is prevented, which results in low-odor and non-toxic coatings. In the present study, it has been demonstrated that polyvinylchloride macrophotoinitiator (PVC-TX containing side chain thioxanthone (2% moieties were successfully prepared by 'click chemistry'. For this purpose, propargyl thioxanthone and polyvinylchloride with side chain azide moieties were reacted in N,N-dimethylformamide for 24 hours at 25°C in order to give corresponding macrophotoinitiator. The synthesized polymer was characterized by 1H-NMR (nuclear magnetic resonance, UV (ultraviolet and fluorescence spectroscopies and water based gel permeation chromatography. Obtained macrophotoinitiator has similar absorption characteristics compared to parent thioxanthone. Its capabilities to act as initiator for the photopolymerization of methacrylic acid, methyl methacrylate, N-vinyl pyrrolidone and styrene in various solvents in the absence and presence of triethylamine media were also examined.

  19. Synthesis of Fluorinated Amphiphilic Block Copolymers Based on PEGMA, HEMA, and MMA via ATRP and CuAAC Click Chemistry

    Directory of Open Access Journals (Sweden)

    Fatime Eren Erol

    2014-01-01

    Full Text Available Synthesis of fluorinated amphiphilic block copolymers via atom transfer radical polymerization (ATRP and Cu(I catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAC was demonstrated. First, a PEGMA and MMA based block copolymer carrying multiple side-chain acetylene moieties on the hydrophobic segment for postfunctionalization was carried out. This involves the synthesis of a series of P(HEMA-co-MMA random copolymers to be employed as macroinitiators in the controlled synthesis of P(HEMA-co-MMA-block-PPEGMA block copolymers by using ATRP, followed by a modification step on the hydroxyl side groups of HEMA via Steglich esterification to afford propargyl side-functional polymer, alkyne-P(HEMA-co-MMA-block-PPEGMA. Finally, click coupling between side-chain acetylene functionalities and 2,3,4,5,6-pentafluorobenzyl azide yielded fluorinated amphiphilic block copolymers. The obtained polymers were structurally characterized by 1H-NMR, 19F-NMR, FT-IR, and GPC. Their thermal characterizations were performed using DSC and TGA.

  20. Study of the Effect of Grafting Method on Surface Polarity of Tempo-Oxidized Nanocellulose Using Polycaprolactone as the Modifying Compound: Esterification versus Click-Chemistry

    Directory of Open Access Journals (Sweden)

    Abdelhaq Benkaddour

    2013-12-01

    Full Text Available Esterification and click-chemistry were evaluated as surface modification treatments for TEMPO-oxidized nanocelluloses (TONC using Polycaprolactone-diol (PCL as modifying compound in order to improve the dispersion of nanofibers in organic media. These two grafting strategies were analyzed and compared. The first consists of grafting directly the PCL onto TONC, and was carried out by esterification between hydroxyl groups of PCL and carboxyl groups of TONC. The second strategy known as click-chemistry is based on the 1,3-dipolar cycloaddition reaction between azides and alkyne terminated moieties to form the triazole ring between PCL and TONC. The grafted samples were characterized by transmission electron microscopy (TEM, Fourier transform infrared spectroscopy (FTIR, X-ray photoelectron spectroscopy (XPS, and Thermogravimetry analysis (TGA. Further, the effects of the two treatments on the surface hydrophobization of TONC were investigated by contact angle measurements. The results show that both methods confirm the success of such a modification and the click reaction was significantly more effective than esterification.