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Sample records for human facilitative nucleobase

  1. Pyrimidine nucleobase radical reactivity in DNA and RNA

    Science.gov (United States)

    Greenberg, Marc M.

    2016-11-01

    Nucleobase radicals are major products of the reactions between nucleic acids and hydroxyl radical, which is produced via the indirect effect of ionizing radiation. The nucleobase radicals also result from hydration of cation radicals that are produced via the direct effect of ionizing radiation. The role that nucleobase radicals play in strand scission has been investigated indirectly using ionizing radiation to generate them. More recently, the reactivity of nucleobase radicals resulting from formal hydrogen atom or hydroxyl radical addition to pyrimidines has been studied by independently generating the reactive intermediates via UV-photolysis of synthetic precursors. This approach has provided control over where the reactive intermediates are produced within biopolymers and facilitated studying their reactivity. The contributions to our understanding of pyrimidine nucleobase radical reactivity by this approach are summarized.

  2. Fluorescent nucleobases as tools for studying DNA and RNA

    Science.gov (United States)

    Xu, Wang; Chan, Ke Min; Kool, Eric T.

    2017-11-01

    Understanding the diversity of dynamic structures and functions of DNA and RNA in biology requires tools that can selectively and intimately probe these biomolecules. Synthetic fluorescent nucleobases that can be incorporated into nucleic acids alongside their natural counterparts have emerged as a powerful class of molecular reporters of location and environment. They are enabling new basic insights into DNA and RNA, and are facilitating a broad range of new technologies with chemical, biological and biomedical applications. In this Review, we will present a brief history of the development of fluorescent nucleobases and explore their utility as tools for addressing questions in biophysics, biochemistry and biology of nucleic acids. We provide chemical insights into the two main classes of these compounds: canonical and non-canonical nucleobases. A point-by-point discussion of the advantages and disadvantages of both types of fluorescent nucleobases is made, along with a perspective into the future challenges and outlook for this burgeoning field.

  3. Proton Transfer in Nucleobases is Mediated by Water

    Energy Technology Data Exchange (ETDEWEB)

    Khistyaev, Kirill; Golan, Amir; Bravaya, Ksenia B.; Orms, Natalie; Krylov, Anna I.; Ahmed, Musahid

    2013-08-08

    Water plays a central role in chemistry and biology by mediating the interactions between molecules, altering energy levels of solvated species, modifying potential energy proles along reaction coordinates, and facilitating ecient proton transport through ion channels and interfaces. This study investigates proton transfer in a model system comprising dry and microhydrated clusters of nucleobases. With mass spectrometry and tunable vacuum ultraviolet synchrotron radiation, we show that water shuts down ionization-induced proton transfer between nucleobases, which is very ecient in dry clusters. Instead, a new pathway opens up in which protonated nucleo bases are generated by proton transfer from the ionized water molecule and elimination of a hydroxyl radical. Electronic structure calculations reveal that the shape of the potential energy prole along the proton transfer coordinate depends strongly on the character of the molecular orbital from which the electron is removed, i.e., the proton transfer from water to nucleobases is barrierless when an ionized state localized on water is accessed. The computed energetics of proton transfer is in excellent agreement with the experimental appearance energies. Possible adiabatic passage on the ground electronic state of the ionized system, while energetically accessible at lower energies, is not ecient. Thus, proton transfer is controlled electronically, by the character of the ionized state, rather than statistically, by simple energy considerations.

  4. Synthesis, structural, solubility and anticancer activity studies of salts using nucleobases and sulfonic acids coformer

    Science.gov (United States)

    Singh, Neetu; Singh, Udai P.; Nikhil, Kumar; Roy, Partha; Singh, Hariji

    2017-10-01

    The reactions of natural and unnatural nucleobases (cytosine (Cyt), adenine (Ade), 5-aminouracil (AU) and caffeine (Caff)) with sulfonic acids coformer (1,5-naphthalenedisulfonic acid, NDSA; 5-sulfosalicylic acid, SSA) resulted in the formation of salts viz. [NDSA.Cyt] (1), [NDSA.Ade] (2), [NDSA.AU] (3), [NDSA.Caff] (4), [SSA.Cyt] (5), [SSA.Ade] (6), [SSA.AU] (7), and [SSA.Caff] (8). The structural analysis revealed that salts 1, 4, 6 and 7 have intermolecular interactions between adjacent nucleobases which form two different homodimer shown in R22 (8) motif and assembled via complementary Nsbnd H⋯O and Nsbnd H⋯N interactions. However, in all other salts an intermediate supramolecular synthon pattern was observed between nucleobases and sulfonic acids. The lattice energy was also calculated by DFT to investigate whether salts were thermodynamically more stable than its coformer. The same was further confirmed by differential scanning calorimetry-thermogravimetric (DSC-TG) analysis. The anticancer activity study of individual nucleobases and their NDSA salts were also performed on human breast (MCF-7) and lung (A 549) cancer cell. The salts formation of nucleobases with sulfonic acids improved their solubility, thereby demonstrating up to 8-fold increase in solubility of nucleobases.

  5. Extraterrestrial Nucleobases in Carbonaceous Chondrites

    Science.gov (United States)

    Martins, Z.; Botta, O.; Fogel, M.; Sephton, M.; Glavin, D.; Watson, J.; Dworkin, J.; Schwartz, A.; Ehrenfreund, P.

    Nucleobases in Carbonaceous Chondrites Z. Martins (1), O. Botta (2), M. L. Fogel (3), M. A. Sephton (4), D. P. Glavin (2), J. S. Watson (5), J. P. Dworkin (2), A. W. Schwartz (6) and P. Ehrenfreund (1,6). (1) Astrobiology Laboratory, Leiden Institute of Chemistry, Leiden, The Netherlands, (2) NASA Goddard Space Flight Center, Goddard Center for Astrobiology, Greenbelt, MD, USA, (3) GL, Carnegie Institution of Washington, Washington DC, USA, (4) Impacts and Astromaterials Research Centre, Department of Earth Science and Engineering, South Kensington Campus, Imperial College, London, UK, (5) Planetary and Space Sciences Research Institute, The Open University, Walton Hall, Milton Keynes, UK, (6) Radboud University Nijmegen, Nijmegen, The Netherlands. E-mail: z.martins@chem.leidenuniv.nl/Phone:+31715274440 Nucleobases are crucial compounds in terrestrial biochemistry, because they are key components of DNA and RNA. Carbonaceous meteorites have been analyzed for nucleobases by different research groups [1-5]. However, significant quantitative and qualitative differences were observed, leading to the controversial about the origin of these nucleobases. In order to establish the origin of these compounds in carbonaceous chondrites and to assess the plausibility of their exogenous delivery to the early Earth, we have performed formic acid extraction of samples of the Murchison meteorite [6], followed by an extensive purification procedure, analysis and quantification by high-performance liquid chromatography with UV absorption detection and gas chromatography-mass spectrometry. Our results were qualitatively consistent with previous results [3, 4], but showed significant quantitative differences. Compound specific carbon isotope values were obtained, using gas chromatography-combustion- isotope ratio mass spectrometry. A soil sample collected in the proximity of the Murchison meteorite fall site was subjected to the same extraction, purification and analysis procedure

  6. Nucleotides, Nucleosides, and Nucleobases

    DEFF Research Database (Denmark)

    Jensen, Kaj Frank; Dandanell, Gert; Hove-Jensen, Bjarne

    2008-01-01

    We review literature on the metabolism of ribo- and deoxyribonucleotides, nucleosides, and nucleobases in Escherichia coli and Salmonella,including biosynthesis, degradation, interconversion, and transport. Emphasis is placed on enzymology and regulation of the pathways, at both the level of gene...

  7. Controlling the orientation of nucleobases by dipole moment interaction with graphene/h-BN interfaces

    KAUST Repository

    Vovusha, Hakkim; Amorim, Rodrigo G.; Scheicher, Ralph H.; Sanyal, Biplab

    2018-01-01

    The interfaces in 2D hybrids of graphene and h-BN provide interesting possibilities of adsorbing and manipulating atomic and molecular entities. In this paper, with the aid of density functional theory, we demonstrate the adsorption characteristics of DNA nucleobases at different interfaces of 2D hybrid nanoflakes of graphene and h-BN. The interfaces provide stronger binding to the nucleobases in comparison to pure graphene and h-BN nanoflakes. It is also revealed that the individual dipole moments of the nucleobases and nanoflakes dictate the orientation of the nucleobases at the interfaces of the hybrid structures. The results of our study point towards a possible route to selectively control the orientation of individual molecules in biosensors.

  8. Controlling the orientation of nucleobases by dipole moment interaction with graphene/h-BN interfaces

    KAUST Repository

    Vovusha, Hakkim

    2018-02-08

    The interfaces in 2D hybrids of graphene and h-BN provide interesting possibilities of adsorbing and manipulating atomic and molecular entities. In this paper, with the aid of density functional theory, we demonstrate the adsorption characteristics of DNA nucleobases at different interfaces of 2D hybrid nanoflakes of graphene and h-BN. The interfaces provide stronger binding to the nucleobases in comparison to pure graphene and h-BN nanoflakes. It is also revealed that the individual dipole moments of the nucleobases and nanoflakes dictate the orientation of the nucleobases at the interfaces of the hybrid structures. The results of our study point towards a possible route to selectively control the orientation of individual molecules in biosensors.

  9. Single Nucleobase Identification Using Biophysical Signatures from Nanoelectronic Quantum Tunneling.

    Science.gov (United States)

    Korshoj, Lee E; Afsari, Sepideh; Khan, Sajida; Chatterjee, Anushree; Nagpal, Prashant

    2017-03-01

    Nanoelectronic DNA sequencing can provide an important alternative to sequencing-by-synthesis by reducing sample preparation time, cost, and complexity as a high-throughput next-generation technique with accurate single-molecule identification. However, sample noise and signature overlap continue to prevent high-resolution and accurate sequencing results. Probing the molecular orbitals of chemically distinct DNA nucleobases offers a path for facile sequence identification, but molecular entropy (from nucleotide conformations) makes such identification difficult when relying only on the energies of lowest-unoccupied and highest-occupied molecular orbitals (LUMO and HOMO). Here, nine biophysical parameters are developed to better characterize molecular orbitals of individual nucleobases, intended for single-molecule DNA sequencing using quantum tunneling of charges. For this analysis, theoretical models for quantum tunneling are combined with transition voltage spectroscopy to obtain measurable parameters unique to the molecule within an electronic junction. Scanning tunneling spectroscopy is then used to measure these nine biophysical parameters for DNA nucleotides, and a modified machine learning algorithm identified nucleobases. The new parameters significantly improve base calling over merely using LUMO and HOMO frontier orbital energies. Furthermore, high accuracies for identifying DNA nucleobases were observed at different pH conditions. These results have significant implications for developing a robust and accurate high-throughput nanoelectronic DNA sequencing technique. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The Formation of Nucleobases from the Ultraviolet Photoirradiation of Purine in Simple Astrophysical Ice Analogues.

    Science.gov (United States)

    Materese, Christopher K; Nuevo, Michel; Sandford, Scott A

    2017-08-01

    Nucleobases are the informational subunits of RNA and DNA and are essential to all known forms of life. The nucleobases can be divided into two groups of molecules: the pyrimidine-based compounds that include uracil, cytosine, and thymine, and the purine-based compounds that include adenine and guanine. Previous work in our laboratory has demonstrated that uracil, cytosine, thymine, and other nonbiological, less common nucleobases can form abiotically from the UV photoirradiation of pyrimidine in simple astrophysical ice analogues containing combinations of H 2 O, NH 3 , and CH 4 . In this work, we focused on the UV photoirradiation of purine mixed with combinations of H 2 O and NH 3 ices to determine whether or not the full complement of biological nucleobases can be formed abiotically under astrophysical conditions. Room-temperature analyses of the resulting photoproducts resulted in the detection of adenine, guanine, and numerous other functionalized purine derivatives. Key Words: Pyrimidine-Nucleobases-Interstellar; Ices-Cometary; Ices-Molecular processes-Prebiotic chemistry. Astrobiology 17, 761-770.

  11. Nucleobase assemblies supported by uranyl cation coordination ...

    Indian Academy of Sciences (India)

    organic hybrid materials using smaller building blocks, which can be ..... nucleobase analogs, in addition to the presence of car- boxylate ... R 2004 Cryst. Eng. Comm. .... Sheldrick G M 2000 SADABS 2.0 (Germany: University of Göttingen). 76.

  12. Probing nucleobase photoprotection with soft x-rays

    Directory of Open Access Journals (Sweden)

    Osipov T.

    2013-03-01

    Full Text Available Nucleobases absorb strongly in the ultraviolet region, leading to molecular excitation into reactive states. The molecules avoid the photoreactions by funnelling the electronic energy into less reactive states on an ultrafast timescale via non-Born-Oppenheimer dynamics. Current theory on the nucleobase thymine discusses two conflicting pathways for the photoprotective dynamics. We present our first results of our free electron laser based UV-pump soft x-ray-probe study of the photoprotection mechanism of thymine. We use the high spatial sensitivity of the Auger electrons emitted after the soft x-ray pulse induced core ionization. Our transient spetra show two timescales on the order of 200 fs and 5 ps, in agreement with previous (all UV ultrafast experiments. The timescales appear at different Auger kinetic energies which will help us to decipher the molecular dynamics.

  13. Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

    Science.gov (United States)

    Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

    2012-06-01

    DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. The origin of efficient triplet state population in sulfur-substituted nucleobases

    Science.gov (United States)

    Mai, Sebastian; Pollum, Marvin; Martínez-Fernández, Lara; Dunn, Nicholas; Marquetand, Philipp; Corral, Inés; Crespo-Hernández, Carlos E.; González, Leticia

    2016-10-01

    Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.

  15. Mechanism Underlying the Nucleobase-Distinguishing Ability of Benzopyridopyrimidine (BPP).

    Science.gov (United States)

    Kochman, Michał A; Bil, Andrzej; Miller, R J Dwayne

    2017-11-02

    Benzopyridopyrimidine (BPP) is a fluorescent nucleobase analogue capable of forming base pairs with adenine (A) and guanine (G) at different sites. When incorporated into oligodeoxynucleotides, it is capable of differentiating between the two purine nucleobases by virtue of the fact that its fluorescence is largely quenched when it is base-paired to guanine, whereas base-pairing to adenine causes only a slight reduction of the fluorescence quantum yield. In the present article, the photophysics of BPP is investigated through computer simulations. BPP is found to be a good charge acceptor, as demonstrated by its positive and appreciably large electron affinity. The selective quenching process is attributed to charge transfer (CT) from the purine nucleobase, which is predicted to be efficient in the BPP-G base pair, but essentially inoperative in the BPP-A base pair. The CT process owes its high selectivity to a combination of two factors: the ionization potential of guanine is lower than that of adenine, and less obviously, the site occupied by guanine enables a greater stabilization of the CT state through electrostatic interactions than the one occupied by adenine. The case of BPP illustrates that molecular recognition via hydrogen bonding can enhance the selectivity of photoinduced CT processes.

  16. Multiple nucleobase transporters contribute to boscalid sensitivity in Aspergillus nidulans.

    Science.gov (United States)

    Kalampokis, Ioannis F; Kapetanakis, George C; Aliferis, Konstantinos A; Diallinas, George

    2018-03-01

    The development of fungicide-resistant fungal populations represents a major challenge for the agrochemical and agri-food sectors, which threatens food supply and security. The issue becomes complex for fungi that cause quantitative and qualitative losses due to mycotoxin biosynthesis. Nonetheless, currently, the molecular details underlying fungicide action and fungal resistance mechanisms are partially known. Here, we have investigated whether plasma membrane transporters contribute to specific fungicide uptake in the model fungus Aspergillus nidulans. Independent physiological tests and toxicity screening of selected fungicides provided evidence that the antifungal activity of Succinate Dehydrogenase Inhibitors (SDHIs) is associated with the expression of several nucleobase-related transporters. In particular, it was shown that a strain genetically inactivated in all seven nucleobase-related transporters is resistant to the fungicide boscalid, whereas none of the single null mutants exhibited significant resistance level. By constructing and testing isogenic strains that over-express each one of the seven transporters, we confirmed that five of them, namely, UapC, AzgA, FycB, CntA, and FurA, contribute to boscalid uptake. Additionally, by employing metabolomics we have examined the effect of boscalid on the metabolism of isogenic strains expressing or genetically lacking boscalid-related nucleobase transporters. The results confirmed the involvement of specific nucleobase transporters in fungicide uptake, leading to the discovery of corresponding metabolites-biomarkers. This work is the first report on the involvement of specific transporters in fungicide uptake and toxicity and their impact on fungal metabolism regulation and results might be further exploited towards the deeper understanding of fungal resistance to fungicides. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Role of Achiral Nucleobases in Multicomponent Chiral Self-Assembly: Purine-Triggered Helix and Chirality Transfer.

    Science.gov (United States)

    Deng, Ming; Zhang, Li; Jiang, Yuqian; Liu, Minghua

    2016-11-21

    Chiral self-assembly is a basic process in biological systems, where many chiral biomolecules such as amino acids and sugars play important roles. Achiral nucleobases usually covalently bond to saccharides and play a significant role in the formation of the double helix structure. However, it remains unclear how the achiral nucleobases can function in chiral self-assembly without the sugar modification. Herein, we have clarified that purine nucleobases could trigger N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to self-assemble into helical nanostructures. Moreover, the helical nanostructure could serve as a matrix and transfer the chirality to an achiral fluorescence probe, thioflavin T (ThT). Upon chirality transfer, the ThT showed not only supramolecular chirality but also circular polarized fluorescence (CPL). Without the nucleobase, the self-assembly processes cannot happen, thus providing an example where achiral molecules played an essential role in the expression and transfer of the chirality. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Origin of the RNA world: The fate of nucleobases in warm little ponds

    Science.gov (United States)

    Pearce, Ben K. D.; Pudritz, Ralph E.; Semenov, Dmitry A.; Henning, Thomas K.

    2017-10-01

    Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds whose wet–dry cycles promoted rapid polymerization. We build a comprehensive numerical model for the evolution of nucleobases in warm little ponds leading to the emergence of the first nucleotides and RNA. We couple Earth's early evolution with complex prebiotic chemistry in these environments. We find that RNA polymers must have emerged very quickly after the deposition of meteorites (less than a few years). Their constituent nucleobases were primarily meteoritic in origin and not from interplanetary dust particles. Ponds appeared as continents rose out of the early global ocean, but this increasing availability of “targets” for meteorites was offset by declining meteorite bombardment rates. Moreover, the rapid losses of nucleobases to pond seepage during wet periods, and to UV photodissociation during dry periods, mean that the synthesis of nucleotides and their polymerization into RNA occurred in just one to a few wet–dry cycles. Under these conditions, RNA polymers likely appeared before 4.17 billion years ago.

  19. Origin of the RNA world: The fate of nucleobases in warm little ponds.

    Science.gov (United States)

    Pearce, Ben K D; Pudritz, Ralph E; Semenov, Dmitry A; Henning, Thomas K

    2017-10-24

    Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds whose wet-dry cycles promoted rapid polymerization. We build a comprehensive numerical model for the evolution of nucleobases in warm little ponds leading to the emergence of the first nucleotides and RNA. We couple Earth's early evolution with complex prebiotic chemistry in these environments. We find that RNA polymers must have emerged very quickly after the deposition of meteorites (less than a few years). Their constituent nucleobases were primarily meteoritic in origin and not from interplanetary dust particles. Ponds appeared as continents rose out of the early global ocean, but this increasing availability of "targets" for meteorites was offset by declining meteorite bombardment rates. Moreover, the rapid losses of nucleobases to pond seepage during wet periods, and to UV photodissociation during dry periods, mean that the synthesis of nucleotides and their polymerization into RNA occurred in just one to a few wet-dry cycles. Under these conditions, RNA polymers likely appeared before 4.17 billion years ago.

  20. Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd)

    DEFF Research Database (Denmark)

    Hrdlicka, Patrick J; Jepsen, Jan S; Nielsen, Claus

    2005-01-01

    convergent synthetic route utilizing diacetone-alpha-D-glucose as starting material. 5-Iodo-substituted EUrd was the most potent inhibitor among the novel nucleobase-modified analogs in in vitro assays against human adenocarcinoma breast and prostate cancer cells with IC50 values down to 35 nM....

  1. Contents Changes of Triterpenic Acids, Nucleosides, Nucleobases, and Saccharides in Jujube (Ziziphus jujuba) Fruit During the Drying and Steaming Process.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-Ao; Zhang, Ying; Qian, Dawei; Tang, Yuping; Zhu, Zhenhua; Wang, Hanqing

    2015-12-12

    Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed.

  2. Functionalized Solid Electrodes for Electrochemical Biosensing of Purine Nucleobases and Their Analogues: A Review

    Science.gov (United States)

    Sharma, Vimal Kumar; Jelen, Frantisek; Trnkova, Libuse

    2015-01-01

    Interest in electrochemical analysis of purine nucleobases and few other important purine derivatives has been growing rapidly. Over the period of the past decade, the design of electrochemical biosensors has been focused on achieving high sensitivity and efficiency. The range of existing electrochemical methods with carbon electrode displays the highest rate in the development of biosensors. Moreover, modification of electrode surfaces based on nanomaterials is frequently used due to their extraordinary conductivity and surface to volume ratio. Different strategies for modifying electrode surfaces facilitate electron transport between the electrode surface and biomolecules, including DNA, oligonucleotides and their components. This review aims to summarize recent developments in the electrochemical analysis of purine derivatives, as well as discuss different applications. PMID:25594595

  3. Functionalized Solid Electrodes for Electrochemical Biosensing of Purine Nucleobases and Their Analogues: A Review

    Directory of Open Access Journals (Sweden)

    Vimal Kumar Sharma

    2015-01-01

    Full Text Available Interest in electrochemical analysis of purine nucleobases and few other important purine derivatives has been growing rapidly. Over the period of the past decade, the design of electrochemical biosensors has been focused on achieving high sensitivity and efficiency. The range of existing electrochemical methods with carbon electrode displays the highest rate in the development of biosensors. Moreover, modification of electrode surfaces based on nanomaterials is frequently used due to their extraordinary conductivity and surface to volume ratio. Different strategies for modifying electrode surfaces facilitate electron transport between the electrode surface and biomolecules, including DNA, oligonucleotides and their components. This review aims to summarize recent developments in the electrochemical analysis of purine derivatives, as well as discuss different applications.

  4. The photochemistry of pyrimidine in realistic astrophysical ices and the production of nucleobases

    International Nuclear Information System (INIS)

    Nuevo, Michel; Materese, Christopher K.; Sandford, Scott A.

    2014-01-01

    Nucleobases, together with deoxyribose/ribose and phosphoric acid, are the building blocks of DNA and RNA for all known life. The presence of nucleobase-like compounds in carbonaceous chondrites delivered to the Earth raises the question of an extraterrestrial origin for the molecules that triggered life on our planet. Whether these molecules are formed in interstellar/protostellar environments, in small parent bodies in the solar system, or both, is currently unclear. Recent experiments show that the UV irradiation of pyrimidine (C 4 H 4 N 2 ) in H 2 O-rich ice mixtures that contain NH 3 , CH 3 OH, or CH 4 leads to the formation of the pyrimidine-based nucleobases uracil, cytosine, and thymine. In this work, we discuss the low-temperature UV irradiation of pyrimidine in realistic astrophysical ice mixtures containing H 2 O, CH 3 OH, and NH 3 , with or without CH 4 , to search for the production of nucleobases and other prebiotic compounds. These experiments show the presence of uracil, urea, glycerol, hexamethylenetetramine, small amino acids, and small carboxylic acids in all samples. Cytosine was only found in one sample produced from ices irradiated with a higher UV dose, while thymine was not found in any sample, even after irradiation with a higher UV dose. Results are discussed to evaluate the role of the photochemistry of pyrimidine in the inventory of organic molecules detected in meteorites and their astrophysical/astrobiological implications.

  5. Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

    Directory of Open Access Journals (Sweden)

    Artur Jabłoński

    2017-11-01

    Full Text Available Fluorescent pyrene–linker–nucleobase (nucleobase = thymine, adenine conjugates with carbonyl and hydroxy functionalities in the linker were synthesized and characterized. X-ray single-crystal structure analysis performed for the pyrene–C(OCH2CH2–thymine (2 conjugate reveals dimers of molecules 2 stabilized by hydrogen bonds between the thymine moieties. The photochemical characterization showed structure-dependent fluorescence properties of the investigated compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer solution. In respect to the complementary oligothymidine T10 template in water, compounds 3 and 5 both show a self-assembling behavior according to canonical base–base pairing. However, in buffer solution, derivative 5 was much more effective than 3 in binding to the T10 template. Furthermore the adenine derivative 5 binds to the double-stranded (dA10–T10 template with a self-assembly ratio of 112%. Such a high value of a self-assembly ratio can be rationalized by a triple-helix-like binding, intercalation, or a mixture of both. Remarkably, compound 5 also shows dual staining pattern in living HeLa cells. Confocal microscopy confirmed that 5 predominantly stains mitochondria but it also accumulates in the nucleoli of the cells.

  6. Characterization of nucleosides and nucleobases in fruits of Ziziphus jujuba by UPLC-DAD-MS.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-Ao; Tang, Yu-Ping; Zhu, Zhen-Hua; Qian, Ye-Fei; Yang, Nian-Yun; Shang, Er-Xin; Qian, Da-Wei

    2010-10-13

    The fruit of Ziziphus jujuba , named dazao in Chinese, has been utilized as food as well as crude drugs in China for thousands of years. To explore the profiles of the nucleosides and nucleobases in this fruit, an ultraperformance liquid chromatograph coupled with a photodiode array detector and electrospray ionization-mass spectrometer method (UPLC-DAD-MS) has been established and validated in this paper. The validated method was successfully applied for the simultaneous characterization and quantitation of 9 nucleosides and nucleobases in 49 dazao samples, which comprised 43 cultivars from 26 cultivation regions. Furthermore, principal component analysis (PCA) was performed to classify the samples on the basis of the contents of the nine analyzed compounds. The results showed that almost all of these dazao samples were rich in nucleosides and nucleobases, although their contents were obviously various, and the proposed method could serve as a prerequisite for quality control of jujube products.

  7. Nucleobase-functionalized grapheme nanoribbons for accurate high-speed DNA sequencing

    NARCIS (Netherlands)

    Paulechka, Eugene; Wassenaar, Tsjerk; Kroenlein, Kenneth; Kazakov, Andrei; Smolyanitsky, Alex

    2016-01-01

    We propose a water-immersed nucleobase-functionalized suspended graphene nanoribbon as an intrinsically selective device for nucleotide detection. The proposed sensing method combines Watson–Crick selective base pairing with graphene's capacity for converting anisotropic lattice strain to changes in

  8. Steric restrictions of RISC in RNA interference identified with size-expanded RNA nucleobases.

    Science.gov (United States)

    Hernández, Armando R; Peterson, Larryn W; Kool, Eric T

    2012-08-17

    Understanding the interactions between small interfering RNAs (siRNAs) and the RNA-induced silencing complex (RISC), the key protein complex of RNA interference (RNAi), is of great importance to the development of siRNAs with improved biological and potentially therapeutic function. Although various chemically modified siRNAs have been reported, relatively few studies with modified nucleobases exist. Here we describe the synthesis and hybridization properties of siRNAs bearing size-expanded RNA (xRNA) nucleobases and their use as a novel and systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 Å using benzo-homologation and retain canonical Watson-Crick base-pairing groups. Our data show that the modified siRNA duplexes display small changes in melting temperature (+1.4 to -5.0 °C); substitutions near the center are somewhat destabilizing to the RNA duplex, while substitutions near the ends are stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells revealed that xRNA nucleobases in the antisense strand reduce activity at some central positions near the seed region but are generally well tolerated near the ends. Most importantly, we observed that xRNA substitutions near the 3'-end increased activity over that of wild-type siRNAs. The data are analyzed in terms of site-dependent steric effects in RISC. Circular dichroism experiments show that single xRNA substitutions do not significantly distort the native A-form helical structure of the siRNA duplex, and serum stability studies demonstrated that xRNA substitutions protect siRNAs against nuclease degradation.

  9. Reaction of cyanide with Pt-nucleobase complexes: preparative, spectroscopic, and structural studies. Unexpected stability of Pt-thymine and Pt-uracil complexes

    International Nuclear Information System (INIS)

    Raudaschl-Sieber, G.; Lippert, B.

    1985-01-01

    In order to improve the understanding of the nature of the strongly bound cisplatin on DNA, the reactivity of a large number of complexes of cis-(NH 3 ) 2 Pt/sup II/ with the model nucleobases, 9-ethylguanine, 9-methyladenine, 1-methylcytisine, 1-methylthymine, and i-methyluracil, toward a large excess of cyanide was studied. The behavior of Pt-nucleobase complexes toward CN - is compared with that of simple Pt-amine complexes, and reactions of thiourea with two selected nucleobase complexes is reported. The relevance of these findings with respect to substitution reactions of Pt-nucleobase complexes and the nature of the tightly DNA-bound Pt, which cannot be removed by excess KCN, is discussed

  10. Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

    Science.gov (United States)

    Xia, Yi; Qu, Fanqi; Peng, Ling

    2010-08-01

    Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

  11. Nucleobases, nucleosides, and nucleotides: versatile biomolecules for generating functional nanomaterials.

    Science.gov (United States)

    Pu, Fang; Ren, Jinsong; Qu, Xiaogang

    2018-02-21

    The incorporation of biomolecules into nanomaterials generates functional nanosystems with novel and advanced properties, presenting great potential for applications in various fields. Nucleobases, nucleosides and nucleotides, as building blocks of nucleic acids and biological coenzymes, constitute necessary components of the foundation of life. In recent years, as versatile biomolecules for the construction or regulation of functional nanomaterials, they have stimulated interest in researchers, due to their unique properties such as structural diversity, multiplex binding sites, self-assembly ability, stability, biocompatibility, and chirality. In this review, strategies for the synthesis of nanomaterials and the regulation of their morphologies and functions using nucleobases, nucleosides, and nucleotides as building blocks, templates or modulators are summarized alongside selected applications. The diverse applications range from sensing, bioimaging, and drug delivery to mimicking light-harvesting antenna, the construction of logic gates, and beyond. Furthermore, some perspectives and challenges in this emerging field are proposed. This review is directed toward the broader scientific community interested in biomolecule-based functional nanomaterials.

  12. UV laser photoactivation of hexachloroplatinate bound to individual nucleobases in vacuo as molecular level probes of a model photopharmaceutical.

    Science.gov (United States)

    Matthews, Edward; Sen, Ananya; Yoshikawa, Naruo; Bergström, Ed; Dessent, Caroline E H

    2016-06-01

    Isolated molecular clusters of adenine, cytosine, thymine and uracil bound to hexachloroplatinate, PtCl6(2-), have been studied using laser electronic photodissociation spectroscopy to investigate photoactivation of a platinum complex in the vicinity of a nucleobase. These metal complex-nucleobase clusters represent model systems for identifying the fundamental photochemical processes occurring in photodynamic platinum drug therapies that target DNA. This is the first study to explore the specific role of a strongly photoactive platinum compound in the aggregate complex. Each of the clusters studied displays a broadly similar absorption spectra, with a strong λmax ∼ 4.6 eV absorption band and a subsequent increase in the absorption intensity towards higher spectral-energy. The absorption bands are traced to ligand-to-metal-charge-transfer excitations on the PtCl6(2-) moiety within the cluster, and result in Cl(-)·nucleobase and PtCl5(-) as primary photofragments. These results demonstrate how selective photoexcitation can drive distinctive photodecay channels for a model photo-pharmaceutical. In addition, cluster absorption due to excitation of nucleobase-centred chromophores is observed in the region around 5 eV. For the uracil cluster, photofragments consistent with ultrafast decay of the excited state and vibrational predissociation on the ground-state surface are observed. However, this decay channel becomes successively weaker on going from thymine to cytosine to adenine, due to differential coupling of the excited states to the electron detachment continuum. These effects demonstrate the distinctive photophysical characteristics of the different nucleobases, and are discussed in the context of the recently recorded photoelectron spectra of theses clusters.

  13. Real-time analysis of self-assembled nucleobases by Venturi easy ambient sonic-spray ionization mass spectrometry.

    Science.gov (United States)

    Na, Na; Shi, Ruixia; Long, Zi; Lu, Xin; Jiang, Fubin; Ouyang, Jin

    2014-10-01

    In this study, the real-time analysis of self-assembled nucleobases was employed by Venturi easy ambient sonic-spray ionization mass spectrometry (V-EASI-MS). With the analysis of three nucleobases including 6-methyluracil (6MU), uracil (U) and thymine (T) as examples, different orders of clusters centered with different metal ions were recorded in both positive and negative modes. Compared with the results obtained by traditional electrospray ionization mass spectrometry (ESI-MS) under the same condition, more clusters with high orders, such as [6MU7+Na](+), [6MU15+2NH4](2+), [6MU10+Na](+), [T7+Na](+), and [T15+2NH4](2+) were detected by V-EASI-MS, which demonstrated the soft ionization ability of V-EASI for studying the non-covalent interaction in a self-assembly process. Furthermore, with the injection of K(+) to the system by a syringe pumping, the real-time monitoring of the formation of nucleobases clusters was achieved by the direct extraction of samples from the system under the Venturi effect. Therefore, the effect of cations on the formation of clusters during self-assembly of nucleobases was demonstrated, which was in accordance with the reports. Free of high voltage, heating or radiation during the ionization, this technique is much soft and suitable for obtaining the real-time information of the self-assembly system, which also makes it quite convenient for extraction samples from the reaction system. This "easy and soft" ionization technique has provided a potential pathway for monitoring and controlling the self-assembly processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. First-principles photoemission spectroscopy in DNA and RNA nucleobases from Koopmans-compliant functionals

    Science.gov (United States)

    Nguyen, Ngoc Linh; Borghi, Giovanni; Ferretti, Andrea; Marzari, Nicola

    The determination of spectral properties of the DNA and RNA nucleobases from first principles can provide theoretical interpretation for experimental data, but requires complex electronic-structure formulations that fall outside the domain of applicability of common approaches such as density-functional theory. In this work, we show that Koopmans-compliant functionals, constructed to enforce piecewise linearity in energy functionals with respect to fractional occupation-i.e., with respect to charged excitations-can predict not only frontier ionization potentials and electron affinities of the nucleobases with accuracy comparable or superior with that of many-body perturbation theory and high-accuracy quantum chemistry methods, but also the molecular photoemission spectra are shown to be in excellent agreement with experimental ultraviolet photoemsision spectroscopy data. The results highlight the role of Koopmans-compliant functionals as accurate and inexpensive quasiparticle approximations to the spectral potential, which transform DFT into a novel dynamical formalism where electronic properties, and not only total energies, can be correctly accounted for.

  15. Occurrence and stability of lone pair–π stacking interactions between ribose and nucleobases in functional RNAs

    KAUST Repository

    Chawla, Mohit; Chermak, Edrisse; Zhang, Qingyun; Bujnicki, Janusz M.; Oliva, Romina; Cavallo, Luigi

    2017-01-01

    The specific folding pattern and function of RNA molecules lies in various weak interactions, in addition to the strong base-base pairing and stacking. One of these relatively weak interactions, characterized by the stacking of the O4′ atom of a ribose on top of the heterocycle ring of a nucleobase, has been known to occur but has largely been ignored in the description of RNA structures. We identified 2015 ribose–base stacking interactions in a high-resolution set of non-redundant RNA crystal structures. They are widespread in structured RNA molecules and are located in structural motifs other than regular stems. Over 50% of them involve an adenine, as we found ribose-adenine contacts to be recurring elements in A-minor motifs. Fewer than 50% of the interactions involve a ribose and a base of neighboring residues, while approximately 30% of them involve a ribose and a nucleobase at least four residues apart. Some of them establish inter-domain or inter-molecular contacts and often implicate functionally relevant nucleotides. In vacuo ribose-nucleobase stacking interaction energies were calculated by quantum mechanics methods. Finally, we found that lone pair–π stacking interactions also occur between ribose and aromatic amino acids in RNA–protein complexes.

  16. Occurrence and stability of lone pair–π stacking interactions between ribose and nucleobases in functional RNAs

    KAUST Repository

    Chawla, Mohit

    2017-08-18

    The specific folding pattern and function of RNA molecules lies in various weak interactions, in addition to the strong base-base pairing and stacking. One of these relatively weak interactions, characterized by the stacking of the O4′ atom of a ribose on top of the heterocycle ring of a nucleobase, has been known to occur but has largely been ignored in the description of RNA structures. We identified 2015 ribose–base stacking interactions in a high-resolution set of non-redundant RNA crystal structures. They are widespread in structured RNA molecules and are located in structural motifs other than regular stems. Over 50% of them involve an adenine, as we found ribose-adenine contacts to be recurring elements in A-minor motifs. Fewer than 50% of the interactions involve a ribose and a base of neighboring residues, while approximately 30% of them involve a ribose and a nucleobase at least four residues apart. Some of them establish inter-domain or inter-molecular contacts and often implicate functionally relevant nucleotides. In vacuo ribose-nucleobase stacking interaction energies were calculated by quantum mechanics methods. Finally, we found that lone pair–π stacking interactions also occur between ribose and aromatic amino acids in RNA–protein complexes.

  17. Adsorption Characteristics of DNA Nucleobases, Aromatic Amino Acids and Heterocyclic Molecules on Silicene and Germanene Monolayers

    KAUST Repository

    Hussain, Tanveer

    2017-09-14

    Binding of DNA/RNA nucleobases, aromatic amino acids and heterocyclic molecules on two-dimensional silicene and germanene sheets have been investigated for the application of sensing of biomolecules using first principle density functional theory calculations. Binding energy range for nucleobases, amino acids and heterocyclic molecules with both the sheets have been found to be (0.43-1.16eV), (0.70-1.58eV) and (0.22-0.96eV) respectively, which along with the binding distances show that these molecules bind to both sheets by physisorption and chemisorption process. The exchange of electric charges between the monolayers and the incident molecules has been examined by means of Bader charge analysis. It has been observed that the introduction of DNA/RNA nucleobases, aromatic amino acids and heterocyclic molecules alters the electronic properties of both silicene and germanene nano sheets as studied by plotting the total (TDOS) and partial (PDOS) density of states. The DOS plots reveal the variation in the band gaps of both silicene and germanene caused by the introduction of studied molecules. Based on the obtained results we suggest that both silicene and germanene monolayers in their pristine form could be useful for sensing of biomolecules.

  18. Influence of the nucleobase on the physicochemical characteristics and biological activities of Sb{sup V}-ribonucleoside complexes

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Claudio S.; Demicheli, Cynthia, E-mail: demichel@netuno.lcc.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Quimica; Rocha, Iara C.M. da; Melo, Maria N. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Parasitologia; Monte Neto, Rubens L.; Frezard, Frederic [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica

    2010-07-01

    The influence of the nucleobase (uracyl, U; cytosine, C; adenine, A; guanine, G) on the physicochemical characteristics and in vitro biological activities of Sb{sup V}-ribonucleoside complexes has been investigated. The 1:1 Sb-U and Sb-C complexes were characterized by NMR and ESI-MS spectroscopies and elemental analysis. The stability constant and the apparent association and dissociation rate constants of 1:1 Sb{sup V}-U, Sb{sup V}-C and Sb{sup V}-A complexes were determined. Although Sb{sup V} most probably binds via oxygen atoms to the same 2' and 3' positions in the different nucleosides, the ribose conformational changes and the physicochemical characteristics of the complex depend on the nucleobase. The nucleobase had a strong influence on the cytotoxicity against macrophages and the antileishmanial activity of the Sb{sup V}-ribonucleoside complexes. The Sb{sup V}-purine complexes were more cytotoxic and more effective against Leishmania chagasi than the Sb{sup V}-pyrimidine complexes, supporting the model that the interaction of Sb{sup V} with purine nucleosides may mediate the antileishmanial activity of pentavalent antimonial drugs. (author)

  19. Molecular dipole-driven electronic structure modifications of DNA/RNA nucleobases on graphene

    Czech Academy of Sciences Publication Activity Database

    Yin, Y.; Červenka, Jiří; Medhekar, N.

    2017-01-01

    Roč. 8, č. 13 (2017), s. 3087-3094 ISSN 1948-7185 R&D Projects: GA ČR GA14-15357S Grant - others:AV ČR(CZ) Fellowship J. E. Purkyně Institutional support: RVO:68378271 Keywords : graphene * DNA * nucleobase * DFT Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 9.353, year: 2016

  20. Adsorption of DNA/RNA nucleobases onto single-layer MoS2 and Li-Doped MoS2: A dispersion-corrected DFT study

    Science.gov (United States)

    Sadeghi, Meisam; Jahanshahi, Mohsen; Ghorbanzadeh, Morteza; Najafpour, Ghasem

    2018-03-01

    The kind of sensing platform in nano biosensor plays an important role in nucleic acid sequence detection. It has been demonstrated that graphene does not have an intrinsic band gap; therefore, transition metal dichalcogenides (TMDs) are desirable materials for electronic base detection. In the present work, a comparative study of the adsorption of the DNA/RNA nucleobases [Adenine (A), Cytosine (C) Guanine (G), Thymine (T) and Uracil (U)] onto the single-layer molybdenum disulfide (MoS2) and Li-doped MoS2 (Li-MoS2) as a sensing surfaces was investigated by using Dispersion-corrected Density Functional Theory (D-DFT) calculations and different measure of equilibrium distances, charge transfers and binding energies for the various nucleobases were calculated. The results revealed that the interactions between the nucleobases and the MoS2 can be strongly enhanced by introducing metal atom, due to significant charge transfer from the Li atom to the MoS2 when Lithium is placed on top of the MoS2. Furthermore, the binding energies of the five nucleobases were in the range of -0.734 to -0.816 eV for MoS2 and -1.47 to -1.80 eV for the Li-MoS2. Also, nucleobases were adsorbed onto MoS2 sheets via the van der Waals (vdW) force. This high affinity and the renewable properties of the biosensing platform demonstrated that Li-MoS2 nanosheet is biocompatible and suitable for nucleic acid analysis.

  1. Glucose-nucleobase pairs within DNA: impact of hydrophobicity, alternative linking unit and DNA polymerase nucleotide insertion studies† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04850e

    Science.gov (United States)

    Vengut-Climent, Empar; Peñalver, Pablo; Lucas, Ricardo; Gómez-Pinto, Irene; Aviñó, Anna; Muro-Pastor, Alicia M.; Galbis, Elsa; de Paz, M. Violante; Fonseca Guerra, Célia; Bickelhaupt, F. Matthias; Eritja, Ramón; González, Carlos

    2018-01-01

    Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside–RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs. When we explored butanetriol instead of glycerol as a wider anchoring unit, we did not gain duplex thermal stability. This result confirmed the necessity of a more conformationally restricted linker to increase the overall duplex stability. Permethylated glucose-nucleobase pairs showed similar stability to glucoside-nucleobase pairs but no selectivity for a specific nucleobase, possibly due to the absence of hydrogen bonds between them. The three-dimensional structure of the duplex solved by NMR located both, the hydrophobic permethylated glucose and the nucleobase, inside the DNA helix as in the case of glucose-nucleobase pairs. Quantum chemical calculations on glucose-nucleobase pairs indicate that the attachment of the sugar to the DNA skeleton through the OH1 or OH4 positions yields the highest binding energies. Moreover, glucose was very selective for guanine when attached through OH1 or OH4 to the DNA. Finally, we examined DNA polymerase insertion of nucleotides in front of the saccharide unit. KF– polymerase from E. coli inserted A and G opposite glc and 6dglc with low efficiency but notable selectivity. It is even capable of extending the new pair although its efficiency depended on the DNA sequence. In contrast, Bst 2.0, SIII and BIOTAQ™ DNA polymerases seem to display a loop-out mechanism possibly due to the flexible glycerol linker used instead of deoxyribose. PMID:29780486

  2. Perceived Benefits of Human Sexuality Peer Facilitators

    Science.gov (United States)

    Butler, Scott M.; Hartzell, Rose M.; Sherwood, Catherine M.

    2008-01-01

    Peer education, facilitation, and counseling programs are commonly utilized in primary and secondary prevention programs within colleges and universities. In addition, peer-based human sexuality discussions have been used as an adjunct to traditional human sexuality pedagogic programs over the last 20 years. Whereas ample evidence suggests that…

  3. Characterisation of nucleosides and nucleobases in Mactra veneriformis by high performance liquid chromatography coupled with diode array detector-mass spectrometry (HPLC-DAD-MS).

    Science.gov (United States)

    Liu, Rui; Ji, Jing; Wang, Lingchong; Chen, Shiyong; Guo, Sheng; Wu, Hao

    2012-11-15

    Mactra veneriformis has been used as sea food and traditional Chinese medicine (TCM) for thousands of years in China. In the present study, a high performance liquid chromatograph coupled with photodiode array detector and electrospray ionisation-mass spectrometer (HPLC-DAD-ESI-MS) method was established for detection of the nucleosides and nucleobases in M. veneriformis from four aquaticultural area of Jiangsu during different harvest time of one year. The validated method was successfully applied to identifying 10 nucleosides and nucleobases in 48 M. veneriformis samples. Quantitative analysis showed that nucleosides and nucleobases are rich in all M. veneriformis samples. However, their contents vary in different areas and harvest times. Principal component analysis (PCA) was used to classify the 48 samples based on the contents of the nucleosides and nucleobases. As a result, the samples could be mainly clustered into four groups, which was similar as aquaticultural areas classification. Based on the results, present method might be applicable for the quality control of M. veneriformis, or even other marine shellfish aquiculture and their products, and the quality of M. veneriformis might be more related with aquaticultural areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. A comprehensive theoretical investigation about the bio-functionalization capability of single walled CNT, BNNT and SiCNT using DNA/RNA nucleobases

    Science.gov (United States)

    Alinezhad, Heshmatollah; Ganji, Masoud Darvish; Soleymani, Elham; Tajbakhsh, Mahmood

    2017-11-01

    By means of Density Functional Theory (DFT) based calculations, we have elucidated the interactions between five nucleobases and three nanotubes, namely: CNT, BNNT and SiCNT. The energetics and equilibrium geometries have been calculated within the framework of revPBE method in combination with third version of Grimme's atom pair-wise dispersion corrections with Becke-Johnson damping (D3BJ). The obtained results in terms of adsorption energy values and geometrical parameters suggest that the overall interactions are divided into two parts: non-covalently and covalently bonded systems as the nucleobases are physisorbed onto the surface of CNT and BNNT (Eads ranges from -0.57 to -0.76 eV and -0.54 to -0.78 eV for CNT and BNNT complexes, respectively) while the type of interactions between nucleobase molecules and SiCNT has been found to be of covalent type with the Eads ranging from -0.61 to -1.8 eV. Moreover, the empirical dispersion corrections have been found to play crucial roles in obtaining reliable geometries and adsorption energy values for the non-covalently bonded systems. The role of solvation on the overall interactions has also been explored using the COSMO model within a media with dielectric constant of 78.39 which resembles the water environment and the results revealed that the interaction strength showed a decreasing trend with increasing the polarity of the system. Considering the adsorption energy differences between each nucleobase and the nanotubes, the SiCNT showed promising performance in differentiating between the nucleobase molecules and exhibited the highest affinity to be biofunctionalized in comparison to other nanotubes. The findings of the present work would be very useful for understanding the underlying phenomena behind the interface interactions and would aid future experimental investigations in the fields of biotechnology and materials science.

  5. Simultaneous fluorescence light-up and selective multicolor nucleobase recognition based on sequence-dependent strong binding of berberine to DNA abasic site.

    Science.gov (United States)

    Wu, Fei; Shao, Yong; Ma, Kun; Cui, Qinghua; Liu, Guiying; Xu, Shujuan

    2012-04-28

    Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012

  6. Catalytic Role of Manganese Oxides in Prebiotic Nucleobases Synthesis from Formamide.

    Science.gov (United States)

    Bhushan, Brij; Nayak, Arunima; Kamaluddin

    2016-06-01

    Origin of life processes might have begun with the formation of important biomonomers, such as amino acids and nucleotides, from simple molecules present in the prebiotic environment and their subsequent condensation to biopolymers. While studying the prebiotic synthesis of naturally occurring purine and pyrimidine derivatives from formamide, the manganese oxides demonstrated not only good binding for formamide but demonstrated novel catalytic activity. A novel one pot manganese oxide catalyzed synthesis of pyrimidine nucleobases like thymine is reported along with the formation of other nucleobases like purine, 9-(hydroxyacetyl) purine, cytosine, 4(3 H)-pyrimidinone and adenine in acceptable amounts. The work reported is significant in the sense that the synthesis of thymine has exhibited difficulties especially under one pot conditions and also such has been reported only under the catalytic activity of TiO2. The lower oxides of manganese were reported to show higher potential as catalysts and their existence were favored by the reducing atmospheric conditions prevalent on early Earth; thereby confirming the hypothesis that mineral having metals in reduced form might have been more active during the course of chemical evolution. Our results further confirm the role of formamide as a probable precursor for the formation of purine and pyrimidine bases during the course of chemical evolution and origin of life.

  7. A Search for Amino Acids and Nucleobases in the Martian Meteorite Roberts Massif 04262 Using Liquid Chromatography-Mass Spectrometry

    Science.gov (United States)

    Callahan, Michael P.; Burton, Aaron S.; Elsila, Jamie E.; Baker, Eleni M.; Smith, Karen E.; Glavin, Daniel P.; Dworkin, Jason P.

    2013-01-01

    The investigation into whether Mars contains signatures of past or present life is of great interest to science and society. Amino acids and nucleobases are compounds that are essential for all known life on Earth and are excellent target molecules in the search for potential Martian biomarkers or prebiotic chemistry. Martian meteorites represent the only samples from Mars that can be studied directly in the laboratory on Earth. Here, we analyzed the amino acid and nucleobase content of the shergottite Roberts Massif (RBT) 04262 using liquid chromatography-mass spectrometry. We did not detect any nucleobases above our detection limit in formic acid extracts; however, we did measure a suite of protein and nonprotein amino acids in hot-water extracts with high relative abundances of beta-alanine and gamma-amino-eta-butyric acid. The presence of only low (to absent) levels of several proteinogenic amino acids and a lack of nucleobases suggest that this meteorite fragment is fairly uncontaminated with respect to these common biological compounds. The distribution of straight-chained amine-terminal eta-omega-amino acids in RBT 04262 resembled those previously measured in thermally altered carbonaceous meteorites. A carbon isotope ratio of -24(0/00) +/- 6(0/00) for beta-alanine in RBT 04262 is in the range of reduced organic carbon previously measured in Martian meteorites (Steele et al. 2012). The presence of eta-omega-amino acids may be due to a high temperature Fischer-Tropschtype synthesis during igneous processing on Mars or impact ejection of the meteorites from Mars, but more experimental data are needed to support these hypotheses.

  8. Adsorption Characteristics of DNA Nucleobases, Aromatic Amino Acids and Heterocyclic Molecules on Silicene and Germanene Monolayers

    KAUST Repository

    Hussain, Tanveer; Vovusha, Hakkim; Kaewmaraya, Thanayut; Amornkitbamrung, Vittaya; Ahuja, Rajeev

    2017-01-01

    Binding of DNA/RNA nucleobases, aromatic amino acids and heterocyclic molecules on two-dimensional silicene and germanene sheets have been investigated for the application of sensing of biomolecules using first principle density functional theory

  9. Hydrophilic interaction ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry for determination of nucleotides, nucleosides and nucleobases in Ziziphus plants.

    Science.gov (United States)

    Guo, Sheng; Duan, Jin-ao; Qian, Dawei; Wang, Hanqing; Tang, Yuping; Qian, Yefei; Wu, Dawei; Su, Shulan; Shang, Erxin

    2013-08-02

    In this study, a rapid and sensitive analytical method was developed for the determination of 20 nucleobases, nucleosides and nucleotides in Ziziphus plants at trace levels by using hydrophilic interaction ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-UHPLC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode. Under the optimized chromatographic conditions, good separation for 20 target compounds were obtained on a UHPLC Amide column with sub-2μm particles within 10min. The overall LODs and LOQs were between 0.11-3.12ngmL(-1) and 0.29-12.48ngmL(-1) for the 20 analytes, respectively. It is the first report about simultaneous analysis of nucleobases, nucleosides and nucleotides in medicinal plants using HILIC-UHPLC-TQ-MS/MS method, which affords good linearity, precision, repeatability and accuracy. The developed method was successfully applied to Ziziphus plant (Z. jujuba, Z. jujuba var. spinosa and Z. mauritiana) samples. The analysis showed that the fruits and leaves of Ziziphus plants are rich in nucleosides and nucleobases as well as nucleotides, and could be selected as the healthy food resources. Our results in present study suggest that HILIC-UHPLC-TQ-MS/MS method could be employed as a useful tool for quality assessment of the samples from the Ziziphus plants as well as other medicinal plants or food samples using nucleotides, nucleosides and nucleobases as markers. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.

    Science.gov (United States)

    Liu, Xinran; Musser, Derek M; Lee, Cheri A; Yang, Xiaorong; Arnold, Jamie J; Cameron, Craig E; Boehr, David D

    2015-10-26

    The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.

  11. Interactions of nucleobases with alkali earth metal cations--electrospray ionization mass spectrometric study.

    Science.gov (United States)

    Frańska, Magdalena

    2007-01-01

    Interactions of nucleobases with alkali earth metal cations have been studied by electrospray ionization mass spectrometry (ESI-MS). Nucleobases containing at least one oxygen atom form stable complexes with alkali earth metal cations. This phenomenon can be explained on the grounds of the well known theory of hard and soft acids and bases. Uracil and thymine make complexes only when in their deprotonoted forms. The cations of great radii (Sr(2+), Ba(2+)) are more prone to form complexes of stoichiometry 1:1 with uracil and thymine than the cations of small radii (Mg(2+), Ca(2+)). On the other hand, Mg(2+) forms complexes of stoichiometry 2:1 and 3:2 with uracil and thymine. Gas-phase stabilities of the 1:1 complexes are higher for the cations of small radii, in contrast to the solution stabilities. For cytosine and 9- methylhypoxantine the 1:1 complexes of their deprotonated forms are observed at higher cone voltage as a result of HCl molecule loss from the complexes containing the counter ion (Cl(-)). In solution, more stable complexes are formed with metal cations of low radii. Gas-phase stability of the complexes formed by deprotonated 9- methyl-hypoxantine increases with increasing metal cation radius.

  12. Automated quantum chemistry based molecular dynamics simulations of electron ionization induced fragmentations of the nucleobases Uracil, Thymine, Cytosine, and Guanine.

    Science.gov (United States)

    Grimme, Stefan; Bauer, Christopher Alexander

    2015-01-01

    The gas-phase decomposition pathways of electron ionization (EI)-induced radical cations of the nucleobases uracil, thymine, cytosine, and guanine are investigated by means of mixed quantum-classical molecular dynamics. No preconceived fragmentation channels are used in the calculations. The results compare well to a plethora of experimental and theoretical data for these important biomolecules. With our combined stochastic and dynamic approach, one can access in an unbiased way the energetically available decomposition mechanisms. Additionally, we are able to separate the EI mass spectra of different tautomers of cytosine and guanine. Our method (previously termed quantum chemistry electron ionization mass spectra) reproduces free nucleobase experimental mass spectra well and provides detailed mechanistic in-sight into high-energy unimolecular decomposition processes.

  13. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

    Directory of Open Access Journals (Sweden)

    Xinran Liu

    2015-10-01

    Full Text Available The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I in the RNA-dependent RNA polymerase (RdRp. We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.

  14. Dispersion Interactions between Urea and Nucleobases Contribute to the Destabilization of RNA by Urea in Aqueous Solution

    Science.gov (United States)

    Kasavajhala, Koushik; Bikkina, Swetha; Patil, Indrajit; MacKerell, Alexander D.; Priyakumar, U. Deva

    2015-01-01

    Urea has long been used to investigate protein folding and, more recently, RNA folding. Studies have proposed that urea denatures RNA by participating in stacking interactions and hydrogen bonds with nucleic acid bases. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated using ab initio calculations (RI-MP2 and CCSD(T) methods with the aug-cc-pVDZ basis set). A total of 29 stable nucleobase-urea stacked complexes are identified in which the intermolecular interaction energies (up to −14 kcal/mol) are dominated by dispersion effects. Natural bond orbital (NBO) and atoms in molecules (AIM) calculations further confirm strong interactions between urea and nucleobases. Calculations on model systems with multiple urea and water molecules interacting with a guanine base lead to a hypothesis that urea molecules along with water are able to form cage-like structures capable of trapping nucleic acid bases in extrahelical states by forming both hydrogen bonded and dispersion interactions, thereby contributing to the unfolding of RNA in the presence of urea in aqueous solution. PMID:25668757

  15. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  16. Facilitators and barriers in the humanization of childbirth practice in Japan

    Directory of Open Access Journals (Sweden)

    Goulet Lise

    2010-05-01

    Full Text Available Abstract Background Humanizing birth means considering women's values, beliefs, and feelings and respecting their dignity and autonomy during the birthing process. Reducing over-medicalized childbirths, empowering women and the use of evidence-based maternity practice are strategies that promote humanized birth. Nevertheless, the territory of birth and its socio-cultural values and beliefs concerning child bearing can deeply affect birthing practices. The present study aims to explore the Japanese child birthing experience in different birth settings where the humanization of childbirth has been indentified among the priority goals of the institutions concerned, and also to explore the obstacles and facilitators encountered in the practice of humanized birth in those centres. Methods A qualitative field research design was used in this study. Forty four individuals and nine institutions were recruited. Data was collected through observation, field notes, focus groups, informal and semi-structured interviews. A qualitative content analysis was performed. Results All the settings had implemented strategies aimed at reducing caesarean sections, and keeping childbirth as natural as possible. The barriers and facilitators encountered in the practice of humanized birth were categorized into four main groups: rules and strategies, physical structure, contingency factors, and individual factors. The most important barriers identified in humanized birth care were the institutional rules and strategies that restricted the presence of a birth companion. The main facilitators were women's own cultural values and beliefs in a natural birth, and institutional strategies designed to prevent unnecessary medical interventions. Conclusions The Japanese birthing institutions which have identified as part of their mission to instate humanized birth have, as a whole, been successful in improving care. However, barriers remain to achieving the ultimate goal

  17. Fast Simultaneous Determination of 13 Nucleosides and Nucleobases in Cordyceps sinensis by UHPLC–ESI–MS/MS

    Directory of Open Access Journals (Sweden)

    Shi-Yu Zong

    2015-12-01

    Full Text Available A reliable ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS method for the fast simultaneous determination of 13 nucleosides and nucleobases in Cordyceps sinensis (C. sinensis with 2-chloroadenosine as internal standard was developed and validated. Samples were ultrasonically extracted in an ice bath thrice, and the optimum analyte separation was performed on an ACQUITY UPLCTM HSS C18 column (100 mm × 2.1 mm, 1.8 μm with gradient elution. All targeted analytes were separated in 5.5 min. Furthermore, all calibration curves showed good linear regression (r > 0.9970 within the test ranges, and the limits of quantitation and detection of the 13 analytes were less than 150 and 75 ng/mL, respectively. The relative standard deviations (RSDs of intra- and inter-day precisions were <6.23%. Recoveries of the quantified analytes ranged within 85.3%–117.3%, with RSD < 6.18%. The developed UHPLC–ESI–MS/MS method was successfully applied to determine nucleosides and nucleobases in 11 batches of C. sinensis samples from different regions in China. The range for the total content in the analyzed samples was 1329–2057 µg/g.

  18. Time-resolved fluorescence sensing of N-acetyl amino acids, nucleobases, nucleotides and DNA by the luminescent Tb (III) - 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde probe

    Energy Technology Data Exchange (ETDEWEB)

    Azab, Hassan A. [Chemistry Department, Faculty of Science, Suez Canal University, 41522 Ismailia (Egypt); Khairy, Gasser M., E-mail: gasser_chemist@yahoo.com [Chemistry Department, Faculty of Science and Arts, Aljouf University, P.O. Box # 2014, Skaka 41421 (Saudi Arabia); Chemistry Department, Faculty of Science, Suez Canal University, 41522 Ismailia (Egypt); Abd El-Ghany, N.; Ahmed, Marwa A. [Chemistry Department, Faculty of Science, Suez Canal University, El-Arish (Egypt)

    2016-08-15

    A time-resolved (gated) luminescence-based method for the detection of some of N-acetyl amino acids, nucleobases, nucleotides, and DNA using terbium- 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde (AOCC) complex in 1:2 metal: ligand ratio in microtiterplate format has been evolved. The linear range for determination of the selected biomolecules is 0.1–1.0 µM. The detection limit was in the range of 0.0371–0.106 µM. The thermodynamic parameters, and binding constants (K) of N-acetyl amino acids, nucleobases, nucleotides with Tb (III) –(AOCC) {sub 2} complex were calculated. Positive and negative values of entropy (ΔS) and enthalpy (ΔH) changes for Tb (III) –(AOCC){sub 2}– N-acetyl amino acids, nucleobases or nucleotides ternary complexes were evaluated. Selectivity of Tb (III) -complex towards different biomolecules has been studied using ratiometric methods of analysis by comparison of biomolecules binding affinities for Tb (III) -complex. Interaction of Tb (III) complex with DNA has been studied.

  19. Time-resolved fluorescence sensing of N-acetyl amino acids, nucleobases, nucleotides and DNA by the luminescent Tb (III) - 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde probe

    International Nuclear Information System (INIS)

    Azab, Hassan A.; Khairy, Gasser M.; Abd El-Ghany, N.; Ahmed, Marwa A.

    2016-01-01

    A time-resolved (gated) luminescence-based method for the detection of some of N-acetyl amino acids, nucleobases, nucleotides, and DNA using terbium- 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde (AOCC) complex in 1:2 metal: ligand ratio in microtiterplate format has been evolved. The linear range for determination of the selected biomolecules is 0.1–1.0 µM. The detection limit was in the range of 0.0371–0.106 µM. The thermodynamic parameters, and binding constants (K) of N-acetyl amino acids, nucleobases, nucleotides with Tb (III) –(AOCC) 2 complex were calculated. Positive and negative values of entropy (ΔS) and enthalpy (ΔH) changes for Tb (III) –(AOCC) 2 – N-acetyl amino acids, nucleobases or nucleotides ternary complexes were evaluated. Selectivity of Tb (III) -complex towards different biomolecules has been studied using ratiometric methods of analysis by comparison of biomolecules binding affinities for Tb (III) -complex. Interaction of Tb (III) complex with DNA has been studied.

  20. Ultraviolet Irradiation of Pyrimidine in Interstellar Ice Analogs: Formation and Photo-Stability of Nucleobases

    Science.gov (United States)

    Nuevo, Michel; Milam, Stefanie N.; Sandford, Scott A.; Elsila, Jamie E.; Dworkin, Jason P.

    2010-01-01

    Astrochemistry laboratory experiments recently showed that molecules of prebiotic interest can potentially form in space, as supported by the detection of amino acids in organic residues formed by the UV photolysis of ices simulating interstellar and cometary environments (H2O, CO, CO2, CH3OH, NH3, etc.). Although the presence of amino acids in the interstellar medium (ISM) is still under debate, experiments and the detection of amino acids in meteorites both support a scenario in which prebiotic molecules could be of extraterrestrial origin, before they are delivered to planets by comets, asteroids, and interplanetary dust particles. Nucleobases, the informational subunits of DNA and RNA, have also been detected in meteorites, although they have not yet been observed in the ISM. Thus, these molecules constitute another family of prebiotic compounds that can possibly form via abiotical processes in astrophysical environments. Nucleobases are nitrogen-bearing cyclic aromatic species with various functional groups attached, which are divided into two classes: pyrimidines (uracil, cytosine, and thymine) and purines (adenine and guanine). In this work, we study how UV irradiation affects pyrimidine mixed in interstellar ice analogs (H2O, NH3, CH3OH). In particular, we show that the UV irradiation of H2O:pyrimidine mixtures leads to the production of oxidized compounds including uracil, and show that both uracil and cytosine are formed upon irradiation of H2O:NH3:pyrimidine mixtures. We also study the photostability of pyrimidine and its photoproducts formed during these experiments.

  1. Meteoritic Input of Amino Acids and Nucleobases: Methodology and Implications for the Origins of Life

    Science.gov (United States)

    Burton, Aaron S.; Stern, Jennifer C.; Elsila, Jamie E.; Glavin, Daniel P.; Dworkin, Jason P.

    2012-01-01

    The discoveries of amino acids of extraterrestrial origin in many meteorites over the last 40 years have revolutionized the Astrobiology field. A variety of non-terrestrial amino acids similar to those found in life on Earth have been detected in meteorites. A few amino acids have even been found with chiral excesses, suggesting that meteorites could have contributed to the origin of homochirality in life on Earth. In addition to amino acids, which have been productively studied for years, sugar-like molecules, activated phosphates, and nucleobases have also been determined to be indigenous to numerous meteorites. Because these molecules are essential for life as we know it, and meteorites have been delivering them to the Earth since accretion, it is plausible that the origin(s) of life on Earth were aided by extraterrestrially-synthesized molecules. Understanding the origins of life on Earth guides our search for life elsewhere, helping to answer the question of whether biology is unique to Earth. This tutorial review focuses on meteoritic amino acids and nucleobases, exploring modern analytical methods and possible formation mechanisms. We will also discuss the unique window that meteorites provide into the chemistry that preceded life on Earth, a chemical record we do not have access to on Earth due to geologic recycling of rocks and the pervasiveness of biology across the planet. Finally, we will address the future of meteorite research, including asteroid sample return mIssIons.

  2. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Robinson, Brian S.; Fetterhoff, Dustin; Dakos, Alexander S.; Roeder, Brent M.; She, Xiwei; Wicks, Robert T.; Witcher, Mark R.; Couture, Daniel E.; Laxton, Adrian W.; Munger-Clary, Heidi; Popli, Gautam; Sollman, Myriam J.; Whitlow, Christopher T.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2018-06-01

    Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient’s own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

  3. Complete-active-space second-order perturbation theory (CASPT2//CASSCF) study of the dissociative electron attachment in canonical DNA nucleobases caused by low-energy electrons (0-3 eV)

    Energy Technology Data Exchange (ETDEWEB)

    Francés-Monerris, Antonio; Segarra-Martí, Javier; Merchán, Manuela; Roca-Sanjuán, Daniel, E-mail: Daniel.Roca@uv.es [Instituto de Ciencia Molecular, Universitat de València, P.O. Box 22085, 46071 València (Spain)

    2015-12-07

    Low-energy (0-3 eV) ballistic electrons originated during the irradiation of biological material can interact with DNA/RNA nucleobases yielding transient-anion species which undergo decompositions. Since the discovery that these reactions can eventually lead to strand breaking of the DNA chains, great efforts have been dedicated to their study. The main fragmentation at the 0-3 eV energy range is the ejection of a hydrogen atom from the specific nitrogen positions. In the present study, the methodological approach introduced in a previous work on uracil [I. González-Ramírez et al., J. Chem. Theory Comput. 8, 2769-2776 (2012)] is employed to study the DNA canonical nucleobases fragmentations of N–H bonds induced by low-energy electrons. The approach is based on minimum energy path and linear interpolation of internal coordinates computations along the N–H dissociation channels carried out at the complete-active-space self-consistent field//complete-active-space second-order perturbation theory level. On the basis of the calculated theoretical quantities, new assignations for the adenine and cytosine anion yield curves are provided. In addition, the π{sub 1}{sup −} and π{sub 2}{sup −} states of the pyrimidine nucleobases are expected to produce the temporary anions at electron energies close to 1 and 2 eV, respectively. Finally, the present theoretical results do not allow to discard neither the dipole-bound nor the valence-bound mechanisms in the range of energies explored, suggesting that both possibilities may coexist in the experiments carried out with the isolated nucleobases.

  4. Synthesis and biological evaluation of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd)

    DEFF Research Database (Denmark)

    Hrdlicka, Patrick J; Jepsen, Jan S; Wengel, Jesper

    2005-01-01

    A series of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd) and its uracil analog (EUrd) have been synthesized. While none of the conformationally restricted analogs displayed anticancer activity, 5-iodo-EUrd and 5-bromo-EUrd disp......-EUrd displayed potent anticancer activity with IC50 values of 35 nM and 0. 73 microM....

  5. Simultaneous analysis of nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry.

    Science.gov (United States)

    Huang, Yang; Zhang, Tingting; Zhao, Yumei; Zhou, Haibo; Tang, Guangyun; Fillet, Marianne; Crommen, Jacques; Jiang, Zhengjin

    2017-09-10

    Nucleobases, nucleosides and ginsenosides, which have a significant impact on the physiological activity of organisms, are reported to be the active components of ginseng, while they are less present in ginseng extracts. Few analytical methods have been developed so far to simultaneously analyze these three classes of compounds with different polarities present in ginseng extracts. In the present study, a simple and efficient analytical method was successfully developed for the simultaneous separation of 17 nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry (SFC-MS). The effect of various experimental factors on the separation performance, such as the column type, temperature and backpressure, the type of modifier and additive, and the concentration of make-up solvent were systematically investigated. Under the selected conditions, the developed method was successfully applied to the quality evaluation of 14 batches of ginseng extracts from different origins. The results obtained for the different batches indicate that this method could be employed for the quality assessment of ginseng extracts. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nucleobases in Space: Laboratory Studies of Polycyclic Aromatic Nitrogen Heterocycles

    Science.gov (United States)

    Elsila, Jamie; Mattioda, Andy; Bernstein, Max; Sandford, Scott; Hudgins, Doug

    2005-01-01

    Polycyclic Aromatic Nitrogen Heterocycles (PANHs) are heterocyclic aromatics Le., PAHs with carbon atoms replaced by a nitrogen atom. These molecules have been detected in meteorite extracts, and in general these nitrogen heterocycles are of astrobiological interest since this class of molecules include nucleobases, basic components of our nucleic acids. These compounds are predicted to be present in the interstellar medium and in Titan tholin, but have received relatively little attention. We will present spectra and reactions of PANHs, frozen in solid H2O at 12 K, conditions germane to astronomical observations. In contrast to simple PAHs, that do not interact strongly with solid H2O, the nitrogen atoms in PANHs are potentially capable of hydrogen bonding with H20 changing their spectra, complicating their remote detection on the surfaces of icy bodies. Moreover, we have studied the photo-chemistry of these interesting compounds under astrophysical conditions and will use our lab studies to assess a potential interstellar heritage of these compounds in carbonaceous chondrites.

  7. Theoretical study of some aspects of the nucleo-bases reactivity: definition of new theoretical tools for the study of chemical reactivity

    International Nuclear Information System (INIS)

    Labet, V.

    2009-09-01

    In this work, three kinds of nucleo-base damages were studied from a theoretical point of view with quantum chemistry methods based on the density-functional theory: the spontaneous deamination of cytosine and its derivatives, the formation of tandem lesion induced by hydroxyl radicals in anaerobic medium and the formation of pyrimidic dimers under exposition to an UV radiation. The complementary use of quantitative static methods allowing the exploration of the potential energy surface of a chemical reaction, and of 'conceptual DFT' principles, leads to information concerning the mechanisms involved and to the rationalization of the differences in the nucleo-bases reactivity towards the formation of a same kind of damage. At the same time, a reflexion was undertaken on the asynchronous concerted mechanism concept, in terms of physical meaning of the transition state, respect of the Maximum Hardness Principle, and determination of the number of primitive processes involved. Finally, a new local reactivity index was developed, relevant to understand the reactivity of a molecular system in an excited state. (author)

  8. The nucleobase cation symporter 1 of Chlamydomonas reinhardtii and that of the evolutionarily distant Arabidopsis thaliana display parallel function and establish a plant-specific solute transport profile.

    Science.gov (United States)

    Schein, Jessica R; Hunt, Kevin A; Minton, Janet A; Schultes, Neil P; Mourad, George S

    2013-09-01

    The single cell alga Chlamydomonas reinhardtii is capable of importing purines as nitrogen sources. An analysis of the annotated C. reinhardtii genome reveals at least three distinct gene families encoding for known nucleobase transporters. In this study the solute transport and binding properties for the lone C. reinhardtii nucleobase cation symporter 1 (CrNCS1) are determined through heterologous expression in Saccharomyces cerevisiae. CrNCS1 acts as a transporter of adenine, guanine, uracil and allantoin, sharing similar - but not identical - solute recognition specificity with the evolutionary distant NCS1 from Arabidopsis thaliana. The results suggest that the solute specificity for plant NCS1 occurred early in plant evolution and are distinct from solute transport specificities of single cell fungal NCS1 proteins. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Radicals derived from histone hydroperoxides damage nucleobases in RNA and DNA

    DEFF Research Database (Denmark)

    Luxford, C; Dean, R T; Davies, Michael Jonathan

    2000-01-01

    Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion......; this is in accord with previous studies with other proteins. These histone hydroperoxides are stable in the absence of exogenous catalysts (e.g., heat, light, and transition metal ions), but in the presence of these agents decompose rapidly to give a variety of radicals which have been identified by EPR spin...... trapping. Histone hydroperoxide-derived radicals generated on decomposition of the hydroperoxides with Cu(+) react with both pyrimidine and purine nucleobases. Thus, with uridine the histone hydroperoxide-derived radicals undergo addition across the C(5)-C(6) double bond of the pyrimidine ring to give...

  10. On modeling biomolecular–surface nonbonded interactions: application to nucleobase adsorption on single-wall carbon nanotube surfaces

    International Nuclear Information System (INIS)

    Akdim, B; Pachter, R; Day, P N; Kim, S S; Naik, R R

    2012-01-01

    In this work we explored the selectivity of single nucleobases towards adsorption on chiral single-wall carbon nanotubes (SWCNTs) by density functional theory calculations. Specifically, the adsorption of molecular models of guanine (G), adenine (A), thymine (T), and cytosine (C), as well as of AT and GC Watson–Crick (WC) base pairs on chiral SWCNT C(6, 5), C(9, 1) and C(8, 3) model structures, was analyzed in detail. The importance of correcting the exchange–correlation functional for London dispersion was clearly demonstrated, yet limitations in modeling such interactions by considering the SWCNT as a molecular model may mask subtle effects in a molecular–macroscopic material system. The trend in the calculated adsorption energies of the nucleobases on same diameter C(6, 5) and C(9, 1) SWCNT surfaces, i.e. G > A > T > C, was consistent with related computations and experimental work on graphitic surfaces, however contradicting experimental data on the adsorption of single-strand short homo-oligonucleotides on SWCNTs that demonstrated a trend of G > C > A > T (Albertorio et al 2009 Nanotechnology 20 395101). A possible role of electrostatic interactions in this case was partially captured by applying the effective fragment potential method, emphasizing that the interplay of the various contributions in modeling nonbonded interactions is complicated by theoretical limitations. Finally, because the calculated adsorption energies for Watson–Crick base pairs have shown little effect upon adsorption of the base pair farther from the surface, the results on SWCNT sorting by salmon genomic DNA could be indicative of partial unfolding of the double helix upon adsorption on the SWCNT surface. (paper)

  11. MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome.

    Science.gov (United States)

    Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J

    2017-06-01

    One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Rationalizing the structural variability of the exocyclic amino groups in nucleobases and their metal complexes: cytosine and adenine.

    Science.gov (United States)

    Fonseca Guerra, Célia; Sanz Miguel, Pablo J; Cebollada, Andrea; Bickelhaupt, F Matthias; Lippert, Bernhard

    2014-07-28

    The exocyclic amino groups of cytosine and adenine nucleobases are normally almost flat, with the N atoms essentially sp(2) hybridized and the lone pair largely delocalized into the heterocyclic rings. However, a change to marked pyramidality of the amino group (N then sp(3) hybridized, lone pair essentially localized at N) occurs during i) involvement of an amino proton in strong hydrogen bonding donor conditions or ii) with monofunctional metal coordination following removal of one of the two protons. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Tutorial Facilitation in the Humanities Based on the Tenets of Carl Rogers

    Science.gov (United States)

    Heim, Caroline

    2012-01-01

    This article introduces a model for group facilitation in the humanities based on Carl Rogers' model for group psychotherapy. Certain aspects of Carl Rogers' reflective learning strategies are reappraised and principles, specific only to psychotherapy, are introduced. Five of Rogers' axioms are applied to the tutorial discussion model: a…

  14. The solute specificity profiles of nucleobase cation symporter 1 (NCS1) from Zea mays and Setaria viridis illustrate functional flexibility.

    Science.gov (United States)

    Rapp, Micah; Schein, Jessica; Hunt, Kevin A; Nalam, Vamsi; Mourad, George S; Schultes, Neil P

    2016-03-01

    The solute specificity profiles (transport and binding) for the nucleobase cation symporter 1 (NCS1) proteins, from the closely related C4 grasses Zea mays and Setaria viridis, differ from that of Arabidopsis thaliana and Chlamydomonas reinhardtii NCS1. Solute specificity profiles for NCS1 from Z. mays (ZmNCS1) and S. viridis (SvNCS1) were determined through heterologous complementation studies in NCS1-deficient Saccharomyces cerevisiae strains. The four Viridiplantae NCS1 proteins transport the purines adenine and guanine, but unlike the dicot and algal NCS1, grass NCS1 proteins fail to transport the pyrimidine uracil. Despite the high level of amino acid sequence similarity, ZmNCS1 and SvNCS1 display distinct solute transport and recognition profiles. SvNCS1 transports adenine, guanine, hypoxanthine, cytosine, and allantoin and competitively binds xanthine and uric acid. ZmNCS1 transports adenine, guanine, and cytosine and competitively binds, 5-fluorocytosine, hypoxanthine, xanthine, and uric acid. The differences in grass NCS1 profiles are due to a limited number of amino acid alterations. These amino acid residues do not correspond to amino acids essential for overall solute and cation binding or solute transport, as previously identified in bacterial and fungal NCS1, but rather may represent residues involved in subtle solute discrimination. The data presented here reveal that within Viridiplantae, NCS1 proteins transport a broad range of nucleobase compounds and that the solute specificity profile varies with species.

  15. Simultaneous Quantitation of Free Amino Acids, Nucleosides and Nucleobases in Sipunculus nudus by Ultra-High Performance Liquid Chromatography with Triple Quadrupole Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Yahui Ge

    2016-03-01

    Full Text Available To evaluate the nutritional and functional value of Sipunculus nudus, a rapid, simple and sensitive analytical method was developed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass detection in multiple-reaction monitoring mode for the simultaneous quantitative determination of 25 free amino acids and 16 nucleosides and nucleobases in S. nudus within 20 min, which was confirmed to be reproducible and accurate. The limits of detection (LODs and quantification (LOQs were between 0.003–0.229 μg/mL and 0.008–0.763 μg/mL for the 41 analytes, respectively. The established method was applied to analyze 19 batches of S. nudus samples from four habitats with two different processing methods. The results showed that S. nudus contained a variety of free amino acids, nucleosides and nucleobases in sufficient quantity and reasonable proportion. They also demonstrated that the contents of these compounds in different parts of S. nudus were significantly discriminating, which were in the order: (highest coelomic fluid > body wall > intestine (lowest. The method is simple and accurate, and could serve as a technical support for establishing quality control of S. nudus and other functional seafoods. Moreover, the research results also laid foundation for further exploitation and development of S. nudus.

  16. Synthesis of 2,6-Substituted 7-(Het)aryl-7-deazapurine Nucleobases (2,4-Disubstituted 5-(Het)aryl-pyrrolo[2,3-d]pyrimidines)

    Czech Academy of Sciences Publication Activity Database

    Sabat, Nazarii; Smolen, Sabina; Nauš, Petr; Perlíková, Pavla; Cebová, M.; Poštová Slavětínská, Lenka; Hocek, Michal

    2017-01-01

    Roč. 49, č. 20 (2017), s. 4623-4650 ISSN 0039-7881 R&D Projects: GA ČR(CZ) GA16-00178S; GA MZd(CZ) NV15-31984A Grant - others:AV ČR(CZ) AP1501 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:61388963 Keywords : deazapurines * pyrrolo[2,3-d]pyrimidines * nucleobases * Suzuki-Miyaura cross-coupling * deprotection * demethylation Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.650, year: 2016

  17. Nucleobases and C2 and C4 Imidazolium Acetate Interactions: FTIR-ATR, Raman and NMR Spectra and ab Initio Calculations Insights

    DEFF Research Database (Denmark)

    Araújo, J. M. M.; Ferreira, Rui; Veiga, H.I.M.

    applications can be designed. The tunable nature of the solubility of various compounds, including molecules of pharmaceutical and biological interest, in RTILs makes extraction them attractive for many separation and purification processes [1;2]. Exploring new applications requires fundamental understanding...... nucleobases is perceived. The results obtained for the three ILs families outlined, Imidazolium-, Phosphonium- and Ammonium-based ILs, show that the ILs containing a carbonyl group in the anion present higher dissolution capabilities. This is due to the establishment of hydrogen bonds between uracil and IL...

  18. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  19. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  20. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts

    Science.gov (United States)

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-01-01

    Abstract Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes. A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students’ satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students’ satisfaction. Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01). This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was

  1. Interrogating Key Positions of Size-Reduced TALE Repeats Reveals a Programmable Sensor of 5-Carboxylcytosine.

    Science.gov (United States)

    Maurer, Sara; Giess, Mario; Koch, Oliver; Summerer, Daniel

    2016-12-16

    Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epigenetic selectivity can be engineered, with potential to establish receptors for the programmable decoding of all human nucleobases. TALE repeats recognize nucleobases via key amino acids in a structurally conserved loop whose backbone is positioned very close to the cytosine 5-carbon. This complicates the engineering of selectivities for large 5-substituents. To interrogate a more promising structural space, we engineered size-reduced repeat loops, performed saturation mutagenesis of key positions, and screened a total of 200 repeat-nucleobase interactions for new selectivities. This provided insight into the structural requirements of TALE repeats for affinity and selectivity, revealed repeats with improved or relaxed selectivity, and resulted in the first selective sensor of 5-carboxylcytosine.

  2. A Liberation Health Approach to Examining Challenges and Facilitators of Peer-to-Peer Human Milk Sharing.

    Science.gov (United States)

    McCloskey, Rebecca J; Karandikar, Sharvari

    2018-04-01

    Human milk sharing between peers is a common and growing practice. Although human milk has been unequivocally established as the ideal food source for infants, much stigma surrounds the practice of human milk sharing. Furthermore, there is little research examining peer-to-peer human milk sharing. Research Aim: We used the liberation health social work model to examine the experiences of mothers who have received donated human milk from a peer. Research questions were as follows: (a) What challenges do recipient mothers experience in peer-to-peer human milk sharing? (b) What supports do recipient mothers identify in peer-to-peer human milk sharing? Researchers conducted in-depth interviews with mothers ( N = 20) in the United States and Canada who were recipients of peer-to-peer human milk sharing. Researchers independently reviewed transcripts and completed open, axial, and selective coding. The authors discussed conflicts in theme identification until agreement was reached. Challenges to peer-to-peer human milk sharing were (a) substantial effort required to secure human milk; (b) institutional barriers; (c) milk bank specific barriers; and (d) lack of societal awareness and acceptance of human milk sharing. Facilitators included (a) informed decision making and transparency and (b) support from healthcare professionals. Despite risks and barriers, participants continued to pursue peer-to-peer human milk sharing. Informed by a liberation health framework, healthcare professionals-rather than universally discouraging human milk sharing between peers-should facilitate open dialogue with parents about the pros and cons of this practice and about screening recommendations to promote safety and mitigate risk.

  3. A fluorescence study of the molecular interactions of harmane with the nucleobases, their nucleosides and mononucleotides.

    Science.gov (United States)

    Balón, M; Muñoz, M A; Carmona, C; Guardado, P; Galán, M

    1999-07-19

    Fluorescence binding studies of harmane to the elemental components of the nucleic acids were undertaken to investigate the origin of the interaction between the drug and DNA. Most of the tested substrates have been found to induce hypochromism in the absorption spectrum of harmane and to quench its fluorescence. The quenching process induced by the nucleobases and their nucleosides is mainly due to the formation of ground state 1:1 complexes. However, in the case of the mononucleotides a dynamic quenching component is also observed. This quenching component is likely due to the excited state interaction of harmane with the phosphate group of the nucleotides. UV-vis spectral changes and quenching measurements have been used to quantify the ground state association constants of the complexes and the quenching rate constants.

  4. The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons.

    Science.gov (United States)

    Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M; Campbell, Michael S; Barrell, Daniel; Martin, Kyle J; Mulley, John F; Ravi, Vydianathan; Lee, Alison P; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E G; Sun, Yi; Hertel, Jana; Beam, Michael J; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H; Litman, Gary W; Litman, Ronda T; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F; Wang, Han; Taylor, John S; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M J; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T; Venkatesh, Byrappa; Holland, Peter W H; Guiguen, Yann; Bobe, Julien; Shubin, Neil H; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H

    2016-04-01

    To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

  5. Better decision making in complex, dynamic tasks training with human-facilitated interactive learning environments

    CERN Document Server

    Qudrat-Ullah, Hassan

    2015-01-01

    This book describes interactive learning environments (ILEs) and their underlying concepts. It explains how ILEs can be used to improve the decision-making process and how these improvements can be empirically verified. The objective of this book is to enhance our understanding of and to gain insights into the process by which human facilitated ILEs are effectively designed and used in improving users’ decision making in complex, dynamic tasks. This book is divided into four major parts. Part I serves as an introduction to the importance and complexity of decision making in dynamic tasks. Part II provides background material, drawing upon relevant literature, for the development of an integrated process model on the effectiveness of human facilitated ILEs in improving decision making in dynamic tasks. Part III focuses on the design, development, and application of FishBankILE in laboratory experiments to gather empirical evidence for the validity of the process model. Finally, part IV presents a comprehensi...

  6. Understanding and changing human behaviour—antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour

    OpenAIRE

    Stålsby Lundborg, Cecilia; Tamhankar, Ashok J.

    2014-01-01

    This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factor...

  7. An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

    KAUST Repository

    Chawla, Mohit

    2015-06-27

    Posttranscriptional modifications greatly enhance the chemical information of RNA molecules, contributing to explain the diversity of their structures and functions. A significant fraction of RNA experimental structures available to date present modified nucleobases, with half of them being involved in H-bonding interactions with other bases, i.e. ‘modified base pairs’. Herein we present a systematic investigation of modified base pairs, in the context of experimental RNA structures. To this end, we first compiled an atlas of experimentally observed modified base pairs, for which we recorded occurrences and structural context. Then, for each base pair, we selected a representative for subsequent quantum mechanics calculations, to find out its optimal geometry and interaction energy. Our structural analyses show that most of the modified base pairs are non Watson–Crick like and are involved in RNA tertiary structure motifs. In addition, quantum mechanics calculations quantify and provide a rationale for the impact of the different modifications on the geometry and stability of the base pairs they participate in.

  8. An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

    KAUST Repository

    Chawla, Mohit; Oliva, R.; Bujnicki, J. M.; Cavallo, Luigi

    2015-01-01

    Posttranscriptional modifications greatly enhance the chemical information of RNA molecules, contributing to explain the diversity of their structures and functions. A significant fraction of RNA experimental structures available to date present modified nucleobases, with half of them being involved in H-bonding interactions with other bases, i.e. ‘modified base pairs’. Herein we present a systematic investigation of modified base pairs, in the context of experimental RNA structures. To this end, we first compiled an atlas of experimentally observed modified base pairs, for which we recorded occurrences and structural context. Then, for each base pair, we selected a representative for subsequent quantum mechanics calculations, to find out its optimal geometry and interaction energy. Our structural analyses show that most of the modified base pairs are non Watson–Crick like and are involved in RNA tertiary structure motifs. In addition, quantum mechanics calculations quantify and provide a rationale for the impact of the different modifications on the geometry and stability of the base pairs they participate in.

  9. Cross-sensory facilitation reveals neural interactions between visual and tactile motion in humans

    Directory of Open Access Journals (Sweden)

    Monica eGori

    2011-04-01

    Full Text Available Many recent studies show that the human brain integrates information across the different senses and that stimuli of one sensory modality can enhance the perception of other modalities. Here we study the processes that mediate cross-modal facilitation and summation between visual and tactile motion. We find that while summation produced a generic, non-specific improvement of thresholds, probably reflecting higher-order interaction of decision signals, facilitation reveals a strong, direction-specific interaction, which we believe reflects sensory interactions. We measured visual and tactile velocity discrimination thresholds over a wide range of base velocities and conditions. Thresholds for both visual and tactile stimuli showed the characteristic dipper function, with the minimum thresholds occurring at a given pedestal speed. When visual and tactile coherent stimuli were combined (summation condition the thresholds for these multi-sensory stimuli also showed a dipper function with the minimum thresholds occurring in a similar range to that for unisensory signals. However, the improvement of multisensory thresholds was weak and not directionally specific, well predicted by the maximum likelihood estimation model (agreeing with previous research. A different technique (facilitation did, however, reveal direction-specific enhancement. Adding a non-informative pedestal motion stimulus in one sensory modality (vision or touch selectively lowered thresholds in the other, by the same amount as pedestals in the same modality. Facilitation did not occur for neutral stimuli like sounds (that would also have reduced temporal uncertainty, nor for motion in opposite direction, even in blocked trials where the subjects knew that the motion was in the opposite direction showing that the facilitation was not under subject control. Cross-sensory facilitation is strong evidence for functionally relevant cross-sensory integration at early levels of sensory

  10. Glucose enhancement of human memory: a comprehensive research review of the glucose memory facilitation effect.

    Science.gov (United States)

    Smith, Michael A; Riby, Leigh M; Eekelen, J Anke M van; Foster, Jonathan K

    2011-01-01

    The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the 'glucose memory facilitation effect'. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Hypothesis of Lithocoding: Origin of the Genetic Code as a "Double Jigsaw Puzzle" of Nucleobase-Containing Molecules and Amino Acids Assembled by Sequential Filling of Apatite Mineral Cellules.

    Science.gov (United States)

    Skoblikow, Nikolai E; Zimin, Andrei A

    2016-05-01

    The hypothesis of direct coding, assuming the direct contact of pairs of coding molecules with amino acid side chains in hollow unit cells (cellules) of a regular crystal-structure mineral is proposed. The coding nucleobase-containing molecules in each cellule (named "lithocodon") partially shield each other; the remaining free space determines the stereochemical character of the filling side chain. Apatite-group minerals are considered as the most preferable for this type of coding (named "lithocoding"). A scheme of the cellule with certain stereometric parameters, providing for the isomeric selection of contacting molecules is proposed. We modelled the filling of cellules with molecules involved in direct coding, with the possibility of coding by their single combination for a group of stereochemically similar amino acids. The regular ordered arrangement of cellules enables the polymerization of amino acids and nucleobase-containing molecules in the same direction (named "lithotranslation") preventing the shift of coding. A table of the presumed "LithoCode" (possible and optimal lithocodon assignments for abiogenically synthesized α-amino acids involved in lithocoding and lithotranslation) is proposed. The magmatic nature of the mineral, abiogenic synthesis of organic molecules and polymerization events are considered within the framework of the proposed "volcanic scenario".

  12. The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons

    Science.gov (United States)

    Braasch, Ingo; Gehrke, Andrew R.; Smith, Jeramiah J.; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M.; Campbell, Michael S.; Barrell, Daniel; Martin, Kyle J.; Mulley, John F.; Ravi, Vydianathan; Lee, Alison P.; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E. G.; Sun, Yi; Hertel, Jana; Beam, Michael J.; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H.; Litman, Gary W.; Litman, Ronda T.; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F.; Wang, Han; Taylor, John S.; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M. J.; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A.; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T.; Venkatesh, Byrappa; Holland, Peter W. H.; Guiguen, Yann; Bobe, Julien; Shubin, Neil H.; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H.

    2016-01-01

    To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before the teleost genome duplication (TGD). The slowly evolving gar genome conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization, and development (e.g., Hox, ParaHox, and miRNA genes). Numerous conserved non-coding elements (CNEs, often cis-regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles of such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses revealed that the sum of expression domains and levels from duplicated teleost genes often approximate patterns and levels of gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes, and the function of human regulatory sequences. PMID:26950095

  13. Parallel workflow tools to facilitate human brain MRI post-processing

    Directory of Open Access Journals (Sweden)

    Zaixu eCui

    2015-05-01

    Full Text Available Multi-modal magnetic resonance imaging (MRI techniques are widely applied in human brain studies. To obtain specific brain measures of interest from MRI datasets, a number of complex image post-processing steps are typically required. Parallel workflow tools have recently been developed, concatenating individual processing steps and enabling fully automated processing of raw MRI data to obtain the final results. These workflow tools are also designed to make optimal use of available computational resources and to support the parallel processing of different subjects or of independent processing steps for a single subject. Automated, parallel MRI post-processing tools can greatly facilitate relevant brain investigations and are being increasingly applied. In this review, we briefly summarize these parallel workflow tools and discuss relevant issues.

  14. Separation of oligopeptides, nucleobases, nucleosides and nucleotides using capillary electrophoresis/electrochromatography with sol-gel modified inner capillary wall.

    Science.gov (United States)

    Svobodová, Jana; Kofroňová, Olga; Benada, Oldřich; Král, Vladimír; Mikšík, Ivan

    2017-09-29

    The aim of this article is to study the modification of an inner capillary wall with sol-gel coating (pure silica sol-gel or silica sol-gel containing porphyrin-brucine conjugate) and determine its influence on the separation process using capillary electrophoresis/electrochromatography method. After modification of the inner capillary surface the separation of analytes was performed using two different phosphate buffers (pH 2.5 and 9.0) and finally the changes in electrophoretic mobilities of various samples were calculated. To confirm that the modification of the inner capillary surface was successful, the parts of the inner surfaces of capillaries were observed using scanning electron microscopy. The analytes used as testing samples were oligopeptides, nucleosides, nucleobases and finally nucleotides. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay

    Directory of Open Access Journals (Sweden)

    Bhaveshkumar D. Dhorajiya

    2014-01-01

    Full Text Available A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3-TBA manifested the best protective effect against DNA damage induced by bleomycin.

  16. GAS PHASE SYNTHESIS OF (ISO)QUINOLINE AND ITS ROLE IN THE FORMATION OF NUCLEOBASES IN THE INTERSTELLAR MEDIUM

    International Nuclear Information System (INIS)

    Parker, Dorian S. N.; Kaiser, Ralf I.; Kostko, Oleg; Troy, Tyler P.; Ahmed, Musahid; Mebel, Alexander M.; Tielens, Alexander G. G. M.

    2015-01-01

    Nitrogen-substituted polycyclic aromatic hydrocarbons (NPAHs) have been proposed to play a key role in the astrochemical evolution of the interstellar medium, yet the formation mechanisms of even their simplest prototypes—quinoline and isoquinoline—remain elusive. Here, we reveal a novel concept that under high temperature conditions representing circumstellar envelopes of carbon stars, (iso)quinoline can be synthesized via the reaction of pyridyl radicals with two acetylene molecules. The facile gas phase formation of (iso)quinoline in circumstellar envelopes defines a hitherto elusive reaction class synthesizing aromatic structures with embedded nitrogen atoms that are essential building blocks in contemporary biological-structural motifs. Once ejected from circumstellar shells and incorporated into icy interstellar grains in cold molecular clouds, these NPAHs can be functionalized by photo processing forming nucleobase-type structures as sampled in the Murchison meteorite

  17. Dissociative electron attachment to the gas-phase nucleobase hypoxanthine

    Energy Technology Data Exchange (ETDEWEB)

    Dawley, M. Michele [Radiation Laboratory, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Tanzer, Katrin; Denifl, Stephan, E-mail: Stephan.Denifl@uibk.ac.at, E-mail: Sylwia.Ptasinska.1@nd.edu [Institut für Ionenphysik und Angewandte Physik, and Center for Molecular Biosciences Innsbruck (CMBI), Leopold-Franzens Universität Innsbruck, Technikerstr. 25, A-6020 Innsbruck (Austria); Carmichael, Ian [Radiation Laboratory, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Ptasińska, Sylwia, E-mail: Stephan.Denifl@uibk.ac.at, E-mail: Sylwia.Ptasinska.1@nd.edu [Radiation Laboratory, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Department of Physics, University of Notre Dame, Notre Dame, Indiana 46556 (United States)

    2015-06-07

    We present high-resolution measurements of the dissociative electron attachment (DEA) to isolated gas-phase hypoxanthine (C{sub 5}H{sub 4}N{sub 4}O, Hyp), a tRNA purine base. The anion mass spectra and individual ion efficiency curves from Hyp were measured as a function of electron energy below 9 eV. The mass spectra at 1 and 6 eV exhibit the highest anion yields, indicating possible common precursor ions that decay into the detectable anionic fragments. The (Hyp − H) anion (C{sub 5}H{sub 3}N{sub 4}O{sup −}) exhibits a sharp resonant peak at 1 eV, which we tentatively assign to a dipole-bound state of the keto-N1H,N9H tautomer in which dehydrogenation occurs at either the N1 or N9 position based upon our quantum chemical computations (B3LYP/6-311+G(d,p) and U(MP2-aug-cc-pVDZ+)) and prior studies with adenine. This closed-shell dehydrogenated anion is the dominant fragment formed upon electron attachment, as with other nucleobases. Seven other anions were also observed including (Hyp − NH){sup −}, C{sub 4}H{sub 3}N{sub 4}{sup −}/C{sub 4}HN{sub 3}O{sup −}, C{sub 4}H{sub 2}N{sub 3}{sup −}, C{sub 3}NO{sup −}/HC(HCN)CN{sup −}, OCN{sup −}, CN{sup −}, and O{sup −}. Most of these anions exhibit broad but weak resonances between 4 and 8 eV similar to many analogous anions from adenine. The DEA to Hyp involves significant fragmentation, which is relevant to understanding radiation damage of biomolecules.

  18. Interactions between Al₁₂X (X = Al, C, N and P) nanoparticles and DNA nucleobases/base pairs: implications for nanotoxicity.

    Science.gov (United States)

    Jin, Peng; Chen, Yongsheng; Zhang, Shengbai B; Chen, Zhongfang

    2012-02-01

    The interactions between neutral Al(12)X(I ( h )) (X = Al, C, N and P) nanoparticles and DNA nucleobases, namely adenine (A), thymine (T), guanine (G) and cytosine (C), as well as the Watson-Crick base pairs (BPs) AT and GC, were investigated by means of density functional theory computations. The Al(12)X clusters can tightly bind to DNA bases and BPs to form stable complexes with negative binding Gibbs free energies at room temperature, and considerable charge transfers occur between the bases/BPs and the Al(12)X clusters. These strong interactions, which are also expected for larger Al nanoparticles, may have potentially adverse impacts on the structure and stability of DNA and thus cause its dysfunction.

  19. Integrating Human Factors Engineering and Information Processing Approaches to Facilitate Evaluations in Criminal Justice Technology Research.

    Science.gov (United States)

    Salvemini, Anthony V; Piza, Eric L; Carter, Jeremy G; Grommon, Eric L; Merritt, Nancy

    2015-06-01

    Evaluations are routinely conducted by government agencies and research organizations to assess the effectiveness of technology in criminal justice. Interdisciplinary research methods are salient to this effort. Technology evaluations are faced with a number of challenges including (1) the need to facilitate effective communication between social science researchers, technology specialists, and practitioners, (2) the need to better understand procedural and contextual aspects of a given technology, and (3) the need to generate findings that can be readily used for decision making and policy recommendations. Process and outcome evaluations of technology can be enhanced by integrating concepts from human factors engineering and information processing. This systemic approach, which focuses on the interaction between humans, technology, and information, enables researchers to better assess how a given technology is used in practice. Examples are drawn from complex technologies currently deployed within the criminal justice system where traditional evaluations have primarily focused on outcome metrics. Although this evidence-based approach has significant value, it is vulnerable to fully account for human and structural complexities that compose technology operations. Guiding principles for technology evaluations are described for identifying and defining key study metrics, facilitating communication within an interdisciplinary research team, and for understanding the interaction between users, technology, and information. The approach posited here can also enable researchers to better assess factors that may facilitate or degrade the operational impact of the technology and answer fundamental questions concerning whether the technology works as intended, at what level, and cost. © The Author(s) 2015.

  20. Human finger-prick induced pluripotent stem cells facilitate the development of stem cell banking.

    Science.gov (United States)

    Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A; Loh, Yuin-Han

    2014-05-01

    Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a "do-it-yourself" basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.

  1. Using a cellular model to explore human-facilitated spread of risk of EAB in Minnesota

    Science.gov (United States)

    Anantha Prasad; Louis Iverson; Matthew Peters; Steve. Matthews

    2011-01-01

    The Emerald Ash Borer has made inroads to Minnesota in the past two years, killing ash trees. We use our spatially explicit cell based model called EAB-SHIFT to calculate the risk of infestation owing to flight characteristics and short distance movement of the insect (insect flight model, IFM), and the human facilitated agents like roads, campgrounds etc. (insect ride...

  2. Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study.

    Science.gov (United States)

    Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

    2016-02-01

    Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This

  3. Ultrasensitive Direct Quantification of Nucleobase Modifications in DNA by Surface-Enhanced Raman Scattering: The Case of Cytosine.

    Science.gov (United States)

    Morla-Folch, Judit; Xie, Hai-nan; Gisbert-Quilis, Patricia; Gómez-de Pedro, Sara; Pazos-Perez, Nicolas; Alvarez-Puebla, Ramon A; Guerrini, Luca

    2015-11-09

    Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single- and double-stranded DNA. The minute amount of DNA required per measurement, in the sub-nanogram regime, removes the necessity of pre-amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low-cost and high-throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Nucleic Acid Base Analog FRET-Pair Facilitating Detailed Structural Measurements in Nucleic Acid Containing Systems

    DEFF Research Database (Denmark)

    Börjesson, Karl; Preus, Søren; El-Sagheer, Afaf

    2009-01-01

    We present the first nucleobase analog fluorescence resonance energy transfer (FRET)-pair. The pair consists of tCO, 1,3-diaza-2-oxophenoxazine, as an energy donor and the newly developed tC(nitro), 7-nitro-1,3-diaza-2-oxophenothiazine, as an energy acceptor. The FRET-pair successfully monitors d...

  5. Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Lijuan [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Thayer, Patrick [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Fan, Huimin [Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai (China); Ledford, Benjamin; Chen, Miao [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Goldstein, Aaron [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Cao, Guohua [School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); He, Jia-Qiang, E-mail: jiahe@vt.edu [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States)

    2016-09-10

    Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

  6. Electron transfer from nucleobase electron adducts to 5-bromouracil. Is guanine an ultimate sink for the electron in irradiated DNA?

    International Nuclear Information System (INIS)

    Nese, C.; Yuan, Z.; Schuchmann, M.N.; Sonntag, C. von

    1992-01-01

    Electron transfer to 5-bromouracil (5-BrU) from nucleobase (N) electron adducts (and their protonated forms) has been studied by product analysis and pulse radiolysis. When an electron is transferred to 5-BrU, the ensuing 5-BrU radical anion rapidly loses a bromide ion; the uracilyl radical thus formed reacts with added t-butanol, yielding uracil. From the uracil yields measured as the function of [N]/[5-BrU] after γ-radiolysis of Ar-saturated solutions it is concluded that thymine and adenine electron adducts and their heteroatom-protonated forms transfer electrons quantitatively to 5-BrU. The data raise the question whether in DNA the guanine moiety may act as the ultimate sink of the electron in competition with other processes such as protonation at C(6) of the thymine electron adduct. (Author)

  7. Understanding and changing human behaviour--antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour.

    Science.gov (United States)

    Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

    2014-05-01

    This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the 'stages of change model', including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to 'global good', so-called 'social marketing', to improve 'welfare of the individual and society' is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement 'antibiotic mainstreaming' as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society.

  8. Deep Space Gateway Facilitates Exploration of Planetary Crusts: A Human/Robotic Exploration Design Reference Campaign to the Lunar Orientale Basin

    Science.gov (United States)

    Head, J. W.; Pieters, C. M.; Scott, D. R.

    2018-02-01

    We outline an Orientale Basin Human/Robotic Architecture that can be facilitated by a Deep Space Gateway International Science Operations Center (DSG-ISOC) (like McMurdo/Antarctica) to address fundamental scientific problems about the Moon and Mars.

  9. Instructional Design, Facilitation, and Perceived Learning Outcomes: An Exploratory Case Study of a Human Trafficking MOOC for Attitudinal Change

    Science.gov (United States)

    Watson, Sunnie Lee; Loizzo, Jamie; Watson, William R.; Mueller, Chad; Lim, Jieun; Ertmer, Peggy A.

    2016-01-01

    This exploratory case study describes the design and facilitation of a massive open online course (MOOC) for attitudinal change regarding human trafficking. It examines the course from the learners', instructor's, and instructional designer's perspectives. Two interviews with the instructor and instructional designer were conducted, and data from…

  10. Theoretical studies on the electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/C*.A(WC)]-Au8 mismatch nucleobase complexes

    Science.gov (United States)

    Srivastava, Ruby

    2018-01-01

    The electronic and optoelectronic properties of [A.2AP(w)/A*.2AP(WC)/C.2AP(w)/C*.2AP(WC)/C.A(w)/ C*.A(WC)]-Au8 metal-mismatch nucleobase complexes are investigated by means of density functional theory and time-dependent methods. We selected these mispairs as 2-aminopurine (2AP) produces incorporation errors when binding with cytosine (C) into the wobble (w) C.2AP(w) mispair, and is tautomerised into Watson-Crick (WC)-like base mispair C*.2AP(WC) and less effectively produces A.2AP(w)/A*.2AP(WC) mispairs. The vertical ionisation potential, vertical electron affinity, hardness and electrophilicity index of these complexes have also been discussed. The modifications of energy levels and charge density distributions of the frontier orbitals are also analysed. The absorption spectra of these complexes lie in the visible region, which suggests their application in fluorescent-bio imaging. The mechanism of cooperativity effect is studied by molecular orbital potential (MEP), atoms-in-molecules (AIM) and natural bond orbital analyses. Most metalated pairs have smaller HOMO-LUMO band gaps than the isolated mismatch nucleobases which suggest interesting consequences for electron transfer through DNA duplexes.

  11. Understanding and changing human behaviour—antibiotic mainstreaming as an approach to facilitate modification of provider and consumer behaviour

    Science.gov (United States)

    Tamhankar, Ashok J.

    2014-01-01

    This paper addresses: 1) Situations where human behaviour is involved in relation to antibiotics, focusing on providers and consumers; 2) Theories about human behaviour and factors influencing behaviour in relation to antibiotics; 3) How behaviour in relation to antibiotics can change; and, 4) Antibiotic mainstreaming as an approach to facilitate changes in human behaviour as regards antibiotics. Influencing human behaviour in relation to antibiotics is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. Further, key concepts are often perceived in different ways by different individuals. While designing and implementing projects or programmes for behavioural change with respect to antibiotics for professionals or consumers it is helpful to consider theories or models of behaviour change, e.g. the ‘stages of change model’, including pre-contemplation, contemplation, preparation, action, and maintenance. People in different stages of change are susceptible to different behaviour modification strategies. Application of marketing principles to ‘global good’, so-called ‘social marketing’, to improve ‘welfare of the individual and society’ is gaining increased attention in public health. In conclusion, just providing correct knowledge is not sufficient although it is a pre-requisite for behaviour modification in the desired direction. We can never change the behaviour of any other human, but we can facilitate for others to change their own behaviour. One possibility is to implement ‘antibiotic mainstreaming’ as a potentially effective way for behaviour modification, i.e. to address consequences for maintaining effective antibiotics in all activities and decisions in society. PMID:24735112

  12. The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

    DEFF Research Database (Denmark)

    Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

    2012-01-01

    In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

  13. Binding mechanisms of DNA/RNA nucleobases adsorbed on graphene under charging: first-principles van der Waals study

    Science.gov (United States)

    Gürel, Hikmet Hakan; Salmankurt, Bahadır

    2017-06-01

    Graphene is a 2D material that has attracted much attention due to its outstanding properties. Because of its high surface area and unique chemical and physical properties, graphene is a good candidate for biological applications. For this reason, a deep understanding of the mechanism of interaction of graphene with biomolecules is required. In this study, theoretical investigation of van der Waals effects has been conducted using density functional theory. Here we show that the order of the binding energies of five nucleobases with graphene is G  >  A  >  T  >  C  >   U. This trend is in good agreement with most of the theoretical and experimental data. Also, the effects of charging on the electronic and structural properties of the graphene-nucleubase systems are studied for the first time. We show that the binding energy can be changed by adding or removing an electron from the system. The results presented in this work provide fundamental insights into the quantum interactions of DNA with carbon-based nanostructures and will be useful for developments in biotechnology and nanotechnology.

  14. Differential bacterial capture and transport preferences facilitate co-growth on dietary xylan in the human gut

    DEFF Research Database (Denmark)

    Leth, Maria Louise; Ejby, Morten; Workman, Christopher

    2018-01-01

    Metabolism of dietary glycans is pivotal in shaping the human gut microbiota. However, the mechanisms that promote competition for glycans among gut commensals remain unclear. Roseburia intestinalis, an abundant butyrate-producing Firmicute, is a key degrader of the major dietary fibre xylan...... of capture and transport preferences as a possible strategy to facilitate co-growth on abundant dietary fibres and may offer a unique route to manipulate the microbiota based on glycan transport preferences in therapeutic interventions to boost distinct taxa....

  15. Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment

    Science.gov (United States)

    Xie, Maorong; Xuan, Baoqin; Shan, Jiaoyu; Pan, Deng; Sun, Yamei; Shan, Zhao; Zhang, Jinping; Yu, Dong

    2014-01-01

    ABSTRACT Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we

  16. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

    Science.gov (United States)

    Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

    Directory of Open Access Journals (Sweden)

    Shumei Man

    2008-01-01

    Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

  18. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    Directory of Open Access Journals (Sweden)

    Kampf Caroline

    2012-09-01

    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  19. pH dependent interaction of biofunctionalized CdS nanoparticles with nucleobases and nucleotides: A fluorimetric study

    International Nuclear Information System (INIS)

    Chatterjee, Anindita; Priyam, Amiya; Bhattacharya, Subhash C.; Saha, Abhijit

    2007-01-01

    The interaction of DNA bases and corresponding nucleotides with CdS nanoparticles (NPs), biofunctionalized by cysteine, has been investigated by absorption and fluorescence spectroscopy. Unique enhancement effect of adenine, in contrast to other nucleobases, on the luminescence of cysteine capped CdS (cys-CdS) NPs at both pH 7.5 and 10.5 was found, the extent of enhancement being much higher at pH 10.5. At the latter pH, the difference optical absorption spectra show development of new peak at 278 nm with corresponding decrease in the absorption of adenine at 260 nm, which is attributed to binding of adenine anion to the CdS surface through N7 of the purine ring. Appearance of a new band at 478 cm -1 and concomitant shift in the C 8 -N 7 vibrations to 1610 cm -1 in the FTIR spectra of cys-CdS NPs with adenine also suggest Cd-N7 binding on the particle surface. Amongst various nucleotides, ATP exhibited maximum luminescence enhancement on CdS NPs for a given change in concentration in the micro-molar range at physiological pH. A quantitative correlation between ATP concentration and PL enhancement of CdS NPs has been established, a step which in future might assist in developing new protocols for fluorescence sensing of adenine nucleotides under certain pathological conditions

  20. Effects and limitations of a nucleobase-driven backmapping procedure for nucleic acids using steered molecular dynamics.

    Science.gov (United States)

    Poblete, Simón; Bottaro, Sandro; Bussi, Giovanni

    2018-03-29

    Coarse-grained models can be of great help to address the problem of structure prediction in nucleic acids. On one hand they can make the prediction more efficient, while on the other hand they can also help to identify the essential degrees of freedom and interactions for the description of a number of structures. With the aim to provide an all-atom representation in an explicit solvent to the predictions of our SPlit and conQueR (SPQR) coarse-grained model of RNA, we recently introduced a backmapping procedure which enforces the predicted structure into an atomistic one by means of steered molecular dynamics. These simulations minimize the ERMSD, a particular metric which deals exclusively with the relative arrangement of nucleobases, between the atomistic representation and the target structure. In this paper, we explore the effects of this approach on the resulting interaction networks and backbone conformations by applying it on a set of fragments using as a target their native structure. We find that the geometry of the target structures can be reliably recovered, with limitations in the regions with unpaired bases such as bulges. In addition, we observe that the folding pathway can also change depending on the parameters used in the definition of the ERMSD and the use of other metrics such as the RMSD. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Facilitated uptake of a bioactive metabolite of maritime pine bark extract (pycnogenol into human erythrocytes.

    Directory of Open Access Journals (Sweden)

    Max Kurlbaum

    Full Text Available Many plant secondary metabolites exhibit some degree of biological activity in humans. It is a common observation that individual plant-derived compounds in vivo are present in the nanomolar concentration range at which they usually fail to display measurable activity in vitro. While it is debatable that compounds detected in plasma are not the key effectors of bioactivity, an alternative hypothesis may take into consideration that measurable concentrations also reside in compartments other than plasma. We analysed the binding of constituents and the metabolite δ-(3,4-dihydroxy-phenyl-γ-valerolactone (M1, that had been previously detected in plasma samples of human consumers of pine bark extract Pycnogenol, to human erythrocytes. We found that caffeic acid, taxifolin, and ferulic acid passively bind to red blood cells, but only the bioactive metabolite M1 revealed pronounced accumulation. The partitioning of M1 into erythrocytes was significantly diminished at higher concentrations of M1 and in the presence of glucose, suggesting a facilitated transport of M1 via GLUT-1 transporter. This concept was further supported by structural similarities between the natural substrate α-D-glucose and the S-isomer of M1. After cellular uptake, M1 underwent further metabolism by conjugation with glutathione. We present strong indication for a transporter-mediated accumulation of a flavonoid metabolite in human erythrocytes and subsequent formation of a novel glutathione adduct. The physiologic role of the adduct remains to be elucidated.

  2. Facilitation as a teaching strategy : experiences of facilitators

    Directory of Open Access Journals (Sweden)

    E Lekalakala-Mokgele

    2006-09-01

    Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

  3. Barriers and Facilitators to Engagement and Retention in Care among Transgender Women Living with Human Immunodeficiency Virus

    Science.gov (United States)

    Sevelius, Jae M.; Patouhas, Enzo; Keatley, JoAnne G.; Johnson, Mallory O.

    2014-01-01

    Background Transgender women have 49 times the odds of human immunodeficiency virus (HIV) infection compared to other groups, yet they are disproportionately underserved by current treatment efforts. Purpose To examine culturally unique barriers and facilitators to engagement and retention in HIV care and strengthen efforts to mitigate health disparities, guided by the Models of Gender Affirmation and Health Care Empowerment. Methods Through 20 interviews and 5 focus groups (n=38), transgender women living with HIV discussed their experiences and life contexts of engagement in and adherence to HIV care and treatment. Results Our participants faced substantial challenges to adhering to HIV care and treatment, including avoidance of healthcare due to stigma and past negative experiences, prioritization of hormone therapy, and concerns about adverse interactions between antiretroviral treatment for HIV and hormone therapy. Receiving culturally competent, transgender-sensitive healthcare was a powerful facilitator of healthcare empowerment. Conclusions Recommendations are offered to inform intervention research and guide providers, emphasizing gender affirming HIV care that integrates transition-related healthcare needs. PMID:24317955

  4. Facilitating Learning at Conferences

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...... and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes...

  5. Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

    Science.gov (United States)

    Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

    2017-05-01

    Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Systems Analysis of Human Visuo-Myoelectric Control Facilitated by Anodal Transcranial Direct Current Stimulation in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Vinh Kha

    2018-04-01

    Full Text Available Induction of neuroplasticity by transcranial direct current stimulation (tDCS applied to the primary motor cortex facilitates motor learning of the upper extremities in healthy humans. The impact of tDCS on lower limb functions has not been studied extensively so far. In this study, we applied a system identification approach to investigate the impact of anodal transcranial direct current stimulation of the leg area of the motor cortex via the human visuo-myoelectric controller. The visuo-myoelectric reaching task (VMT involves ballistic muscle contraction after a visual cue. We applied a black box approach using a linear ARX (Auto-regressive with eXogenous input model for a visuomotor myoelectric reaching task. We found that a 20th order finite impulse response (FIR model captured the TARGET (single input—CURSOR (single output dynamics during a VMT. The 20th order FIR model was investigated based on gain/phase margin analysis, which showed a significant (p < 0.01 effect of anodal tDCS on the gain margin of the VMT system. Also, response latency and the corticomuscular coherence (CMC time delay were affected (p < 0.05 by anodal tDCS when compared to sham tDCS. Furthermore, gray box simulation results from a Simplified Spinal-Like Controller (SSLC model demonstrated that the input-output function for motor evoked potentials (MEP played an essential role in increasing muscle activation levels and response time improvement post-tDCS when compared to pre-tDCS baseline performance. This computational approach can be used to simulate the behavior of the neuromuscular controller during VMT to elucidate the effects of adjuvant treatment with tDCS.

  7. DNA-mediated strand displacement facilitates sensitive electronic detection of antibodies in human serums.

    Science.gov (United States)

    Dou, Baoting; Yang, Jianmei; Shi, Kai; Yuan, Ruo; Xiang, Yun

    2016-09-15

    We describe here the development of a sensitive and convenient electronic sensor for the detection of antibodies in human serums. The sensor is constructed by self-assembly formation of a mixed monolayer containing the small molecule epitope conjugated double stranded DNA probes on gold electrode. The target antibody binds the epitope on the dsDNA probe and lowers the melting temperature of the duplex, which facilitates the displacement of the antibody-linked strand of the duplex probe by an invading methylene blue-tagged single stranded DNA (MB-ssDNA) through the strand displacement reaction and leads to the capture of many MB-ssDNA on the sensor surface. Subsequent electrochemical oxidation of the methylene blue labels results in amplified current response for sensitive monitoring of the antibodies. The antibody assay conditions are optimized and the sensor exhibits a linear range between 1.0 and 25.0nM with a detection limit of 0.67nM for the target antibody. The sensor is also selective and can be employed to detect the target antibodies in human serum samples. With the advantages of using small molecule epitope as the antibody recognition element over traditional antigen, the versatile manipulability of the DNA probes and the unique properties of the electrochemical transduction technique, the developed sensor thus hold great potential for simple and sensitive detection of different antibodies and other proteins in real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Hydrated Electron Transfer to Nucleobases in Aqueous Solutions Revealed by Ab Initio Molecular Dynamics Simulations.

    Science.gov (United States)

    Zhao, Jing; Wang, Mei; Fu, Aiyun; Yang, Hongfang; Bu, Yuxiang

    2015-08-03

    We present an ab initio molecular dynamics (AIMD) simulation study into the transfer dynamics of an excess electron from its cavity-shaped hydrated electron state to a hydrated nucleobase (NB)-bound state. In contrast to the traditional view that electron localization at NBs (G/A/C/T), which is the first step for electron-induced DNA damage, is related only to dry or prehydrated electrons, and a fully hydrated electron no longer transfers to NBs, our AIMD simulations indicate that a fully hydrated electron can still transfer to NBs. We monitored the transfer dynamics of fully hydrated electrons towards hydrated NBs in aqueous solutions by using AIMD simulations and found that due to solution-structure fluctuation and attraction of NBs, a fully hydrated electron can transfer to a NB gradually over time. Concurrently, the hydrated electron cavity gradually reorganizes, distorts, and even breaks. The transfer could be completed in about 120-200 fs in four aqueous NB solutions, depending on the electron-binding ability of hydrated NBs and the structural fluctuation of the solution. The transferring electron resides in the π*-type lowest unoccupied molecular orbital of the NB, which leads to a hydrated NB anion. Clearly, the observed transfer of hydrated electrons can be attributed to the strong electron-binding ability of hydrated NBs over the hydrated electron cavity, which is the driving force, and the transfer dynamics is structure-fluctuation controlled. This work provides new insights into the evolution dynamics of hydrated electrons and provides some helpful information for understanding the DNA-damage mechanism in solution. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Work System Assessment to Facilitate the Dissemination of a Quality Improvement Program for Optimizing Blood Culture Use: A Case Study Using a Human Factors Engineering Approach.

    Science.gov (United States)

    Xie, Anping; Woods-Hill, Charlotte Z; King, Anne F; Enos-Graves, Heather; Ascenzi, Judy; Gurses, Ayse P; Klaus, Sybil A; Fackler, James C; Milstone, Aaron M

    2017-11-20

    Work system assessments can facilitate successful implementation of quality improvement programs. Using a human factors engineering approach, we conducted a work system assessment to facilitate the dissemination of a quality improvement program for optimizing blood culture use in pediatric intensive care units at 2 hospitals. Semistructured face-to-face interviews were conducted with clinicians from Johns Hopkins All Children's Hospital and University of Virginia Medical Center. Interview data were analyzed using qualitative content analysis. Blood culture-ordering practices are influenced by various work system factors, including people, tasks, tools and technologies, the physical environment, organizational conditions, and the external environment. A clinical decision-support tool could facilitate implementation by (1) standardizing blood culture-ordering practices, (2) ensuring that prescribing clinicians review the patient's condition before ordering a blood culture, (3) facilitating critical thinking, and (4) empowering nurses to communicate with physicians and advocate for adherence to blood culture-ordering guidelines. The success of interventions for optimizing blood culture use relies heavily on the local context. A work system analysis using a human factors engineering approach can identify key areas to be addressed for the successful dissemination of quality improvement interventions. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Interactive Learning in SME-University Collaborations: A Conceptual Framework for Facilitating Interaction

    DEFF Research Database (Denmark)

    Filip, Diane

    2013-01-01

    . The facilitation process focuses on interactive learning and is divided into phases, which makes it easier for SMEs to progressive engage in innovation projects with researchers. In-depth interviews with the facilitators of the programme were conducted and focused on barriers to collaboration, human interaction......, and lessons learned. From the facilitators’ perspective, a conceptual model capturing the main actor’s activities in each phase paralleled with an illustration of the narrowed gap from the human interaction is presented in the paper. The main findings addressed the issues of human-based and system......-based barriers. One of the lessons learned is the importance of human interaction of narrowing the perceived gap by mitigating the human-based barriers, and to some extent also system-based barriers. The case presented in this paper has managerial and innovation policy implications....

  11. Adult maturational processes and the facilitating environment.

    Science.gov (United States)

    Acklin, M W

    1986-09-01

    The psychoanalytic theory of religion has been seriously limited in its development, largely owing to Freud's emphasis on religion's neurotic elements and an overemphasis on the infantile origins of religious development. This paper offers a conceptual framework and advances the thesis, based on contemporary psychoanalytic, developmental theory, that 1) Erikson's concept of epigenesis has applicability across the life span; 2) that beyond-the-self identity is constituent to human maturation and self-completion; 3) that successful adult maturation requires a mirroring-facilitating environment; and 4) that religious values, meanings, images, and communities play an essential role-as-elements of the facilitating environment of later life.

  12. Empirical evaluation of a forecasting model for successful facilitation ...

    African Journals Online (AJOL)

    During 2000 the annual Facilitator Customer Satisfaction Survey was ... the forecasting model is successful concerning the CSI value and a high positive linear ... namely that of human behaviour to incorporate other influences than just the ...

  13. Argumentation: A Methodology to Facilitate Critical Thinking.

    Science.gov (United States)

    Makhene, Agnes

    2017-06-20

    Caring is a difficult nursing activity that involves a complex nature of a human being in need of complex decision-making and problem solving through the critical thinking process. It is mandatory that critical thinking is facilitated in general and in nursing education particularly in order to render care in diverse multicultural patient care settings. This paper aims to describe how argumentation can be used to facilitate critical thinking in learners. A qualitative, exploratory and descriptive design that is contextual was used. Purposive sampling method was used to draw a sample and Miles and Huberman methodology of qualitative analysis was used to analyse data. Lincoln and Guba's strategies were employed to ensure trustworthiness, while Dhai and McQuoid-Mason's principles of ethical consideration were used. Following data analysis the findings were integrated within literature which culminated into the formulation of guidelines that can be followed when using argumentation as a methodology to facilitate critical thinking.

  14. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Directory of Open Access Journals (Sweden)

    Juan Roberto Rodriguez-Madoz

    Full Text Available The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272 improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  15. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Science.gov (United States)

    Rodriguez-Madoz, Juan Roberto; San Jose-Eneriz, Edurne; Rabal, Obdulia; Zapata-Linares, Natalia; Miranda, Estibaliz; Rodriguez, Saray; Porciuncula, Angelo; Vilas-Zornoza, Amaia; Garate, Leire; Segura, Victor; Guruceaga, Elizabeth; Agirre, Xabier; Oyarzabal, Julen; Prosper, Felipe

    2017-01-01

    The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  16. Ca2+ improves organization of single-stranded DNA bases in human Rad51 filament, explaining stimulatory effect on gene recombination.

    KAUST Repository

    Fornander, Louise H

    2012-02-22

    Human RAD51 protein (HsRad51) catalyses the DNA strand exchange reaction for homologous recombination. To clarify the molecular mechanism of the reaction in vitro being more effective in the presence of Ca(2+) than of Mg(2+), we have investigated the effect of these ions on the structure of HsRad51 filament complexes with single- and double-stranded DNA, the reaction intermediates. Flow linear dichroism spectroscopy shows that the two ionic conditions induce significantly different structures in the HsRad51/single-stranded DNA complex, while the HsRad51/double-stranded DNA complex does not demonstrate this ionic dependence. In the HsRad51/single-stranded DNA filament, the primary intermediate of the strand exchange reaction, ATP/Ca(2+) induces an ordered conformation of DNA, with preferentially perpendicular orientation of nucleobases relative to the filament axis, while the presence of ATP/Mg(2+), ADP/Mg(2+) or ADP/Ca(2+) does not. A high strand exchange activity is observed for the filament formed with ATP/Ca(2+), whereas the other filaments exhibit lower activity. Molecular modelling suggests that the structural variation is caused by the divalent cation interfering with the L2 loop close to the DNA-binding site. It is proposed that the larger Ca(2+) stabilizes the loop conformation and thereby the protein-DNA interaction. A tight binding of DNA, with bases perpendicularly oriented, could facilitate strand exchange.

  17. Leadership Development Through Peer-Facilitated Simulation in Nursing Education.

    Science.gov (United States)

    Brown, Karen M; Rode, Jennifer L

    2018-01-01

    Baccalaureate nursing graduates must possess leadership skills, yet few opportunities exist to cultivate leadership abilities in a clinical environment. Peer-facilitated learning may increase the leadership skills of competence, self-confidence, self-reflection, and role modeling. Facilitating human patient simulation provides opportunities to develop leadership skills. With faculty supervision, senior baccalaureate students led small-group simulation experiences with sophomore and junior peers and then conducted subsequent debriefings. Quantitative and qualitative descriptive data allowed evaluation of students' satisfaction with this teaching innovation and whether the experience affected students' desire to take on leadership roles. Students expressed satisfaction with the peer-facilitated simulation experience and confidence in mastering the content while developing necessary skills for practice. Peer-facilitated simulation provides an opportunity for leadership development and learning. Study results can inform the development of nursing curricula to best develop the leadership skills of nursing students. [J Nurs Educ. 2018;57(1):53-57.]. Copyright 2018, SLACK Incorporated.

  18. Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors

    OpenAIRE

    Wu, Shwu-Yuan; Zhou, Tianyuan; Chiang, Cheng-Ming

    2003-01-01

    Mediator is a general cofactor implicated in the functions of many transcriptional activators. Although Mediator with different protein compositions has been isolated, it remains unclear how Mediator facilitates activator-dependent transcription, independent of its general stimulation of basal transcription. To define the mechanisms of Mediator function, we isolated two forms of human Mediator complexes (Mediator-P.5 and Mediator-P.85) and demonstrated that Mediator-P.5 clearly functions by e...

  19. A model of human motor sequence learning explains facilitation and interference effects based on spike-timing dependent plasticity.

    Directory of Open Access Journals (Sweden)

    Quan Wang

    2017-08-01

    Full Text Available The ability to learn sequential behaviors is a fundamental property of our brains. Yet a long stream of studies including recent experiments investigating motor sequence learning in adult human subjects have produced a number of puzzling and seemingly contradictory results. In particular, when subjects have to learn multiple action sequences, learning is sometimes impaired by proactive and retroactive interference effects. In other situations, however, learning is accelerated as reflected in facilitation and transfer effects. At present it is unclear what the underlying neural mechanism are that give rise to these diverse findings. Here we show that a recently developed recurrent neural network model readily reproduces this diverse set of findings. The self-organizing recurrent neural network (SORN model is a network of recurrently connected threshold units that combines a simplified form of spike-timing dependent plasticity (STDP with homeostatic plasticity mechanisms ensuring network stability, namely intrinsic plasticity (IP and synaptic normalization (SN. When trained on sequence learning tasks modeled after recent experiments we find that it reproduces the full range of interference, facilitation, and transfer effects. We show how these effects are rooted in the network's changing internal representation of the different sequences across learning and how they depend on an interaction of training schedule and task similarity. Furthermore, since learning in the model is based on fundamental neuronal plasticity mechanisms, the model reveals how these plasticity mechanisms are ultimately responsible for the network's sequence learning abilities. In particular, we find that all three plasticity mechanisms are essential for the network to learn effective internal models of the different training sequences. This ability to form effective internal models is also the basis for the observed interference and facilitation effects. This suggests that

  20. Facilitating job retention for chronically ill employees: perspectives of line managers and human resource managers.

    Science.gov (United States)

    Haafkens, Joke A; Kopnina, Helen; Meerman, Martha G M; van Dijk, Frank J H

    2011-05-17

    Chronic diseases are a leading contributor to work disability and job loss in Europe. Recent EU policies aim to improve job retention among chronically ill employees. Disability and occupational health researchers argue that this requires a coordinated and pro-active approach at the workplace by occupational health professionals, line managers (LMs) and human resource managers (HRM). Little is known about the perspectives of LMs an HRM on what is needed to facilitate job retention among chronically ill employees. The aim of this qualitative study was to explore and compare the perspectives of Dutch LMs and HRM on this issue. Concept mapping methodology was used to elicit and map statements (ideas) from 10 LMs and 17 HRM about what is needed to ensure continued employment for chronically ill employees. Study participants were recruited through a higher education and an occupational health services organization. Participants generated 35 statements. Each group (LMs and HRM) sorted these statements into six thematic clusters. LMs and HRM identified four similar clusters: LMs and HRM must be knowledgeable about the impact of chronic disease on the employee; employees must accept responsibility for work retention; work adaptations must be implemented; and clear company policy. Thematic clusters identified only by LMs were: good manager/employee cooperation and knowledge transfer within the company. Unique clusters identified by HRM were: company culture and organizational support. There were both similarities and differences between the views of LMs and HRM on what may facilitate job retention for chronically ill employees. LMs perceived manager/employee cooperation as the most important mechanism for enabling continued employment for these employees. HRM perceived organizational policy and culture as the most important mechanism. The findings provide information about topics that occupational health researchers and planners should address in developing job retention

  1. Facilitating job retention for chronically ill employees: perspectives of line managers and human resource managers

    Directory of Open Access Journals (Sweden)

    Meerman Martha GM

    2011-05-01

    Full Text Available Abstract Background Chronic diseases are a leading contributor to work disability and job loss in Europe. Recent EU policies aim to improve job retention among chronically ill employees. Disability and occupational health researchers argue that this requires a coordinated and pro-active approach at the workplace by occupational health professionals, line managers (LMs and human resource managers (HRM. Little is known about the perspectives of LMs an HRM on what is needed to facilitate job retention among chronically ill employees. The aim of this qualitative study was to explore and compare the perspectives of Dutch LMs and HRM on this issue. Methods Concept mapping methodology was used to elicit and map statements (ideas from 10 LMs and 17 HRM about what is needed to ensure continued employment for chronically ill employees. Study participants were recruited through a higher education and an occupational health services organization. Results Participants generated 35 statements. Each group (LMs and HRM sorted these statements into six thematic clusters. LMs and HRM identified four similar clusters: LMs and HRM must be knowledgeable about the impact of chronic disease on the employee; employees must accept responsibility for work retention; work adaptations must be implemented; and clear company policy. Thematic clusters identified only by LMs were: good manager/employee cooperation and knowledge transfer within the company. Unique clusters identified by HRM were: company culture and organizational support. Conclusions There were both similarities and differences between the views of LMs and HRM on what may facilitate job retention for chronically ill employees. LMs perceived manager/employee cooperation as the most important mechanism for enabling continued employment for these employees. HRM perceived organizational policy and culture as the most important mechanism. The findings provide information about topics that occupational health

  2. Practice Facilitators' and Leaders' Perspectives on a Facilitated Quality Improvement Program.

    Science.gov (United States)

    McHugh, Megan; Brown, Tiffany; Liss, David T; Walunas, Theresa L; Persell, Stephen D

    2018-04-01

    Practice facilitation is a promising approach to helping practices implement quality improvements. Our purpose was to describe practice facilitators' and practice leaders' perspectives on implementation of a practice facilitator-supported quality improvement program and describe where their perspectives aligned and diverged. We conducted interviews with practice leaders and practice facilitators who participated in a program that included 35 improvement strategies aimed at the ABCS of heart health (aspirin use in high-risk individuals, blood pressure control, cholesterol management, and smoking cessation). Rapid qualitative analysis was used to collect, organize, and analyze the data. We interviewed 17 of the 33 eligible practice leaders, and the 10 practice facilitators assigned to those practices. Practice leaders and practice facilitators both reported value in the program's ability to bring needed, high-quality resources to practices. Practice leaders appreciated being able to set the schedule for facilitation and select among the 35 interventions. According to practice facilitators, however, relying on practice leaders to set the pace of the intervention resulted in a lower level of program intensity than intended. Practice leaders preferred targeted assistance, particularly electronic health record documentation guidance and linkages to state smoking cessation programs. Practice facilitators reported that the easiest interventions were those that did not alter care practices. The dual perspectives of practice leaders and practice facilitators provide a more holistic picture of enablers and barriers to program implementation. There may be greater opportunities to assist small practices through simple, targeted practice facilitator-supported efforts rather than larger, comprehensive quality improvement projects. © 2018 Annals of Family Medicine, Inc.

  3. A qualitative, interprofessional analysis of barriers to and facilitators of implementation of the Department of Veterans Affairs' Clostridium difficile prevention bundle using a human factors engineering approach.

    Science.gov (United States)

    Yanke, Eric; Moriarty, Helene; Carayon, Pascale; Safdar, Nasia

    2018-03-01

    Clostridium difficile infection (CDI) is increasingly prevalent, severe, and costly. Adherence to infection prevention practices remains suboptimal. More effective strategies to implement guidelines and evidence are needed. Interprofessional focus groups consisting of physicians, resident physicians, nurses, and health technicians were conducted for a quality improvement project evaluating adherence to the Department of Veterans Affairs' (VA) nationally mandated C difficile prevention bundle. Qualitative analysis with a visual matrix display identified barrier and facilitator themes guided by the Systems Engineering Initiative for Patient Safety model, a human factors engineering approach. Several themes, encompassing both barriers and facilitators to bundle adherence, emerged. Rapid turnaround time of C difficile polymerase chain reaction testing was a facilitator of timely diagnosis. Too few, poorly located, and cluttered sinks were barriers to appropriate hand hygiene. Patient care workload and the time-consuming process of contact isolation precautions were also barriers to adherence. Multiple work system components serve as barriers to and facilitators of adherence to the VA CDI prevention bundle among an interprofessional group of health care workers. Organizational factors appear to significantly influence bundle adherence. Interprofessional perspectives are needed to identify barriers to and facilitators of bundle implementation, which is a necessary first step to address adherence to bundled infection prevention practices. Published by Elsevier Inc.

  4. African Journal of Cross-Cultural Psychology and Sport Facilitation ...

    African Journals Online (AJOL)

    Focus and Scope. The African Journal of Cross-Cultural Psychology and Sport Facilitation is a professional journal of the Association of Psychology in Sport and Human Behaviour. It publishes a wide variety of original articles and reports relevant to cultural and sport behaviour, theoretical propositions, research outcomes ...

  5. Subcortical structures in humans can be facilitated by transcranial direct current stimulation

    NARCIS (Netherlands)

    Nonnekes, Johan Hendrik; Arrogi, Anass; Munneke, Moniek; van Asseldonk, Edwin H.F.; Oude Nijhuis, Lars; Geurts, Alexander; Weerdesteyn, Vivian

    2014-01-01

    BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability via application of a weak direct current. Interestingly, it was demonstrated in cats that tDCS can facilitate subcortical structures as well (Bolzonii et al., J

  6. Customized Body Mapping to Facilitate the Ergonomic Design of Sportswear.

    Science.gov (United States)

    Cao, Mingliang; Li, Yi; Guo, Yueping; Yao, Lei; Pan, Zhigeng

    2016-01-01

    A successful high-performance sportswear design that considers human factors should result in a significant increase in thermal comfort and reduce energy loss. The authors describe a body-mapping approach that facilitates the effective ergonomic design of sportswear. Their general framework can be customized based on the functional requirements of various sports and sportswear, the desired combination and selection of mapping areas for the human body, and customized quantitative data distribution of target physiological indicators.

  7. ZFP521 regulates murine hematopoietic stem cell function and facilitates MLL-AF9 leukemogenesis in mouse and human cells.

    Science.gov (United States)

    Garrison, Brian S; Rybak, Adrian P; Beerman, Isabel; Heesters, Balthasar; Mercier, Francois E; Scadden, David T; Bryder, David; Baron, Roland; Rossi, Derrick J

    2017-08-03

    The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521 / Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis whose function in HSC biology remains elusive. Competitive serial transplantation assays using Zfp521 -deficient mice revealed that ZFP521 regulates HSC self-renewal and differentiation. In contrast, ectopic expression of ZFP521 in HSCs led to a robust maintenance of progenitor activity in vitro. Transcriptional analysis of human acute myeloid leukemia (AML) patient samples revealed that ZNF521 is highly and specifically upregulated in AMLs with MLL translocations. Using an MLL-AF9 murine leukemia model and serial transplantation studies, we show that ZFP521 is not required for leukemogenesis, although its absence leads to a significant delay in leukemia onset. Furthermore, knockdown of ZNF521 reduced proliferation in human leukemia cell lines possessing MLL-AF9 translocations. Taken together, these results identify ZNF521/ZFP521 as a critical regulator of HSC function, which facilitates MLL-AF9-mediated leukemic disease in mice.

  8. Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

    Science.gov (United States)

    Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

    2017-05-01

    Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

  9. Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

    Science.gov (United States)

    Fu, Qinqin; Yuan, Y Adam

    2013-03-01

    Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

  10. A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.

    Science.gov (United States)

    Spandorfer, Philip R; Mace, Sharon E; Okada, Pamela J; Simon, Harold K; Allen, Coburn H; Spiro, David M; Friend, Keith; Harb, George; Lebel, Francois

    2012-11-01

    Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children. This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration. The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire. 148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration

  11. Role of the heat capacity change in understanding and modeling melting thermodynamics of complementary duplexes containing standard and nucleobase-modified LNA.

    Science.gov (United States)

    Hughesman, Curtis B; Turner, Robin F B; Haynes, Charles A

    2011-06-14

    Melting thermodynamic data obtained by differential scanning calorimetry (DSC) are reported for 43 duplexed oligonucleotides containing one or more locked nucleic acid (LNA) substitutions. The measured heat capacity change (ΔC(p)) for the helix-to-coil transition is used to compute the changes in enthalpy and entropy for melting of an LNA-bearing duplex at the T(m) of its corresponding isosequential unmodified DNA duplex to allow rigorous thermodynamic analysis of the stability enhancements provided by LNA substitutions. Contrary to previous studies, our analysis shows that the origin of the improved stability is almost exclusively a net reduction (ΔΔS° thermodynamics and the increased melting temperature (ΔT(m)) of heteroduplexes formed between an unmodified DNA strand and a complementary strand containing any number and configuration of standard LNA nucleotides A, T, C, and G. This single-base thermodynamic (SBT) model requires only four entropy-related parameters in addition to ΔC(p). Finally, DSC data for 20 duplexes containing the nucleobase-modified LNAs 2-aminoadenine (D) and 2-thiothymine (H) are reported and used to determine SBT model parameters for D and H. The data and model suggest that along with the greater stability enhancement provided by D and H bases relative to their corresponding A and T analogues, the unique pseudocomplementary properties of D-H base pairs may make their use appealing for in vitro and in vivo applications.

  12. Parenteral nutrition facilitates activation of coagulation but not of fibrinolysis during human endotoxemia

    NARCIS (Netherlands)

    van der Poll, T.; Levi, M. [=Marcel M.; Braxton, C. C.; Coyle, S. M.; Roth, M.; ten Cate, J. W.; Lowry, S. F.

    1998-01-01

    Venous thrombosis and bacterial infections are common complications of parenteral nutrition. To test the hypothesis that infection facilitates activation of coagulation during parenteral nutrition, healthy subjects were intravenously injected with endotoxin (2 ng/kg) after they had received either 1

  13. Learning facilitating leadership

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

    2016-01-01

    This paper explains how engineering students at a Danish university acquired the necessary skills to become emergent facilitators of organisational development. The implications of this approach are discussed and related to relevant viewpoints and findings in the literature. The methodology deplo....... By connecting the literature, the authors’ and engineering students’ reflections on facilitator skills, this paper adds value to existing academic and practical discussions on learning facilitating leadership....

  14. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    Science.gov (United States)

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

  15. Facilitation Processes and Skills Supporting EcoCity Development

    Directory of Open Access Journals (Sweden)

    Carmen Antuña-Rozado

    2018-03-01

    Full Text Available Ecocities can provide solutions for the improvement of human settlements around the world and the living conditions therein, but in the authors’ experience, only as long as they are able to address the following questions correctly: How to formulate an ecocity concept that, considering issues of general concern, can be at the same time adapted to different local conditions? What are the instruments supporting the development and implementation of ecocity solutions? VTT’s EcoCity concept for sustainable community and neighbourhood regeneration and development has been designed in response to the first question. Likewise, specific methodologies and effective facilitation processes and skills have been developed in response to the second question. Since the methodologies have been discussed in a previous scientific article, the present one focuses on the facilitation processes and skills, and also on other related, fundamental aspects like participation, adaptation, capacity building, etc. Facilitation processes supporting EcoCity development require matching “hard” and “soft” skills in a fluid way. The main findings are discussed with the help of two case studies: one in Medellín (Colombia, and the other one in Zambia.

  16. Barriers and facilitators to primary care or human immunodeficiency virus clinics providing methadone or buprenorphine for the management of opioid dependence.

    Science.gov (United States)

    Turner, Barbara J; Laine, Christine; Lin, Yi-Ting; Lynch, Kevin

    Federal initiatives aim to increase office-based treatment of opioid dependence, but, to our knowledge, factors associated with willingness to deliver this care have not been defined. The objective of this study was to describe clinics' willingness to provide methadone hydrochloride or buprenorphine hydrochloride for opioid dependence. The design of the study was a survey conducted in New York State. Two hundred sixty-one directors of primary care and/or human immunodeficiency virus specialty clinics (response rate, 61.1%) that serve Medicaid enrollees were questioned. Outcomes were willingness to provide methadone and buprenorphine. Predictors included clinic characteristics, attitudes about drug users and their treatment, and reported barriers and facilitators to treatment. Clinics were more willing to provide buprenorphine than methadone treatment (59.8% vs 32.6%; P methadone. Willingness was positively associated with continuing medical education credits for training, but negatively associated with greater concern about medication abuse. Immediate telephone access to an addiction expert was associated with willingness to provide buprenorphine (AOR, 2.08; 95% CI, 1.15-3.76). Greater willingness to provide methadone was associated with a belief that methadone-treated patients should be seen along with other patients (AOR, 6.20; 95% CI, 1.78-21.64), methadone program affiliation (AOR, 4.76; 95% CI, 1.64-13.82), and having more patients with chronic pain in the clinic (AOR, 2.80; 95% CI, 1.44-5.44). These clinics serving Medicaid enrollees were more receptive to buprenorphine than methadone treatment. Willingness to provide this care was greater in clinics offering human immunodeficiency virus services, treating more chronic pain, or affiliated with methadone programs. Accessible addiction experts and continuing medical education for training may facilitate adoption of this care.

  17. Cyclophilins facilitate dissociation of the human papillomavirus type 16 capsid protein L1 from the L2/DNA complex following virus entry.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Williams, Carlyn; Kim, Seong Man; Garcea, Robert L; Sapp, Martin

    2012-09-01

    Human papillomaviruses (HPV) are composed of the major and minor capsid proteins, L1 and L2, that encapsidate a chromatinized, circular double-stranded DNA genome. At the outset of infection, the interaction of HPV type 16 (HPV16) (pseudo)virions with heparan sulfate proteoglycans triggers a conformational change in L2 that is facilitated by the host cell chaperone cyclophilin B (CyPB). This conformational change results in exposure of the L2 N terminus, which is required for infectious internalization. Following internalization, L2 facilitates egress of the viral genome from acidified endosomes, and the L2/DNA complex accumulates at PML nuclear bodies. We recently described a mutant virus that bypasses the requirement for cell surface CyPB but remains sensitive to cyclosporine for infection, indicating an additional role for CyP following endocytic uptake of virions. We now report that the L1 protein dissociates from the L2/DNA complex following infectious internalization. Inhibition and small interfering RNA (siRNA)-mediated knockdown of CyPs blocked dissociation of L1 from the L2/DNA complex. In vitro, purified CyPs facilitated the dissociation of L1 pentamers from recombinant HPV11 L1/L2 complexes in a pH-dependent manner. Furthermore, CyPs released L1 capsomeres from partially disassembled HPV16 pseudovirions at slightly acidic pH. Taken together, these data suggest that CyPs mediate the dissociation of HPV L1 and L2 capsid proteins following acidification of endocytic vesicles.

  18. Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax®23 are serotype specific and facilitate opsonophagocytosis.

    Science.gov (United States)

    Smith, Kenneth; Muther, Jennifer J; Duke, Angie L; McKee, Emily; Zheng, Nai-Ying; Wilson, Patrick C; James, Judith A

    2013-05-01

    B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Facilitating Group Decision-Making: Facilitator's Subjective Theories on Group Coordination

    Directory of Open Access Journals (Sweden)

    Michaela Kolbe

    2008-10-01

    Full Text Available A key feature of group facilitation is motivating and coordinating people to perform their joint work. This paper focuses on group coordination which is a prerequisite to group effectiveness, especially in complex tasks. Decision-making in groups is a complex task that consequently needs to be coordinated by explicit rather than implicit coordination mechanisms. Based on the embedded definition that explicit coordination does not just happen but is purposely executed by individuals, we argue that individual coordination intentions and mechanisms should be taken into account. Thus far, the subjective perspective of coordination has been neglected in coordination theory, which is understandable given the difficulties in defining and measuring subjective aspects of group facilitation. We therefore conducted focused interviews with eight experts who either worked as senior managers or as experienced group facilitators and analysed their approaches to group coordination using methods of content analysis. Results show that these experts possess sophisticated mental representations of their coordination behaviour. These subjective coordination theories can be organised in terms of coordination schemes in which coordination-releasing situations are facilitated by special coordination mechanisms that, in turn, lead to the perception of specific consequences. We discuss the importance of these subjective coordination theories for effectively facilitating group decision-making and minimising process losses. URN: urn:nbn:de:0114-fqs0901287

  20. Proprioceptive neuromuscular facilitation in HTLV-I-associated myelopathy/tropical spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Santos de Britto

    2014-01-01

    Full Text Available Introduction: Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP can impact the independence and motricity of patients. The aims of this study were to estimate the effects of physiotherapy on the functionality of patients with HAM/TSP during the stable phase of the disease using proprioceptive neuromuscular facilitation (PNF and to compare two methods of treatment delivery. Methods: Fourteen patients with human T cell lymphotropic virus type I (HTLV-I were randomly allocated into two groups. In group I (seven patients, PNF was applied by the therapist, facilitating the functional activities of rolling, sitting and standing, walking and climbing and descending stairs. In group II (seven patients, PNF was self-administered using an elastic tube, and the same activities were facilitated. Experiments were conducted for 1h twice per week for 12 weeks. Low-back pain, a modified Ashworth scale, the functional independence measure (FIM and the timed up and go test (TUG were assessed before and after the interventions. Results: In the within-group evaluation, low-back pain was significantly reduced in both groups, the FIM improved in group II, and the results of the TUG improved in group I. In the inter-group analysis, only the tone was lower in group II than in group I. Conclusions: Both PNF protocols were effective in treating patients with HAM/TSP.

  1. Audiovisual integration facilitates monkeys' short-term memory.

    Science.gov (United States)

    Bigelow, James; Poremba, Amy

    2016-07-01

    Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.

  2. Containers, facilitators, innovators?

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Merisalo, Maria; Inkinen, Tommi

    2018-01-01

    : are they containers, facilitators or innovators? This is investigated here through empirical material derived from 27 interviews with top departmental management in three Finnish cities (Helsinki, Espoo and Vantaa). The results show that local city governments (LCGs) consider cities as facilitators of innovation...

  3. Novice facilitators and the use of scripts for managing facilitated modelling workshops

    DEFF Research Database (Denmark)

    Tavella, Elena; Papadopoulos, Thanos

    2015-01-01

    There is limited research on the use of scripts by novice facilitators (novices) in Facilitated Modelling (FM) workshops. To address this gap, this paper illustrates how novices—supported by scripts—switch between and combine facilitation skills and competencies to successfully manage FM workshops...... and achieve outcomes. This illustration is based on a micro-level analysis of a transcript from a Viable System Model workshop held in a food cooperative in Copenhagen, Denmark. Through our findings we identify two distinct script-supported FM behaviours and related script-supported facilitation practices...... that enable novices to (a) acquire skills and competencies; and (b) switch between and combine skills and competencies to successfully manage workshops and achieve outcomes. Our study links micro-level considerations to a meta-level framework that relates the script-supported FM behaviours and practices...

  4. TRX-LOGOS - a graphical tool to demonstrate DNA information content dependent upon backbone dynamics in addition to base sequence.

    Science.gov (United States)

    Fortin, Connor H; Schulze, Katharina V; Babbitt, Gregory A

    2015-01-01

    for molecular evolutionary genetics analysis to visually compare the human Forkhead box/FOX protein evolution to its binding site evolution. We also compared the DNA binding signatures of human TP53 tumor suppressor determined by two different laboratory methods (SELEX and ChIP-seq). Further analysis of the entire yeast genome, center aligned at the start codon, also revealed a distinct sequence-independent 3 bp periodic pattern in information content, present only in coding region, and perhaps indicative of the non-random organization of the genetic code. TRX-LOGOS is useful in any situation in which important information content in DNA can be better visualized at the positions of phosphate linkages (i.e. dinucleotides) where the dynamic properties of the DNA backbone functions to facilitate DNA-protein interaction.

  5. Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization

    Science.gov (United States)

    Miyamoto, Mayumi; Matsuzaki, Kentaro; Katakura, Masanori; Hara, Toshiko; Tanabe, Yoko; Shido, Osamu

    2015-10-01

    The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

  6. Nanomaterial categorization for assessing risk potential to facilitate regulatory decision-making.

    Science.gov (United States)

    Godwin, Hilary; Nameth, Catherine; Avery, David; Bergeson, Lynn L; Bernard, Daniel; Beryt, Elizabeth; Boyes, William; Brown, Scott; Clippinger, Amy J; Cohen, Yoram; Doa, Maria; Hendren, Christine Ogilvie; Holden, Patricia; Houck, Keith; Kane, Agnes B; Klaessig, Frederick; Kodas, Toivo; Landsiedel, Robert; Lynch, Iseult; Malloy, Timothy; Miller, Mary Beth; Muller, Julie; Oberdorster, Gunter; Petersen, Elijah J; Pleus, Richard C; Sayre, Philip; Stone, Vicki; Sullivan, Kristie M; Tentschert, Jutta; Wallis, Philip; Nel, Andre E

    2015-01-01

    For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.

  7. Dynamics of self-assembled cytosine nucleobases on graphene

    Science.gov (United States)

    Saikia, Nabanita; Johnson, Floyd; Waters, Kevin; Pandey, Ravindra

    2018-05-01

    Molecular self-assembly of cytosine (C n ) bases on graphene was investigated using molecular dynamics methods. For free-standing C n bases, simulation conditions (gas versus aqueous) determine the nature of self-assembly; the bases prefer to aggregate in the gas phase and are stabilized by intermolecular H-bonds, while in the aqueous phase, the water molecules disrupt base-base interactions, which facilitate the formation of π-stacked domains. The substrate-induced effects, on the other hand, find the polarity and donor-acceptor sites of the bases to govern the assembly process. For example, in the gas phase, the assembly of C n bases on graphene displays short-range ordered linear arrays stabilized by the intermolecular H-bonds. In the aqueous phase, however, there are two distinct configurations for the C n bases assembly on graphene. For the first case corresponding to low surface coverage, the bases are dispersed on graphene and are isolated. The second configuration archetype is disordered linear arrays assembled with medium and high surface coverage. The simulation results establish the role of H-bonding, vdW π-stacking, and the influence of graphene surface towards the self-assembly. The ability to regulate the assembly into well-defined patterns can aid in the design of self-assembled nanostructures for the next-generation DNA based biosensors and nanoelectronic devices.

  8. Visual explorer facilitator's guide

    CERN Document Server

    Palus, Charles J

    2010-01-01

    Grounded in research and practice, the Visual Explorer™ Facilitator's Guide provides a method for supporting collaborative, creative conversations about complex issues through the power of images. The guide is available as a component in the Visual Explorer Facilitator's Letter-sized Set, Visual Explorer Facilitator's Post card-sized Set, Visual Explorer Playing Card-sized Set, and is also available as a stand-alone title for purchase to assist multiple tool users in an organization.

  9. Virtual lesions of the IFG abolish response facilitation for biological and non-biological cues

    Directory of Open Access Journals (Sweden)

    Roger D Newman-Norlund

    2010-03-01

    Full Text Available Humans are faster to perform a given action following observation of that same action. Converging evidence suggests that the human mirror neuron system (MNS plays an important role in this phenomenon. However, the specificity of the neural mechanisms governing this effect remain controversial. Specialist theories of imitation suggest that biological cues are maximally capable of eliciting imitative facilitation. Generalist models, on the other hand, posit a broader role for the MNS in linking visual stimuli with appropriate responses. In the present study, we investigated the validity of these two theoretical approaches by disrupting the left and right inferior frontal gyrus (IFG during the preparation of congruent (imitative and incongruent (complementary actions cued by either biological (hand or non-biological (static dot stimuli. Delivery of TMS over IFG abolished imitative response facilitation. Critically, this effect was identical whether actions were cued by biological or non-biological stimuli. This finding argues against theories of imitation in which biological stimuli are treated preferentially and stresses the notion of the IFG as a vital center of general perception-action coupling in the human brain.

  10. Intelligent virtual agents as language trainers facilitate multilingualism.

    Science.gov (United States)

    Macedonia, Manuela; Groher, Iris; Roithmayr, Friedrich

    2014-01-01

    intelligent virtual agents (IVAs) with human appearance and the capability to teach foreign language vocabulary. We report results from studies that we have conducted with Billie, an IVA employed as a vocabulary trainer, as well as research findings on the acceptance of the agent as a trainer by adults and children. The results show that Billie can train humans as well as a human teacher can and that both adults and children accept the IVA as a trainer. The advantages of IVAs are multiple. First, their teaching methods can be based on neuropsychological research findings concerning memory and learning practice. Second, virtual teachers can provide individualized training. Third, they coach users during training, are always supportive, and motivate learners to train. Fourth, agents will reside in the user's mobile devices and thus be at the user's disposal everywhere and anytime. Agents in apps will make foreign language training accessible to anybody at low cost. This will enable people around the world, including physically, financially, and geographically disadvantaged persons, to learn a foreign language and help to facilitate multilingualism.

  11. Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

    International Nuclear Information System (INIS)

    Inoue-Toyoda, Maki; Kato, Kohsuke; Nagata, Kyosuke; Yoshikawa, Hiroyuki

    2015-01-01

    Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX

  12. Expert and novice facilitated modelling

    DEFF Research Database (Denmark)

    Tavella, Elena; Papadopoulos, Thanos

    2015-01-01

    , and empirically supports the claim that facilitation skills can be taught to participants to enable them to self-facilitate workshops. Differences were also found, which led to the introduction of a new dimension—‘internal versus external’ facilitation. The implications of our findings for effective training...

  13. Biomarkers of cigarette smoking and DNA methylating agents: Raman, SERS and DFT study of 3-methyladenine and 7-methyladenine

    Science.gov (United States)

    Harroun, Scott G.; Zhang, Yaoting; Chen, Tzu-Heng; Ku, Ching-Rong; Chang, Huan-Tsung

    2017-04-01

    3-Methyladenine and 7-methyladenine are biomarkers of DNA damage from exposure to methylating agents. For example, the concentration of 3-methyladenine increases significantly in the urine of cigarette smokers. Surface-enhanced Raman spectroscopy (SERS) has shown much potential for detection of biomolecules, including DNA. Much work has been dedicated to the canonical nucleobases, with comparatively fewer investigations of modified DNA and modified DNA nucleobases. Herein, Raman spectroscopy and SERS are used to examine the adsorption orientations of 3-methyladenine and 7-methyladenine on Ag nanoparticles. Density functional theory (DFT) calculations at the B3LYP level are used to support the conclusions via simulated spectra of the nucleobases and of Ag+/nucleobase complexes. The results herein show that 7-methyladenine adsorbs upright via its N3 and N9 atoms side, similarly to adenine. 3-Methyladenine adsorbs in a very tilted or flat orientation on the Ag nanoparticles. These findings will be useful for future SERS or other nanoparticle-based bioanalytical assays for detection of these methyladenines or other modified nucleobases.

  14. Bacterial Multidrug Efflux Pumps of the Major Facilitator Superfamily as Targets for Modulation.

    Science.gov (United States)

    Kumar, Sanath; He, Guixin; Kakarla, Prathusha; Shrestha, Ugina; Ranjana, K C; Ranaweera, Indrika; Willmon, T Mark; Barr, Sharla R; Hernandez, Alberto J; Varela, Manuel F

    2016-01-01

    Causative agents of infectious disease that are multidrug resistant bacterial pathogens represent a serious public health concern due to the increasingly difficult nature of achieving efficacious clinical treatments. Of the various acquired and intrinsic antimicrobial agent resistance determinants, integral-membrane multidrug efflux pumps of the major facilitator superfamily constitute a major mechanism of bacterial resistance. The major facilitator superfamily (MFS) encompasses thousands of known related secondary active and passive solute transporters, including multidrug efflux pumps, from bacteria to humans. This review article addresses recent developments involving the targeting by various modulators of bacterial multidrug efflux pumps from the major facilitator superfamily. It is currently of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of therapeutic agents against recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.

  15. Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir

    International Nuclear Information System (INIS)

    Santiago, Francisco; Oguma, Junya; Brown, Anthony M.C.; Laurence, Jeffrey

    2012-01-01

    Highlights: ► First demonstration of direct role for noncanonical Wnt in osteoclast differentiation. ► Demonstration of Ryk as a Wnt5a/b receptor in inhibition of canonical Wnt signaling. ► Modulation of noncanonical Wnt signaling by a clinically important drug, ritonavir. ► Establishes a mechanism for an important clinical problem: HIV-associated bone loss. -- Abstract: Wnt proteins that signal via the canonical Wnt/β-catenin pathway directly regulate osteoblast differentiation. In contrast, most studies of Wnt-related effects on osteoclasts involve indirect changes. While investigating bone mineral density loss in the setting of human immunodeficiency virus (HIV) infection and its treatment with the protease inhibitor ritonavir (RTV), we observed that RTV decreased nuclear localization of β-catenin, critical to canonical Wnt signaling, in primary human and murine osteoclast precursors. This occurred in parallel with upregulation of Wnt5a and Wnt5b transcripts. These Wnts typically stimulate noncanonical Wnt signaling, and this can antagonize the canonical Wnt pathway in many cell types, dependent upon Wnt receptor usage. We now document RTV-mediated upregulation of Wnt5a/b protein in osteoclast precursors. Recombinant Wnt5b and retrovirus-mediated expression of Wnt5a enhanced osteoclast differentiation from human and murine monocytic precursors, processes facilitated by RTV. In contrast, canonical Wnt signaling mediated by Wnt3a suppressed osteoclastogenesis. Both RTV and Wnt5b inhibited canonical, β-catenin/T cell factor-based Wnt reporter activation in osteoclast precursors. RTV- and Wnt5-induced osteoclast differentiation were dependent upon the receptor-like tyrosine kinase Ryk, suggesting that Ryk may act as a Wnt5a/b receptor in this context. This is the first demonstration of a direct role for Wnt signaling pathways and Ryk in regulation of osteoclast differentiation, and its modulation by a clinically important drug, ritonavir. These studies

  16. Neural substrates of social facilitation effects on incentive-based performance

    Science.gov (United States)

    Chib, Vikram S; Adachi, Ryo; O’Doherty, John P

    2018-01-01

    Abstract Throughout our lives we must perform tasks while being observed by others. Previous studies have shown that the presence of an audience can cause increases in an individual’s performance as compared to when they are not being observed—a phenomenon called ‘social facilitation’. However, the neural mechanisms underlying this effect, in the context of skilled-task performance for monetary incentives, are not well understood. We used functional magnetic resonance imaging to monitor brain activity while healthy human participants performed a skilled-task during conditions in which they were paid based on their performance and observed and not observed by an audience. We found that during social facilitation, social signals represented in the dorsomedial prefrontal cortex (dmPFC) enhanced reward value computations in ventromedial prefrontal cortex (vmPFC). We also found that functional connectivity between dmPFC and ventral striatum was enhanced when participants exhibited social facilitation effects, indicative of a means by which social signals serve to modulate brain regions involved in regulating behavioral motivation. These findings illustrate how neural processing of social judgments gives rise to the enhanced motivational state that results in social facilitation of incentive-based performance. PMID:29648653

  17. Reward association facilitates distractor suppression in human visual search.

    Science.gov (United States)

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Purine 3':5'-cyclic nucleotides with the nucleobase in a syn orientation: cAMP, cGMP and cIMP.

    Science.gov (United States)

    Řlepokura, Katarzyna Anna

    2016-06-01

    Purine 3':5'-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3':5'-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3':5'-cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3':5'-cyclic phosphate 0.3-hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3':5'-cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H11N5O7P(-)·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3':5'-cyclic phosphate tetrahydrate, Na(+)·C10H10N4O7P(-)·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP(-) in (IV) and cIMP(-) in (V)] are syn conformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib-H...Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn-anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter-nucleotide contacts in (I)-(V) have been systematized in terms of the chemical groups involved. All five structures display three-dimensional hydrogen-bonded networks.

  19. One-electron oxidation of DNA: mechanism and consequences.

    Science.gov (United States)

    Schuster, Gary B

    2009-01-01

    All living organisms store the information necessary to maintain life in their DNA. Any process that damages DNA and causes loss or corruption of that information threatens the viability of the organism. One-electron oxidation is such a process. Loss of an electron from DNA generates a radical cation that is located primarily on its nucleobases. The radical cation migrates reversibly through duplex DNA by hopping until it is eventually trapped in an irreversible chemical reaction. The particular sequence of nucleobases in a DNA oligomer determines both the efficiency of hopping and the specific location and nature of the damaging chemical reaction. In its normal aqueous solutions, DNA is a polyanion because of the negative charge carried by its phosphate groups. Counter ions (typically Na(+)) to the phosphate groups play an important role in facilitating both the migration of the radical cation and in its eventual reaction with H(2)O. Irreversible reaction of a radical cation with H(2)O in duplex DNA occurs preferentially at the most reactive site. In normal DNA that is comprised of the four common DNA nucleobases, reaction occurs most commonly at a guanine and results in its conversion primarily to 8-oxo-7,8-dihydroguanine (8-OxoG). Both electronic and steric effects control the outcome of this process. If the DNA oligomer does not contain a suitable guanine, then reaction of the radical cation occurs at the thymine of a TT step primarily by a tandem process. The general outcomes revealed in the one-electron oxidation of DNA oligomers in solution appear to be generally valid also for more complex DNA structures and for the cellular DNA of living organisms.

  20. Developing facilitation skills--a narrative.

    Science.gov (United States)

    Newton, Jennifer M

    2003-07-01

    Effective facilitation has been identified in the literature as one of three elements, along with context and evidence, that have a dynamic and coexisting relationship to enable the successful uptake of evidence into practice. This paper presents an overview of the concept of facilitation within the context of practice development, ahead of a personal and professional reflective account of a 'developing facilitator'. In the summer of 2001, the author was instrumental in organising the first Practice Development School in Melbourne. Thrown in at the deep end, she found herself co-facilitating with an experienced practice developer from the United Kingdom. Having never facilitated in the arena of an action learning group, nor worked in the field of practice development, there was initially a sense of impending overload and drowning in the new knowledge and skills that needed to be acquired. Drawing upon the work of narrative inquiry the author shares her experiences in the anticipation that in telling her story it will assist others in their journey of becoming a facilitator.

  1. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

    Science.gov (United States)

    Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

    2017-05-01

    challenging due to the difficulty of recapitulating the complex angiogenic extracellular matrix (ECM) environment. Herein, we present a simple and practical method to create an angiogenic 3D environment via incorporation of human lung fibroblast-derived matrix (hFDM) into collagen hydrogel. We found that hFDM offers a significantly improved angiogenic microenvironment for HUVECs on 2D substrates and in 3D construct. A synergistic effect of hFDM and angiogenic growth factors has been well confirmed in 3D condition. The prevascularized 3D collagen constructs also facilitate skin wound healing. We believe that current system should be a convenient and powerful platform in engineering 3D vasculature in vitro, and in delivering cells for therapeutic purposes in vivo. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Medical students' and facilitators' experiences of an Early Professional Contact course: active and motivated students, strained facilitators.

    Science.gov (United States)

    von Below, Bernhard; Hellquist, Gunilla; Rödjer, Stig; Gunnarsson, Ronny; Björkelund, Cecilia; Wahlqvist, Mats

    2008-12-02

    Today, medical students are introduced to patient contact, communication skills, and clinical examination in the preclinical years of the curriculum with the purpose of gaining clinical experience. These courses are often evaluated from the student perspective. Reports with an additional emphasis on the facilitator perspective are scarce. According to constructive alignment, an influential concept from research in higher education, the learning climate between students and teachers is also of great importance. In this paper, we approach the learning climate by studying both students' and facilitators' course experiences.In 2001, a new "Early Professional Contact" longitudinal strand through term 1-4, was introduced at the Sahlgrenska Academy, University of Gothenburg, Sweden. General practitioners and hospital specialists were facilitators.The aim of this study was to assess and analyse students' and clinical facilitators' experiences of the Early Professional Contact course and to illuminate facilitators' working conditions. Inspired by a Swedish adaptation of the Course Experience Questionnaire, an Early Professional Contact Questionnaire was constructed. In 2003, on the completion of the first longitudinal strand, a student and facilitator version was distributed to 86 students and 21 facilitators. In the analysis, both Chi-square and the Mann-Whitney tests were used. Sixty students (70%) and 15 facilitators (71%) completed the questionnaire. Both students and facilitators were satisfied with the course. Students reported gaining iiration for their future work as doctors along with increased confidence in meeting patients. They also reported increased motivation for biomedical studies. Differences in attitudes between facilitators and students were found. Facilitators experienced a greater workload, less reasonable demands and less support, than students. In this project, a new Early Professional Contact course was analysed from both student and facilitator

  3. Medical students' and facilitators' experiences of an Early Professional Contact course: Active and motivated students, strained facilitators

    Directory of Open Access Journals (Sweden)

    Gunnarsson Ronny

    2008-12-01

    Full Text Available Abstract Background Today, medical students are introduced to patient contact, communication skills, and clinical examination in the preclinical years of the curriculum with the purpose of gaining clinical experience. These courses are often evaluated from the student perspective. Reports with an additional emphasis on the facilitator perspective are scarce. According to constructive alignment, an influential concept from research in higher education, the learning climate between students and teachers is also of great importance. In this paper, we approach the learning climate by studying both students' and facilitators' course experiences. In 2001, a new "Early Professional Contact" longitudinal strand through term 1–4, was introduced at the Sahlgrenska Academy, University of Gothenburg, Sweden. General practitioners and hospital specialists were facilitators. The aim of this study was to assess and analyse students' and clinical facilitators' experiences of the Early Professional Contact course and to illuminate facilitators' working conditions. Methods Inspired by a Swedish adaptation of the Course Experience Questionnaire, an Early Professional Contact Questionnaire was constructed. In 2003, on the completion of the first longitudinal strand, a student and facilitator version was distributed to 86 students and 21 facilitators. In the analysis, both Chi-square and the Mann-Whitney tests were used. Results Sixty students (70% and 15 facilitators (71% completed the questionnaire. Both students and facilitators were satisfied with the course. Students reported gaining iiration for their future work as doctors along with increased confidence in meeting patients. They also reported increased motivation for biomedical studies. Differences in attitudes between facilitators and students were found. Facilitators experienced a greater workload, less reasonable demands and less support, than students. Conclusion In this project, a new Early

  4. Training facilitators and supervisors

    DEFF Research Database (Denmark)

    Kjær, Louise Binow; O Connor, Maja; Krogh, Kristian

    At the Master’s program in Medicine at Aarhus University, Denmark, we have developed a faculty development program for facilitators and supervisors in 4 progressing student modules in communication, cooperation, and leadership. 1) A course for module 1 and 3 facilitators inspired by the apprentic...

  5. Barriers and facilitators to establishing a national public health observatory

    Directory of Open Access Journals (Sweden)

    Shalini Pooransingh

    Full Text Available OBJECTIVE: To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO in Trinidad and Tobago. METHODS: A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. RESULTS: The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1 provide information to support evidence-informed decision-making for health policy and strategic planning; 2 facilitate data management by establishing data policies, procedures, and standards; 3 increase the use of data by synthesizing and disseminating information; and 4 provide data for benchmarking. However, a number of barriers were identified, including 1 the perception that data collection is not valued; 2 untimely availability of data; 3 limited data synthesis, dissemination, and utilization to inform decision-making; and 4 challenges related to the allocation of human resources and existing information technology. CONCLUSIONS: Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean.

  6. Barriers and facilitators to establishing a national public health observatory.

    Science.gov (United States)

    Pooransingh, Shalini; Misir, Akenath; Ramdath, Dan; Ramsewak, Samuel; Jaglal, Susan; Cameron, Cathy; Goel, Vivek

    2015-11-01

    To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO) in Trinidad and Tobago. A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1) provide information to support evidence-informed decision-making for health policy and strategic planning; 2) facilitate data management by establishing data policies, procedures, and standards; 3) increase the use of data by synthesizing and disseminating information; and 4) provide data for benchmarking. However, a number of barriers were identified, including 1) the perception that data collection is not valued; 2) untimely availability of data; 3) limited data synthesis, dissemination, and utilization to inform decision-making; and 4) challenges related to the allocation of human resources and existing information technology. Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean.

  7. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    LENUS (Irish Health Repository)

    Roche, Richard Ap

    2009-01-01

    BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal\\/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA\\/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  8. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

    Directory of Open Access Journals (Sweden)

    Prendergast Julie

    2009-11-01

    Full Text Available Abstract Background Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1 engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.. An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS was used to measure metabolite levels in seven voxels of interest (VOIs (including hippocampus before and after learning. Results Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho ratio. Conclusion Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  9. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    Science.gov (United States)

    Roche, Richard Ap; Mullally, Sinéad L; McNulty, Jonathan P; Hayden, Judy; Brennan, Paul; Doherty, Colin P; Fitzsimons, Mary; McMackin, Deirdre; Prendergast, Julie; Sukumaran, Sunita; Mangaoang, Maeve A; Robertson, Ian H; O'Mara, Shane M

    2009-11-20

    Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho) ratio. Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  10. Happy creativity: Listening to happy music facilitates divergent thinking.

    Science.gov (United States)

    Ritter, Simone M; Ferguson, Sam

    2017-01-01

    Creativity can be considered one of the key competencies for the twenty-first century. It provides us with the capacity to deal with the opportunities and challenges that are part of our complex and fast-changing world. The question as to what facilitates creative cognition-the ability to come up with creative ideas, problem solutions and products-is as old as the human sciences, and various means to enhance creative cognition have been studied. Despite earlier scientific studies demonstrating a beneficial effect of music on cognition, the effect of music listening on creative cognition has remained largely unexplored. The current study experimentally tests whether listening to specific types of music (four classical music excerpts systematically varying on valance and arousal), as compared to a silence control condition, facilitates divergent and convergent creativity. Creativity was higher for participants who listened to 'happy music' (i.e., classical music high on arousal and positive mood) while performing the divergent creativity task, than for participants who performed the task in silence. No effect of music was found for convergent creativity. In addition to the scientific contribution, the current findings may have important practical implications. Music listening can be easily integrated into daily life and may provide an innovative means to facilitate creative cognition in an efficient way in various scientific, educational and organizational settings when creative thinking is needed.

  11. Online interprofessional education facilitation: A scoping review.

    Science.gov (United States)

    Evans, Sherryn Maree; Ward, Catherine; Reeves, Scott

    2018-04-22

    The use of online media to deliver interprofessional education (IPE) is becoming more prevalent across health professions education settings. Facilitation of IPE activities is known to be critical to the effective delivery of IPE, however, specifics about the nature of online IPE facilitation remains unclear. To explore the health professions education literature to understand the extent, range and nature of research on online IPE facilitation. Scoping review methodology was used to guide a search of four electronic databases for relevant papers. Of the 2095 abstracts initially identified, after screening of both abstracts and full-text papers, 10 studies were selected for inclusion in this review. Following abstraction of key information from each study, a thematic analysis was undertaken. Three key themes emerged to describe the nature of the IPE facilitation literature: (1) types of online IPE facilitation contributions, (2) the experience of online IPE facilitation and (3) personal outcomes of online IPE facilitation. These IPE facilitation themes were particularly focused on facilitation of interprofessional student teams on an asynchronous basis. While the included studies provide some insight into the nature of online IPE facilitation, future research is needed to better understand facilitator contributions, and the facilitation experience and associated outcomes, both relating to synchronous and asynchronous online environments.

  12. Ancient humans and the origin of modern humans.

    Science.gov (United States)

    Kelso, Janet; Prüfer, Kay

    2014-12-01

    Recent advances in sequencing technologies and molecular methods have facilitated the sequencing of DNA from ancient human remains which has, in turn, provided unprecedented insight into human history. Within the past 4 years the genomes of Neandertals and Denisovans, as well as the genomes of at least two early modern humans, have been sequenced. These sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from Neandertals into modern human populations outside of Africa, and admixture from Denisovans into modern human populations in Oceania. Recent results indicate that some of these introgressed regions may have been advantageous for modern humans as they expanded into new regions outside of Africa. Copyright © 2014. Published by Elsevier Ltd.

  13. Intelligent Virtual Agents as Language Trainers Facilitate Multilingualism

    Directory of Open Access Journals (Sweden)

    Manuela eMacedonia

    2014-04-01

    Full Text Available In this paper we introduce a new generation of language trainers: intelligent virtual agents (IVAs with human appearance and the capability to teach foreign language vocabulary. We report results from studies that we have conducted with Billie, an IVA employed as a vocabulary trainer, as well as research findings on the acceptance of the agent as a trainer by adults and children. The results show that Billie can train humans as well as a human teacher can and that both adults and children accept the IVA as a trainer. The advantages of IVAs are multiple. First, their teaching methods can be based on neuropsychological research findings concerning memory and learning practice. Second, virtual teachers can provide individualized training. Third, they coach users during training, are always supportive, and motivate learners to train. Fourth, agents will reside in the user’s mobile devices and thus be at the user’s disposal everywhere and anytime. Agents in apps will make foreign language training accessible to anybody at low cost. This will enable people around the world, including physically, financially and geographically disadvantaged persons, to learn a foreign language and help to facilitate multilingualism.

  14. Augmented Reality as a Visualizing facilitator in Nursing Education

    DEFF Research Database (Denmark)

    Rahn, Annette; Kjærgaard, Hanne Wacher

    2014-01-01

    Title: Augmented Reality as a visualizing facilitator in nursing education Background: Understanding the workings of the biological human body is as complex as the body itself, and because of their complexity, the phenomena of respiration and lung anatomy pose a special problem for nursing students......’ understanding within anatomy and physiology. Aim: Against this background, the current project set out to investigate how and to what extent the application of augmented reality (AR) could help students gain a better understanding through an increased focus on contextualized visualization. The overall aim...

  15. ATP-dependent human RISC assembly pathways.

    Science.gov (United States)

    Yoda, Mayuko; Kawamata, Tomoko; Paroo, Zain; Ye, Xuecheng; Iwasaki, Shintaro; Liu, Qinghua; Tomari, Yukihide

    2010-01-01

    The assembly of RNA-induced silencing complex (RISC) is a key process in small RNA-mediated gene silencing. In humans, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are incorporated into RISCs containing the Argonaute (AGO) subfamily proteins Ago1-4. Previous studies have proposed that, unlike Drosophila melanogaster RISC assembly pathways, human RISC assembly is coupled with dicing and is independent of ATP. Here we show by careful reexamination that, in humans, RISC assembly and dicing are uncoupled, and ATP greatly facilitates RISC loading of small-RNA duplexes. Moreover, all four human AGO proteins show remarkably similar structural preferences for small-RNA duplexes: central mismatches promote RISC loading, and seed or 3'-mid (guide position 12-15) mismatches facilitate unwinding. All these features of human AGO proteins are highly reminiscent of fly Ago1 but not fly Ago2.

  16. Coal export facilitation

    International Nuclear Information System (INIS)

    Eeles, L.

    1998-01-01

    There is a wide range of trade barriers, particularly tariffs, in current and potential coal market. Commonwealth departments in Australia play a crucial role in supporting government industry policies. This article summarises some of more recent activities of the Department of Primary Industries and Energy (DPIE) in facilitating the export of Australian Coals. Coal export facilitation activities are designed to assist the Australian coal industry by directing Commonwealth Government resources towards issues which would be inappropriate or difficult for the industry to address itself

  17. Can training improve human performance

    International Nuclear Information System (INIS)

    Waylett, W.J. Jr.

    1986-01-01

    The nuclear industry has made a significant commitment to improve training through the implementation of performance-based training programs. Senior management expects that human performance improvement will result from this significant resource allocation. The author examines this hypothesis and discusses other issues that may interfere with enhancing human performance through training. The integration of quality improvement concepts to support training is also discussed by the author, who was a pioneer facilitator during the development of Florida Power and Light Company's Quality Improvement Program. Critical success factors are proposed based on the author's experience as a plant manager, training manager and quality facilitator

  18. Facilitative root interactions in intercrops

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, H.; Jensen, E.S.

    2005-01-01

    of root architecture, exudation of growth stimulating substances, and biofumigation. Facilitative root interactions are most likely to be of importance in nutrient poor soils and in low-input agroecosystems due to critical interspecific competition for plant growth factors. However, studies from more...... nitrogen transfer between legumes and non-leguminous plants, exploitation of the soil via mycorrhizal fungi and soil-plant processes which alter the mobilisation of plant growth resources such as through exudation of amino acids, extra-cellular enzymes, acidification, competition-induced modification......Facilitation takes place when plants ameliorate the environment of their neighbours, and increase their growth and survival. Facilitation occurs in natural ecosystems as well as in agroecosystems. We discuss examples of facilitative root interactions in intercropped agroecosystems; including...

  19. Facilitating Multiple Intelligences Through Multimodal Learning Analytics

    Directory of Open Access Journals (Sweden)

    Ayesha PERVEEN

    2018-01-01

    Full Text Available This paper develops a theoretical framework for employing learning analytics in online education to trace multiple learning variations of online students by considering their potential of being multiple intelligences based on Howard Gardner’s 1983 theory of multiple intelligences. The study first emphasizes the need to facilitate students as multiple intelligences by online education systems and then suggests a framework of the advanced form of learning analytics i.e., multimodal learning analytics for tracing and facilitating multiple intelligences while they are engaged in online ubiquitous learning. As multimodal learning analytics is still an evolving area, it poses many challenges for technologists, educationists as well as organizational managers. Learning analytics make machines meet humans, therefore, the educationists with an expertise in learning theories can help technologists devise latest technological methods for multimodal learning analytics and organizational managers can implement them for the improvement of online education. Therefore, a careful instructional design based on a deep understanding of students’ learning abilities, is required to develop teaching plans and technological possibilities for monitoring students’ learning paths. This is how learning analytics can help design an adaptive instructional design based on a quick analysis of the data gathered. Based on that analysis, the academicians can critically reflect upon the quick or delayed implementation of the existing instructional design based on students’ cognitive abilities or even about the single or double loop learning design. The researcher concludes that the online education is multimodal in nature, has the capacity to endorse multiliteracies and, therefore, multiple intelligences can be tracked and facilitated through multimodal learning analytics in an online mode. However, online teachers’ training both in technological implementations and

  20. Can human eyes prevent perceptual narrowing for monkey faces in human infants?

    Science.gov (United States)

    Damon, Fabrice; Bayet, Laurie; Quinn, Paul C; Hillairet de Boisferon, Anne; Méary, David; Dupierrix, Eve; Lee, Kang; Pascalis, Olivier

    2015-07-01

    Perceptual narrowing has been observed in human infants for monkey faces: 6-month-olds can discriminate between them, whereas older infants from 9 months of age display difficulty discriminating between them. The difficulty infants from 9 months have processing monkey faces has not been clearly identified. It could be due to the structural characteristics of monkey faces, particularly the key facial features that differ from human faces. The current study aimed to investigate whether the information conveyed by the eyes is of importance. We examined whether the presence of Caucasian human eyes in monkey faces allows recognition to be maintained in 6-month-olds and facilitates recognition in 9- and 12-month-olds. Our results revealed that the presence of human eyes in monkey faces maintains recognition for those faces at 6 months of age and partially facilitates recognition of those faces at 9 months of age, but not at 12 months of age. The findings are interpreted in the context of perceptual narrowing and suggest that the attenuation of processing of other-species faces is not reversed by the presence of human eyes. © 2015 Wiley Periodicals, Inc.

  1. Role enactment of facilitation in primary care

    DEFF Research Database (Denmark)

    Due, Tina Drud; Thorsen, Thorkil; Waldorff, Frans Boch

    2017-01-01

    facilitation visits in 13 practice settings and had interviews and focus groups with facilitators. We applied an explorative approach in data collection and analysis, and conducted an inductive thematic analysis. RESULTS: The facilitators mainly enacted four facilitator roles: teacher, super user, peer...

  2. Role enactment of facilitation in primary care

    DEFF Research Database (Denmark)

    Due, Tina Drud; Thorsen, Thorkil; Waldorff, Frans Boch

    2017-01-01

    facilitation visits in 13 practice settings and had interviews and focus groups with facilitators. We applied an explorative approach in data collection and analysis, and conducted an inductive thematic analysis. Results: The facilitators mainly enacted four facilitator roles: teacher, super user, peer...

  3. Structure-function relationship of a plant NCS1 member - Homology modeling and mutagenesis identified residues critical for substrate specificity of PLUTO, a nucleobase transporter from arabidopsis

    KAUST Repository

    Witz, Sandra

    2014-03-12

    Plastidic uracil salvage is essential for plant growth and development. So far, PLUTO, the plastidic nucleobase transporter from Arabidopsis thaliana is the only known uracil importer at the inner plastidic membrane which represents the permeability barrier of this organelle. We present the first homology model of PLUTO, the sole plant NCS1 member from Arabidopsis based on the crystal structure of the benzyl hydantoin transporter MHP1 from Microbacterium liquefaciens and validated by molecular dynamics simulations. Polar side chains of residues Glu-227 and backbones of Val-145, Gly-147 and Thr-425 are proposed to form the binding site for the three PLUTO substrates uracil, adenine and guanine. Mutational analysis and competition studies identified Glu-227 as an important residue for uracil and to a lesser extent for guanine transport. A differential response in substrate transport was apparent with PLUTO double mutants E227Q G147Q and E227Q T425A, both of which most strongly affected adenine transport, and in V145A G147Q, which markedly affected guanine transport. These differences could be explained by docking studies, showing that uracil and guanine exhibit a similar binding mode whereas adenine binds deep into the catalytic pocket of PLUTO. Furthermore, competition studies confirmed these results. The present study defines the molecular determinants for PLUTO substrate binding and demonstrates key differences in structure-function relations between PLUTO and other NCS1 family members. 2014 Witz et al.

  4. Crop domestication facilitated rapid geographic expansion of a specialist pollinator, the squash bee Peponapis pruinosa

    Science.gov (United States)

    Over the past 10,000 years, humans have facilitated rapid range expansions of animal, plants and microorganisms, often accompanying agriculture’s spread. Three squash species were early domesticates in the New World. Their spreading cultivation out of the Southwest across much of today’s USA has bee...

  5. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    Science.gov (United States)

    Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

  6. Practical-theological facilitation as skilled helping

    Directory of Open Access Journals (Sweden)

    Elmo Pienaar

    2013-11-01

    Full Text Available The article discussed the idea of skilled helping in relation to what has been put forward as practical theological facilitation. It has been argued that various helping relationships, amongst which the author refers to coaching, facilitation, and therapy has more in common than what differentiates them if epistemology is viewed as a unifying concept. As such the scope of practical theology in terms of the contexts and themes in which it might be involved is said to widen. The public dimension of the organisational context, more so than the congregational context, has been put forward as an important habitus of practical-theological facilitation. The organisational involvement of the practical-theological facilitator in terms of professional-vocational skilled helping takes on an actual role through facilitation and other helping modalities.

  7. The human and fire connection

    Science.gov (United States)

    Theresa B. Jain

    2014-01-01

    We refer to fire as a natural disturbance, but unlike other disturbances such as forest insects and diseases, fire has had an intimate relationship with humans. Fire facilitated human evolution over two million years ago when our ancestors began to use fire to cook. Fire empowered our furbearers to adapt to cold climates, allowing humans to disperse and settle into...

  8. Facilitation of decommissioning light water reactors

    International Nuclear Information System (INIS)

    Moore, E.B. Jr.

    1979-12-01

    Information on design features, special equipment, and construction methods useful in the facilitation of decommissioning light water reactors is presented. A wide range of facilitation methods - from improved documentation to special decommissioning tools and techniques - is discussed. In addition, estimates of capital costs, cost savings, and radiation dose reduction associated with these facilitation methods are given

  9. Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

    Science.gov (United States)

    Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

    2016-01-01

    Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

  10. BTFS: The Border Trade Facilitation System

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, L.R.

    1999-03-18

    The author demonstrates the Border Trade Facilitation System (BTFS), an agent-based bilingual e-commerce system built to expedite the regulation, control, and execution of commercial trans-border shipments during the delivery phase. The system was built to serve maquila industries at the US/Mexican border. The BTFS uses foundation technology developed here at Sandia Laboratories' Advanced Information Systems Lab (AISL), including a distributed object substrate, a general-purpose agent development framework, dynamically generated agent-human interaction via the World-Wide Web, and a collaborative agent architecture. This technology is also the substrate for the Multi-Agent Simulation Management System (MASMAS) proposed for demonstration at this conference. The BTFS executes authenticated transactions among agents performing open trading over the Internet. With the BTFS in place, one could conduct secure international transactions from any site with an Internet connection and a web browser. The BTFS is currently being evaluated for commercialization.

  11. Theoretical investigation of nuclear quadrupole interactions in DNA at first-principles level

    Energy Technology Data Exchange (ETDEWEB)

    Mahato, Dip N. [State University of New York at Albany, Department of Physics (United States); Dubey, Archana [University of Central Florida, Department of Physics (United States); Pink, R. H. [State University of New York at Albany, Department of Physics (United States); Scheicher, R. H. [Uppsala University, Condensed Matter Theory Group, Department of Physics and Materials Science (Sweden); Badu, S. R. [State University of New York at Albany, Department of Physics (United States); Nagamine, K. [University of California at Riverside, Department of Physics (United States); Torikai, E. [Yamanashi University, Department of Electrical Engineering (Japan); Saha, H. P.; Chow, Lee [University of Central Florida, Department of Physics (United States); Huang, M. B. [State University of New York at Albany, College of Nanoscale Science and Engineering (United States); Das, T. P., E-mail: tpd56@albany.edu [State University of New York at Albany, Department of Physics (United States)

    2008-01-15

    We have studied the nuclear quadrupole interactions (NQI) of the {sup 14}N, {sup 17}O and {sup 2}H nuclei in the nucleobases cytosine, adenine, guanine and thymine in the free state as well as when they are bonded to the sugar ring in DNA, simulated through a CH{sub 3} group attached to the nucleobases. The nucleobase uracil, which replaces thymine in RNA, has also been studied. Our results show that there are substantial indirect effects of the bonding with the sugar group in the nucleic acids on the NQI parameters e{sup 2}qQ/h and {eta}. It is hoped that measurements of these NQI parameters in DNA will be available in the future to compare with our predictions. Our results provide the conclusion that for any property dependent on the electronic structures of the nucleic acids, the effects of the bonding between the nucleobases and the nucleic acid backbones have to be included.

  12. Goal-congruent default network activity facilitates cognitive control.

    Science.gov (United States)

    Spreng, R Nathan; DuPre, Elizabeth; Selarka, Dhawal; Garcia, Juliana; Gojkovic, Stefan; Mildner, Judith; Luh, Wen-Ming; Turner, Gary R

    2014-10-15

    Substantial neuroimaging evidence suggests that spontaneous engagement of the default network impairs performance on tasks requiring executive control. We investigated whether this impairment depends on the congruence between executive control demands and internal mentation. We hypothesized that activation of the default network might enhance performance on an executive control task if control processes engage long-term memory representations that are supported by the default network. Using fMRI, we scanned 36 healthy young adult humans on a novel two-back task requiring working memory for famous and anonymous faces. In this task, participants (1) matched anonymous faces interleaved with anonymous face, (2) matched anonymous faces interleaved with a famous face, or (3) matched a famous faces interleaved with an anonymous face. As predicted, we observed a facilitation effect when matching famous faces, compared with anonymous faces. We also observed greater activation of the default network during these famous face-matching trials. The results suggest that activation of the default network can contribute to task performance during an externally directed executive control task. Our findings provide evidence that successful activation of the default network in a contextually relevant manner facilitates goal-directed cognition. Copyright © 2014 the authors 0270-6474/14/3414108-07$15.00/0.

  13. Sub-50 fs excited state dynamics of 6-chloroguanine upon deep ultraviolet excitation.

    Science.gov (United States)

    Mondal, Sayan; Puranik, Mrinalini

    2016-05-18

    The photophysical properties of natural nucleobases and their respective nucleotides are ascribed to the sub-picosecond lifetime of their first singlet states in the UV-B region (260-350 nm). Electronic transitions of the ππ* type, which are stronger than those in the UV-B region, lie at the red edge of the UV-C range (100-260 nm) in all isolated nucleobases. The lowest energetic excited states in the UV-B region of nucleobases have been investigated using a plethora of experimental and theoretical methods in gas and solution phases. The sub-picosecond lifetime of these molecules is not a general attribute of all nucleobases but specific to the five primary nucleobases and a few xanthine and methylated derivatives. To determine the overall UV photostability, we aim to understand the effect of more energetic photons lying in the UV-C region on nucleobases. To determine the UV-C initiated photophysics of a nucleobase system, we chose a halogen substituted purine, 6-chloroguanine (6-ClG), that we had investigated previously using resonance Raman spectroscopy. We have performed quantitative measurements of the resonance Raman cross-section across the Bb absorption band (210-230 nm) and constructed the Raman excitation profiles. We modeled the excitation profiles using Lee and Heller's time-dependent theory of resonance Raman intensities to extract the initial excited state dynamics of 6-ClG within 30-50 fs after photoexcitation. We found that imidazole and pyrimidine rings of 6-ClG undergo expansion and contraction, respectively, following photoexcitation to the Bb state. The amount of distortions of the excited state structure from that of the ground state structure is reflected by the total internal reorganization energy that is determined at 112 cm(-1). The contribution of the inertial component of the solvent response towards the total reorganization energy was obtained at 1220 cm(-1). In addition, our simulation also yields an instantaneous response of the first

  14. Social facilitation of cognition in rhesus monkeys: audience vs. coaction

    Directory of Open Access Journals (Sweden)

    Amélie J. Reynaud

    2015-12-01

    Full Text Available Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect, or a passive spectator (audience effect changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad performed a simple cognitive task consisting in touching images to obtain food treats, alone versus in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however 4 times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

  15. Brug af mindfulness til facilitering

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2011-01-01

    Gennem de senere år er mindfulness gået fra udelukkende at være en eksistentiel praksis til også at være en behandlingsform og senest til også at blive brugt som et praktisk redskab i erhvervslivet. Denne artikel viser, at mindfulness også kan anvendes i forbindelse med facilitering. Facilitering...... er et værktøj, som bruges i arbejdslivet fx til møder og konferencer, hvor en gruppe mennesker er samlet for at lære eller udrette noget sammen. Det nye ved at kombinere mindfulness med facilitering er, at fokus hermed ændres fra individet, som er centrum for den eksistentielle fordybelse eller det...... terapeutiske forløb, til gruppen, som er udgangspunktet i facilitering. Artiklen viser, hvordan mindfulness konkret kan bruges på gruppeniveau og diskuterer samtidig hvilke problemer, der kan være forbundet hermed. Baseret på vores egne erfaringer, diskuterer vi, hvordan mindfulness kan påvirke en gruppes...

  16. Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

    OpenAIRE

    Krstulović, Luka; Ismaili, Hamit; Višnjevac, Aleksandar; Glavaš-Obrovac, Ljubica; Žinić, Biserka

    2012-01-01

    A series of new aliphatic N-sulfonylamidino thymine derivatives containing nucleobase, N-sulfonyl and amidine pharmacophores in the structure were synthesized by Cu(I)-catalyzed threecomponent coupling of 1-propargyl thymine, benzenesulfonyl azides and amines or ammonium salts. Preliminary in vitro antitumor screening (human cervix adenocarcinoma -HeLa and leukemia cells - Jurkat) revealed promising activities of N,N-diethyl- (2) and N-4-cyanobenzyl- (6) derivatives of 4-acetamido...

  17. Laser facilitates vaccination

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2016-01-01

    Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

  18. NCBI nr-aa BLAST: CBRC-ETEL-01-0405 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-0405 gb|EAX10438.1| solute carrier family 23 (nucleobase transporters)..., member 2, isoform CRA_a [Homo sapiens] gb|EAX10440.1| solute carrier family 23 (nucleobase transporters), member 2, isoform CRA_a [Homo sapiens] EAX10438.1 1e-176 90% ...

  19. NCBI nr-aa BLAST: CBRC-ETEL-01-0405 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-0405 ref|XP_001164748.1| PREDICTED: solute carrier family 23 (nucleobase transporters...), member 2 isoform 2 [Pan troglodytes] ref|XP_001164789.1| PREDICTED: solute carrier family 23 (nucleobase transporte...rs), member 2 isoform 3 [Pan troglodytes] XP_001164748.1 1e-176 90% ...

  20. Human DNA polymerase alpha uses a combination of positive and negative selectivity to polymerize purine dNTPs with high fidelity

    Czech Academy of Sciences Publication Activity Database

    Beckman, J.; Kincaid, K.; Hocek, Michal; Spratt, T.; Engels, J.; Cosstick, R.; Kuchta, R. D.

    2007-01-01

    Roč. 46, č. 2 (2007), s. 448-460 ISSN 0006-2960 R&D Projects: GA MŠk LC512 Grant - others:NIH(US) GM54194; NIH(US) TW007372-01; Army Research Office(US) W911NF-05-1-0172; DFG(DE) SFB 579 Institutional research plan: CEZ:AV0Z40550506 Keywords : DNA polymerase * nucleoside triphosphates * modified nucleobases Subject RIV: CC - Organic Chemistry Impact factor: 3.368, year: 2007

  1. Returning to Humanity's Moral Heritages

    Science.gov (United States)

    Narvaez, Darcia

    2016-01-01

    The main arguments of my lecture were how humans are failing themselves and devastating earth's biosphere, at least in part, because they became uncooperative with two key ecological inheritances: raising the young within the human evolved developmental niche and, as part of this, facilitating the development of a deep attachment to, knowledge of…

  2. Electron collisions with biomolecules

    International Nuclear Information System (INIS)

    McKoy, V; Winstead, C

    2008-01-01

    We report on results of recent studies of collisions of low-energy electrons with nucleobases and other DNA constituents. A particular focus of these studies has been the identification and characterization of resonances that play a role in electron attachment leading to strand breaks in DNA. Comparison of the calculated resonance positions with results of electron transmission measurements is quite encouraging. However, the higher-lying π* resonances of the nucleobases appear to be of mixed elastic and core-excited character. Such resonant channel coupling raises the interesting possibility that the higher π*resonances in the nucleobases may promote dissociation of DNA by providing doorway states to triplet excited states.

  3. Multi-level human motion analysis for surveillance applications

    NARCIS (Netherlands)

    Lao, W.; Han, Jungong; With, de P.H.N.; Rabbani, M.; Stevenson, R.L.

    2009-01-01

    In this paper, we study a flexible framework for semantic analysis of human motion from a monocular surveillance video. Successful trajectory estimation and human-body modeling facilitate the semantic analysis of human activities in video sequences. As a first contribution, we propose a flexible

  4. Psychosocial job characteristics and psychological distress / well-being: the mediating role of personal goal facilitation.

    Science.gov (United States)

    Pisanti, Renato; van der Doef, Margot; Maes, Stan; Violani, Cristiano; Lazzari, David

    2016-01-01

    This study examined the mediating role of personal goal facilitation through work (PGFW), defined as perceptions of the extent to which one's job facilitates the attainment of one's personal goals, in the association between psychosocial job characteristics and psychological distress and job-related well-being. Questionnaire data from 217 nurses (84% female, with a mean age of 42.7 years, SD=7.2) were analyzed. Participants completed the following measures: the Leiden Quality of Work Questionnaire for Nurses, Workplace Goal Facilitation Inventory, Maslach Burnout Inventory-Human Services Survey, and Utrecht Work Engagement Scale (short version). A cross-sectional study design was applied. Hierarchical multiple regression analyses were conducted. The results indicated that unfavorable psychosocial job characteristics (high demands, low control, and low social support) were associated with lower PGFW. Furthermore, personal goal facilitation through work explained significant additional variance (from 2 to 11%) in psychological distress (somatic complaints and emotional exhaustion) and job-related well-being (personal accomplishment, job satisfaction, and work engagement), controlling for demographic indicators and psychosocial job characteristics. Finally, the results provided support for the mediating effects of PGFW between all psychosocial job characteristics and all outcomes, except in the case of depersonalization. This study suggests that hindered personal goal facilitation may be a mechanism through which psychosocial job characteristics have a negative impact on employees' well-being.

  5. Facilitation of contrast detection in near-peripheral vision.

    Science.gov (United States)

    Giorgi, Robert G; Soong, Grace P; Woods, Russell L; Peli, Eli

    2004-12-01

    Foveal detection of a Gabor patch (target) is facilitated by collinear, displaced high-contrast flankers. Polat and Sagi reported that the same phenomenon occurred in the periphery, but no data were presented [Proc. Natl. Acad. Sci. 91 (1994) 1206]. Others have found no facilitation in a limited number of conditions tested. To resolve this apparent conflict, we measured lateral facilitation in the near-periphery using a range of stimulus parameters. We found facilitation for a range of target-flanker distances for peripheral eccentricities up to 6 degrees , but the magnitude of the effect was less than found in central vision. Facilitation varied across subjects and with spatial frequency. Flanker contrast had no effect over the range evaluated (10-80%). Equal facilitation was found for two global arrangements of the stimulus pattern. Facilitation was found using a temporal, but not a spatial two-alternative forced-choice paradigm, accounting for the different results among previous studies. This finding supports previous indications of the role of attention in altering such facilitation. The value of facilitation from lateral interactions for persons with central vision impairment, who have to shift their attention to a peripheral locus constantly, needs to be examined.

  6. Facilitating peer learning in study groups

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2009-01-01

    In 2008 University of Aarhus, Denmark, issued a report concerning student experience with the study environment. Among the university's eight faculties, the Danish School of Education (DPU) held the sad record of having the lowest student well-being. This led to an action research project...... 'Facilitating study environment' at one of DPU's educations in spring 2009. The pilot project consisted of three elements: Facilitated study groups, a student bar with facilitated activities, and academic identity events. Subsequently, we have studied students' experiences with the project. This paper outlines...... the preliminary results from the facilitated study groups. After one term (February-May), student satisfaction with both the social and the disciplinary environment had increased. The project shows how academic and social integration can be achieved with minimum faculty member involvement. This is done by relying...

  7. The Politics of Naming: Critiquing "Learner-Centred" and "Teacher as Facilitator" in English Language and Humanities Classrooms

    Science.gov (United States)

    Ha, Phan Le

    2014-01-01

    "Learner-centred" and "teacher as facilitator," among the most influential concepts (re)shaping education over the past decades, are often represented as bringing democratic participation, equality, and empowerment to learners and helping transform and liberate societies. At the same time, these concepts are constructed in…

  8. Challenges of Research and Human Capital Development in Nigeria

    Science.gov (United States)

    Chikwe, Christian K.; Ogidi, Reuben C.; Nwachukwu, K.

    2015-01-01

    The paper discussed the challenges of research and human capital development in Nigeria. Research and human capital development are critical to the development of any nation. Research facilitates human capital development. A high rating in human capital development indices places a country among the leading countries of the world. The paper…

  9. How Facilitation May Interfere with Ecological Speciation

    Directory of Open Access Journals (Sweden)

    P. Liancourt

    2012-01-01

    Full Text Available Compared to the vast literature linking competitive interactions and speciation, attempts to understand the role of facilitation for evolutionary diversification remain scarce. Yet, community ecologists now recognize the importance of positive interactions within plant communities. Here, we examine how facilitation may interfere with the mechanisms of ecological speciation. We argue that facilitation is likely to (1 maintain gene flow among incipient species by enabling cooccurrence of adapted and maladapted forms in marginal habitats and (2 increase fitness of introgressed forms and limit reinforcement in secondary contact zones. Alternatively, we present how facilitation may favour colonization of marginal habitats and thus enhance local adaptation and ecological speciation. Therefore, facilitation may impede or pave the way for ecological speciation. Using a simple spatially and genetically explicit modelling framework, we illustrate and propose some first testable ideas about how, when, and where facilitation may act as a cohesive force for ecological speciation. These hypotheses and the modelling framework proposed should stimulate further empirical and theoretical research examining the role of both competitive and positive interactions in the formation of incipient species.

  10. Anti-parallel triplexes

    DEFF Research Database (Denmark)

    Kosbar, Tamer R.; Sofan, Mamdouh A.; Waly, Mohamed A.

    2015-01-01

    about 6.1 °C when the TFO strand was modified with Z and the Watson-Crick strand with adenine-LNA (AL). The molecular modeling results showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72 Å, respectively) was formed between the protonated 3-aminopropyn-1-yl chain and one...... of the phosphate groups in Watson-Crick strand. Also, it was shown that the nucleobase Y made a good stacking and binding with the other nucleobases in the TFO and Watson-Crick duplex, respectively. In contrast, the nucleobase Z with LNA moiety was forced to twist out of plane of Watson-Crick base pair which......The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel triplexes modified with these two monomers is determined. When, the anti...

  11. The Human-Robot Interaction Operating System

    Science.gov (United States)

    Fong, Terrence; Kunz, Clayton; Hiatt, Laura M.; Bugajska, Magda

    2006-01-01

    In order for humans and robots to work effectively together, they need to be able to converse about abilities, goals and achievements. Thus, we are developing an interaction infrastructure called the "Human-Robot Interaction Operating System" (HRI/OS). The HRI/OS provides a structured software framework for building human-robot teams, supports a variety of user interfaces, enables humans and robots to engage in task-oriented dialogue, and facilitates integration of robots through an extensible API.

  12. Facilitation Skills for Library Professionals

    OpenAIRE

    O'Shea, Anne; Matheson, Laura

    2010-01-01

    Session summary: Brainstorming, problem-solving, team-building and group communication – all of these things can be made easier through facilitation! Come to this fun, interactive workshop to learn techniques and exercises to boost your group meetings. Taught by two information professionals with formal facilitation training and experience, this workshop will give you theory, hands-on practice time and feedback. What participants will learn: Participants will learn techniques to he...

  13. GRAFISK FACILITERING - En magtanalyse af styringen i konsulentværktøjet grafisk facilitering

    OpenAIRE

    Munch, Anna; Boholt, Marianne

    2012-01-01

    Abstract The topic of this thesis is the relatively new consultancy tool of graphic facilitation (GF). GF is a method that combines hand-drawn images and big picture thinking. A graphic facilitator leads a group through a process that results in visual output such as a poster or pamphlet. Our thesis analyses this management tool from a power perspective in an attempt to determine the power relations inherent in its practice. Our theoretical basis is French philosopher Michel Foucault’s theory...

  14. Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η.

    Science.gov (United States)

    O'Flaherty, D K; Patra, A; Su, Y; Guengerich, F P; Egli, M; Wilds, C J

    2016-08-01

    DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O 4 -Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4- O 4 bond on processing by human DNA polymerase η (hPol η ) was studied for oligonucleotides containing O 4 -methylthymidine, O 4 -ethylthymidine, and analogs restricting the O 4 -methylene group in an anti -orientation. Primer extension assays revealed that the O 4 -alkyl orientation influences hPol η bypass. Crystal structures of hPol η •DNA•dNTP ternary complexes with O 4 -methyl- or O 4 -ethylthymidine in the template strand showed the nucleobase of the former lodged near the ceiling of the active site, with the syn - O 4 -methyl group engaged in extensive hydrophobic interactions. This unique arrangement for O 4 -methylthymidine with hPol η , inaccessible for the other analogs due to steric/conformational restriction, is consistent with differences observed for nucleotide incorporation and supports the concept that lesion conformation influences extension across DNA damage. Together, these results provide mechanistic insights on the mutagenicity of O 4 MedT and O 4 EtdT when acted upon by hPol η .

  15. Technology-Facilitated Diagnosis and Treatment of Individuals with Autism Spectrum Disorder: An Engineering Perspective

    Directory of Open Access Journals (Sweden)

    Xiongyi Liu

    2017-10-01

    Full Text Available The rapid development of computer and robotic technologies in the last decade is giving hope to perform earlier and more accurate diagnoses of the Autism Spectrum Disorder (ASD, and more effective, consistent, and cost-conscious treatment. Besides the reduced cost, the main benefit of using technology to facilitate treatment is that stimuli produced during each session of the treatment can be controlled, which not only guarantees consistency across different sessions, but also makes it possible to focus on a single phenomenon, which is difficult even for a trained professional to perform, and deliver the stimuli according to the treatment plan. In this article, we provide a comprehensive review of research on recent technology-facilitated diagnosis and treat of children and adults with ASD. Different from existing reviews on this topic, which predominantly concern clinical issues, we focus on the engineering perspective of autism studies. All technology facilitated systems used for autism studies can be modeled as human machine interactive systems where one or more participants would constitute as the human component, and a computer-based or a robotic-based system would be the machine component. Based on this model, we organize our review with the following questions: (1 What are presented to the participants in the studies and how are the content and delivery methods enabled by technologies? (2 How are the reactions/inputs collected from the participants in response to the stimuli in the studies? (3 Are the experimental procedure and programs presented to participants dynamically adjustable based on the responses from the participants, and if so, how? and (4 How are the programs assessed?

  16. Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective

    OpenAIRE

    Martina C. Cornel; Carla G. van El

    2017-01-01

    More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especia...

  17. An exploration of tutors' experiences of facilitating problem-based learning. Part 2--implications for the facilitation of problem based learning.

    Science.gov (United States)

    Haith-Cooper, Melanie

    2003-01-01

    This paper is the second of two parts exploring a study that was undertaken to investigate the role of the tutor in facilitating problem-based learning (PBL). The first part focussed on the methodological underpinnings of the study. This paper aims to focus on the findings of the study and their implications for the facilitation of PBL. Six essential themes emerged from the findings that described the facilitation role. The tutors believed that their facilitation role was essentially structured around the decision of when to intervene and how to intervene in the PBL process. Modelling and non-verbal communication were seen as essential strategies for the facilitator. Underpinning these decisions was the need to trust in the philosophy of PBL. However, within many of the themes, there was a divergence of opinion as to how the role should actually be undertaken. Despite this, these findings have implications for the future role of PBL facilitators in Health Professional Education.

  18. Knowledge and exercise of human rights, and barriers and facilitators to claiming rights: a cross-sectional study of female sex workers and high-risk men who have sex with men in Andhra Pradesh, India

    OpenAIRE

    Ganju, Deepika; Patel, Sangram Kishor; Prabhakar, Parimi; Adhikary, Rajatashurva

    2016-01-01

    Background HIV prevention interventions recognize the need to protect the rights of key populations and support them to claim their rights as a vulnerability reduction strategy. This study explores knowledge of human rights, and barriers and facilitators to claiming rights, among female sex workers (FSWs) and high-risk men who have sex with men (HR-MSM) who are beneficiaries of a community mobilization intervention in Andhra Pradesh, India. Methods Data are drawn from a cross-sectional survey...

  19. Streamlining air import operations by trade facilitation measures

    Directory of Open Access Journals (Sweden)

    Yuri da Cunha Ferreira

    2017-12-01

    Full Text Available Global operations are subject to considerable uncertainties. Due to the Trade Facilitation Agreement that became effective in February 2017, the study of measures to streamline customs controls is urgent. This study aims to assess the impact of trade facilitation measures on import flows. An experimental study was performed in the largest cargo airport in South America through discrete-event simulation and design of experiments. Operation impacts of three trade facilitation measures are assessed on import flow by air. We shed light in the following trade facilitation measures: the use of X-ray equipment for physical inspection; increase of the number of qualified companies in the trade facilitation program; performance targets for customs officials. All trade facilitation measures used indicated potential to provide more predictability, cost savings, time reduction, and increase in security in international supply chain.

  20. Anthropogenic Habitats Facilitate Dispersal of an Early Successional Obligate: Implications for Restoration of an Endangered Ecosystem.

    Directory of Open Access Journals (Sweden)

    Katrina E Amaral

    Full Text Available Landscape modification and habitat fragmentation disrupt the connectivity of natural landscapes, with major consequences for biodiversity. Species that require patchily distributed habitats, such as those that specialize on early successional ecosystems, must disperse through a landscape matrix with unsuitable habitat types. We evaluated landscape effects on dispersal of an early successional obligate, the New England cottontail (Sylvilagus transitionalis. Using a landscape genetics approach, we identified barriers and facilitators of gene flow and connectivity corridors for a population of cottontails in the northeastern United States. We modeled dispersal in relation to landscape structure and composition and tested hypotheses about the influence of habitat fragmentation on gene flow. Anthropogenic and natural shrubland habitats facilitated gene flow, while the remainder of the matrix, particularly development and forest, impeded gene flow. The relative influence of matrix habitats differed between study areas in relation to a fragmentation gradient. Barrier features had higher explanatory power in the more fragmented site, while facilitating features were important in the less fragmented site. Landscape models that included a simultaneous barrier and facilitating effect of roads had higher explanatory power than models that considered either effect separately, supporting the hypothesis that roads act as both barriers and facilitators at all spatial scales. The inclusion of LiDAR-identified shrubland habitat improved the fit of our facilitator models. Corridor analyses using circuit and least cost path approaches revealed the importance of anthropogenic, linear features for restoring connectivity between the study areas. In fragmented landscapes, human-modified habitats may enhance functional connectivity by providing suitable dispersal conduits for early successional specialists.

  1. Ontologies and Possibilities of Human Rights: Exploring Dissensus to Facilitate Reconciliation in Post-Conflict Education Contexts

    Science.gov (United States)

    du Preez, Petro; Becker, Anne

    2016-01-01

    In light of growing critique of human rights and human rights education, this article explores ontologies of human rights, the possibilities they present for dissensus and how this could influence human rights education in post-conflict education contexts towards reconciliation. We draw on Dembour's (2010) categorisation of the different schools…

  2. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    Science.gov (United States)

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Toward Facilitative Mentoring and Catalytic Interventions

    Science.gov (United States)

    Smith, Melissa K.; Lewis, Marilyn

    2015-01-01

    In TESOL teacher mentoring, giving advice can be conceptualized as a continuum, ranging from directive to facilitative feedback. The goal, over time, is to lead toward the facilitative end of the continuum and specifically to catalytic interventions that encourage self-reflection and autonomous learning. This study begins by examining research on…

  4. Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament.

    KAUST Repository

    Fornander, Louise H

    2013-12-03

    The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.

  5. Facilitators for practice change in Spanish community pharmacy.

    Science.gov (United States)

    Gastelurrutia, Miguel A; Benrimoj, S I Charlie; Castrillon, Carla C; de Amezua, María J Casado; Fernandez-Llimos, Fernando; Faus, Maria J

    2009-02-01

    To identify and prioritise facilitators for practice change in Spanish community pharmacy. Spanish community pharmacies. Qualitative study. Thirty-three semi-structured interviews were conducted with community pharmacists (n = 15) and pharmacy strategists (n = 18), and the results were examined using the content analysis method. In addition, two nominal groups (seven community pharmacists and seven strategists) were formed to identify and prioritise facilitators. Results of both techniques were then triangulated. Facilitators for practice change. Twelve facilitators were identified and grouped into four domains (D1: Pharmacist; D2: Pharmacy as an organisation; D3: Pharmaceutical profession; D4: Miscellaneous). Facilitators identified in D1 include: the need for more clinical education at both pre- and post-graduate levels; the need for clearer and unequivocal messages from professional leaders about the future of the professional practice; and the need for a change in pharmacists' attitudes. Facilitators in D2 are: the need to change the reimbursement system to accommodate cognitive service delivery as well as dispensing; and the need to change the front office of pharmacies. Facilitators identified in D3 are: the need for the Spanish National Professional Association to take a leadership role in the implementation of cognitive services; the need to reduce administrative workload; and the need for universities to reduce the gap between education and research. Other facilitators identified in this study include: the need to increase patients' demand for cognitive services at pharmacies; the need to improve pharmacist-physician relationships; the need for support from health care authorities; and the need for improved marketing of cognitive services and their benefits to society, including physicians and health care authorities. Twelve facilitators were identified. Strategists considered clinical education and pharmacists' attitude as the most important, and

  6. Identification of human tissue cross-presenting dendritic cells

    OpenAIRE

    Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

  7. Exploring the metal coordination properties of the pyrimidine part of purine nucleobases: isomerization reactions in heteronuclear Pt(II)/Pd(II) of 9-methyladenine.

    Science.gov (United States)

    Ibáñez, Susana; Albertí, Francisca M; Sanz Miguel, Pablo J; Lippert, Bernhard

    2011-10-17

    The synthesis and characterization of three heteronuclear Pt(2)Pd(2) (4, 5) and PtPd(2) (6) complexes of the model nucleobase 9-methyladenine (9-MeA) is reported. The compounds were prepared by reacting [Pt(NH(3))(3)(9-MeA-N7)](ClO(4))(2) (1) with [Pd(en)(H(2)O)(2)](ClO(4))(2) at different ratios r between Pt and Pd, with the goal to probe Pd(II) binding to any of the three available nitrogen atoms, N1, N3, N6 or combinations thereof. Pd(II) coordination occurs at N1 and at the deprotonated N6 positions, yet not at N3. 4 and 5 are isomers of [{(en)Pd}(2){N1,N6-9-MeA(-)-N7)Pt(NH(3))(3)}(2)](ClO(4))(6)·nH(2)O, with a head-head orientation of the two bridging 9-MeA(-) ligands in 4 and a head-tail orientation in 5. 6 is [{(en)Pd}(2)(OH)(N1,N6-9MeA(-)-N7)Pt(NH(3))(3)](ClO(4))(4)·4H(2)O, hence a condensation product between [Pt(NH(3))(3)(9-MeA-N7)](2+) and a μ-OH bridged dinuclear (en)Pd-OH-Pd(en) unit, which connects the N1 and N6 positions of 9-MeA(-) in an intramolecular fashion. 4 and 5, which slowly interconvert in aqueous solution, display distinct structural differences such as significantly different intramolecular Pd···Pd contacts (3.124 0(16) Å in 4; 2.986 6(14) Å in 5), among others. Binding of (en)Pd(II) to the exocyclic N6 atom in 4 and 5 is accompanied by a large movement of Pd(II) out of the 9-MeA(-) plane and a trend to a further shortening of the C6-N6 bond as compared to free 9-MeA. The packing patterns of 4 and 5 reveal substantial anion-π interactions.

  8. Facilitating classroom based interprofessional learning: a grounded theory study of university educators' perceptions of their role adequacy as facilitators.

    Science.gov (United States)

    Derbyshire, Julie A; Machin, Alison I; Crozier, Suzanne

    2015-01-01

    The provision of inter professional learning (IPL) within undergraduate programmes is now well established within many Higher Education Institutions (HEIs). IPL aims to better equip nurses and other health professionals with effective collaborative working skills and knowledge to improve the quality of patient care. Although there is still ambiguity in relation to the optimum timing and method for delivering IPL, effective facilitation is seen as essential. This paper reports on a grounded theory study of university educators' perceptions of the knowledge and skills needed for their role adequacy as IPL facilitators. Data was collected using semi structured interviews with nine participants who were theoretically sampled from a range of professional backgrounds, with varied experiences of education and involvement in facilitating IPL. Constant comparative analysis was used to generate four data categories: creating and sustaining an IPL group culture through transformational IPL leadership (core category), readiness for IPL facilitation, drawing on past interprofessional learning and working experiences and role modelling an interprofessional approach. The grounded theory generated from this study, although propositional, suggests that role adequacy for IPL facilitation is dependent on facilitator engagement in a process of 'transformational interprofessional learning leadership' to create and sustain a group culture. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. On novice facilitators doing research

    DEFF Research Database (Denmark)

    Tavella, Elena

    2018-01-01

    Opportunities for novices to facilitate Problem Structuring Methods (PSMs) workshops are limited, especially because of a lack of access to real-world interventions and confidence in their capabilities. Novices are usually young academics building their careers through publishing. Publishing...... is challenging if facilitation and opportunities for data collection are limited. To address this challenge, this paper suggests autoethnography as a framework for addressing difficulties that novices face in conducting research and publishing on PSMs. This suggestion grows out of a literature study...

  10. Emotion processing facilitates working memory performance.

    Science.gov (United States)

    Lindström, Björn R; Bohlin, Gunilla

    2011-11-01

    The effect of emotional stimulus content on working memory performance has been investigated with conflicting results, as both emotion-dependent facilitation and impairments are reported in the literature. To clarify this issue, 52 adult participants performed a modified visual 2-back task with highly arousing positive stimuli (sexual scenes), highly arousing negative stimuli (violent death) and low-arousal neutral stimuli. Emotional stimulus processing was found to facilitate task performance relative to that of neutral stimuli, both in regards to response accuracy and reaction times. No emotion-dependent differences in false-alarm rates were found. These results indicate that emotional information can have a facilitating effect on working memory maintenance and processing of information.

  11. Facilitators in Ambivalence

    Science.gov (United States)

    Karlsson, Mikael R.; Erlandson, Peter

    2018-01-01

    This is part of a larger ethnographical study concerning how school development in a local educational context sets cultural and social life in motion. The main data "in this article" consists of semi-structural interviews with teachers (facilitators) who have the responsibility of carrying out a project about formative assessment in…

  12. Human Resource Development to Facilitate Experiential Learning: The Case of Yahoo Japan

    Science.gov (United States)

    Matsuo, Makoto

    2015-01-01

    Although work experiences are recognized as important mechanisms for developing leaders in organizations, existing research has focused primarily on work assignments rather than on human resource development (HRD) systems that promote experiential learning of managers. The primary goal of this study was to develop an HRD model for facilitating…

  13. 50 CFR 600.752 - Use of conveners and facilitators.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Use of conveners and facilitators. 600.752..., by consensus. The facilitator may be the same person as the convener used under paragraph (a) of this... facilitator, the FNP shall select, by consensus, a person to serve as facilitator. A person designated to...

  14. A human centered GeoVisualization framework to facilitate visual exploration of telehealth data: a case study.

    Science.gov (United States)

    Joshi, Ashish; de Araujo Novaes, Magdala; Machiavelli, Josiane; Iyengar, Sriram; Vogler, Robert; Johnson, Craig; Zhang, Jiajie; Hsu, Chiehwen E

    2012-01-01

    Public health data is typically organized by geospatial units. Routine geographic monitoring of health data enables an understanding of the spatial patterns of events in terms of causes and controls. GeoVisualization (GeoVis) allows users to see information hidden both visually and explicitly on a map. Despite the applicability of GeoVis in public health, it is still underused for visualizing public health data. The objective of this study is to examine the perception of telehealth users' to utilize GeoVis as a proof of concept to facilitate visual exploration of telehealth data in Brazil using principles of human centered approach and cognitive fit theory. A mixed methods approach combining qualitative and quantitative assessments was utilized in this cross sectional study conducted at the Telehealth Center of the Federal University of Pernambuco (NUTE-UFPE), Recife, Brazil. A convenient sample of 20 participants currently involved in NUTES was drawn during a period of Sep-Oct 2011. Data was gathered using previously tested questionnaire surveys and in-person interviews. Socio-demographic Information such as age, gender, prior education, familiarity with the use of computer and GeoVis was gathered. Other information gathered included participants' prior spatial analysis skills, level of motivation and use of GeoVis in telehealth. Audio recording was done for all interviews conducted in both English and Portuguese, and transcription of the audio content to English was done by a certified translator. Univariate analysis was performed and means and standard deviations were reported for the continuous variables and frequency distributions for the categorical variables. For the open-ended questions, we utilized a grounded theory to identify themes and their relationship as they emerge from the data. Analysis of the quantitative data was performed using SAS V9.1 and qualitative data was performed using NVivo9. The average age of participants was 28 years (SD=7), a

  15. Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.

    Science.gov (United States)

    Egeblad, Louise; Welin, Martin; Flodin, Susanne; Gräslund, Susanne; Wang, Liya; Balzarini, Jan; Eriksson, Staffan; Nordlund, Pär

    2012-01-01

    To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg) around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

  16. Barriers and Facilitators to Community Mobility for Assistive Technology Users

    Directory of Open Access Journals (Sweden)

    Natasha Layton

    2012-01-01

    Full Text Available Mobility is frequently described in terms of individual body function and structures however contemporary views of disability also recognise the role of environment in creating disability. Aim. To identify consumer perspectives regarding barriers and facilitators to optimal mobility for a heterogeneous population of impaired Victorians who use assistive technology in their daily lives. Method. An accessible survey investigated the impact of supports or facilitators upon actual and desired life outcomes and health-related quality of life, from 100 AT users in Victoria, Australia. This paper reports upon data pertaining to community mobility. Results. A range of barriers and enablers to community mobility were identified including access to AT devices, environmental interventions, public transport, and inclusive community environs. Substantial levels of unmet need result in limited personal mobility and community participation. Outcomes fall short of many principles enshrined in current policy and human rights frameworks. Conclusion. AT devices as well as accessible and inclusive home and community environs are essential to maximizing mobility for many. Given the impact of the environment upon the capacity of individuals to realise community mobility, this raises the question as to whether rehabilitation practitioners, as well as prescribing AT devices, should work to build accessible communities via systemic advocacy.

  17. Demystifying facilitation of multi-actor learning processes

    NARCIS (Netherlands)

    Groot, A.E.

    2002-01-01

    This thesis aims to demystify the facilitation of participatory processes in order to improve the performance of the facilitation professional. As our society is increasingly recognised as pluralistic, characterised by

  18. Distinct Purine Distribution in Carbonaceous Chondrites

    Science.gov (United States)

    Callahan, Michael P.; Smith, Karen E.; Cleaves, Henderson J.; Ruzicka, Josef; Stern, Jennifer C.; Glavin, Daniel P.; House, Christopher H.; Dworkin, Jason P.

    2011-01-01

    Carbonaceous chondrite meteorites are known to contain a diverse suite of organic compounds, many of which are essential components of biochemistry. Amino acids, which are the monomers of proteins, have been extensively studied in such meteorites (e.g. Botta and Bada 2002; Pizzarello et aI., 2006). The origin of amino acids in meteorites has been firmly established as extraterrestrial based on their detection typically as racemic mixtures of amino acids, the presence of many non-protein amino acids, and non-terrestrial values for compound-specific deuterium, carbon, and nitrogen isotopic measurements. In contrast to amino acids, nucleobases in meteorites have been far less studied. Nucleobases are substituted one-ring (pyrimidine) or two-ring (purine) nitrogen heterocyclic compounds and serve as the information carriers of nucleic acids and in numerous coenzymes. All of the purines (adenine, guanine, hypoxanthine, and xanthine) and pyrimidines (uracil) previously reported in meteorites are biologically common and could be interpreted as the result of terrestrial contamination (e.g. van del' Velden and Schwartz, 1974.) Unlike other meteoritic organics, there have been no observations of stochastic molecular diversity of purines and pyrimidines in meteorites, which has been a criterion for establishing extraterrestrial origin. Maltins et al. (2008) performed compound-specific stable carbon isotope measurements for uracil and xanthine in the Murchison meteorite. They assigned a non-terrestrial origin for these nucleobases; however, the possibility that interfering indigenous molecules (e.g. carboxylic acids) contributed to the 13C-enriched isotope values for these nucleobases cannot be completely ruled out. Thus, the origin of these meteoritic nucleobases has never been established unequivocally. Here we report on our investigation of extracts of II different carbonaceous chondrites covering various petrographic types (Cl, CM, and CR) and degrees of aqueous alteration

  19. Laminin-411 Is a Vascular Ligand for MCAM and Facilitates TH17 Cell Entry into the CNS

    Science.gov (United States)

    Flanagan, Ken; Fitzgerald, Kent; Baker, Jeanne; Regnstrom, Karin; Gardai, Shyra; Bard, Frederique; Mocci, Simonetta; Seto, Pui; You, Monica; Larochelle, Catherine; Prat, Alexandre; Chow, Samuel; Li, Lauri; Vandevert, Chris; Zago, Wagner; Lorenzana, Carlos; Nishioka, Christopher; Hoffman, Jennifer; Botelho, Raquel; Willits, Christopher; Tanaka, Kevin; Johnston, Jennifer; Yednock, Ted

    2012-01-01

    TH17 cells enter tissues to facilitate pathogenic autoimmune responses, including multiple sclerosis (MS). However, the adhesion molecules involved in the unique migratory capacity of TH17 cells, into both inflamed and uninflamed tissues remain unclear. Herein, we characterize MCAM (CD146) as an adhesion molecule that defines human TH17 cells in the circulation; following in vitro restimulation of human memory T cells, nearly all of the capacity to secrete IL-17 is contained within the population of cells expressing MCAM. Furthermore, we identify the MCAM ligand as laminin 411, an isoform of laminin expressed within the vascular endothelial basement membranes under inflammatory as well as homeotstatic conditions. Purified MCAM-Fc binds to laminin 411 with an affinity of 27 nM, and recognizes vascular basement membranes in mouse and human tissue. MCAM-Fc binding was undetectable in tissue from mice with targeted deletion of laminin 411, indicating that laminin 411 is a major tissue ligand for MCAM. An anti-MCAM monoclonal antibody, selected for inhibition of laminin binding, as well as soluble MCAM-Fc, inhibited T cell adhesion to laminin 411 in vitro. When administered in vivo, the antibody reduced TH17 cell infiltration into the CNS and ameliorated disease in an animal model of MS. Our data suggest that MCAM and laminin 411 interact to facilitate TH17 cell entry into tissues and promote inflammation. PMID:22792325

  20. Influences of peer facilitation in general practice - a qualitative study

    DEFF Research Database (Denmark)

    Due, Tina Drud; Kousgaard, Marius Brostrøm; Waldorff, Frans Boch

    2018-01-01

    of the visited practices to gain a more detailed understanding of how peer facilitation influenced practices and how they valued the facilitation. METHODS: The facilitation intervention was conducted in general practice in the Capital Region of Denmark with the purpose of supporting the implementation of chronic...... visits had increased their knowledge and skills as well as their motivation and confidence to change. These positive influences were ascribed to a) the facilitation approach b) the credibility and know-how associated with the facilitators' being peers c) the recurring visits providing protected time...... and invoking a sense of commitment. Despite these positive influences, both the facilitation and the change process were impeded by several challenges, e.g. competing priorities, heavy workload, problems with information technology and in some cases inadequate facilitation. CONCLUSION: Practice facilitation...

  1. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  2. Mindfulness for group facilitation

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2014-01-01

    In this paper, we argue that mindfulness techniques can be used for enhancing the outcome of group performance. The word mindfulness has different connotations in the academic literature. Broadly speaking there is ‘mindfulness without meditation’ or ‘Western’ mindfulness which involves active...... thinking and ‘Eastern’ mindfulness which refers to an open, accepting state of mind, as intended with Buddhist-inspired techniques such as meditation. In this paper, we are interested in the latter type of mindfulness and demonstrate how Eastern mindfulness techniques can be used as a tool for facilitation....... A brief introduction to the physiology and philosophy of Eastern mindfulness constitutes the basis for the arguments of the effect of mindfulness techniques. The use of mindfulness techniques for group facilitation is novel as it changes the focus from individuals’ mindfulness practice...

  3. Psychological needs and the facilitation of integrative processes.

    Science.gov (United States)

    Ryan, R M

    1995-09-01

    The assumption that there are innate integrative or actualizing tendencies underlying personality and social development is reexamined. Rather than viewing such processes as either nonexistent or as automatic, I argue that they are dynamic and dependent upon social-contextual supports pertaining to basic human psychological needs. To develop this viewpoint, I conceptually link the notion of integrative tendencies to specific developmental processes, namely intrinsic motivation; internalization; and emotional integration. These processes are then shown to be facilitated by conditions that fulfill psychological needs for autonomy, competence, and relatedness, and forestalled within contexts that frustrate these needs. Interactions between psychological needs and contextual supports account, in part, for the domain and situational specificity of motivation, experience, and relative integration. The meaning of psychological needs (vs. wants) is directly considered, as are the relations between concepts of integration and autonomy and those of independence, individualism, efficacy, and cognitive models of "multiple selves."

  4. Using CdTe/ZnSe core/shell quantum dots to detect DNA and damage to DNA

    Directory of Open Access Journals (Sweden)

    Moulick A

    2017-02-01

    Full Text Available Amitava Moulick,1,2 Vedran Milosavljevic,1,2 Jana Vlachova,1,2 Robert Podgajny,3 David Hynek,1,2 Pavel Kopel,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University, 2Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic; 3Faculty of Chemistry, Jagiellonian University, Krakow, Poland Abstract: CdTe/ZnSe core/shell quantum dot (QD, one of the strongest and most highly luminescent nanoparticles, was directly synthesized in an aqueous medium to study its individual interactions with important nucleobases (adenine, guanine, cytosine, and thymine in detail. The results obtained from the optical analyses indicated that the interactions of the QDs with different nucleobases were different, which reflected in different fluorescent emission maxima and intensities. The difference in the interaction was found due to the different chemical behavior and different sizes of the formed nanoconjugates. An electrochemical study also confirmed that the purines and pyrimidines show different interactions with the core/shell QDs. Based on these phenomena, a novel QD-based method is developed to detect the presence of the DNA, damage to DNA, and mutation. The QDs were successfully applied very easily to detect any change in the sequence (mutation of DNA. The QDs also showed their ability to detect DNAs directly from the extracts of human cancer (PC3 and normal (PNT1A cells (detection limit of 500 pM of DNA, which indicates the possibilities to use this easy assay technique to confirm the presence of living organisms in extreme environments. Keywords: nanoparticles, nucleobases, biosensor, fluorescence, mutation

  5. Using facilitative skills in project management

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne; Jacobsen, Peter

    2013-01-01

    Project management can be seen as a profession, discipline and conceptual framework. It has been developed from different fields, including military engineering, mechanical engineering, social sciences and construction. During recent decades, there has been a number of challenges as to its efficacy...... cooperation, mediated by interconnected and diversified systems, is becoming more and more common. These relatively new forms of interaction imply new demands on skills and methods facilitating project cooperation within and among various organizations. Given the pervasiveness of these demands, project...... managers are frequently finding themselves in situations where using facilitating skills is not an option, but a requirement. Facilitation is to be viewed as a process of ‘obstetric’ aid to meet the challenges of coping with the changing conditions for project management described briefly above...

  6. Mental Health Facilitator (MHF) Service Implementation in Schools in Malawi, Africa: A Strategy for Increasing Community Human Resources

    Science.gov (United States)

    Luke, Melissa; Hinkle, J. Scott; Schweiger, Wendi; Henderson, Donna

    2016-01-01

    The Mental Health Facilitator (MHF) program utilizes a population-based curriculum and has been implemented in Malawi for the past seven years. This article reports findings from an ethnographic study that explored how 40 MHF stakeholders have experienced the MHF program. This transdisciplinary program is a 30-hour training in community mental…

  7. Facilitating Transfers

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    to specific logics of temporalisation and spatial expansion of a diverse set of social processes in relation to, for example, the economy, politics, science and the mass media. On this background, the paper will more concretely develop a conceptual framework for classifying different contextual orders...... that the essential functional and normative purpose of regulatory governance is to facilitate, stabilise and justify the transfer of condensed social components (such as economic capital and products, political decisions, legal judgements, religious beliefs and scientific knowledge) from one social contexts...

  8. Facilitation of learning: part 1.

    Science.gov (United States)

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-06

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning.

  9. A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells

    NARCIS (Netherlands)

    C. Buecker (Christa); H.H. Chen; J.M. Polo (Jose); L. Daheron (Laurence); L. Bu (Lei); T.S. Barakat (Tahsin Stefan); P. Okwieka (Patricia); A. Porter (Andrew); J.H. Gribnau (Joost); K. Hochedlinger (Konrad); N. Geijsen (Niels)

    2010-01-01

    textabstractMurine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human

  10. Teachers as Friendship Facilitators: Respeto and Personalismo.

    Science.gov (United States)

    Turnbull, Ann P.; Pereira, Lourdes; Blue-Banning, Martha

    2000-01-01

    This article highlights three teachers who were actively involved as friendship facilitators by illuminating their use of a friendship-facilitator framework with three students with moderate/severe disabilities. The framework includes three strategies: finding opportunities to bring children and youth together, acknowledging individual strengths…

  11. CDK1 inhibition facilitates formation of syncytiotrophoblasts and expression of human Chorionic Gonadotropin

    KAUST Repository

    Ullah, Rahim; Dar, Saira; Ahmad, Tanvir; de Renty, Christelle; Usman, Mohammad; DePamphilis, Melvin L.; Faisal, Amir; Shahzad-ul-Hussan, Syed; Ullah, Zakir

    2018-01-01

    The human placental syncytiotrophoblast (STB) cells play essential roles in embryo implantation and nutrient exchange between the mother and the fetus. STBs are polyploid which are formed by fusion of diploid cytotrophoblast (CTB) cells

  12. Staphylococcus aureus MnhF mediates cholate efflux and facilitates survival under human colonic conditions

    OpenAIRE

    Sannasiddappa, Thippeswamy; Hood, Graham; Hanson, Kevan; Costabile, Adele; Gibson, Glenn; Clarke, Simon

    2015-01-01

    Resistance to the innate defenses of the intestine is crucial for the survival and carriage of Staphylococcus aureus, a common colonizer of the human gut. Bile salts produced by the liver and secreted into the intestines are one such group of molecules with potent antimicrobial activity. The mechanisms by which S. aureus is able to resist such defenses in order to colonize and survive in the human gut are unknown. Here we show that mnhF confers resistance to bile salts, which can be abrogated...

  13. Disturbance-mediated facilitation by an intertidal ecosystem engineer.

    Science.gov (United States)

    Wright, Jeffrey T; Gribben, Paul E

    2017-09-01

    Ecosystem engineers facilitate communities by providing a structural habitat that reduces abiotic stress or predation pressure for associated species. However, disturbance may damage or move the engineer to a more stressful environment, possibly increasing the importance of facilitation for associated communities. In this study, we determined how disturbance to intertidal boulders (i.e., flipping) and the subsequent movement of a structural ecosystem engineer, the tube-forming serpulid worm Galeolaria caespitosa, from the bottom (natural state, low abiotic stress) to the top (disturbed state, high abiotic stress) surface of boulders influenced the importance of facilitation for intertidal communities across two intertidal zones. Theory predicts stronger relative facilitation should occur in the harsher environments of the top of boulders and the high intertidal zone. To test this prediction, we experimentally positioned boulders with the serpulids either face up or face down for 12 months in low and high zones in an intertidal boulder field. There were very different communities associated with the different boulders and serpulids had the strongest facilitative effects on the more stressful top surface of boulders with approximately double the species richness compared to boulders lacking serpulids. Moreover, within the serpulid matrix itself there was also approximately double the species richness (both zones) and abundance (high zone only) of small invertebrates on the top of boulders compared to the bottom. The high relative facilitation on the top of boulders reflected a large reduction in temperature by the serpulid matrix on that surface (up to 10°C) highlighting a key role for modification of the abiotic environment in determining the community-wide facilitation. This study has demonstrated that disturbance and subsequent movement of an ecosystem engineer to a more stressful environment increased the importance of facilitation and allowed species to

  14. Facilitation as a management discipline to support organizational development processes

    DEFF Research Database (Denmark)

    Møller, Laura; Goduscheit, René Chester

    2015-01-01

    facilitation may be employed as a method to support organisational development processes. The article unfolds the concept of facilitation, identifies the processes that merit facilitation and demonstrates how facilitation work may be approached. The first step in the process is acknowledgement of the need...

  15. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.

    Directory of Open Access Journals (Sweden)

    Sanne Hindriksen

    Full Text Available The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC. We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.

  16. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.

    Science.gov (United States)

    Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A

    2017-01-01

    The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC). We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.

  17. When Humanoid Robots Become Human-Like Interaction Partners: Corepresentation of Robotic Actions

    Science.gov (United States)

    Stenzel, Anna; Chinellato, Eris; Bou, Maria A. Tirado; del Pobil, Angel P.; Lappe, Markus; Liepelt, Roman

    2012-01-01

    In human-human interactions, corepresenting a partner's actions is crucial to successfully adjust and coordinate actions with others. Current research suggests that action corepresentation is restricted to interactions between human agents facilitating social interaction with conspecifics. In this study, we investigated whether action…

  18. Facilitating North-South Partnerships for Sustainable Agriculture

    Science.gov (United States)

    Termeer, C. J. A. M.; Hilhorst, T.; Oorthuizen, J.

    2010-01-01

    The increased number of development cooperation and sustainable agriculture partnerships brings with it new challenges for professionals who are asked to facilitate these partnering processes. In this article we shed more light on the world of development cooperation and we explore questions that facilitators working with North-South partnerships…

  19. Analysis of cis-elements that facilitate extrachromosomal persistence of human papillomavirus genomes

    International Nuclear Information System (INIS)

    Pittayakhajonwut, Daraporn; Angeletti, Peter C.

    2008-01-01

    Human papillomaviruses (HPVs) are maintained latently in dividing epithelial cells as nuclear plasmids. Two virally encoded proteins, E1, a helicase, and E2, a transcription factor, are important players in replication and stable plasmid maintenance in host cells. Recent experiments in yeast have demonstrated that viral genomes retain replication and maintenance function independently of E1 and E2 [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002). Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. J. Virol. 76(7), 3350-8; Kim, K., Angeletti, P.C., Hassebroek, E.C., and Lambert, P.F. (2005). Identification of cis-acting elements that mediate the replication and maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae. J. Virol. 79(10), 5933-42]. Flow cytometry studies of EGFP-reporter vectors containing subgenomic HPV fragments with or without a human ARS (hARS), revealed that six fragments located in E6-E7, E1-E2, L1, and L2 regions showed a capacity for plasmid stabilization in the absence of E1 and E2 proteins. Interestingly, four fragments within E7, the 3' end of L2, and the 5' end of L1 exhibited stability in plasmids that lacked an hARS, indicating that they possess both replication and maintenance functions. Two fragments lying in E1-E2 and the 3' region of L1 were stable only in the presence of hARS, that they contained only maintenance function. Mutational analyses of HPV16-GFP reporter constructs provided evidence that genomes lacking E1 and E2 could replicate to an extent similar to wild type HPV16. Together these results support the concept that cellular factors influence HPV replication and maintenance, independently, and perhaps in conjunction with E1 and E2, suggesting a role in the persistent phase of the viral lifecycle

  20. Why (we think) facilitation works: insights from organizational learning theory.

    Science.gov (United States)

    Berta, Whitney; Cranley, Lisa; Dearing, James W; Dogherty, Elizabeth J; Squires, Janet E; Estabrooks, Carole A

    2015-10-06

    Facilitation is a guided interactional process that has been popularized in health care. Its popularity arises from its potential to support uptake and application of scientific knowledge that stands to improve clinical and managerial decision-making, practice, and ultimately patient outcomes and organizational performance. While this popular concept has garnered attention in health services research, we know that both the content of facilitation and its impact on knowledge implementation vary. The basis of this variation is poorly understood, and understanding is hampered by a lack of conceptual clarity. In this paper, we argue that our understanding of facilitation and its effects is limited in part by a lack of clear theoretical grounding. We propose a theoretical home for facilitation in organizational learning theory. Referring to extant literature on facilitation and drawing on theoretical literature, we discuss the features of facilitation that suggest its role in contributing to learning capacity. We describe how facilitation may contribute to generating knowledge about the application of new scientific knowledge in health-care organizations. Facilitation's promise, we suggest, lies in its potential to stimulate higher-order learning in organizations through experimenting with, generating learning about, and sustaining small-scale adaptations to organizational processes and work routines. The varied effectiveness of facilitation observed in the literature is associated with the presence or absence of factors known to influence organizational learning, since facilitation itself appears to act as a learning mechanism. We offer propositions regarding the relationships between facilitation processes and key organizational learning concepts that have the potential to guide future work to further our understanding of the role that facilitation plays in learning and knowledge generation.

  1. HGVA: the Human Genome Variation Archive

    OpenAIRE

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-01-01

    Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

  2. Charge transfer in pi-stacked systems including DNA

    International Nuclear Information System (INIS)

    Siebbeles, L.D.A.

    2003-01-01

    Charge migration in DNA is a subject of intense current study motivated by long-range detection of DNA damage and the potential application of DNA as a molecular wire in nanoscale electronic devices. A key structural element, which makes DNA a medium for long-range charge transfer, is the array of stacked base pairs in the interior of the double helix. The overlapping pi-orbitals of the nucleobases provide a pathway for motion of charge carriers generated on the stack. This 'pi-pathway' resembles the columnarly stacked macrocyclic cores in discotic materials such as triphenylenes. The structure of these pi-stacked systems is highly disordered with dynamic fluctuations occurring on picosecond to nanosecond time scales. Theoretical calculations, concerning the effects of structural disorder and nucleobase sequence in DNA, on the dynamics of charge carriers are presented. Electronic couplings and localization energies of charge carriers were calculated using density functional theory (DFT). Results for columnarly stacked triphenylenes and DNA nucleobases are compared. The results are used to provide insight into the factors that control the mobility of charge carriers. Further, experimental results on the site-selective oxidation of guanine nucleobases in DNA (hot spots for DNA damage) are analyzed on basis of the theoretical results

  3. Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice

    OpenAIRE

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear con...

  4. Human activity and the spread of Phytophthora ramorum

    Science.gov (United States)

    Hall J. Cushman; Michelle Cooper; Ross K. Meentemeyer; Shelly Benson

    2008-01-01

    Increasing numbers of studies are finding that humans can facilitate the spread of exotic plant species in protected wildlands. Hiking trails commonly serve as conduits for invaders and the number of exotic plant species occurring in protected areas is often correlated positively with visitation rates. Despite such evidence linking human activity to the spread of...

  5. Detection of nucleic acids by graphene-based devices: A first-principles study

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hua [School of Physics and Electronics, Central South University, Changsha 410083 (China); School of Physics and Electronic Science, Changsha University of Science and Technology, Changsha 410114 (China); Xu, Hui, E-mail: xuhui@csu.edu.cn, E-mail: ouyangfp06@tsinghua.org.cn; Ni, Xiang; Lin Peng, Sheng; Liu, Qi; Ping OuYang, Fang, E-mail: xuhui@csu.edu.cn, E-mail: ouyangfp06@tsinghua.org.cn [School of Physics and Electronics, Central South University, Changsha 410083 (China)

    2014-04-07

    Based on first-principles quantum transport calculations, we design a graphene-based biosensor device, which is composed of graphene nanoribbons electrodes and a biomolecule. It is found that when different nucleobases or poly nucleobase chains are located in the nanogap, the device presents completely different transport properties, showing different current informations. And the change of currents from 2 to 5 orders of magnitude for four different nucleobases suggests a great ability of discrimination by utilizing such a device. The physical mechanism of this phenomenon originates from their different chemical composition and structure. Moreover, we also explore the coupling effect of several neighboring bases and the size effect of the nanogap on transport properties. Our results show the possibility of rapid sequencing DNA by measuring such a transverse-current of the device, and provide a new idea for sequencing DNA.

  6. Asexual sporulation facilitates adaptation

    NARCIS (Netherlands)

    Zhang, Jianhua; Debets, A.J.M.; Verweij, P.E.; Melchers, W.J.G.; Zwaan, B.J.; Schoustra, S.E.

    2015-01-01

    Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole resistance mutations in A. fumigatus facilitating

  7. Chimpanzees and humans mimic pupil-size of conspecifics.

    Directory of Open Access Journals (Sweden)

    Mariska E Kret

    Full Text Available Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes. We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  8. Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers.

    Science.gov (United States)

    Thurtle-Schmidt, Bryan H; Stroud, Robert M

    2016-09-20

    Boron is essential for plant growth because of its incorporation into plant cell walls; however, in excess it is toxic to plants. Boron transport and homeostasis in plants is regulated in part by the borate efflux transporter Bor1, a member of the solute carrier (SLC) 4 transporter family with homology to the human bicarbonate transporter Band 3. Here, we present the 4.1-Å resolution crystal structure of Arabidopsis thaliana Bor1. The structure displays a dimeric architecture in which dimerization is mediated by centralized Gate domains. Comparisons with a structure of Band 3 in an outward-open state reveal that the Core domains of Bor1 have rotated inwards to achieve an occluded state. Further structural comparisons with UapA, a xanthine transporter from the nucleobase-ascorbate transporter family, show that the downward pivoting of the Core domains relative to the Gate domains may access an inward-open state. These results suggest that the SLC4, SLC26, and nucleobase-ascorbate transporter families all share an elevator transport mechanism in which alternating access is provided by Core domains that carry substrates across a membrane.

  9. Self-assembling, dynamic alphaPNAs

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2009-01-01

    In the recent report published in Science, Ghadiri and coworkers describe dynamic tPNAs, alphaPNA derivatives with a nucleobase attached via a thioester bond that are a step forward toward self-repairing and replicating molecules.......In the recent report published in Science, Ghadiri and coworkers describe dynamic tPNAs, alphaPNA derivatives with a nucleobase attached via a thioester bond that are a step forward toward self-repairing and replicating molecules....

  10. Impact of Prolonged Blood Incubation and Extended Serum Storage at Room Temperature on the Human Serum Metabolome

    Directory of Open Access Journals (Sweden)

    Beate Kamlage

    2018-01-01

    Full Text Available Metabolomics is a powerful technology with broad applications in life science that, like other -omics approaches, requires high-quality samples to achieve reliable results and ensure reproducibility. Therefore, along with quality assurance, methods to assess sample quality regarding pre-analytical confounders are urgently needed. In this study, we analyzed the response of the human serum metabolome to pre-analytical variations comprising prolonged blood incubation and extended serum storage at room temperature by using gas chromatography-mass spectrometry (GC-MS and liquid chromatography-tandem mass spectrometry (LC-MS/MS -based metabolomics. We found that the prolonged incubation of blood results in a statistically significant 20% increase and 4% decrease of 225 tested serum metabolites. Extended serum storage affected 21% of the analyzed metabolites (14% increased, 7% decreased. Amino acids and nucleobases showed the highest percentage of changed metabolites in both confounding conditions, whereas lipids were remarkably stable. Interestingly, the amounts of taurine and O-phosphoethanolamine, which have both been discussed as biomarkers for various diseases, were 1.8- and 2.9-fold increased after 6 h of blood incubation. Since we found that both are more stable in ethylenediaminetetraacetic acid (EDTA blood, EDTA plasma should be the preferred metabolomics matrix.

  11. Uptake of human papillomavirus (HPV) vaccination in Hong Kong: Facilitators and barriers among adolescent girls and their parents.

    Science.gov (United States)

    Yuen, Winnie Wing Yan; Lee, Albert; Chan, Paul K S; Tran, Lynn; Sayko, Erica

    2018-01-01

    The present study is aimed at assessing the feasibility of delivering the HPV (human papillomavirus) vaccine to girls through a school-based program in Hong Kong, as well as to examine the facilitators and barriers associated with their participation. We approached 1,229 eligible girls aged 9 to 14 at eight schools in Hong Kong to join the program and then delivered the bivalent HPV vaccine at 0 and 6 months over the course of one school year. The students and their parents completed separate questionnaires to indicate their decision on whether or not to participate, and to assess their knowledge of cervical cancer and the HPV vaccine. The overall vaccine uptake was 81.4% (1,000/1,229) for the first dose and 80.8% (993/1,229) for the second dose. Parents and students were given separate questionnaires and asked whether or not they would like to participate in the vaccination program. 87.1% (1,010/1,160) of parents and 84.9% (974/1,147) of students indicated that they would join the program. The reasons associated with parents' decision not to vaccinate their daughters primarily included concerns around side effects and safety. Multivariate regression analysis showed that parents who thought that the vaccine would protect their daughter from getting cervical cancer (OR = 3.16, 95% CI = 1.39-7.15, p parents who had never heard of the vaccine (OR = .15, 95% CI = .03-.71, p vaccine (OR = .39, 95% CI = .19-.81, p HPV vaccine with high uptake rate in a school setting is feasible in Hong Kong. Engaging key stakeholders including school administrators, teachers and community physicians, and providing relevant information on safety and vaccine effectiveness to parents were important to the success of the program.

  12. Probing the DNA Structural Requirements for Facilitated Diffusion

    Science.gov (United States)

    2015-01-01

    DNA glycosylases perform a genome-wide search to locate damaged nucleotides among a great excess of undamaged nucleotides. Many glycosylases are capable of facilitated diffusion, whereby multiple sites along the DNA are sampled during a single binding encounter. Electrostatic interactions between positively charged amino acids and the negatively charged phosphate backbone are crucial for facilitated diffusion, but the extent to which diffusing proteins rely on the double-helical structure DNA is not known. Kinetic assays were used to probe the DNA searching mechanism of human alkyladenine DNA glycosylase (AAG) and to test the extent to which diffusion requires B-form duplex DNA. Although AAG excises εA lesions from single-stranded DNA, it is not processive on single-stranded DNA because dissociation is faster than N-glycosidic bond cleavage. However, the AAG complex with single-stranded DNA is sufficiently stable to allow for DNA annealing when a complementary strand is added. This observation provides evidence of nonspecific association of AAG with single-stranded DNA. Single-strand gaps, bubbles, and bent structures do not impede the search by AAG. Instead, these flexible or bent structures lead to the capture of a nearby site of damage that is more efficient than that of a continuous B-form duplex. The ability of AAG to negotiate these helix discontinuities is inconsistent with a sliding mode of diffusion but can be readily explained by a hopping mode that involves microscopic dissociation and reassociation. These experiments provide evidence of relatively long-range hops that allow a searching protein to navigate around DNA binding proteins that would serve as obstacles to a sliding protein. PMID:25495964

  13. A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

    Science.gov (United States)

    Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

    2015-02-01

    Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

  14. Knowledge and exercise of human rights, and barriers and facilitators to claiming rights: a cross-sectional study of female sex workers and high-risk men who have sex with men in Andhra Pradesh, India.

    Science.gov (United States)

    Ganju, Deepika; Patel, Sangram Kishor; Prabhakar, Parimi; Adhikary, Rajatashurva

    2016-11-17

    HIV prevention interventions recognize the need to protect the rights of key populations and support them to claim their rights as a vulnerability reduction strategy. This study explores knowledge of human rights, and barriers and facilitators to claiming rights, among female sex workers (FSWs) and high-risk men who have sex with men (HR-MSM) who are beneficiaries of a community mobilization intervention in Andhra Pradesh, India. Data are drawn from a cross-sectional survey (2014) among 2400 FSWs and 1200 HR-MSM. Human rights awareness was assessed by asking respondents if they had heard of human rights (yes/no); those reporting awareness of rights were asked to spontaneously name specific rights from the following five pre-defined categories: right to health; dignity/equality; education; property; and freedom from discrimination. Respondents were classified into two groups: more knowledgeable (could identify two or more rights) and less knowledgeable (could identify one or no right). Univariate and bivariate analyses and chi-square tests were used. Data were analyzed using STATA 11.2. Overall 17% FSWs and 8% HR-MSM were not aware of their rights. Among those aware, 62% and 31% respectively were aware of just one or no right (less knowledgeable); only around half (54% vs 57%) were aware of health rights, and fewer (20% vs 16%) aware of their right to freedom from discrimination. Notably, 27% and 17% respectively had not exercised their rights. Barriers to claiming rights among FSWs and HR-MSM were neighbors (35% vs 37%), lack of knowledge (15% vs 14%), stigma (13% vs 22%) and spouse (19% FSWs). Community organizations (COs) were by far the leading facilitator in claiming rights (57% vs 72%). The study findings show that awareness of human rights is limited among FSWs and HR-MSM, and a large proportion have not claimed their rights, elevating their HIV vulnerability. For a sustained HIV response, community mobilization efforts must focus on building key populations

  15. Investigation to identify the inhibitors and facilitators of excessive absenteeism in a mining environment / Dianne Williamson

    OpenAIRE

    Williamson, Dianne

    2013-01-01

    The objective of the study was to identify the facilitators and inhibitors of excessive absenteeism in a mining environment. Absenteeism can be one of the most important human resource issues in any organisation. Absenteeism can be really difficult, but with good understanding of what causes absenteeism and how to reduce it, organisations can limit the negative side effects of employee attendance issues. Absenteeism is not only a behaviour caused by an individual's character...

  16. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  17. Characterization of molecular signature of the roots of Paeonia lactiflora during growth

    Institute of Scientific and Technical Information of China (English)

    LIU Pei; XU Yuan; YAN Hui; CHEN Jing; SHANG Er-Xin; QIAN Da-Wei; JIANG Shu; DUAN Jin-Ao

    2017-01-01

    The roots ofPaeoniae lactiflora Pall.are widely consumed as crude drugs in Asian countries due to their remarkable beneficial health effects.The present research was undertaken to illuminate the dynamic changes in metabolites and enzymes and facilitate selection of the harvesting time when the herb can provide optimum health benefits.P.lactiflora roots were analyzed at 12 stages of growth for monoterpenoid glycosides,phenols,nucleosides,nucleobases,amino acids,and polysaccharides by high-performance liquid chromatography with photodiode array detector,ultra-high pressure liquid chromatography coupled with tandem mass spectrometry,and UV spectrophotometry.The enzyme activities of plant β-glucosidases and esterases were determined by UV methods.The total content of monoterpenoid glycosides and phenols peaked in December.For nucleosides and nucleobases,the highest content appeared in April.The maximum phasic accumulation of the total amino acids took place in March,and the content of total polysaccharides reached a peak value in September.December,April,and March were selected as the appropriate harvesting times for producing natural medicinal or health food products.Plant β-glucosidases and esterases showed the highest activity in December and May,respectively.When the activity of β-glucosidase increased,esterase activity decreased,while the contents of oxypaeoniflora and paeoniflorin increased.When esterase activity increased,the contents of benzoylpaeoniflorin,paeoniflorin,and gallic acid decreased.In conclusion,the results from the present study would be useful in determination of the suitable time for harvesting P.lactiflora roots for medicinal purposes.

  18. Human Centered Hardware Modeling and Collaboration

    Science.gov (United States)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  19. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

    Science.gov (United States)

    Nagasawa, Miho; Mitsui, Shouhei; En, Shiori; Ohtani, Nobuyo; Ohta, Mitsuaki; Sakuma, Yasuo; Onaka, Tatsushi; Mogi, Kazutaka; Kikusui, Takefumi

    2015-04-17

    Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment. Copyright © 2015, American Association for the Advancement of Science.

  20. From Teaching to Facilitation

    DEFF Research Database (Denmark)

    de Graaff, Erik

    2013-01-01

    A shift from teaching to learning is characteristic of the introduction of Problem Based Learning (PBL) in an existing school. As a consequence the teaching staff has to be trained in skills like facilitating group work and writing cases. Most importantly a change in thinking about teaching...

  1. Virtual Research Environments: The role of the facilitator

    CSIR Research Space (South Africa)

    Bowers, N

    2012-06-01

    Full Text Available This conference presentation discusses the authors' duties as the facilitators of the POL-SABINA Natural Products Virtual Research Environment. In summary, they facilitated the use and content population of the Natural Products Virtual Research...

  2. Human-like object tracking and gaze estimation with PKD android.

    Science.gov (United States)

    Wijayasinghe, Indika B; Miller, Haylie L; Das, Sumit K; Bugnariu, Nicoleta L; Popa, Dan O

    2016-05-01

    As the use of robots increases for tasks that require human-robot interactions, it is vital that robots exhibit and understand human-like cues for effective communication. In this paper, we describe the implementation of object tracking capability on Philip K. Dick (PKD) android and a gaze tracking algorithm, both of which further robot capabilities with regard to human communication. PKD's ability to track objects with human-like head postures is achieved with visual feedback from a Kinect system and an eye camera. The goal of object tracking with human-like gestures is twofold : to facilitate better human-robot interactions and to enable PKD as a human gaze emulator for future studies. The gaze tracking system employs a mobile eye tracking system (ETG; SensoMotoric Instruments) and a motion capture system (Cortex; Motion Analysis Corp.) for tracking the head orientations. Objects to be tracked are displayed by a virtual reality system, the Computer Assisted Rehabilitation Environment (CAREN; MotekForce Link). The gaze tracking algorithm converts eye tracking data and head orientations to gaze information facilitating two objectives: to evaluate the performance of the object tracking system for PKD and to use the gaze information to predict the intentions of the user, enabling the robot to understand physical cues by humans.

  3. Human-like object tracking and gaze estimation with PKD android

    Science.gov (United States)

    Wijayasinghe, Indika B.; Miller, Haylie L.; Das, Sumit K.; Bugnariu, Nicoleta L.; Popa, Dan O.

    2016-05-01

    As the use of robots increases for tasks that require human-robot interactions, it is vital that robots exhibit and understand human-like cues for effective communication. In this paper, we describe the implementation of object tracking capability on Philip K. Dick (PKD) android and a gaze tracking algorithm, both of which further robot capabilities with regard to human communication. PKD's ability to track objects with human-like head postures is achieved with visual feedback from a Kinect system and an eye camera. The goal of object tracking with human-like gestures is twofold: to facilitate better human-robot interactions and to enable PKD as a human gaze emulator for future studies. The gaze tracking system employs a mobile eye tracking system (ETG; SensoMotoric Instruments) and a motion capture system (Cortex; Motion Analysis Corp.) for tracking the head orientations. Objects to be tracked are displayed by a virtual reality system, the Computer Assisted Rehabilitation Environment (CAREN; MotekForce Link). The gaze tracking algorithm converts eye tracking data and head orientations to gaze information facilitating two objectives: to evaluate the performance of the object tracking system for PKD and to use the gaze information to predict the intentions of the user, enabling the robot to understand physical cues by humans.

  4. DBGC: A Database of Human Gastric Cancer

    Science.gov (United States)

    Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

  5. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Science.gov (United States)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  6. Dynamic representations of human body movement.

    Science.gov (United States)

    Kourtzi, Z; Shiffrar, M

    1999-01-01

    Psychophysical and neurophysiological studies suggest that human body motions can be readily recognized. Human bodies are highly articulated and can move in a nonrigid manner. As a result, we perceive highly dissimilar views of the human form in motion. How does the visual system integrate multiple views of a human body in motion so that we can perceive human movement as a continuous event? The results of a set of priming experiments suggest that motion can readily facilitate the linkage of different views of a moving human. Positive priming was found for novel views of a human body that fell within the path of human movement. However, no priming was observed for novel views outside the path of motion. Furthermore, priming was restricted to those views that satisfied the biomechanical constraints of human movement. These results suggest that visual representation of human movement may be based upon the movement limitations of the human body and may reflect a dynamic interaction of motion and object-recognition processes.

  7. Ethical use of social media to facilitate qualitative research.

    Science.gov (United States)

    Lunnay, Belinda; Borlagdan, Joseph; McNaughton, Darlene; Ward, Paul

    2015-01-01

    Increasingly, qualitative health researchers might consider using social media to facilitate communication with participants. Ambiguity surrounding the potential risks intrinsic to social media could hinder ethical conduct and discourage use of this innovative method. We used some core principles of traditional human research ethics, that is, respect, integrity, and beneficence, to design our photo elicitation research that explored the social influences of drinking alcohol among 34 underage women in metropolitan South Australia. Facebook aided our communication with participants, including correspondence ranging from recruitment to feeding back results and sharing research data. This article outlines the ethical issues we encountered when using Facebook to interact with participants and provides guidance to researchers planning to incorporate social media as a tool in their qualitative studies. In particular, we raise the issues of privacy and confidentiality as contemporary risks associated with research using social media. © The Author(s) 2014.

  8. Singing can facilitate foreign language learning.

    Science.gov (United States)

    Ludke, Karen M; Ferreira, Fernanda; Overy, Katie

    2014-01-01

    This study presents the first experimental evidence that singing can facilitate short-term paired-associate phrase learning in an unfamiliar language (Hungarian). Sixty adult participants were randomly assigned to one of three "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing. Participants in the singing condition showed superior overall performance on a collection of Hungarian language tests after a 15-min learning period, as compared with participants in the speaking and rhythmic speaking conditions. This superior performance was statistically significant (p sing" learning method can facilitate verbatim memory for spoken foreign language phrases.

  9. Location-based data dissemination with human mobility using online density estimation

    NARCIS (Netherlands)

    Le Viet Duc, L Duc; Scholten, Johan; Havinga, Paul J.M.; Ngo, Hung

    The emerging wave of technology in human-centric devices such as smart phones, tablets, and other small wearable sensor modules facilitates pervasive systems and applications to be economically deployed on a large scale with human participation. To exploit such environment, data gathering and

  10. Recurrent DNA inversion rearrangements in the human genome

    DEFF Research Database (Denmark)

    Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia

    2007-01-01

    Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome...... to human genomic variation is discussed........ In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located...

  11. Demystifying facilitation of multi-actor learning processes

    OpenAIRE

    Groot, A.E.

    2002-01-01

    This thesis aims to demystify the facilitation of participatory processes in order to improve the performance of the facilitation professional. As our society is increasingly recognised as pluralistic, characterised by multiple actors with different interests, values and perceptions, participation has become a popular means of bringing about social and technical change. Across the globe, whether in agricultural devel...

  12. How do humans affect wildlife nematodes?

    Science.gov (United States)

    Weinstein, Sara B.; Lafferty, Kevin D.

    2015-01-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host–parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  13. Facilitating conditions for boundary-spanning behavior in governance networks

    OpenAIRE

    Meerkerk, Ingmar; Edelenbos, Jurian

    2017-01-01

    textabstractThis article examines the impact of two facilitating conditions for boundary-spanning behaviour in urban governance networks. While research on boundary spanning is growing, there is little attention for antecedents. Combining governance network literature on project management and organizational literature on facilitative and servant leadership, we examine two potential conditions: a facilitative project management style and executive support. We conducted survey research among p...

  14. When and Why Mimicry is Facilitated and Attenuated

    NARCIS (Netherlands)

    Stel, Mariëlle; van Dijk, Eric; van Baaren, Rick B.

    2016-01-01

    Although people tend to mimic others automatically, mimicry is facilitated or attenuated depending on the specific context. In the current paper, the authors discuss when mimicry is facilitated and attenuated depending on characteristics of situations, targets, and observers. On the basis of the

  15. Supporting Online AP Students: The Rural Facilitator and Considerations for Training

    Science.gov (United States)

    Hendrix, Nicole; Degner, Katherine

    2016-01-01

    Online courses supplemented by on-site facilitators help many rural students pursue advanced coursework, but research is warranted to better understand facilitator role and training needs. This study examined facilitation experiences, demographic characteristics, and professional development activities of rural on-site facilitators associated with…

  16. Bursty communication patterns facilitate spreading in a threshold-based epidemic dynamics.

    Science.gov (United States)

    Takaguchi, Taro; Masuda, Naoki; Holme, Petter

    2013-01-01

    Records of social interactions provide us with new sources of data for understanding how interaction patterns affect collective dynamics. Such human activity patterns are often bursty, i.e., they consist of short periods of intense activity followed by long periods of silence. This burstiness has been shown to affect spreading phenomena; it accelerates epidemic spreading in some cases and slows it down in other cases. We investigate a model of history-dependent contagion. In our model, repeated interactions between susceptible and infected individuals in a short period of time is needed for a susceptible individual to contract infection. We carry out numerical simulations on real temporal network data to find that bursty activity patterns facilitate epidemic spreading in our model.

  17. Bursty communication patterns facilitate spreading in a threshold-based epidemic dynamics.

    Directory of Open Access Journals (Sweden)

    Taro Takaguchi

    Full Text Available Records of social interactions provide us with new sources of data for understanding how interaction patterns affect collective dynamics. Such human activity patterns are often bursty, i.e., they consist of short periods of intense activity followed by long periods of silence. This burstiness has been shown to affect spreading phenomena; it accelerates epidemic spreading in some cases and slows it down in other cases. We investigate a model of history-dependent contagion. In our model, repeated interactions between susceptible and infected individuals in a short period of time is needed for a susceptible individual to contract infection. We carry out numerical simulations on real temporal network data to find that bursty activity patterns facilitate epidemic spreading in our model.

  18. Flexible Human Behavior Analysis Framework for Video Surveillance Applications

    Directory of Open Access Journals (Sweden)

    Weilun Lao

    2010-01-01

    Full Text Available We study a flexible framework for semantic analysis of human motion from surveillance video. Successful trajectory estimation and human-body modeling facilitate the semantic analysis of human activities in video sequences. Although human motion is widely investigated, we have extended such research in three aspects. By adding a second camera, not only more reliable behavior analysis is possible, but it also enables to map the ongoing scene events onto a 3D setting to facilitate further semantic analysis. The second contribution is the introduction of a 3D reconstruction scheme for scene understanding. Thirdly, we perform a fast scheme to detect different body parts and generate a fitting skeleton model, without using the explicit assumption of upright body posture. The extension of multiple-view fusion improves the event-based semantic analysis by 15%–30%. Our proposed framework proves its effectiveness as it achieves a near real-time performance (13–15 frames/second and 6–8 frames/second for monocular and two-view video sequences.

  19. Germination phenology determines the propensity for facilitation and competition.

    Science.gov (United States)

    Leverett, Lindsay D

    2017-09-01

    A single plant can interact both positively and negatively with its neighbors through the processes of facilitation and competition, respectively. Much of the variation in the balance of facilitation and competition that individuals experience can be explained by the degree of physical stress and the sizes or ages of plants during the interaction. Germination phenology partly controls both of these factors, but its role in defining the facilitation-competition balance has not been explicitly considered. I performed an experiment in a population of the winter annual Arabidopsis thaliana (Brassicaceae) to test whether germinating during physically stressful periods leads to facilitation while germinating during periods that promote growth and reproduction leads to competition. I manipulated germination and neighbor presence across two years in order to quantify the effects of the local plant community on survival, fecundity, and total fitness as a function of germination phenology. Neighbors increased survival when germination occurred under conditions that were unsuitable for survival, but they reduced fecundity in germinants that were otherwise the most fecund. Later germination was associated with facilitation in the first year but competition in the second year. These episodes of facilitation and competition opposed each other, leading to no net effect of neighbors when averaged over all cohorts. These results indicate that variation in germination timing can explain some of the variation in the facilitation-competition balance in plant communities. © 2017 by the Ecological Society of America.

  20. Reversal Learning in Humans and Gerbils: Dynamic Control Network Facilitates Learning.

    Science.gov (United States)

    Jarvers, Christian; Brosch, Tobias; Brechmann, André; Woldeit, Marie L; Schulz, Andreas L; Ohl, Frank W; Lommerzheim, Marcel; Neumann, Heiko

    2016-01-01

    Biologically plausible modeling of behavioral reinforcement learning tasks has seen great improvements over the past decades. Less work has been dedicated to tasks involving contingency reversals, i.e., tasks in which the original behavioral goal is reversed one or multiple times. The ability to adjust to such reversals is a key element of behavioral flexibility. Here, we investigate the neural mechanisms underlying contingency-reversal tasks. We first conduct experiments with humans and gerbils to demonstrate memory effects, including multiple reversals in which subjects (humans and animals) show a faster learning rate when a previously learned contingency re-appears. Motivated by recurrent mechanisms of learning and memory for object categories, we propose a network architecture which involves reinforcement learning to steer an orienting system that monitors the success in reward acquisition. We suggest that a model sensory system provides feature representations which are further processed by category-related subnetworks which constitute a neural analog of expert networks. Categories are selected dynamically in a competitive field and predict the expected reward. Learning occurs in sequentialized phases to selectively focus the weight adaptation to synapses in the hierarchical network and modulate their weight changes by a global modulator signal. The orienting subsystem itself learns to bias the competition in the presence of continuous monotonic reward accumulation. In case of sudden changes in the discrepancy of predicted and acquired reward the activated motor category can be switched. We suggest that this subsystem is composed of a hierarchically organized network of dis-inhibitory mechanisms, dubbed a dynamic control network (DCN), which resembles components of the basal ganglia. The DCN selectively activates an expert network, corresponding to the current behavioral strategy. The trace of the accumulated reward is monitored such that large sudden

  1. Acer negundo invasion along a successional gradient: early direct facilitation by native pioneers and late indirect facilitation by conspecifics.

    Science.gov (United States)

    Saccone, Patrick; Pagès, Jean-Philippe; Girel, Jacky; Brun, Jean-Jacques; Michalet, Richard

    2010-08-01

    *Here, we analysed the role of direct and indirect plant interactions in the invasion process of Acer negundo along a natural successional gradient in the Middle Rhone floodplain (France). We addressed two questions: What are the responses of the invasive Acer seedlings to native communities' effects along the successional gradient? What are the effects of the invasive Acer adult trees on the native communities? *In the three communities (Salix, Acer and Fraxinus stands) we transplanted juveniles of the invasive and juveniles of the natives within the forest and in experimental gaps, and with and without the herb layer. We also quantified changes in understory functional composition, light, nitrogen and moisture among treatments. *Acer seedlings were directly facilitated for survival in the Salix and Acer communities and indirectly facilitated for growth by adult Acer through the reduction of the abundance of highly competitive herbaceous competitors. *We conclude that direct facilitation by the tree canopy of the native pioneer Salix is very likely the main biotic process that induced colonization of the invasive Acer in the floodplain and that indirect facilitation by adult conspecifics contributed to population establishment.

  2. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  3. Spatial part-set cuing facilitation.

    Science.gov (United States)

    Kelley, Matthew R; Parasiuk, Yuri; Salgado-Benz, Jennifer; Crocco, Megan

    2016-07-01

    Cole, Reysen, and Kelley [2013. Part-set cuing facilitation for spatial information. Journal of Experimental Psychology: Learning, Memory, & Cognition, 39, 1615-1620] reported robust part-set cuing facilitation for spatial information using snap circuits (a colour-coded electronics kit designed for children to create rudimentary circuit boards). In contrast, Drinkwater, Dagnall, and Parker [2006. Effects of part-set cuing on experienced and novice chess players' reconstruction of a typical chess midgame position. Perceptual and Motor Skills, 102(3), 645-653] and Watkins, Schwartz, and Lane [1984. Does part-set cuing test for memory organization? Evidence from reconstructions of chess positions. Canadian Journal of Psychology/Revue Canadienne de Psychologie, 38(3), 498-503] showed no influence of part-set cuing for spatial information when using chess boards. One key difference between the two procedures was that the snap circuit stimuli were explicitly connected to one another, whereas chess pieces were not. Two experiments examined the effects of connection type (connected vs. unconnected) and cue type (cued vs. uncued) on memory for spatial information. Using chess boards (Experiment 1) and snap circuits (Experiment 2), part-set cuing facilitation only occurred when the stimuli were explicitly connected; there was no influence of cuing with unconnected stimuli. These results are potentially consistent with the retrieval strategy disruption hypothesis, as well as the two- and three-mechanism accounts of part-set cuing.

  4. Trade Facilitation in Ethiopia:

    African Journals Online (AJOL)

    Tilahun_EK

    so doing, it attempts to examine how Ethiopia's WTO Accession and trade facilitation ... the more expensive imports, exports and production becomes rendering. Ethiopian ..... can reserve the right to refuse requests of importers for the fifth valuation method to ..... units may find it easier to deal with post clearance audit. In the ...

  5. Vacuum ultraviolet photoionization of carbohydrates and nucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Joong-Won, E-mail: jshin@govst.edu [Division of Science, Governors State University, University Park, Illinois 60484-0975 (United States); Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872 (United States); Bernstein, Elliot R., E-mail: erb@lamar.colostate.edu [Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872 (United States)

    2014-01-28

    Carbohydrates (2-deoxyribose, ribose, and xylose) and nucleotides (adenosine-, cytidine-, guanosine-, and uridine-5{sup ′}-monophosphate) are generated in the gas phase, and ionized with vacuum ultraviolet photons (VUV, 118.2 nm). The observed time of flight mass spectra of the carbohydrate fragmentation are similar to those observed [J.-W. Shin, F. Dong, M. Grisham, J. J. Rocca, and E. R. Bernstein, Chem. Phys. Lett. 506, 161 (2011)] for 46.9 nm photon ionization, but with more intensity in higher mass fragment ions. The tendency of carbohydrate ions to fragment extensively following ionization seemingly suggests that nucleic acids might undergo radiation damage as a result of carbohydrate, rather than nucleobase fragmentation. VUV photoionization of nucleotides (monophosphate-carbohydrate-nucleobase), however, shows that the carbohydrate-nucleobase bond is the primary fragmentation site for these species. Density functional theory (DFT) calculations indicate that the removed carbohydrate electrons by the 118.2 nm photons are associated with endocyclic C–C and C–O ring centered orbitals: loss of electron density in the ring bonds of the nascent ion can thus account for the observed fragmentation patterns following carbohydrate ionization. DFT calculations also indicate that electrons removed from nucleotides under these same conditions are associated with orbitals involved with the nucleobase-saccharide linkage electron density. The calculations give a general mechanism and explanation of the experimental results.

  6. Vacuum ultraviolet photoionization of carbohydrates and nucleotides

    International Nuclear Information System (INIS)

    Shin, Joong-Won; Bernstein, Elliot R.

    2014-01-01

    Carbohydrates (2-deoxyribose, ribose, and xylose) and nucleotides (adenosine-, cytidine-, guanosine-, and uridine-5 ′ -monophosphate) are generated in the gas phase, and ionized with vacuum ultraviolet photons (VUV, 118.2 nm). The observed time of flight mass spectra of the carbohydrate fragmentation are similar to those observed [J.-W. Shin, F. Dong, M. Grisham, J. J. Rocca, and E. R. Bernstein, Chem. Phys. Lett. 506, 161 (2011)] for 46.9 nm photon ionization, but with more intensity in higher mass fragment ions. The tendency of carbohydrate ions to fragment extensively following ionization seemingly suggests that nucleic acids might undergo radiation damage as a result of carbohydrate, rather than nucleobase fragmentation. VUV photoionization of nucleotides (monophosphate-carbohydrate-nucleobase), however, shows that the carbohydrate-nucleobase bond is the primary fragmentation site for these species. Density functional theory (DFT) calculations indicate that the removed carbohydrate electrons by the 118.2 nm photons are associated with endocyclic C–C and C–O ring centered orbitals: loss of electron density in the ring bonds of the nascent ion can thus account for the observed fragmentation patterns following carbohydrate ionization. DFT calculations also indicate that electrons removed from nucleotides under these same conditions are associated with orbitals involved with the nucleobase-saccharide linkage electron density. The calculations give a general mechanism and explanation of the experimental results

  7. Positive experiences with a specialist as facilitator in general practice

    DEFF Research Database (Denmark)

    Kousgaard, Marius Brostrøm; Thorsen, Thorkil

    2012-01-01

    The use of facilitators for quality improvement in general practice has accelerated during the past decade. As general practitioners (GPs) or pharmacists have typically been used as facilitators, there is a lack of knowledge of how other professionals function as facilitators. This article explores...

  8. Facilitation: A Novel Way to Improve Students' Well-being

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine Olesen; Madsen, Lene Møller

    2013-01-01

    In this article we analyze a project that used facilitation techniques, which are known from training in industry, to improve the study environment at a public research university in Denmark. In 2009, the project was initiated in one graduate program; and it has subsequently been modified...... and institutionalized. The project did not change the teaching format, but introduced facilitated study-groups using peer learning. Itwas successful in increasing students’ well-being. While peer learning and study groups are well-known in higher education, facilitation is a different and novel tool. We argue...... that facilitation makes study groups more inclusive, and they provide the potential for deep learning by structuring the learning situation...

  9. Increasing awareness about self and facilitation practice in preparation for transitioning to a new role – the critical reflective process of becoming a certified professional facilitator

    Directory of Open Access Journals (Sweden)

    Pauline Bergin

    2015-11-01

    Full Text Available Background and context: I have been working as a practice developer in the Australian healthcare system for more than 10 years. For the last seven of those I was a lead facilitator for a practice development programme that is being implemented across a large statewide health service. The programme’s purpose is to create person-centred care environments that enable patient and staff empowerment. My role was in a small team that supported facilitators predominantly at local health district and state levels. The intent was to phase out the team over time as capacity increased and local teams gained the required skills and knowledge to continue implementing the programme. During the two-year final transition phase, a strategic plan was implemented to guide the development of systems and capacity that would support the programme once the team had exited. A decision was made to shorten the phasing-out period and during this transition period I found myself facing an unknown and unpredictable future, for the first time in my career promoting something other than my clinical nursing skills. As I transitioned into an independent facilitator role I wanted to consolidate my expertise as a facilitator, to gain further learning in specific areas and to achieve recognition of the facilitation skill set I had honed over time, and which has now become my way of working. Given that my experience was limited to the healthcare context, diverse though it is, I pondered which of my skills would stand me in good stead to enable groups and organisations as an independent professional facilitator and what additional skills I’d need. I was encouraged to become a certified professional facilitator by colleagues who were using process facilitation and person-centredness more broadly. This paper reflects my experience of the preparation, assessment and accreditation process, the feedback I received from my international assessors and how these are influencing my

  10. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Karottki, Dorina Gabriela

    2014-01-01

    at different locations (spatial variability), times (temporal variability) or particle size fraction across different experimental systems of acellular conditions, cultured cells, animals and humans. Nevertheless, there is substantial variation in the genotoxic, inflammation and oxidative stress potential......Generation of oxidatively damaged DNA by particulate matter (PM) is hypothesized to occur via production of reactive oxygen species (ROS) and inflammation. We investigated this hypothesis by comparing ROS production, inflammation and oxidatively damaged DNA in different experimental systems...... investigating air pollution particles. There is substantial evidence indicating that exposure to air pollution particles was associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans, which is supported by observations of elevated levels of genotoxicity...

  11. Can Questions Facilitate Learning from Illustrated Science Texts?

    Science.gov (United States)

    Iding, Marie K.

    1997-01-01

    Examines the effectiveness of using questions to facilitate processing of diagrams in science texts. Investigates three different elements in experiments on college students. Finds that questions about illustrations do not facilitate learning. Discusses findings with reference to cognitive load theory, the dual coding perspective, and the…

  12. Using Text Mining to Characterize Online Discussion Facilitation

    Science.gov (United States)

    Ming, Norma; Baumer, Eric

    2011-01-01

    Facilitating class discussions effectively is a critical yet challenging component of instruction, particularly in online environments where student and faculty interaction is limited. Our goals in this research were to identify facilitation strategies that encourage productive discussion, and to explore text mining techniques that can help…

  13. Teacher’s action zone in facilitating group dynamics

    Directory of Open Access Journals (Sweden)

    Dagmara Gałajda

    2012-01-01

    Full Text Available As believed by many researchers (Dörnyei & Murphey 2003, Hadfield 1992, classroom climate is strongly determined by the dynamics of the learning group and its development over time. For this reason, the role of the teacher in facilitating group processes seems to be of primary importance since it is the teacher who has long been regarded as the group leader in both teacher-centred and learner-centred classrooms.The presentation focuses not only on positive but also on negative forms of classroom dynamics together with management techniques for dealing with conflicts, educational alienation and psychological defensiveness. This, in turn, leads to the concept of facilitator style based on Heron’s (2006 model of facilitation, which consists of six dimensions and three modes. In the paper particular emphasis is placed on the presentation and comparison of various theories of leadership, namely Heron’s system of facilitation, Hersey and Blanchard’s situational-leadership theory (1982 and Bass and Avolio’s transactional versus transformational leadership theory (1984.

  14. The Motivation-Facilitation Theory of Prenatal Care Access.

    Science.gov (United States)

    Phillippi, Julia C; Roman, Marian W

    2013-01-01

    Despite the availability of services, accessing health care remains a problem in the United States and other developed countries. Prenatal care has the potential to improve perinatal outcomes and decrease health disparities, yet many women struggle with access to care. Current theories addressing access to prenatal care focus on barriers, although such knowledge is minimally useful for clinicians. We propose a middle-range theory, the motivation-facilitation theory of prenatal care access, which condenses the prenatal care access process into 2 interacting components: motivation and facilitation. Maternal motivation is the mother's desire to begin and maintain care. Facilitation represents the goal of the clinic to create easy, open access to person-centered beneficial care. This simple model directs the focus of research and change to the interface of the woman and the clinic and encourages practice-level interventions that facilitate women entering and maintaining prenatal care. © 2013 by the American College of Nurse‐Midwives.

  15. Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2013-12-01

    Objective. Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach. NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main results. The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for the successful encoding of sample phase information on more difficult DMS trials. This was validated by the delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the sample phase which facilitated task performance in the subsequent, delayed match phase, on difficult trials that required more precise encoding of sample information. Significance. These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain.

  16. Facilitation of Adult Development

    Science.gov (United States)

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  17. Facilitating and Inhibiting Factors of Sexual Behavior among Migrants in Transition from Mexico to the United States

    OpenAIRE

    Guerra-Ordoñez, Jesús Alejandro; Benavides-Torres, Raquel A.; Zapata-Garibay, Rogelio; Onofre-Rodríguez, Dora Julia; Márquez-Vega, María Aracely; Zamora-Carmona, Gabriela

    2017-01-01

    Introduction Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the most prevalent infectious diseases in the border region of Mexico due to the flow of migrants under desperate conditions, encouraging casual and unprotected sex. Since this has become a binational public health problem, it is important to understand the factors that predict these sexual behaviors. The aim of the current study was to investigate the facilitators and inhibitors of transitio...

  18. Facilitating and Inhibiting Factors of Sexual Behavior among Migrants in Transition from Mexico to the United States

    OpenAIRE

    Jesús Alejandro Guerra-Ordoñez; Jesús Alejandro Guerra-Ordoñez; Raquel A. Benavides-Torres; Rogelio Zapata-Garibay; Dora Julia Onofre-Rodríguez; María Aracely Márquez-Vega; Gabriela Zamora-Carmona

    2017-01-01

    IntroductionHuman immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the most prevalent infectious diseases in the border region of Mexico due to the flow of migrants under desperate conditions, encouraging casual and unprotected sex. Since this has become a binational public health problem, it is important to understand the factors that predict these sexual behaviors. The aim of the current study was to investigate the facilitators and inhibitors of transition in...

  19. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  20. Facilitators and barriers to non-medical prescribing - A systematic review and thematic synthesis.

    Science.gov (United States)

    Graham-Clarke, Emma; Rushton, Alison; Noblet, Timothy; Marriott, John

    2018-01-01

    Non-medical prescribing has the potential to deliver innovative healthcare within limited finances. However, uptake has been slow, and a proportion of non-medical prescribers do not use the qualification. This systematic review aimed to describe the facilitators and barriers to non-medical prescribing in the United Kingdom. The systematic review and thematic analysis included qualitative and mixed methods papers reporting facilitators and barriers to independent non-medical prescribing in the United Kingdom. The following databases were searched to identify relevant papers: AMED, ASSIA, BNI, CINAHL, EMBASE, ERIC, MEDLINE, Open Grey, Open access theses and dissertations, and Web of Science. Papers published between 2006 and March 2017 were included. Studies were quality assessed using a validated tool (QATSDD), then underwent thematic analysis. The protocol was registered with PROSPERO (CRD42015019786). Of 3991 potentially relevant identified studies, 42 were eligible for inclusion. The studies were generally of moderate quality (83%), and most (71%) were published 2007-2012. The nursing profession dominated the studies (30/42). Thematic analysis identified three overarching themes: non-medical prescriber, human factors, and organisational aspects. Each theme consisted of several sub-themes; the four most highly mentioned were 'medical professionals', 'area of competence', 'impact on time' and 'service'. Sub-themes were frequently interdependent on each other, having the potential to act as a barrier or facilitator depending on circumstances. Addressing the identified themes and subthemes enables strategies to be developed to support and optimise non-medical prescribing. Further research is required to identify if similar themes are encountered by other non-medical prescribing groups than nurses and pharmacists.

  1. Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

    Science.gov (United States)

    Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

    2012-01-01

    The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

  2. Independent Coactors May Improve Performance and Lower Workload: Viewing Vigilance Under Social Facilitation.

    Science.gov (United States)

    Claypoole, Victoria L; Szalma, James L

    2018-04-01

    The purpose of the present study was to examine the effects of an independent coactor on vigilance task performance. It was hypothesized that the presence of an independent coactor would improve performance in terms of the proportion of false alarms while also increasing perceived workload and stress. Vigilance, or the ability to maintain attention for extended periods, is of great interest to human factors psychologists. Substantial work has focused on improving vigilance task performance, typically through motivational interventions. Of interest to vigilance researchers is the application of social facilitation as a means of enhancing vigilance. Social facilitation seeks to explain how social presence may improve performance. A total of 100 participants completed a 24-min vigil either alone or in the presence of an independent (confederate) coactor. Participants completed measures of perceived workload and stress. The results indicated that performance (i.e., proportion of false alarms) was improved for those who completed the vigil in the presence of an independent coactor. Interestingly, perceived workload was actually lower for those who completed the vigil in the presence of an independent coactor, although perceived stress was not affected by the manipulation. Authors of future research should extend these findings to other forms of social facilitation and examine vigilance task performance in social contexts in order to determine the utility of social presence for improving vigilance. The use of coactors may be an avenue for organizations to consider utilizing to improve performance because of its relative cost-effectiveness and easy implementation.

  3. Barriers and Facilitators for implementing programmes and services to address hyperglycaemia in pregnancy in low and middle income countries

    DEFF Research Database (Denmark)

    Nielsen, Karoline Kragelund; Damm, Peter; Bygbjerg, Ib C

    2018-01-01

    AIMS: An estimated 87.6% of hyperglycaemia in pregnancy cases is in low and middle income countries (LMICs). The aim of this study is to review the evidence on barriers and facilitators to programmes and services addressing hyperglycaemia in pregnancy in LMICs. METHODS: A systematic review...... they relate to capacity in terms of human and material resources; availability of feasible and appropriate guidelines; organizational management and referral pathways. Individual level barriers and facilitators include knowledge; risk perception; illness beliefs; financial condition; work obligations......; concerns for the baby and hardship associated with services. At the social and societal level, perceptions and norms related to women's roles, mobility and health; the knowledge and support of the women's social network; and structural aspects are important influencing factors. CONCLUSIONS: Numerous...

  4. Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective

    Directory of Open Access Journals (Sweden)

    Martina C. Cornel

    2017-08-01

    Full Text Available More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

  5. Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective.

    Science.gov (United States)

    Cornel, Martina C; van El, Carla G

    2017-01-01

    More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

  6. Accommodating human values in the climate regime

    Directory of Open Access Journals (Sweden)

    Rosalind Cook

    2008-12-01

    Full Text Available The climate regime addresses one of the most important challenges facing humankind today. However, while the environmental and economic sides of the problem are well represented, it lacks the inclusion of social and human aspects. The human rights regime, in contrast, is a regime which has been established precisely to implement human values. This article ex-plains the problems of climate change in terms of human values and argues that some proce-dures from the human rights regime offer possibilities for improvement. It is submitted that through the inclusion of human rights instruments, such as individual communication, pro-gressive realisation and authoritative interpretation, the inclusion of human values into the climate regime will be facilitated. This article presents these instruments and discusses their potential for inclusion in the climate regime.

  7. Schema-driven facilitation of new hierarchy learning in the transitive inference paradigm

    Science.gov (United States)

    Kumaran, Dharshan

    2013-01-01

    Prior knowledge, in the form of a mental schema or framework, is viewed to facilitate the learning of new information in a range of experimental and everyday scenarios. Despite rising interest in the cognitive and neural mechanisms underlying schema-driven facilitation of new learning, few paradigms have been developed to examine this issue in humans. Here we develop a multiphase experimental scenario aimed at characterizing schema-based effects in the context of a paradigm that has been very widely used across species, the transitive inference task. We show that an associative schema, comprised of prior knowledge of the rank positions of familiar items in the hierarchy, has a marked effect on transitivity performance and the development of relational knowledge of the hierarchy that cannot be accounted for by more general changes in task strategy. Further, we show that participants are capable of deploying prior knowledge to successful effect under surprising conditions (i.e., when corrective feedback is totally absent), but only when the associative schema is robust. Finally, our results provide insights into the cognitive mechanisms underlying such schema-driven effects, and suggest that new hierarchy learning in the transitive inference task can occur through a contextual transfer mechanism that exploits the structure of associative experiences. PMID:23782509

  8. Schema-driven facilitation of new hierarchy learning in the transitive inference paradigm.

    Science.gov (United States)

    Kumaran, Dharshan

    2013-06-19

    Prior knowledge, in the form of a mental schema or framework, is viewed to facilitate the learning of new information in a range of experimental and everyday scenarios. Despite rising interest in the cognitive and neural mechanisms underlying schema-driven facilitation of new learning, few paradigms have been developed to examine this issue in humans. Here we develop a multiphase experimental scenario aimed at characterizing schema-based effects in the context of a paradigm that has been very widely used across species, the transitive inference task. We show that an associative schema, comprised of prior knowledge of the rank positions of familiar items in the hierarchy, has a marked effect on transitivity performance and the development of relational knowledge of the hierarchy that cannot be accounted for by more general changes in task strategy. Further, we show that participants are capable of deploying prior knowledge to successful effect under surprising conditions (i.e., when corrective feedback is totally absent), but only when the associative schema is robust. Finally, our results provide insights into the cognitive mechanisms underlying such schema-driven effects, and suggest that new hierarchy learning in the transitive inference task can occur through a contextual transfer mechanism that exploits the structure of associative experiences.

  9. Impact of Student vs Faculty Facilitators on Motivational Interviewing Student Outcomes.

    Science.gov (United States)

    Widder-Prewett, Rebecca; Draime, Juanita A; Cameron, Ginger; Anderson, Douglas; Pinkerton, Mark; Chen, Aleda M H

    2017-08-01

    Objective. To determine the impact of student or faculty facilitation on student self-assessed attitudes, confidence, and competence in motivational interviewing (MI) skills; actual competence; and evaluation of facilitator performance. Methods. Second-year pharmacy (P2) students were randomly assigned to a student or faculty facilitator for a four-hour, small-group practice of MI skills. MI skills were assessed in a simulated patient encounter with the mMITI (modified Motivational Interviewing Treatment Integrity) tool. Students completed a pre-post, 6-point, Likert-type assessment addressing the research objectives. Differences were assessed using a Mann-Whitney U test. Results. Student (N=44) post-test attitudes, confidence, perceived or actual competence, and evaluations of facilitator performance were not different for faculty- and student-facilitated groups. Conclusion. Using pharmacy students as small-group facilitators did not affect student performance and were viewed as equally favorable. Using pharmacy students as facilitators can lessen faculty workload and provide an outlet for students to develop communication and facilitation skills that will be needed in future practice.

  10. African-American Fathers' Perspectives on Facilitators and Barriers to Father-Son Sexual Health Communication.

    Science.gov (United States)

    Randolph, Schenita D; Coakley, Tanya; Shears, Jeffrey; Thorpe, Roland J

    2017-06-01

    African-American males ages 13 through 24 are disproportionately affected by sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), accounting for over half of all HIV infections in this age group in the United States. Clear communication between African-American parents and their youth about sexual health is associated with higher rates of sexual abstinence, condom use, and intent to delay initiation of sexual intercourse. However, little is known about African-American fathers' perceptions of what facilitates and inhibits sexual health communication with their preadolescent and adolescent sons. We conducted focus groups with 29 African-American fathers of sons ages 10-15 to explore perceived facilitators and barriers for father-son communication about sexual health. Participants were recruited from barbershops in metropolitan and rural North Carolina communities highly affected by STIs and HIV, and data were analyzed using content analysis. Three factors facilitated father-son communication: (a) fathers' acceptance of their roles and responsibilities; (b) a positive father-son relationship; and (c) fathers' ability to speak directly to their sons about sex. We also identified three barriers: (a) fathers' difficulty in initiating sexual health discussions with their sons; (b) sons' developmental readiness for sexual health information; and (c) fathers' lack of experience in talking with their own fathers about sex. These findings have implications for father-focused prevention interventions aimed at reducing risky sexual behaviors in adolescent African-American males. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

    Science.gov (United States)

    Janovitz, Tyler; Wong, Susan; Young, Neal S; Oliveira, Thiago; Falck-Pedersen, Erik

    2017-11-01

    The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparison of educational facilitation approaches for Grade R ...

    African Journals Online (AJOL)

    The Early Childhood Development Manager in Mpumalanga is faced with the problem of providing evidence-based guidance of the best facilitation approach in the Grade R context. An investigation on the effect of facilitation, i.e. play-based or formal instruction, on Grade R performance scores in English Additional ...

  13. Facilitating creativity in handicapped and non-handicapped children ...

    African Journals Online (AJOL)

    The prime objective of this paper is to create awareness on the presence of the handicapped in Nigeria and the need to facilitate creative potentials in handicapped and non-handicapped children. Various factors that could facilitate creativity and other factors that could inhibit creativity were discussed. The implications for ...

  14. Implementing healthier foodservice guidelines in hospital and federal worksite cafeterias: barriers, facilitators and keys to success.

    Science.gov (United States)

    Jilcott Pitts, S B; Graham, J; Mojica, A; Stewart, L; Walter, M; Schille, C; McGinty, J; Pearsall, M; Whitt, O; Mihas, P; Bradley, A; Simon, C

    2016-12-01

    Healthy foodservice guidelines are being implemented in worksites and healthcare facilities to increase access to healthy foods by employees and public populations. However, little is known about the barriers to and facilitators of implementation. The present study aimed to examine barriers to and facilitators of implementation of healthy foodservice guidelines in federal worksite and hospital cafeterias. Using a mixed-methods approach, including a quantitative survey followed by a qualitative, in-depth interview, we examined: (i) barriers to and facilitators of implementation; (ii) behavioural design strategies used to promote healthier foods and beverages; and (iii) how implementation of healthy foodservice guidelines influenced costs and profitability. We used a purposive sample of five hospital and four federal worksite foodservice operators who recently implemented one of two foodservice guidelines: the United States Department of Health and Human Services/General Services Administration Health and Sustainability Guidelines ('Guidelines') in federal worksites or the Partnership for a Healthier America Hospital Healthier Food Initiative ('Initiative') in hospitals. Descriptive statistics were used to analyse quantitative survey data. Qualitative data were analysed using a deductive approach. Implementation facilitators included leadership support, adequate vendor selections and having dietitians assist with implementation. Implementation barriers included inadequate selections from vendors, customer complaints and additional expertise required for menu labelling. Behavioural design strategies used most frequently included icons denoting healthier options, marketing using social media and placement of healthier options in prime locations. Lessons learned can guide subsequent steps for future healthy foodservice guideline implementation in similar settings. © 2016 The British Dietetic Association Ltd.

  15. Facilitation of voluntary goal-directed action by reward cues.

    Science.gov (United States)

    Lovibond, Peter F; Colagiuri, Ben

    2013-10-01

    Reward-associated cues are known to influence motivation to approach both natural and man-made rewards, such as food and drugs. However, the mechanisms underlying these effects are not well understood. To model these processes in the laboratory with humans, we developed an appetitive Pavlovian-instrumental transfer procedure with a chocolate reward. We used a single unconstrained response that led to an actual rather than symbolic reward to assess the strength of reward motivation. Presentation of a chocolate-paired cue, but not an unpaired cue, markedly enhanced instrumental responding over a 30-s period. The same pattern was observed with 10-s and 30-s cues, showing that close cue-reward contiguity is not necessary for facilitation of reward-directed action. The results confirm that reward-related cues can instigate voluntary action to obtain that reward. The effectiveness of long-duration cues suggests that in clinical settings, attention should be directed to both proximal and distal cues for reward.

  16. A Gestalt Point of View on Facilitating Growth in Counseling

    Science.gov (United States)

    Harman, Robert L.

    1975-01-01

    If counselors are to be facilitators of client growth, it would seem essentail that they become familiar with the concept of growth and ways to facilitate it. The author defines growth from a gestalt therapy point of view and provides techniques and examples of ways to facilitate client growth. (Author)

  17. Types of internal facilitation activities in hospitals implementing evidence-based interventions.

    Science.gov (United States)

    Baloh, Jure; Zhu, Xi; Ward, Marcia M

    2017-01-25

    Implementation models, frameworks, and theories recognize the importance of activities that facilitate implementation success. However, little is known about internal facilitation activities that hospital personnel engage in during implementation efforts. The aim of the study was to examine internal facilitation activities at 10 critical access hospitals in rural Iowa during their implementation of TeamSTEPPS, a patient safety intervention, and to identify characteristics that distinguish different types of facilitation activities. We followed 10 critical access hospitals for 2 years after the onset of implementation, conducting quarterly interviews with key informants. On the basis of the transcripts from the first two quarters, a coding template was developed using inductive analyses. The template was then applied deductively to code all interview transcripts. Using comparative analysis, we examined the characteristics that distinguish between the facilitation types. We identified four types of facilitation activities-Leadership, Buy-in, Customization, and Accountability. Individuals and teams engaged in different types of facilitation activities, both in a planned and an ad hoc manner. These activities targeted at both people and practices and exhibited varying temporal patterns (start and peak time). There are four types of facilitation activities that hospitals engage in while implementing evidence-based practices, offering a parsimonious way to characterize facilitation activities. New theoretical and empirical research opportunities are discussed. Understanding the types of facilitation activities and their distinguishing characteristics can assist managers in planning and executing implementations of evidence-based interventions.

  18. Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates.

    Science.gov (United States)

    Hodge, L D; Barrett, J M; Welter, D A

    1995-04-01

    There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G-specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell.

  19. Distinct olfactory cross-modal effects on the human motor system.

    Directory of Open Access Journals (Sweden)

    Simone Rossi

    Full Text Available BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications.

  20. Barriers and facilitators of mental health screening in pregnancy.

    Science.gov (United States)

    Kingston, Dawn; Austin, Marie-Paule; Heaman, Maureen; McDonald, Sheila; Lasiuk, Gerri; Sword, Wendy; Giallo, Rebecca; Hegadoren, Kathy; Vermeyden, Lydia; van Zanten, Sander Veldhuyzen; Kingston, Joshua; Jarema, Karly; Biringer, Anne

    2015-11-01

    Access to mental health services during pregnancy is most commonly mobilized through formal mental health screening. However, few studies to date have identified barriers and facilitators that affect pregnant women's responses to mental health screening. The objective was to identify barriers and facilitators that influence pregnant women's responses to the screening process and factors associated with their identification. This multi-site, cross-sectional survey recruited pregnant women >16 years of age who spoke/read English in Alberta, Canada. Main outcomes were barriers and facilitators of mental health screening. Descriptive statistics were generated to identify the most common barriers and facilitators and multivariable logistic regression models were conducted to determine factors associated with barriers and facilitators. Study participation rate was 92% (460/500). Women's most common barriers were: significant others normalizing their emotional difficulties; desiring to handle mental health problems on their own; preferring to discuss feelings with significant others; and not knowing what emotions were 'normal'. Women who identified these barriers were more likely not to have been treated previously for mental illness, were primiparous, and could not be completely honest with their provider. Main facilitators were provider characteristics (sensitive, interested), reassurance that mental healthcare is a part of routine prenatal care, hearing that other women have emotional problems during pregnancy and knowing that help was available. The sample comprised largely Caucasian, well-educated, and partnered women, which limits generalizability of the findings. Personal and stigma-related barriers influence pregnant women's responses to mental health screening. Efforts to minimize barriers and enhance facilitators should be explored as potential strategies for optimizing prenatal mental health screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Factors Affecting Rural Facilitators’ Role: Iran

    OpenAIRE

    Azimi, Farideh; Kamali, Mohammad Bagher

    2011-01-01

    This study aimed to examine key factors affecting rural female facilitators’ role in participatory rural development in Tehran Province. Since the researchers intended to have a better insight into the facilitators’ role and employ inquiry as a learning forum for bringing about changes for all participants, they preferred to use a case study based upon an appreciative inquiry method. The study divided the factors affecting the facilitators’ role into two main categories: driving factors...

  2. Learning to Facilitate (Online) Meetings

    DEFF Research Database (Denmark)

    Reimann, Peter; Bull, Susan; Vatrapu, Ravi

    2013-01-01

    We describe an approach to teaching collaboration skills directly by building on competences for meeting facilitation. (Online) meetings provide a rich arena to practice collaboration since they can serve multiple purposes: learning, problem solving, decision making, idea generation and advancement...

  3. African Journal of Cross-Cultural Psychology and Sport Facilitation ...

    African Journals Online (AJOL)

    African Journal of Cross-Cultural Psychology and Sport Facilitation: Advanced Search. Journal Home > African Journal of Cross-Cultural Psychology and Sport Facilitation: Advanced Search. Log in or Register to get access to full text downloads.

  4. Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

    Science.gov (United States)

    Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

    2017-12-01

    Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

  5. Facilitating Transfers

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    2018-01-01

    Departing from the paradox that globalisation has implied an increase, rather than a decrease, in contextual diversity, this paper re-assesses the function, normative purpose and location of Regulatory Governance Frameworks in world society. Drawing on insights from sociology of law and world...... society studies, the argument advanced is that Regulatory Governance Frameworks are oriented towards facilitating transfers of condensed social components, such as economic capital and products, legal acts, political decisions and scientific knowledge, from one legally-constituted normative order, i.......e. contextual setting, to another. Against this background, it is suggested that Regulatory Governance Frameworks can be understood as schemes which act as ‘rites of passage’ aimed at providing legal stabilisation to social processes characterised by liminality, i.e ambiguity, hybridity and in-betweenness....

  6. Purine Restriction Induces Pronounced Translational Upregulation of the NT1 Adenosine/Pyrimidine Nucleoside Transporter in Leishmania major

    OpenAIRE

    Ortiz, Diana; Valdés, Raquel; Sanchez, Marco A.; Hayenga, Johanna; Elya, Carolyn; Detke, Siegfried; Landfear, Scott M.

    2010-01-01

    Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gen...

  7. Critical Perspectives on Clandestine Migration Facilitation: An Overview of Migrant Smuggling Research

    Directory of Open Access Journals (Sweden)

    Gabriella Sanchez

    2017-02-01

    The dichotomist script of smugglers as predators and migrants and asylum seekers as victims that dominates narratives of clandestine migration has often obscured the perspectives of those who rely on smugglers for their mobility. This has not only silenced migrants and asylum seekers’ efforts to reach safety, but also the collective knowledge their communities use to secure their mobility amid increased border militarization and migration controls. This paper provides an overview of contemporary, empirical scholarship on clandestine migration facilitation.  It then argues that the processes leading to clandestine or irregular migration are not merely the domain of criminal groups. Rather, they also involve a series of complex mechanisms of protection crafted within migrant and refugee communities as attempts to reduce the vulnerabilities known to be inherent to clandestine journeys. Both criminal and less nefarious efforts are shaped by and in response to enforcement measures worldwide on the part of nation-states to control migration flows. Devised within migrant and refugee communities, and mobilized formally and informally among their members, strategies to facilitate clandestine or irregular migration constitute a system of human security rooted in generations-long, historical notions of solidarity, tradition, reciprocity, and affect (Khosravi 2010. Yet amid concerns over national and border security, and the reemergence of nationalism, said strategies have become increasingly stigmatized, traveling clandestinely being perceived as an inherently — and uniquely — criminal activity.  This contribution constitutes an attempt to critically rethink the framework present in everyday narratives of irregular migration facilitation. It is a call to incorporate into current protection dialogues the perceptions of those who rely on criminalized migration mechanisms to fulfill mobility goals, and in so doing, articulate and inform solutions towards promoting

  8. Facilitating Conversations about Managerial Identities

    DEFF Research Database (Denmark)

    Madsen, Mona Toft

    -based organization in the engineering consulting sector b) a reflection meeting, where the same three managers were gathered, and conversations were facilitated based on identity work in the context of earlier interviews. More specifically, three themes were discussed; flat organizational structure, tensions between...

  9. Speculative prototypes and exogenous ethnographies: Experiencing relationships beyond the human

    DEFF Research Database (Denmark)

    Jönsson, Li; Ulv Lenskjold, Tau

    2017-01-01

    This article deals with the role that speculative design prototypes have as means to intervene in contexts of everyday life in order to explore, and possibly facilitate, new types of relationships between human and non-human beings. Focusing on an off-centered design of the human, it seeks to exp...... to explore what types of new possibilities may arise when speculation in design meets the practice of doing what might be termed an "exogenous ethnography"....

  10. Forensic toxicology in drug-facilitated sexual assault.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

    2013-09-01

    The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

  11. Characteristic sounds facilitate visual search.

    Science.gov (United States)

    Iordanescu, Lucica; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2008-06-01

    In a natural environment, objects that we look for often make characteristic sounds. A hiding cat may meow, or the keys in the cluttered drawer may jingle when moved. Using a visual search paradigm, we demonstrated that characteristic sounds facilitated visual localization of objects, even when the sounds carried no location information. For example, finding a cat was faster when participants heard a meow sound. In contrast, sounds had no effect when participants searched for names rather than pictures of objects. For example, hearing "meow" did not facilitate localization of the word cat. These results suggest that characteristic sounds cross-modally enhance visual (rather than conceptual) processing of the corresponding objects. Our behavioral demonstration of object-based cross-modal enhancement complements the extensive literature on space-based cross-modal interactions. When looking for your keys next time, you might want to play jingling sounds.

  12. Barriers and Facilitators to Central Venous Catheter Insertion: A Qualitative Study.

    Science.gov (United States)

    Cameron, Kenzie A; Cohen, Elaine R; Hertz, Joelle R; Wayne, Diane B; Mitra, Debi; Barsuk, Jeffrey H

    2018-03-14

    The aims of the study were to identify perceived barriers and facilitators to central venous catheter (CVC) insertion among healthcare providers and to understand the extent to which an existing Simulation-Based Mastery Learning (SBML) program may address barriers and leverage facilitators. Providers participating in a CVC insertion SBML train-the-trainer program, in addition to intensive care unit nurse managers, were purposively sampled from Veterans Administration Medical Centers located in geographically diverse areas. We conducted semistructured interviews to assess perceptions of barriers and facilitators to CVC insertion. Deidentified transcripts were analyzed using a grounded theory approach and the constant comparative method. We subsequently mapped identified barriers and facilitators to our SBML curriculum to determine whether or not the curriculum addresses these factors. We interviewed 28 providers at six Veterans Administration Medical Centers, identifying the following five overarching factors of perceived barriers to CVC insertion: (1) equipment, (2) personnel/staff, (3) setting or organizational context, (4) patient or provider, and (5) time-related barriers. Three overarching factors of facilitators emerged: (1) equipment, (2) personnel, and (3) setting or organizational context facilitators. The SBML curriculum seems to address most identified barriers, while leveraging many facilitators; building on the commonly identified facilitator of nursing staff contribution by expanding the curriculum to explicitly include nurse involvement could improve team efficiency and organizational culture of safety. Many identified facilitators (e.g., ability to use ultrasound, personnel confidence/competence) were also identified as barriers. Evidence-based SBML programs have the potential to amplify these facilitators while addressing the barriers by providing an opportunity to practice and master CVC insertion skills.

  13. Nominal group technique-elicited barriers and facilitators to following the Dietary Guidelines for solid fats and added sugars in children: The HEALTH Study

    Science.gov (United States)

    The US population has a high intake of discretionary solid fats and added sugars (SoFAS) which currently exceeds federal dietary recommendations. The goal of this study was to identify barriers and facilitators to following the DGA. Thirty-eight 5th grade children across six Human Nutrition Resear...

  14. Dynamics of group knowledge production in facilitated modelling workshops

    DEFF Research Database (Denmark)

    Tavella, Elena; Franco, L. Alberto

    2015-01-01

    by which models are jointly developed with group members interacting face-to-face, with or without computer support. The models produced are used to inform negotiations about the nature of the issues faced by the group, and how to address them. While the facilitated modelling literature is impressive......, the workshop. Drawing on the knowledge-perspective of group communication, we conducted a micro-level analysis of a transcript of a facilitated modelling workshop held with the management team of an Alternative Food Network in the UK. Our analysis suggests that facilitated modelling interactions can take...

  15. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    International Nuclear Information System (INIS)

    Tong, Meng; Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R.

    2013-01-01

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  16. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

    2013-04-15

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  17. Ghana - Land Tenure Facilitation Impact Evaluation

    Data.gov (United States)

    Millennium Challenge Corporation — The MCC-supported Land Title Facilitation Activity (LTF) in Ghana was designed to increase investment and productivity by strengthening property rights. In Ghana,...

  18. 50 CFR 17.107 - Facilitating enforcement.

    Science.gov (United States)

    2010-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or refuge...

  19. COGNITIVE FATIGUE FACILITATES PROCEDURAL SEQUENCE LEARNING

    Directory of Open Access Journals (Sweden)

    Guillermo eBorragán

    2016-03-01

    Full Text Available Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue. We tested the hypothesis that cognitive fatigue, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, twenty-three young healthy adults were administered a serial reaction time task (SRTT following the induction of high or low levels of cognitive fatigue, in a counterbalanced order. Cognitive fatigue was induced using the Time load Dual-back (TloadDback paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual's optimal performance capacity. In line with our hypothesis, reaction times in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement showed more of a benefit from the sequential components than from motor. Altogether, our results suggest a paradoxical, facilitating impact of cognitive fatigue on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms.

  20. Facilitating small groups: how to encourage student learning.

    Science.gov (United States)

    Kitchen, Mark

    2012-02-01

    Many clinicians are involved in medical education, with small group teaching (SGT) forming a significant part of their work. Most facilitate these sessions by experience and common sense: less than one-third of them have received formal training in SGT. Evidence suggests small group productivity depends on good facilitation rather than on topic knowledge. Applying the fundamental concepts of SGT will lead to improvements in the quality of clinicians' teaching and in student learning. Good SGT creates the perfect environment for learning and discussion, without the need for didactic teaching. SGT emphasises the role of students in sharing and discussing their ideas in a safe learning environment, without domination by the tutor. This article provides clinicians with basic requirements for effective session design and planning, explains how to encourage student participation, how to manage students as a group, how to manage student learning, and how to recognise and deal with problems. Active facilitation and group management is the key to success in SGT, and consequently better learning outcomes. Improving the facilitation skills of clinical teachers makes teaching more effective, stimulating, and enjoyable for both tutors and students. © Blackwell Publishing Ltd 2012.

  1. Prepulse inhibition and facilitation of the postauricular reflex, a vestigial remnant of pinna startle.

    Science.gov (United States)

    Hackley, Steven A; Ren, Xi; Underwood, Amy; Valle-Inclán, Fernando

    2017-04-01

    If the postauricular reflex (PAR) is to be used effectively in studies of emotion and attention, its sensitivity to basic modulatory effects such as prepulse inhibition and facilitation must be determined. Two experiments were carried out with healthy young adults to assess the effects of transient and sustained visual prestimuli on the pinna-flexion response to trains of startle probes. In the first experiment, participants passively viewed a small white square. It was displayed from 1,000 ms prior to onset of a train of noise bursts until the end of that train. Relative to no-prepulse control trials, PAR amplitude was inhibited, possibly due to the withdrawal of attentional resources from the auditory modality. In the second experiment, participants performed a visual oddball task in which irrelevant trains of startle probes followed most briefly displayed task stimuli (checkerboards). Prepulse inhibition was observed when a transient stimulus preceded the first probe at a lead time of 100 ms. Amplitude facilitation was observed at longer lead times. In addition to documenting the existence of prepulse inhibition and facilitation, the data suggest that the PAR is not elicited by visual stimuli, that temporal expectancy does not influence its amplitude or latency, and that this vestigial microreflex is resistant to habituation. Results are interpreted in light of a recent theory that the human PAR is a highly degraded pinna startle, in which the reflex arc no longer includes the startle center (nucleus reticularis pontis caudalis). © 2017 Society for Psychophysiological Research.

  2. Facilitation of transscleral drug delivery by drug loaded magnetic polymeric particles.

    Science.gov (United States)

    Mousavikhamene, Zeynab; Abdekhodaie, Mohammad J; Ahmadieh, Hamid

    2017-10-01

    A unique method was used to facilitate ocular drug delivery from periocular route by drug loaded magnetic sensitive particles. Injection of particles in periocular space along the eye axis followed by application of magnetic field in front of the eye would trigger the magnetic polymeric particles to move along the direction of magnetic force and reside against the outer surface of the sclera. This technique prevents removal of drug in the periocular space, observed in conventional transscleral drug delivery systems and hence higher amount of drug can enter the eye in a longer period of time. The experiments were performed by fresh human sclera and an experimental setup. Experimental setup was designed by side by side diffusion cell and hydrodynamic and thermal simulation of the posterior segment of the eye were applied. Magnetic polymeric particles were synthesized by alginate as a model polymer, iron oxide nanoparticles as a magnetic agent and diclofenac sodium as a model drug and characterized by SEM, TEM, DLS and FT-IR techniques. According to the SEM images, the size range of particles is around 60 to 800nm. The results revealed that the cumulative drug transfer from magnetic sensitive particles across the sclera improves by 70% in the presence of magnetic field. The results of this research show promising method of drug delivery to use magnetic properties to facilitate drug delivery to the back of the eye. Copyright © 2017. Published by Elsevier B.V.

  3. Colloid-Facilitated Transport of Radionuclides Through The Vadose Zone

    International Nuclear Information System (INIS)

    Markus Flury; James B. Harsh; John F. McCarthy' Peter C. Lichtner; John M. Zachara

    2007-01-01

    The main purpose of this project was to advance the basic scientific understanding of colloid and colloid-facilitated Cs transport of radionuclides in the vadose zone. We focused our research on the hydrological and geochemical conditions beneath the leaking waste tanks at the USDOE Hanford reservation. Specific objectives were (1) to determine the lability and thermodynamic stability of colloidal materials, which form after reacting Hanford sediments with simulated Hanford Tank Waste, (2) to characterize the interactions between colloidal particles and contaminants, i.e., Cs and Eu, (3) to determine the potential of Hanford sediments for in situ mobilization of colloids, (4) to evaluate colloid-facilitated radionuclide transport through sediments under unsaturated flow, (5) to implement colloid-facilitated contaminant transport mechanisms into a transport model, and (6) to improve conceptual characterization of colloid-contaminant-soil interactions and colloid-facilitated transport for clean-up procedures and long-term risk assessment

  4. Human factors: A major issue in plant aging

    International Nuclear Information System (INIS)

    Widrig, R.D.

    1985-01-01

    Humans play a significant role in the effects of aging on safe and reliable operation of nuclear power plants. These human issues may be more important than the issues of materials and component degradation with age. Human actions can accelerate or decelerate physical aging of a plant. And an aging plant can have a significant negative impact on staff quality and performance. The purpose of this paper is to provide some insights into the nature of these human factors issues and their relationship to plant aging. An early awareness of these issues facilitates timely action to at least mitigate these problems before they become insurmountable

  5. Crystal Structure of the Human Laminin Receptor Precursor

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson,K.; Wu, J.; Hubbard, S.; Meruelo, D.

    2008-01-01

    The human laminin receptor (LamR) interacts with many ligands, including laminin, prions, Sindbis virus, and the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and has been implicated in a number of diseases. LamR is overexpressed on tumor cells, and targeting LamR elicits anti-cancer effects. Here, we report the crystal structure of human LamR, which provides insights into its function and should facilitate the design of novel therapeutics targeting LamR.

  6. Semantic Coherence Facilitates Distributional Learning.

    Science.gov (United States)

    Ouyang, Long; Boroditsky, Lera; Frank, Michael C

    2017-04-01

    Computational models have shown that purely statistical knowledge about words' linguistic contexts is sufficient to learn many properties of words, including syntactic and semantic category. For example, models can infer that "postman" and "mailman" are semantically similar because they have quantitatively similar patterns of association with other words (e.g., they both tend to occur with words like "deliver," "truck," "package"). In contrast to these computational results, artificial language learning experiments suggest that distributional statistics alone do not facilitate learning of linguistic categories. However, experiments in this paradigm expose participants to entirely novel words, whereas real language learners encounter input that contains some known words that are semantically organized. In three experiments, we show that (a) the presence of familiar semantic reference points facilitates distributional learning and (b) this effect crucially depends both on the presence of known words and the adherence of these known words to some semantic organization. Copyright © 2016 Cognitive Science Society, Inc.

  7. Formation and suppression of acoustic memories during human sleep.

    Science.gov (United States)

    Andrillon, Thomas; Pressnitzer, Daniel; Léger, Damien; Kouider, Sid

    2017-08-08

    Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear. Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase. We played samples of acoustic noise to sleeping human listeners. Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening. Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening. Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep). We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression. Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.

  8. The extension of a DNA double helix by an additional Watson-Crick base pair on the same backbone

    DEFF Research Database (Denmark)

    Kumar, P.; Sharma, P. K.; Madsen, Charlotte S.

    2013-01-01

    Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand.......Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand....

  9. Hypochlorite-induced damage to DNA, RNA, and polynucleotides

    DEFF Research Database (Denmark)

    Hawkins, Clare Louise; Davies, Michael Jonathan

    2002-01-01

    favored exocyclic amines. EPR experiments have also provided evidence for the rapid addition of pyrimidine-derived nitrogen-centered radicals to other nucleobases to give dimers and the oxidation of DNA by radicals derived from preformed nucleoside chloramines. Direct reaction of HOCl with plasmid DNA...... on the nature of the nucleobase on which they are formed, with chloramines formed from ring heterocyclic amine groups being less stable than those formed on exocyclic amines (RNH2 groups). Evidence is presented for chlorine transfer from the former, kinetically favored, sites to the more thermodynamically...

  10. [Terrorism and human behavior].

    Science.gov (United States)

    Leistedt, S J

    2018-04-01

    Theories of religion are essential for understanding current trends in terrorist activities. The aim of this work is to clarify religion's role in facilitating terror and outline in parallel with recent theoretical developments on terrorism and human behaviour. Several databases were used such as PubCentral, Scopus, Medline and Science Direct. The search terms "terrorism", "social psychology", "religion", "evolution", and "cognition" were used to identify relevant studies in the databases. This work examines, in a multidimensional way, how terrorists employ these features of religion to achieve their goals. In the same way, it describes how terrorists use rituals to conditionally associate emotions with sanctified symbols that are emotionally evocative and motivationally powerful, fostering group solidarity, trust, and cooperation. Religious beliefs, including promised rewards in the afterlife, further serve to facilitate cooperation by altering the perceived payoffs of costly actions, including suicide bombing. The adolescent pattern of brain development is unique, and young adulthood presents an ideal developmental stage to attract recruits and enlist them in high-risk behaviors. This work offers insights, based on this translational analysis, concerning the links between religion, terrorism and human behavior. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  11. Evolution of Transcriptional Regulatory Networks in Pseudomonas aeruginosa During Long Time Growth in Human Hosts

    DEFF Research Database (Denmark)

    Andresen, Eva Kammer

    extent these observations relate to natural microbial populations. The focus of this thesis has been to study how regulatory networks evolve in natural systems. By using a particular infectious disease scenario (human associated persistent airway infections caused by the bacterium Pseudomonas aeruginosa...... in global regulator genes facilitate the generation of novel phenotypes which again facilitate the shift in life-style of the bacterium from an environmental opportunistic pathogen to a human airway specific pathogen. These findings are not only applicable to P. aeruginosa specific studies, but suggest that...

  12. Shared learning in general practice--facilitators and barriers.

    Science.gov (United States)

    van de Mortel, Thea; Silberberg, Peter; Ahern, Christine

    2013-03-01

    Capacity for teaching in general practice clinics is limited. Shared learning sessions are one form of vertically integrated teaching that may ameliorate capacity constraints. This study sought to understand the perceptions of general practitioner supervisors, learners and practice staff of the facilitators of shared learning in general practice clinics. Using a grounded theory approach, semistructured interviews were conducted and analysed to generate a theory about the topic. Thirty-five stakeholders from nine general practices participated. Facilitators of shared learning included enabling factors such as small group facilitation skills, space, administrative support and technological resources; reinforcing factors such as targeted funding, and predisposing factors such as participant attributes. Views from multiple stakeholders suggest that the implementation of shared learning in general practice clinics would be supported by an ecological approach that addresses all these factors.

  13. Identification of genes important for growth of asymptomatic bacteriuria Escherichia coli in urine.

    Science.gov (United States)

    Vejborg, Rebecca M; de Evgrafov, Mari R; Phan, Minh Duy; Totsika, Makrina; Schembri, Mark A; Hancock, Viktoria

    2012-09-01

    Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine.

  14. Paradoxical facilitation of working memory after basolateral amygdala damage.

    Directory of Open Access Journals (Sweden)

    Barak Morgan

    Full Text Available Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical

  15. Automatic Video-based Analysis of Human Motion

    DEFF Research Database (Denmark)

    Fihl, Preben

    The human motion contains valuable information in many situations and people frequently perform an unconscious analysis of the motion of other people to understand their actions, intentions, and state of mind. An automatic analysis of human motion will facilitate many applications and thus has...... received great interest from both industry and research communities. The focus of this thesis is on video-based analysis of human motion and the thesis presents work within three overall topics, namely foreground segmentation, action recognition, and human pose estimation. Foreground segmentation is often...... the first important step in the analysis of human motion. By separating foreground from background the subsequent analysis can be focused and efficient. This thesis presents a robust background subtraction method that can be initialized with foreground objects in the scene and is capable of handling...

  16. Assisting victims of human trafficking: strategies to facilitate identification, exit from trafficking, and the restoration of wellness.

    Science.gov (United States)

    Hodge, David R

    2014-04-01

    Human trafficking is a pressing social justice concern. Social work is uniquely situated to address this problem. However, despite the profession's commitment to social justice, the scholarship to equip social workers to address this issue has been largely absent from professional discourse. To address this gap, this article helps social work practitioners to assist victims of human trafficking. After orienting readers to the scope and process of human trafficking, the topics of victim identification, exit from trafficking, and the restoration of psychological wellness are discussed. By equipping themselves in these three areas, practitioners can advance social justice on behalf of some of the most exploited people in the world.

  17. The Relationship of Facilitative Functioning to Effective Peer Supervision

    Science.gov (United States)

    Seligman, Linda

    1978-01-01

    This study investigates peer supervision. The criterion used was counselor trainees' growth in facilitative functioning. The study sought to ascertain whether the facilitative counselor trainee was also the effective peer supervisor, to provide information on evaluating peer-supervisory experience, and to shed light on the most effective…

  18. Designing museum exhibits that facilitate visitor reflection and discussion

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; Andersen, Hanne Møller; King, Heather

    2016-01-01

    This paper explores how four design principles (curiosity, challenge, narratives and participation) facilitate reflection and discussion among young visitors in the issues-based exhibition Dear, Difficult Body. The investigation is based on a mixed-method approach combining questionnaire and inte......This paper explores how four design principles (curiosity, challenge, narratives and participation) facilitate reflection and discussion among young visitors in the issues-based exhibition Dear, Difficult Body. The investigation is based on a mixed-method approach combining questionnaire...... and interview data. The implementation of design principles resulted in a variety of exhibits which variously prompted reflection and discussion on the part of visitors. Exhibits with narratives, for example, here defined as both personal and expert narratives, were found to be effective in facilitating...... personal reflection but also prompted discussion. Participation, defined as including both physical interaction with exhibits, and dialogic interaction between visitors, facilitated the sharing of ideas and feelings between visitors. Exhibits with elements of curiosity and challenge were found to attract...

  19. The need to redefine genomic data sharing: A focus on data accessibility

    Directory of Open Access Journals (Sweden)

    Tempest A. van Schaik

    2014-12-01

    Full Text Available DNAdigest's mission is to investigate and address the issues hindering efficient and ethical genomic data sharing in the human genomics research community. We conducted contextual interviews with human genomics researchers in clinical, academic or industrial R&D settings about their experience with accessing and sharing human genomic data. The qualitative interviews were followed by an online survey which provided quantitative support for our findings. Here we present the generalised workflow for accessing human genomic data through both public and restricted-access repositories and discuss reported points of frustration and their possible improvements. We discuss how data discoverability and accessibility are lacking in current mechanisms and how these are the prerequisites for adoption of best practices in the research community. We summarise current initiatives related to genomic data discovery and present a new data discovery platform available at http://nucleobase.co.uk.

  20. YBYRÁ facilitates comparison of large phylogenetic trees.

    Science.gov (United States)

    Machado, Denis Jacob

    2015-07-01

    The number and size of tree topologies that are being compared by phylogenetic systematists is increasing due to technological advancements in high-throughput DNA sequencing. However, we still lack tools to facilitate comparison among phylogenetic trees with a large number of terminals. The "YBYRÁ" project integrates software solutions for data analysis in phylogenetics. It comprises tools for (1) topological distance calculation based on the number of shared splits or clades, (2) sensitivity analysis and automatic generation of sensitivity plots and (3) clade diagnoses based on different categories of synapomorphies. YBYRÁ also provides (4) an original framework to facilitate the search for potential rogue taxa based on how much they affect average matching split distances (using MSdist). YBYRÁ facilitates comparison of large phylogenetic trees and outperforms competing software in terms of usability and time efficiency, specially for large data sets. The programs that comprises this toolkit are written in Python, hence they do not require installation and have minimum dependencies. The entire project is available under an open-source licence at http://www.ib.usp.br/grant/anfibios/researchSoftware.html .

  1. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    Science.gov (United States)

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  2. Facilitation of Mourning During Childhood.

    Science.gov (United States)

    Kliman, Gilbert; And Others

    This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

  3. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier.

    Science.gov (United States)

    Curis, Céline; Percher, Florent; Jeannin, Patricia; Montange, Thomas; Chevalier, Sébastien A; Seilhean, Danielle; Cartier, Luis; Couraud, Pierre-Olivier; Gout, Olivier; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel; Afonso, Philippe V

    2016-08-15

    Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1-infected lymphocytes, both in chronically infected cell lines and in primary infected CD4(+) T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-κB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear

  4. Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

    Science.gov (United States)

    Deacon, Naomi L; McEvoy, R Doug; Stadler, Daniel L; Catcheside, Peter G

    2017-09-01

    Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO 2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO 2 and 3.0 ± 0.2% O 2 ) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO 2 , O 2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea. NEW & NOTEWORTHY Both arousal state and concomitant CO 2 levels are known modulators of the effects of intermittent hypoxia on

  5. Avian and human influenza virus compatible sialic acid receptors in little brown bats.

    Science.gov (United States)

    Chothe, Shubhada K; Bhushan, Gitanjali; Nissly, Ruth H; Yeh, Yin-Ting; Brown, Justin; Turner, Gregory; Fisher, Jenny; Sewall, Brent J; Reeder, DeeAnn M; Terrones, Mauricio; Jayarao, Bhushan M; Kuchipudi, Suresh V

    2017-04-06

    Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.

  6. Bilateral Alternating Auditory Stimulations Facilitate Fear Extinction and Retrieval

    Directory of Open Access Journals (Sweden)

    Sarah Boukezzi

    2017-06-01

    Full Text Available Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD. Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS during eye movement desensitization and reprocessing (EMDR therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to determine if these previous results found in animals can be reproduced in humans. Twenty-two healthy participants took part in a classical fear conditioning, extinction, and extinction recall paradigm. Behavioral responses (fear expectations as well as psychophysiological measures (skin conductance responses, SCRs were recorded. The results showed a significant fear expectation decrease during fear extinction with BLS. Additionally, SCR for fear extinction retrieval were significantly lower with BLS. Our results demonstrate the importance of BLS to reduce negative emotions, and provide a successful model to further explore the neural mechanisms underlying the sole BLS effect in the EMDR.

  7. Facilitated Articulation of Implicit Knowledge in Textile Design

    DEFF Research Database (Denmark)

    Bang, Anne Louise

    2009-01-01

    This is a report from an ongoing research project and as such it is work in progress. The paper proposes an exploratory approach in order to enable end-users to contribute with their experiences of emotional values of fabrics in use. It is suggested that the textile designer with her repertoire...... of (experiential, implicit and tacit) textile design knowledge should facilitate the articulation process. The paper specifically draws on a series of workshops conducted within the collaborating company inviting all employees to participate. The series of workshops were based on a game-like setting and introduced...... - being a textile designer herself, who functioned as the facilitator. This paper uses two examples from the series of workshops to exemplify a facilitated articulation of implicit knowledge in textile design. From the examples the following themes are synthesised as being important for articulation...

  8. How academic teachers perceive and facilitate creativity

    DEFF Research Database (Denmark)

    Bjørner, Thomas; Kofoed, Lise B.

    2013-01-01

    We will present a case study result from a cross-disciplinary education called Medialogy, which is taught in the Technical and Science Faculty at Aalborg University. The aim of Medialogy is to facilitate creativity within technical solutions. The intention of this paper is to answer the following......: how do the Medialogy teachers perceive creativity and how do they facilitate it? Many of the answers point to the pedagogical approach used in problem-based learning, which are perceived as an important element for the creative process. In this paper we will also argue the importance of including...

  9. The choice of facilitators in medical tourism.

    Science.gov (United States)

    Gan, Lydia L; Frederick, James R

    2018-01-01

    The study identified which of the four facilitators (themselves, agents, insurers, or doctors) consumers are most likely to use when they travel for various medical procedures. A survey conducted between 2011 and 2014 yielded 964 responses. The multinomial logistic regression results showed that being 51-64 years old was positively related to going on their own or using agents to arrange for knee replacements. Having a high school education or less was positively linked to using both agents and insurers to facilitate knee replacements, whereas having a bachelor's degree was negatively associated with going on their own for stem cell therapy.

  10. Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism.

    Science.gov (United States)

    Rühli, Frank; van Schaik, Katherine; Henneberg, Maciej

    2016-11-01

    The field of evolutionary medicine uses evolutionary principles to understand changes in human anatomy and physiology that have occurred over time in response to environmental changes. Through this evolutionary-based approach, we can understand disease as a consequence of anatomical and physiological "trade-offs" that develop to facilitate survival and reproduction. We demonstrate how diachronic study of human anatomy and physiology is fundamental for an increased understanding of human health and disease. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

  11. Stabilization of Transfected Cells Expressing Low-Incidence Blood Group Antigens: Novel Methods Facilitating Their Use as Reagent-Cells.

    Directory of Open Access Journals (Sweden)

    Cecilia González

    Full Text Available The identification of erythrocyte antibodies in the serum of patients rely on panels of human red blood cells (RBCs, which coexpress many antigens and are not easily available for low-incidence blood group phenotypes. These problems have been addressed by generating cell lines expressing unique blood group antigens, which may be used as an alternative to human RBCs. However, the use of cell lines implies several drawbacks, like the requirement of cell culture facilities and the high cost of cryopreservation. The application of cell stabilization methods could facilitate their use as reagent cells in clinical laboratories.We generated stably-transfected cells expressing low-incidence blood group antigens (Dia and Lua. High-expresser clones were used to assess the effect of TransFix® treatment and lyophilization as cell preservation methods. Cells were kept at 4°C and cell morphology, membrane permeability and antigenic properties were evaluated at several time-points after treatment.TransFix® addition to cell suspensions allows cell stabilization and proper antigen detection for at least 120 days, despite an increase in membrane permeability and a reduction in antigen expression levels. Lyophilized cells showed minor morphological changes and antigen expression levels were rather conserved at days 1, 15 and 120, indicating a high stability of the freeze-dried product. These stabilized cells have been proved to react specifically with human sera containing alloantibodies.Both stabilization methods allow long-term preservation of the transfected cells antigenic properties and may facilitate their distribution and use as reagent-cells expressing low-incidence antigens, overcoming the limited availability of such rare RBCs.

  12. Handwriting generates variable visual input to facilitate symbol learning

    Science.gov (United States)

    Li, Julia X.; James, Karin H.

    2015-01-01

    Recent research has demonstrated that handwriting practice facilitates letter categorization in young children. The present experiments investigated why handwriting practice facilitates visual categorization by comparing two hypotheses: That handwriting exerts its facilitative effect because of the visual-motor production of forms, resulting in a direct link between motor and perceptual systems, or because handwriting produces variable visual instances of a named category in the environment that then changes neural systems. We addressed these issues by measuring performance of 5 year-old children on a categorization task involving novel, Greek symbols across 6 different types of learning conditions: three involving visual-motor practice (copying typed symbols independently, tracing typed symbols, tracing handwritten symbols) and three involving visual-auditory practice (seeing and saying typed symbols of a single typed font, of variable typed fonts, and of handwritten examples). We could therefore compare visual-motor production with visual perception both of variable and similar forms. Comparisons across the six conditions (N=72) demonstrated that all conditions that involved studying highly variable instances of a symbol facilitated symbol categorization relative to conditions where similar instances of a symbol were learned, regardless of visual-motor production. Therefore, learning perceptually variable instances of a category enhanced performance, suggesting that handwriting facilitates symbol understanding by virtue of its environmental output: supporting the notion of developmental change though brain-body-environment interactions. PMID:26726913

  13. Spatial olfactory learning facilitates long-term depression in the hippocampus.

    Science.gov (United States)

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2013-10-01

    Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1 h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24 h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1st odor exposure, the animals remembered the odors and their relative positions. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  14. Clinical expectations: what facilitators expect from ESL students on clinical placement.

    Science.gov (United States)

    San Miguel, Caroline; Rogan, Fran

    2012-03-01

    Many nursing students for whom English is a second language (ESL) face challenges related to communication on clinical placement and although clinical facilitators are not usually trained language assessors, they are often in a position of needing to assess ESL students' clinical language performance. Little is known, however, about the particular areas of clinical performance facilitators focus on when they are assessing ESL students. This paper discusses the results of a study of facilitators' written assessment comments about the clinical performance of a small group of ESL nursing students over a two and a half year period. These comments were documented on students' clinical assessment forms at the end of each placement. The results provide a more detailed insight into facilitators' expectations of students' language performance and the particular challenges faced by ESL students and indicate that facilitators have clear expectations of ESL students regarding communication, learning styles and professional demeanour. These findings may help both ESL students and their facilitators better prepare for clinical placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Barriers and Facilitators of HPV Vaccination in the VFC Program.

    Science.gov (United States)

    Fleming, Wayne S; Sznajder, Kristin K; Nepps, Margaret; Boktor, Sameh W

    2018-06-01

    This study determined facilitators and barriers to human papillomavirus (HPV) vaccination perceived by providers of healthcare in the federally funded Pennsylvania Vaccines for Children (PA VFC) program. The cross-sectional study gathered descriptive data through a survey research design. Providers of healthcare were recruited through an email containing a link to an 18-question online survey. The survey was divided into four main sections which assessed the perceived facilitators and barriers to HPV vaccination of PA VFC program-eligibles. Survey respondents represented 65 of 66 Pennsylvania counties covered by the PA VFC Program. The study recruited 772 PA VFC participating healthcare facilities for a response rate of 52%. Ninety eight percent of the responding facilities reported that they offered the HPV vaccine. The most common barriers to vaccine administration were the parental belief that HPV vaccination is associated with sexual activity and parent/patient refusal of the HPV vaccination which together accounted for (44%) of responses. The majority of respondents (75.6%) indicated counseling parents and adolescents on the benefits of HPV vaccination was a very important factor in HPV vaccination uptake. Healthcare provider facility based training (32%) and web-based training for healthcare providers (22%) were the most recommended avenues for HPV training. The most common barrier to HPV vaccination was identified as the parental misconception that HPV vaccination is associated with sexual activity. Providers believed that the best way to increase HPV vaccination is through counseling parents and adolescents on the benefits of HPV vaccination and to correct misconceptions and change attitudes. Providers are desirous of receiving HPV web-based or workplace training.

  16. Herpes simplex virus type 2 glycoprotein H interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells.

    Science.gov (United States)

    Cheshenko, Natalia; Trepanier, Janie B; González, Pablo A; Eugenin, Eliseo A; Jacobs, William R; Herold, Betsy C

    2014-09-01

    Herpes simplex virus (HSV) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. Previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. These studies were designed to test the hypothesis that integrin αvβ3 signaling promotes the release of intracellular calcium (Ca2+) stores and contributes to viral entry and cell-to-cell spread. Transfection of cells with small interfering RNA (siRNA) targeting integrin αvβ3, but not other integrin subunits, or treatment with cilengitide, an Arg-Gly-Asp (RGD) mimetic, impaired HSV-induced Ca2+ release, viral entry, plaque formation, and cell-to-cell spread of HSV-1 and HSV-2 in human cervical and primary genital tract epithelial cells. Coimmunoprecipitation studies and proximity ligation assays indicated that integrin αvβ3 interacts with glycoprotein H (gH). An HSV-2 gH-null virus was engineered to further assess the role of gH in the virus-induced signaling cascade. The gH-2-null virus bound to cells and activated Akt to induce a small Ca2+ response at the plasma membrane, but it failed to trigger the release of cytoplasmic Ca2+ stores and was impaired for entry and cell-to-cell spread. Silencing of integrin αvβ3 and deletion of gH prevented phosphorylation of focal adhesion kinase (FAK) and the transport of viral capsids to the nuclear pore. Together, these findings demonstrate that integrin signaling is activated downstream of virus-induced Akt signaling and facilitates viral entry through interactions with gH by activating the release of intracellular Ca2+ and FAK phosphorylation. These findings suggest a new target for HSV treatment and suppression. Herpes simplex viruses are the leading cause of genital disease worldwide, the most common infection associated with neonatal encephalitis, and a major cofactor for HIV acquisition and transmission. There is no effective vaccine. These

  17. Perancangan SIMRS Terintegrasi Modul Human Resource Development Pada Rumah Sakit Pendidikan

    Directory of Open Access Journals (Sweden)

    A.A Primaningrat Gita Puspita

    2015-11-01

    Full Text Available Human resources at the hospital consists of many kind of disciplines and professions that can be divided into Medical and Non-Medical Personnel. Management Information System Human Resource Development Module needed to accelerate and facilitate the processing of employee data and helpful for management decision making. The module also needs to be integrated with the Payroll Module to facilitate the process of Payroll and remuneration in the hospital. Stage of the system design was conducted by TAS (Total Architecture Syntesis, they are the determination of initial scope, determination of needs, determination of business processes, system design, and evaluation. Human Resource Development Module contains the data collection process, transfer, performance assessment, absences, schedulin, hiring, and reporting. Payroll module contains Payroll and remuneration. This work described by Data Flow Diagrams, Database Structure, and User Interface Design. This design can be used as guidelines for programmers in the manufacture of Hospital Information System are integrated.

  18. Taking a Step Back: Learning without the Facilitator on Solo Activities

    Science.gov (United States)

    Williams, Andy

    2012-01-01

    The purpose of this study is to report on the nature of student learning resulting from an open facilitation approach to solo activities. Three key moments of facilitator intervention were identified at which the facilitator was encouraged to take a step back from directing the experience. They are the pre-activity brief, the mid-activity visit…

  19. Can Genetics Predict Sports Injury? The Association of the Genes GDF5, AMPD1, COL5A1 and IGF2 on Soccer Player Injury Occurrence

    Directory of Open Access Journals (Sweden)

    Kiah McCabe

    2018-03-01

    Full Text Available Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players, including 46 professional, 98 semi-professional and 145 amateur players, were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT (nucleobase genotype of the GDF5 gene, TT and CT (nucleobase genotypes of AMPD1 gene, TT genotype of COL5A1 and GG (nucleobase genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.

  20. Base-modified GDP-mannose derivatives and their substrate activity towards a yeast mannosyltransferase.

    Science.gov (United States)

    Collier, Alice; Wagner, Gerd K

    2017-11-27

    We have previously developed a new class of inhibitors and chemical probes for glycosyltransferases through base-modification of the sugar-nucleotide donor. The key feature of these donor analogues is the presence of an additional substituent at the nucleobase. To date, the application of this general concept has been limited to UDP-sugars and UDP-sugar-dependent glycosyltransferases. Herein, we report for the first time the application of our approach to a GDP-mannose-dependent mannosyltransferase. We have prepared four GDP-mannose derivatives with an additional substituent at either position 6 or 8 of the nucleobase. These donor analogues were recognised as donor substrates by the mannosyltransferase Kre2p from yeast, albeit with significantly lower turnover rates than the natural donor GDP-mannose. The presence of the additional substituent also redirected enzyme activity from glycosyl transfer to donor hydrolysis. Taken together, our results suggest that modification of the donor nucleobase is, in principle, a viable strategy for probe and inhibitor development against GDP-mannose-dependent GTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A new biarticular actuator design facilitates control of leg function in BioBiped3.

    Science.gov (United States)

    Sharbafi, Maziar Ahmad; Rode, Christian; Kurowski, Stefan; Scholz, Dorian; Möckel, Rico; Radkhah, Katayon; Zhao, Guoping; Rashty, Aida Mohammadinejad; Stryk, Oskar von; Seyfarth, Andre

    2016-07-01

    Bioinspired legged locomotion comprises different aspects, such as (i) benefiting from reduced complexity control approaches as observed in humans/animals, (ii) combining embodiment with the controllers and (iii) reflecting neural control mechanisms. One of the most important lessons learned from nature is the significant role of compliance in simplifying control, enhancing energy efficiency and robustness against perturbations for legged locomotion. In this research, we investigate how body morphology in combination with actuator design may facilitate motor control of leg function. Inspired by the human leg muscular system, we show that biarticular muscles have a key role in balancing the upper body, joint coordination and swing leg control. Appropriate adjustment of biarticular spring rest length and stiffness can simplify the control and also reduce energy consumption. In order to test these findings, the BioBiped3 robot was developed as a new version of BioBiped series of biologically inspired, compliant musculoskeletal robots. In this robot, three-segmented legs actuated by mono- and biarticular series elastic actuators mimic the nine major human leg muscle groups. With the new biarticular actuators in BioBiped3, novel simplified control concepts for postural balance and for joint coordination in rebounding movements (drop jumps) were demonstrated and approved.

  2. Formal and informal facilitators of learning capability: the moderating effect of learning climate

    OpenAIRE

    ELENA REVILLA

    2006-01-01

    Organizations need to put in practice the most favourable conditions to facilitate learning capability. The different ways of thinking about learning in organizations distinguish two kinds of learning facilitators: formal and informal facilitators. In this paper, we suggest that organizations undertake both types of learning facilitators, but considering that informal facilitators may act as potential moderators of the effects of formal ones. We have focused on one comprehensive informal faci...

  3. The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I

    DEFF Research Database (Denmark)

    Røder, Gustav Andreas; Geironson, Linda; Darabi, Anna

    2009-01-01

    ). Using a biochemical peptide-MHC-I-binding assay, recombinant Tpn(1-87) was found to specifically facilitate peptide-dependent folding of HLA-A*0201. Furthermore, we used Tpn(1-87) to generate a monoclonal antibody, alphaTpn(1-87)/80, specific for natural human Tpn and capable of cellular staining of ER......Tapasin (Tpn) is an ER chaperone that is uniquely dedicated to MHC-I biosynthesis. It binds MHC-I molecules, integrates them into peptide-loading complexes, and exerts quality control of the bound peptides; only when an "optimal peptide" is bound will the MHC-I be released and exported to the cell...... surface for presentation to T cells. The exact mechanisms of Tpn quality control and the criteria for being an optimal peptide are still unknown. Here, we have generated a recombinant fragment of human Tpn, Tpn(1-87) (representing the 87 N-terminal and ER-luminal amino acids of the mature Tpn protein...

  4. Aloe vera Induced Biomimetic Assemblage of Nucleobase into Nanosized Particles

    Science.gov (United States)

    Chauhan, Arun; Zubair, Swaleha; Sherwani, Asif; Owais, Mohammad

    2012-01-01

    Aim Biomimetic nano-assembly formation offers a convenient and bio friendly approach to fabricate complex structures from simple components with sub-nanometer precision. Recently, biomimetic (employing microorganism/plants) synthesis of metal and inorganic materials nano-particles has emerged as a simple and viable strategy. In the present study, we have extended biological synthesis of nano-particles to organic molecules, namely the anticancer agent 5-fluorouracil (5-FU), using Aloe vera leaf extract. Methodology The 5-FU nano- particles synthesized by using Aloe vera leaf extract were characterized by UV, FT-IR and fluorescence spectroscopic techniques. The size and shape of the synthesized nanoparticles were determined by TEM, while crystalline nature of 5-FU particles was established by X-ray diffraction study. The cytotoxic effects of 5-FU nanoparticles were assessed against HT-29 and Caco-2 (human adenocarcinoma colorectal) cell lines. Results Transmission electron microscopy and atomic force microscopic techniques confirmed nano-size of the synthesized particles. Importantly, the nano-assembled 5-FU retained its anticancer action against various cancerous cell lines. Conclusion In the present study, we have explored the potential of biomimetic synthesis of nanoparticles employing organic molecules with the hope that such developments will be helpful to introduce novel nano-particle formulations that will not only be more effective but would also be devoid of nano-particle associated putative toxicity constraints. PMID:22403622

  5. Handling a challenging context: experiences of facilitating evidence-based elderly care.

    Science.gov (United States)

    Nygårdh, Annette; Ahlström, Gerd; Wann-Hansson, Christine

    2016-03-01

    To explore improvement facilitators' experiences of handling their commission to implement evidence-based practice in elderly care for frail older persons. Improvement facilitators were put in place across Sweden in a time-limited project by the government, with one part of the project being to evaluate the model before establishing this facilitation of evidence-based practice in elderly care. Two focus groups were interviewed twice. Each group comprised three respondents. The interviews were analysed using qualitative content analysis. A main theme, 'Moving forward by adjusting to the circumstances', described how the improvement facilitators handle their commitment. Five subthemes emerged: identifying barriers, keeping focus, maintaining motivation, building bridges and finding balance. The improvement facilitators' commitment is ambiguous because of unclear leadership of, and responsibility for the national investment. They have to handle leaders' different approaches and justify the need for evidence-based practice. The improvement facilitators did not reflect on the impact of programme adaptations on evidence-based practice. The findings emphasise the need for collaboration between the improvement facilitator and the nurse manager. To fully implement evidence-based practice, negotiations with current practitioners for adaptation to local conditions are necessary. Furthermore, the value of improving organisational performance needs to be rigorously communicated throughout the organisation. © 2015 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd.

  6. CDK1 inhibition facilitates formation of syncytiotrophoblasts and expression of human Chorionic Gonadotropin

    KAUST Repository

    Ullah, Rahim

    2018-05-17

    Aims The human placental syncytiotrophoblast (STB) cells play essential roles in embryo implantation and nutrient exchange between the mother and the fetus. STBs are polyploid which are formed by fusion of diploid cytotrophoblast (CTB) cells. Abnormality in STBs formation can result in pregnancy-related disorders. While a number of genes have been associated with CTB fusion the initial events that trigger cell fusion are not well understood. Primary objective of this study was to enhance our understanding about the molecular mechanism of placental cell fusion. Methods FACS and microscopic analysis was used to optimize Forskolin-induced fusion of BeWo cells (surrogate of CTBs) and subsequently, changes in the expression of different cell cycle regulator genes were analyzed through Western blotting and qPCR. Immunohistochemistry was performed on the first trimester placental tissue sections to validate the results in the context of placental tissue. Effect of Cyclin Dependent Kinase 1 (CDK1) inhibitor, RO3306, on BeWo cell fusion was studied by microscopy and FACS, and by monitoring the expression of human Chorionic Gonadotropin (hCG) by Western blotting and qPCR. Results The data showed that the placental cell fusion was associated with down regulation of CDK1 and its associated cyclin B, and significant decrease in DNA replication. Moreover, inhibition of CDK1 by an exogenous inhibitor induced placental cell fusion and expression of hCG. Conclusion Here, we report that the placental cell fusion can be induced by inhibiting CDK1. This study has a high therapeutic significance to manage pregnancy related abnormalities.

  7. Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

    Directory of Open Access Journals (Sweden)

    Matthias Hofmann

    2009-08-01

    Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

  8. Facilitating participation

    DEFF Research Database (Denmark)

    Skøtt, Bo

    2018-01-01

    the resulting need for a redefinition of library competence. In doing this, I primarily address the first two questions from Chapter 1 and how they relate to the public’s informal, leisure-time activities in a networked society. In particular, I focus on the skills of reflexive self-perception and informed...... opinion formation. Further, I point out the significance which these informal leisure-time activities have for public library staff’s cultural dissemination skills. In this way, I take on the question of the skills required for facilitating the learning of a participatory public (cf. Chapter 1......), exemplifying with the competence required of library staff. My discussion will proceed by way of a literature review. In the next section, I shall explain how and what sources were chosen and section three and four present the theoretical framework and how the applied theories are related. In the fifth section...

  9. The 'patient's physician one-step removed': the evolving roles of medical tourism facilitators.

    Science.gov (United States)

    Snyder, Jeremy; Crooks, Valorie A; Adams, Krystyna; Kingsbury, Paul; Johnston, Rory

    2011-09-01

    Medical tourism involves patients travelling internationally to receive medical services. This practice raises a range of ethical issues, including potential harms to the patient's home and destination country and risks to the patient's own health. Medical tourists often engage the services of a facilitator who may book travel and accommodation and link the patient with a hospital abroad. Facilitators have the potential to exacerbate or mitigate the ethical concerns associated with medical tourism, but their roles are poorly understood. 12 facilitators were interviewed from 10 Canadian medical tourism companies. Three themes were identified: facilitators' roles towards the patient, health system and medical tourism industry. Facilitators' roles towards the patient were typically described in terms of advocacy and the provision of information, but limited by facilitators' legal liability. Facilitators felt they played a positive role in the lives of their patients and the Canadian health system and served as catalysts for reform, although they noted an adversarial relationship with some Canadian physicians. Many facilitators described personally visiting medical tourism sites and forming personal relationships with surgeons abroad, but noted the need for greater regulation of their industry. Facilitators play a substantial and evolving role in the practice of medical tourism and may be entering a period of professionalisation. Because of the key role of facilitators in determining the effects of medical tourism on patients and public health, this paper recommends a planned conversation between medical tourism stakeholders to define and shape facilitators' roles.

  10. In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development

    Directory of Open Access Journals (Sweden)

    John Steven

    2017-10-01

    Full Text Available Molecular engineering to increase the percentage identity to common human immunoglobulin sequences of non-human therapeutic antibodies and scaffolds has become standard practice. This strategy is often used to reduce undesirable immunogenic responses, accelerating the clinical development of candidate domains. The first humanized shark variable domain (VNAR was reported by Kovalenko and colleagues and used the anti-human serum albumin (HSA domain, clone E06, as a model to construct a number of humanized versions including huE06v1.10. This study extends this work by using huE06v1.10 as a template to isolate domains with improved biophysical properties and reduced antigenicity. Random mutagenesis was conducted on huE06v1.10 followed by refinement of clones through an off-rate ranking-based selection on target antigen. Many of these next-generation binders retained high affinity for target, together with good species cross-reactivity. Lead domains were assessed for any tendency to dimerize, tolerance to N- and C-terminal fusions, affinity, stability, and relative antigenicity in human dendritic cell assays. Functionality of candidate clones was verified in vivo through the extension of serum half-life in a typical drug format. From these analyses the domain, BA11, exhibited negligible antigenicity, high stability and high affinity for mouse, rat, and HSA. When these attributes were combined with demonstrable functionality in a rat model of PK, the BA11 clone was established as our clinical candidate.

  11. The Role of the Facilitator on Total Quality Management Teams.

    Science.gov (United States)

    Eakin, William L.

    1993-01-01

    As Total Quality Management teams work to improve organizational processes, several types of facilitators emerge: the director, the workhorse, and the cheerleader. Experience at the University of Kansas illustrates how different facilitator styles can affect team learning. (MSE)

  12. Through the eyes of the student: Best practices in clinical facilitation.

    Science.gov (United States)

    Muthathi, Immaculate S; Thurling, Catherine H; Armstrong, Susan J

    2017-08-28

    Clinical facilitation is an essential part of the undergraduate nursing curriculum. A number of studies address the issue of clinical facilitation in South Africa, but there remains a lack of knowledge and understanding regarding what students perceive as best practice in clinical facilitation of their learning. To determine what type of clinical facilitation undergraduate students believe should be offered by clinical facilitators (nurse educators, professional nurses and clinical preceptors) in the clinical area in order to best facilitate their learning. A qualitative, exploratory and descriptive study was conducted. Purposive sampling was performed to select nursing students from the second, third and fourth year of studies from a selected nursing education institution in Johannesburg. The sampling resulted in one focus group for each level of nursing, namely second, third and fourth year nursing students. Interviews were digitally recorded and transcribed verbatim, thematic data analysis was used and trustworthiness was ensured by applying credibility, dependability, confirmability and transferability. The data revealed that participants differentiated between best practices in clinical facilitation in the clinical skills laboratory and clinical learning environment. In the clinical skills laboratory, pre-contact preparation, demonstration technique and optimising group learning were identified as best practices. In the clinical learning environment, a need for standardisation of procedures in simulation and practice, the allocation and support for students also emerged. There is a need for all nurses involved in undergraduate nursing education to reflect on how they approach clinical facilitation, in both clinical skills laboratory and clinical learning environment. There is also a need to improve consistency in clinical practices between the nursing education institution and the clinical learning environment so as to support students' adaptation to clinical

  13. Handwriting generates variable visual output to facilitate symbol learning.

    Science.gov (United States)

    Li, Julia X; James, Karin H

    2016-03-01

    Recent research has demonstrated that handwriting practice facilitates letter categorization in young children. The present experiments investigated why handwriting practice facilitates visual categorization by comparing 2 hypotheses: that handwriting exerts its facilitative effect because of the visual-motor production of forms, resulting in a direct link between motor and perceptual systems, or because handwriting produces variable visual instances of a named category in the environment that then changes neural systems. We addressed these issues by measuring performance of 5-year-old children on a categorization task involving novel, Greek symbols across 6 different types of learning conditions: 3 involving visual-motor practice (copying typed symbols independently, tracing typed symbols, tracing handwritten symbols) and 3 involving visual-auditory practice (seeing and saying typed symbols of a single typed font, of variable typed fonts, and of handwritten examples). We could therefore compare visual-motor production with visual perception both of variable and similar forms. Comparisons across the 6 conditions (N = 72) demonstrated that all conditions that involved studying highly variable instances of a symbol facilitated symbol categorization relative to conditions where similar instances of a symbol were learned, regardless of visual-motor production. Therefore, learning perceptually variable instances of a category enhanced performance, suggesting that handwriting facilitates symbol understanding by virtue of its environmental output: supporting the notion of developmental change though brain-body-environment interactions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Near-peer role modeling: Can fourth-year medical students, recognized for their humanism, enhance reflection among second-year students in a physical diagnosis course?

    Directory of Open Access Journals (Sweden)

    Mimi McEvoy

    2016-09-01

    Full Text Available Introduction: Humanism is cultivated through reflection and self-awareness. We aimed to employ fourth-year medical students, recognized for their humanism, to facilitate reflective sessions for second-year medical students with the intention of positively influencing reflective process toward humanistic development. Methods/Analysis: A total of 186 students were randomly assigned to one of three comparison arms: eight groups of eight students (64 students were facilitated by a fourth-year student who was a Gold Humanism Honor Society member (GHHS; eight groups (64 students by a volunteer non-GHHS student; and seven groups (58 students were non-facilitated. Before sessions, second-year students set learning goals concerning interactions with patients; fourth-year students received training materials on facilitation. Groups met twice during their 10 clinical site visits. At the last session, students completed a reflective assignment on their goal progress. Comparative mixed method analyses were conducted among the three comparison arms on reflection (reflective score on in-session assignment and session satisfaction (survey in addition to a thematic analysis of responses on the in-session assignment. Results: We found significant differences among all three comparison arms on students’ reflective scores (p=0.0003 and satisfaction (p=0.0001. T-tests comparing GHHS- and non-GHHS-facilitated groups showed significantly higher mean reflective scores for GHHS-facilitated groups (p=0.033; there were no differences on session satisfaction. Thematic analysis of students’ reflections showed attempts at self-examination, but lacked depth in addressing emotions. There was a common focus on achieving comfort and confidence in clinical skills performance. Discussion/Conclusions: Near peers, recognized for their humanism, demonstrated significant influence in deepening medical students’ reflections surrounding patient interactions or humanistic

  15. I Reach Faster When I See You Look: Gaze Effects in Human-Human and Human-Robot Face-to-Face Cooperation.

    Science.gov (United States)

    Boucher, Jean-David; Pattacini, Ugo; Lelong, Amelie; Bailly, Gerrard; Elisei, Frederic; Fagel, Sascha; Dominey, Peter Ford; Ventre-Dominey, Jocelyne

    2012-01-01

    Human-human interaction in natural environments relies on a variety of perceptual cues. Humanoid robots are becoming increasingly refined in their sensorimotor capabilities, and thus should now be able to manipulate and exploit these social cues in cooperation with their human partners. Previous studies have demonstrated that people follow human and robot gaze, and that it can help them to cope with spatially ambiguous language. Our goal is to extend these findings into the domain of action, to determine how human and robot gaze can influence the speed and accuracy of human action. We report on results from a human-human cooperation experiment demonstrating that an agent's vision of her/his partner's gaze can significantly improve that agent's performance in a cooperative task. We then implement a heuristic capability to generate such gaze cues by a humanoid robot that engages in the same cooperative interaction. The subsequent human-robot experiments demonstrate that a human agent can indeed exploit the predictive gaze of their robot partner in a cooperative task. This allows us to render the humanoid robot more human-like in its ability to communicate with humans. The long term objectives of the work are thus to identify social cooperation cues, and to validate their pertinence through implementation in a cooperative robot. The current research provides the robot with the capability to produce appropriate speech and gaze cues in the context of human-robot cooperation tasks. Gaze is manipulated in three conditions: Full gaze (coordinated eye and head), eyes hidden with sunglasses, and head fixed. We demonstrate the pertinence of these cues in terms of statistical measures of action times for humans in the context of a cooperative task, as gaze significantly facilitates cooperation as measured by human response times.

  16. Physiology and culture of the human blastocyst.

    Science.gov (United States)

    Gardner, David K; Lane, Michelle; Schoolcraft, William B

    2002-01-01

    The human embryo undergoes many changes in physiology during the first 4 days of life as it develops and differentiates from a fertilized oocyte to the blastocyst stage. Concomitantly, the embryo is exposed to gradients of nutrients within the female reproductive tract and exhibits changes in its own nutrient requirements and utilization. Determining the nature of such nutrient gradients in the female tract and the changing requirements of the embryo has facilitated the formulation of stage-specific culture media designed to support embryo development throughout the preimplantation period. Resultant implantation rates attained with the culture and transfer of human blastocysts are higher than those associated with the transfer of cleavage stage embryos to the uterus. Such increases in implantation rates have facilitated the establishment of high pregnancy rates while reducing the number of embryos transferred. With the introduction of new scoring systems for the blastocyst and the non-invasive assessment of metabolic activity of individual embryos, it should be possible to move to single blastocyst transfer for the majority of patients.

  17. Developing a facilitation model to promote organisational development in primary care practices

    Directory of Open Access Journals (Sweden)

    Elwyn Glyn

    2006-06-01

    Full Text Available Abstract Background The relationship between effective organisation of general practices and health improvement is widely accepted. The Maturity Matrix is an instrument designed to assess organisational development in general practice settings and to stimulate quality improvement. It is undertaken by a practice team with the aid of a facilitator. There is a tradition in the primary care systems in many countries of using practice visitors to educate practice teams about how to improve. However the role of practice visitors as facilitators who enable teams to plan practice-led organisational development using quality improvement instruments is less well understood. The objectives of the study were to develop and explore a facilitation model to support practice teams in stimulating organisational development using a quality improvement instrument called the Maturity Matrix. A qualitative study based on transcript analysis was adopted. Method A model of facilitation was constructed based on a review of relevant literature. Audio tapes of Maturity Matrix assessment sessions with general practices were transcribed and facilitator skills were compared to the model. The sample consisted of two facilitators working with twelve general practices based in UK primary care. Results The facilitation model suggested that four areas describing eighteen skills were important. The four areas are structuring the session, obtaining consensus, handling group dynamics and enabling team learning. Facilitators effectively employed skills associated with the first three areas, but less able to consistently stimulate team learning. Conclusion This study suggests that facilitators need careful preparation for their role and practices need protected time in order to make best use of practice-led quality improvement instruments. The role of practice visitor as a facilitator is becoming important as the need to engender ownership of the quality improvement process by

  18. Developing a facilitation model to promote organisational development in primary care practices.

    Science.gov (United States)

    Rhydderch, Melody; Edwards, Adrian; Marshall, Martin; Elwyn, Glyn; Grol, Richard

    2006-06-19

    The relationship between effective organisation of general practices and health improvement is widely accepted. The Maturity Matrix is an instrument designed to assess organisational development in general practice settings and to stimulate quality improvement. It is undertaken by a practice team with the aid of a facilitator. There is a tradition in the primary care systems in many countries of using practice visitors to educate practice teams about how to improve. However the role of practice visitors as facilitators who enable teams to plan practice-led organisational development using quality improvement instruments is less well understood. The objectives of the study were to develop and explore a facilitation model to support practice teams in stimulating organisational development using a quality improvement instrument called the Maturity Matrix. A qualitative study based on transcript analysis was adopted. A model of facilitation was constructed based on a review of relevant literature. Audio tapes of Maturity Matrix assessment sessions with general practices were transcribed and facilitator skills were compared to the model. The sample consisted of two facilitators working with twelve general practices based in UK primary care. The facilitation model suggested that four areas describing eighteen skills were important. The four areas are structuring the session, obtaining consensus, handling group dynamics and enabling team learning. Facilitators effectively employed skills associated with the first three areas, but less able to consistently stimulate team learning. This study suggests that facilitators need careful preparation for their role and practices need protected time in order to make best use of practice-led quality improvement instruments. The role of practice visitor as a facilitator is becoming important as the need to engender ownership of the quality improvement process by practices increases.

  19. An Analysis of Instructional Facilitators' Relationships with Teachers and Principals

    Science.gov (United States)

    Range, Bret G.; Pijanowski, John C.; Duncan, Heather; Scherz, Susan; Hvidston, David

    2014-01-01

    This study examines the perspectives of Wyoming instructional facilitators, concerning three coaching constructs--namely, their instructional leadership roles, teachers' instructional practices, and the support that they receive from principals and teachers. Findings suggest that instructional facilitators were positive about their instructional…

  20. RANTES modulates the release of glutamate in human neocortex.

    Science.gov (United States)

    Musante, Veronica; Longordo, Fabio; Neri, Elisa; Pedrazzi, Marco; Kalfas, Fotios; Severi, Paolo; Raiteri, Maurizio; Pittaluga, Anna

    2008-11-19

    The effects of the recombinant chemokine human RANTES (hRANTES) on the release of glutamate from human neocortex glutamatergic nerve endings were investigated. hRANTES facilitated the spontaneous release of d [(3)H]D-aspartate ([(3)H]DASP-) by binding Pertussis toxin-sensitive G-protein-coupled receptors (GPCRs), whose activation caused Ca(2+) mobilization from inositol trisphosphate-sensitive stores and cytosolic tyrosine kinase-mediated phosphorylations. Facilitation of release switched to inhibition when the effects of hRANTES on the 12 mM K(+)-evoked [(3)H]D-ASP exocytosis were studied. Inhibition of exocytosis relied on activation of Pertussis toxin-sensitive GPCRs negatively coupled to adenylyl cyclase. Both hRANTES effects were prevented by met-RANTES, an antagonist at the chemokine receptors (CCRs) of the CCR1, CCR3, and CCR5 subtypes. Interestingly, human neocortex glutamatergic nerve endings seem to possess all three receptor subtypes. Blockade of CCR1 and CCR5 by antibodies against the extracellular domain of CCRs prevented both the hRANTES effect on [(3)H]D-ASP release, whereas blockade of CCR3 prevented inhibition, but not facilitation, of release. The effects of RANTES on the spontaneous and the evoked release of [(3)H]D-ASP were also observed in experiments with mouse cortical synaptosomes, which may therefore represent an appropriate animal model to study RANTES-induced effects on neurotransmission. It is concluded that glutamate transmission can be modulated in opposite directions by RANTES acting at distinct CCR receptor subtypes coupled to different transduction pathways, consistent with the multiple and sometimes contrasting effects of the chemokine.

  1. Trade Facilitation Provisions in Regional Trade Agreements: Discriminatory or Non-discriminatory?

    Directory of Open Access Journals (Sweden)

    Innwon Park

    2016-12-01

    Full Text Available The RTAs with trade facilitation provisions have been expected to generate a larger net trade-creating effect and complement the discriminatory feature of RTAs but have yet to be empirically proven. Recognizing the limitations of existing studies, we conducted a quantitative analysis on the effects of RTAs with and without trade facilitation provisions on both intra- and extra-bloc trade by using a modified gravity equation. We applied the Poisson Pseudo-Maximum Likelihood (PPML estimation with time varying exporter and importer fixed effect method to panel data consisting of 45,770 country pairs covering 170 countries for 2000-2010. We found that the trade facilitation provisions in existing RTAs are non-discriminatory by generating more intra- and extra-bloc trade in general. In particular, we found that the trade effects of RTAs in the APEC region are much stronger than the general case covering all RTAs in the world. In addition, as we control the trade effect of a country's trade facilitation, which is ranked by the World Bank's logistic performance index, RTAs consisting of trade facilitation provisions are discriminatory for trade in final goods and non-discriminatory for trade in intermediate goods. Overall, we endeavor to "explain," instead of "hypothesizing," why most of the recent RTAs contain trade facilitation provisions, especially in light of the deepening regional interdependence through trade in parts and components under global value chains and support the necessity of multilateralizing RTAs by implementing non-discriminatory trade facilitation provisions.

  2. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organizational settings, the paper explores how knowledge exchange can be conceptualized as going on in four...... distinct situations of exchange denominated organizational exchange yielding extrinsic rewards, organizational exchange yielding intrinsic rewards, financial exchange, and social exchange. The paper argues that each situation of exchange has distinct assumptions about individual behaviour...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  3. Piracetam, an AMPAkine drug, facilitates memory consolidation in the day-old chick.

    Science.gov (United States)

    Samartgis, Jodi R; Schachte, Leslie; Hazi, Agnes; Crowe, Simon F

    2012-12-01

    Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Robot Faces that Follow Gaze Facilitate Attentional Engagement and Increase Their Likeability.

    Science.gov (United States)

    Willemse, Cesco; Marchesi, Serena; Wykowska, Agnieszka

    2018-01-01

    Gaze behavior of humanoid robots is an efficient mechanism for cueing our spatial orienting, but less is known about the cognitive-affective consequences of robots responding to human directional cues. Here, we examined how the extent to which a humanoid robot (iCub) avatar directed its gaze to the same objects as our participants affected engagement with the robot, subsequent gaze-cueing, and subjective ratings of the robot's characteristic traits. In a gaze-contingent eyetracking task, participants were asked to indicate a preference for one of two objects with their gaze while an iCub avatar was presented between the object photographs. In one condition, the iCub then shifted its gaze toward the object chosen by a participant in 80% of the trials (joint condition) and in the other condition it looked at the opposite object 80% of the time (disjoint condition). Based on the literature in human-human social cognition, we took the speed with which the participants looked back at the robot as a measure of facilitated reorienting and robot-preference, and found these return saccade onset times to be quicker in the joint condition than in the disjoint condition. As indicated by results from a subsequent gaze-cueing tasks, the gaze-following behavior of the robot had little effect on how our participants responded to gaze cues. Nevertheless, subjective reports suggested that our participants preferred the iCub following participants' gaze to the one with a disjoint attention behavior, rated it as more human-like and as more likeable. Taken together, our findings show a preference for robots who follow our gaze. Importantly, such subtle differences in gaze behavior are sufficient to influence our perception of humanoid agents, which clearly provides hints about the design of behavioral characteristics of humanoid robots in more naturalistic settings.

  5. Characteristics and critical success factors for implementing problem-based learning in a human resource-constrained country.

    Science.gov (United States)

    Giva, Karen R N; Duma, Sinegugu E

    2015-08-31

    Problem-based learning (PBL) was introduced in Malawi in 2002 in order to improve the nursing education system and respond to the acute nursing human resources shortage. However, its implementation has been very slow throughout the country. The objectives of the study were to explore and describe the goals that were identified by the college to facilitate the implementation of PBL, the resources of the organisation that facilitated the implementation of PBL, the factors related to sources of students that facilitated the implementation of PBL, and the influence of the external system of the organisation on facilitating the implementation of PBL, and to identify critical success factors that could guide the implementation of PBL in nursing education in Malawi. This is an ethnographic, exploratory and descriptive qualitative case study. Purposive sampling was employed to select the nursing college, participants and documents for review.Three data collection methods, including semi-structured interviews, participant observation and document reviews, were used to collect data. The four steps of thematic analysis were used to analyse data from all three sources. Four themes and related subthemes emerged from the triangulated data sources. The first three themes and their subthemes are related to the characteristics related to successful implementation of PBL in a human resource-constrained nursing college, whilst the last theme is related to critical success factors that contribute to successful implementation of PBL in a human resource-constrained country like Malawi. This article shows that implementation of PBL is possible in a human resource-constrained country if there is political commitment and support.

  6. Barriers and facilitators to exchanging health information: a systematic review.

    Science.gov (United States)

    Eden, Karen B; Totten, Annette M; Kassakian, Steven Z; Gorman, Paul N; McDonagh, Marian S; Devine, Beth; Pappas, Miranda; Daeges, Monica; Woods, Susan; Hersh, William R

    2016-04-01

    We conducted a systematic review of studies assessing facilitators and barriers to use of health information exchange (HIE). We searched MEDLINE, PsycINFO, CINAHL, and the Cochrane Library databases between January 1990 and February 2015 using terms related to HIE. English-language studies that identified barriers and facilitators of actual HIE were included. Data on study design, risk of bias, setting, geographic location, characteristics of the HIE, perceived barriers and facilitators to use were extracted and confirmed. Ten cross-sectional, seven multiple-site case studies, and two before-after studies that included data from several sources (surveys, interviews, focus groups, and observations of users) evaluated perceived barriers and facilitators to HIE use. The most commonly cited barriers to HIE use were incomplete information, inefficient workflow, and reports that the exchanged information that did not meet the needs of users. The review identified several facilitators to use. Incomplete patient information was consistently mentioned in the studies conducted in the US but not mentioned in the few studies conducted outside of the US that take a collective approach toward healthcare. Individual patients and practices in the US may exercise the right to participate (or not) in HIE which effects the completeness of patient information available to be exchanged. Workflow structure and user roles are key but understudied. We identified several facilitators in the studies that showed promise in promoting electronic health data exchange: obtaining more complete patient information; thoughtful workflow that folds in HIE; and inclusion of users early in implementation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Essence: Facilitating Software Innovation

    DEFF Research Database (Denmark)

    Aaen, Ivan

    2008-01-01

      This paper suggests ways to facilitate creativity and innovation in software development. The paper applies four perspectives – Product, Project, Process, and People –to identify an outlook for software innovation. The paper then describes a new facility–Software Innovation Research Lab (SIRL......) – and a new method concept for software innovation – Essence – based on views, modes, and team roles. Finally, the paper reports from an early experiment using SIRL and Essence and identifies further research....

  8. Facilitating community-based interprofessional education and ...

    African Journals Online (AJOL)

    Facilitating community-based interprofessional education and collaborative practice in a health sciences faculty: Student perceptions and experiences. ... It became apparent that students need to be prepared to work in interprofessional groups. The overall intervention was perceived positively, allowing students to become ...

  9. Innovation and learning facilitated by play

    DEFF Research Database (Denmark)

    Hansen, Poul H. Kyvsgård; O´Connor, Rory

    2008-01-01

    "This paper describes an approach to facilitate interaction between students and industrial companies in a problem based learning environment. The approach is adapted from a methodology developed at the LEGO Company and relies on an improved ability to communicate complex problems when using...

  10. Facilitated subcutaneous immunoglobulin administration (fSCIg)

    DEFF Research Database (Denmark)

    Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

    2016-01-01

    and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

  11. BFEE: A User-Friendly Graphical Interface Facilitating Absolute Binding Free-Energy Calculations.

    Science.gov (United States)

    Fu, Haohao; Gumbart, James C; Chen, Haochuan; Shao, Xueguang; Cai, Wensheng; Chipot, Christophe

    2018-03-26

    Quantifying protein-ligand binding has attracted the attention of both theorists and experimentalists for decades. Many methods for estimating binding free energies in silico have been reported in recent years. Proper use of the proposed strategies requires, however, adequate knowledge of the protein-ligand complex, the mathematical background for deriving the underlying theory, and time for setting up the simulations, bookkeeping, and postprocessing. Here, to minimize human intervention, we propose a toolkit aimed at facilitating the accurate estimation of standard binding free energies using a geometrical route, coined the binding free-energy estimator (BFEE), and introduced it as a plug-in of the popular visualization program VMD. Benefitting from recent developments in new collective variables, BFEE can be used to generate the simulation input files, based solely on the structure of the complex. Once the simulations are completed, BFEE can also be utilized to perform the post-treatment of the free-energy calculations, allowing the absolute binding free energy to be estimated directly from the one-dimensional potentials of mean force in simulation outputs. The minimal amount of human intervention required during the whole process combined with the ergonomic graphical interface makes BFEE a very effective and practical tool for the end-user.

  12. Developing the Developers: Supporting and Researching the Learning of Professional Development Facilitators

    Science.gov (United States)

    Perry, Emily; Boylan, Mark

    2018-01-01

    Research on teacher professional development is extensive but there are fewer studies about the practitioners who facilitate professional development. Here we report on a pilot programme for professional development facilitators rooted in a cycle of action research. Informed by a categorisation of professional knowledge and skills of facilitators,…

  13. Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

    Science.gov (United States)

    Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

    2013-01-31

    Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

  14. Digital technology and human development: A charter for nature conservation

    NARCIS (Netherlands)

    Maffey, G.; Homans, H.; Banks, K.; Arts, K.A.J.

    2015-01-01

    The application of digital technology in conservation holds much potential for advancing the understanding of, and facilitating interaction with, the natural world. In other sectors, digital technology has long been used to engage communities and share information. Human development—which holds

  15. Twelve tips for facilitating Millennials' learning.

    Science.gov (United States)

    Roberts, David H; Newman, Lori R; Schwartzstein, Richard M

    2012-01-01

    The current, so-called "Millennial" generation of learners is frequently characterized as having deep understanding of, and appreciation for, technology and social connectedness. This generation of learners has also been molded by a unique set of cultural influences that are essential for medical educators to consider in all aspects of their teaching, including curriculum design, student assessment, and interactions between faculty and learners.  The following tips outline an approach to facilitating learning of our current generation of medical trainees.  The method is based on the available literature and the authors' experiences with Millennial Learners in medical training.  The 12 tips provide detailed approaches and specific strategies for understanding and engaging Millennial Learners and enhancing their learning.  With an increased understanding of the characteristics of the current generation of medical trainees, faculty will be better able to facilitate learning and optimize interactions with Millennial Learners.

  16. Pharmacists' perceptions of facilitators and barriers to lifelong learning.

    Science.gov (United States)

    Hanson, Alan L; Bruskiewitz, Ruth H; Demuth, James E

    2007-08-15

    To reevaluate facilitators of and barriers to pharmacists' participation in lifelong learning previously examined in a 1990 study. A survey instrument was mailed to 274 pharmacists who volunteered to participate based on a prior random sample survey. Data based on perceptions of facilitators and barriers to lifelong learning, as well as self-perception as a lifelong learner, were analyzed and compared to a similar 1990 survey. The response rate for the survey was 88%. The top 3 facilitators and barriers to lifelong learning from the 2003 and the 1990 samples were: (1) personal desire to learn; (2) requirement to maintain professional licensure; and (3) enjoyment/relaxation provided by learning as change of pace from the "routine." The top 3 barriers were: (1) job constraints; (2) scheduling (location, distance, time) of group learning activities; and (3) family constraints (eg, spouse, children, personal). Respondents' broad self-perception as lifelong learners continued to be highly positive overall, but remained less positive relative to more specific lifelong learning skills such as the ability to identify learning objectives as well as to evaluate learning outcomes. Little has changed in the last decade relative to how pharmacists view themselves as lifelong learners, as well as what they perceive as facilitators and barriers to lifelong learning. To address factors identified as facilitators and barriers, continuing education (CE) providers should focus on pharmacists' time constraints, whether due to employment, family responsibilities, or time invested in the educational activity itself, and pharmacists' internal motivations to learn (personal desire, enjoyment), as well as external forces such as mandatory CE for relicensure.

  17. Medical Education to Enhance Critical Consciousness: Facilitators' Experiences.

    Science.gov (United States)

    Zaidi, Zareen; Vyas, Rashmi; Verstegen, Danielle; Morahan, Page; Dornan, Tim

    2017-11-01

    To analyze educators' experiences of facilitating cultural discussions in two global health professions education programs and what these experiences had taught them about critical consciousness. A multicultural research team conducted in-depth interviews with 16 faculty who had extensive experience facilitating cultural discussions. They analyzed transcripts of the interviews thematically, drawing sensitizing insights from Gramsci's theory of cultural hegemony. Collaboration and conversation helped the team self-consciously examine their positions toward the data set and be critically reflexive. Participant faculty used their prior experience facilitating cultural discussions to create a "safe space" in which learners could develop critical consciousness. During multicultural interactions they recognized and explicitly addressed issues related to power differentials, racism, implicit bias, and gender bias. They noted the need to be "facile in attending to pain" as learners brought up traumatic experiences and other sensitive issues including racism and the impact of power dynamics. They built relationships with learners by juxtaposing and exploring the sometimes-conflicting norms of different cultures. Participants were reflective about their own understanding and tendency to be biased. They aimed to break free of such biases while role modeling how to have the courage to speak up. Experience had given facilitators in multicultural programs an understanding of their responsibility to promote critical consciousness and social justice. How faculty without prior experience or expertise could develop those values and skills is a topic for future research.

  18. Human Endothelial Cells: Use of Heparin in Cloning and Long-Term Serial Cultivation

    Science.gov (United States)

    Thornton, Susan C.; Mueller, Stephen N.; Levine, Elliot M.

    1983-11-01

    Endothelial cells from human blood vessels were cultured in vitro, with doubling times of 17 to 21 hours for 42 to 79 population doublings. Cloned human endothelial cell strains were established for the first time and had similar proliferative capacities. This vigorous cell growth was achieved by addition of heparin to culture medium containing reduced concentrations of endothelial cell growth factor. The routine cloning and long-term culture of human endothelial cells will facilitate studying the human endothelium in vitro.

  19. Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells.

    Science.gov (United States)

    Ernst, Katharina; Schmid, Johannes; Beck, Matthias; Hägele, Marlen; Hohwieler, Meike; Hauff, Patricia; Ückert, Anna Katharina; Anastasia, Anna; Fauler, Michael; Jank, Thomas; Aktories, Klaus; Popoff, Michel R; Schiene-Fischer, Cordelia; Kleger, Alexander; Müller, Martin; Frick, Manfred; Barth, Holger

    2017-06-02

    Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C. difficile toxin CDT are composed of a transport (B) and a separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells and subsequently transport of the A-components from acidic endosomes into the cytosol, where the latter ADP-ribosylate G-actin resulting in cell rounding and cell death causing clinical symptoms. Protein folding enzymes, including Hsp90 and peptidyl-prolyl cis/trans isomerases facilitate transport of the A-components across endosomal membranes. Here, we identified Hsp70 as a novel host cell factor specifically interacting with A-components of C2, iota and CDT toxins to facilitate their transport into the cell cytosol. Pharmacological Hsp70-inhibition specifically prevented pH-dependent trans-membrane transport of A-components into the cytosol thereby protecting living cells and stem cell-derived human miniguts from intoxication. Thus, Hsp70-inhibition might lead to development of novel therapeutic strategies to treat diseases associated with bacterial ADP-ribosylating toxins.

  20. Relationship of Physical Activity Facilitators and Body Mass Index in Kashan Elderly

    Directory of Open Access Journals (Sweden)

    Zahra Khalili

    2015-12-01

    Full Text Available Introduction: There are many factors that affect the level of physical activity and body mass index of the elderly. The current study aimed to assess the relationship of  physical activity facilitators and body mass index of Kashan elderly. Methods: The cross-sectional study sampled 400 elderly older than 60 referred to 10 healthcare centers in Kashan, 2014, via multistage quota method. Participations were tested under demographic characters, body mass index(BMI level, and exercise benefits part of exercise benefits and barrier scale (persian  version for measurig  physical activity facilitators. Data were analyzed in SPSS software, descriptive statistic, Spearman correlation test, Chi-Square and Ordinal regression. Results: Of the participations73.6% were overweight or obese. Median and interquartile range (IQR of  physical activity facilitators was 75 and 33 respectively. The most prominent  physical activity facilitators was" physical activity increases my physical ability, (83.2%. There was a significantly inverse relationship between  physical activity facilitators  score and BMI of participants (r=-0.233, P=0.001. Ordinal regression evealed that mostly predictor of  BMI among  physical activity facilitators was "physical activity improves the quality of my work " (OR=8.683, P=0.001. Conclusion: Results identified  physical activity facilitators directly is related to improve physical circumstances of the elderly people. Surly poviding  physical activity facilitators through educational and interventional programs may improve the health status of aging population.

  1. Nurses' perceptions of facilitating genuineness in a nurse–patient relationship

    Directory of Open Access Journals (Sweden)

    Anna Elizabeth Van den Heever

    2015-06-01

    Results: When groups were compared, statistically significant differences were identified in nurses' perceptions of facilitating genuineness with respect to age, years' experience as a nurse and qualifications. It is recommended that nurses' awareness of genuineness and its facilitation should involve learning through socialisation and self-awareness.

  2. Design Facilitation as Emerging Practice: Analyzing How Designers Support Multi-stakeholder Co-creation

    Directory of Open Access Journals (Sweden)

    Manuela Aguirre

    Full Text Available Designers increasingly find themselves facilitating large-scale design events. Yet few have explored design facilitation as an emerging practice. This article examines the design facilitation practices used in two Norwegian case studies of multi-stakeholder events. We focus on the contextually designed tools designers create to help them facilitate. We then explore some critical dimensions of design facilitation. When used as visual overlays, facilitators’ explicit knowledge of these dimensions can improve their capacity to analyze, evaluate, and plan how to design and use contextual tools during design events. By plotting how designers use facilitation tools sequentially during events, we render the flow of design facilitation practice visible and accessible. We suggest that an explicit awareness of these dimensions and flows can enable designers to build more inclusive and inspiring tools, orchestrate the flow of long-term participatory processes more deliberately, and better equip participants to work with complex systemic change.

  3. Barriers and facilitators to end-of-life communication in advanced chronic organ failure.

    Science.gov (United States)

    Van den Heuvel, Liza Amc; Spruit, Martijn A; Schols, Jos Mga; Hoving, Ciska; Wouters, Emiel Fm; Janssen, Daisy Ja

    2016-05-01

    The aim of this quantitative, cross-sectional study was to identify barriers and facilitators to end-of-life communication experienced by family caregivers of patients with advanced chronic organ failure and to examine agreement in barriers and facilitators between family caregivers and patients. Patients and family caregivers were interviewed using the barriers and facilitators questionnaire. Agreement was determined using intraclass correlation coefficients for continuous variables and Cohen's kappa for categorical variables. A total of 158 patients and family caregiver dyads were included. The most important barriers for family caregivers were related to uncertainty about expected care and focus on staying alive instead of dying. The facilitators were related to trust in and competence of their physician and earlier experiences with death in their (social) environment. For most barriers and facilitators, agreement between patients and family caregivers was fair to moderate. Differences in barriers and facilitators between patients and family caregivers ask for an individual approach to facilitate end-of-life communication.

  4. Whose statistical reasoning is facilitated by a causal structure intervention?

    Science.gov (United States)

    McNair, Simon; Feeney, Aidan

    2015-02-01

    People often struggle when making Bayesian probabilistic estimates on the basis of competing sources of statistical evidence. Recently, Krynski and Tenenbaum (Journal of Experimental Psychology: General, 136, 430-450, 2007) proposed that a causal Bayesian framework accounts for peoples' errors in Bayesian reasoning and showed that, by clarifying the causal relations among the pieces of evidence, judgments on a classic statistical reasoning problem could be significantly improved. We aimed to understand whose statistical reasoning is facilitated by the causal structure intervention. In Experiment 1, although we observed causal facilitation effects overall, the effect was confined to participants high in numeracy. We did not find an overall facilitation effect in Experiment 2 but did replicate the earlier interaction between numerical ability and the presence or absence of causal content. This effect held when we controlled for general cognitive ability and thinking disposition. Our results suggest that clarifying causal structure facilitates Bayesian judgments, but only for participants with sufficient understanding of basic concepts in probability and statistics.

  5. Facilitated IEP Meetings. PHP-c90

    Science.gov (United States)

    PACER Center, 2004

    2004-01-01

    To help special education planning teams reach agreements, the Minnesota Department of Education and the Minnesota Special Education Mediation Service (MNSEMS) provide the option of facilitated IEP meetings. This option is available for IEP (Individualized Education Program), IIIP (Individual Interagency Intervention Plan), and IFSP (Individual…

  6. Facilitated inter-firm collaboration in Ghana

    DEFF Research Database (Denmark)

    Kuada, John Ernest; Sørensen, Olav Jull

    2005-01-01

    Since the mid-1980s, aid agencies have endorsed the need to support private enterprise development in developing countries as an instrument for overall economic development and poverty reduction. Facilitation of collaboration between developed and developing country firms has become one of the mo...

  7. Facilitating Learning Spaces in Forum Theatre

    Science.gov (United States)

    Rae, Jan

    2013-01-01

    Purpose: The purpose of this paper is to evaluate the extent to which forum theatre interventions can support non-hierarchical approaches to learning, development and change management initiatives in organisations. Design/methodology/approach: Semi-structured interviews were carried out with theatre consultancies, actors/facilitators,…

  8. Human rights literacy: Moving towards rights-based education and ...

    African Journals Online (AJOL)

    Our theoretical framework examines the continual process of moving towards an open and democratic society through the facilitation of human rights literacy, rights-based education and transformative action. We focus specifically on understandings of dignity, equality and freedom, as both rights (legal claims) and values ...

  9. Weighing the costs: Implementing the SLMTA programme in Zimbabwe using internal versus external facilitators

    Directory of Open Access Journals (Sweden)

    Edwin Shumba

    2014-11-01

    Objectives: To evaluate the financial costs of SLMTA implementation using two models (external facilitators; and internal local or MoHCW facilitators from the perspective of the implementing partner and to estimate resources needed to scale up the programme nationally in all 10 provinces. Methods: The average expenditure per laboratory was calculated based on accounting records; calculations included implementing partner expenses but excluded in-kind contributions and salaries of local facilitators and trainees. We also estimated theoretical financial costs, keeping all contextual variables constant across the two models. Resource needs for future national expansion were estimated based on a two-phase implementation plan, in which 12 laboratories in each of five provinces would implement SLMTA per phase; for the internal facilitator model, 20 facilitators would be trained at the beginning of each phase. Results: The average expenditure to implement SLMTA in 11 laboratories using external facilitators was approximately US$5800 per laboratory; expenditure in 19 laboratories using internal facilitators was approximately $6000 per laboratory. The theoretical financial cost of implementing a 12-laboratory SLMTA cohort keeping all contextual variables constant would be approximately $58 000 using external facilitators; or $15 000 using internal facilitators, plus $86 000 to train 20 facilitators. The financial cost for subsequent SLMTA cohorts using the previously-trained internal facilitators would be approximately $15 000, yielding a break-even point of 2 cohorts, at $116 000 for either model. Estimated resources required for national implementation in 120 laboratories would therefore be $580 000 using external facilitators ($58 000 per province and $322 000 using internal facilitators ($86 000 for facilitator training in each of two phases plus $15 000 for SLMTA implementation in each province. Conclusion: Investing in training of internal facilitators will

  10. Facilitating Adoption of Web Tools for Problem and Project Based Learning Activities

    DEFF Research Database (Denmark)

    Khalid, Md. Saifuddin; Rongbutsri, Nikorn; Buus, Lillian

    2012-01-01

    and project based learning. In the area of problem and project based learning, facilitation is the core term and the teacher often has the role as facilitator or moderator instead of a teacher teaching. Technology adoption for learning activities needs facilitation, which is mostly absent. Sustainable......This paper builds on research directions from ‘activity theory’ and ‘learning design’ to provide ‘facilitation’ for students standing within decision making related to selection of web 2.0 tools and university provided web-based applications for supporting students activities within problem...... adoption might be facilitated based on tool appropriation with activities associated with courses and projects. Our mapping of different tools in a framework is reported based on interviews, observations, narratives and survey. A direction towards facilitation process for adoption is discussed as part...

  11. The Effectiveness of Remote Facilitation in Simulation-Based Pediatric Resuscitation Training for Medical Students.

    Science.gov (United States)

    Ohta, Kunio; Kurosawa, Hiroshi; Shiima, Yuko; Ikeyama, Takanari; Scott, James; Hayes, Scott; Gould, Michael; Buchanan, Newton; Nadkarni, Vinay; Nishisaki, Akira

    2017-08-01

    To assess the effectiveness of pediatric simulation by remote facilitation. We hypothesized that simulation by remote facilitation is more effective compared to simulation by an on-site facilitator. We defined remote facilitation as a facilitator remotely (1) introduces simulation-based learning and simulation environment, (2) runs scenarios, and (3) performs debriefing with an on-site facilitator. A remote simulation program for medical students during pediatric rotation was implemented. Groups were allocated to either remote or on-site facilitation depending on the availability of telemedicine technology. Both groups had identical 1-hour simulation sessions with 2 scenarios and debriefing. Their team performance was assessed with behavioral assessment tool by a trained rater. Perception by students was evaluated with Likert scale (1-7). Fifteen groups with 89 students participated in a simulation by remote facilitation, and 8 groups with 47 students participated in a simulation by on-site facilitation. Participant demographics and previous simulation experience were similar. Both groups improved their performance from first to second scenario: groups by remote simulation (first [8.5 ± 4.2] vs second [13.2 ± 6.2], P = 0.003), and groups by on-site simulation (first [6.9 ± 4.1] vs second [12.4 ± 6.4], P = 0.056). The performance improvement was not significantly different between the 2 groups (P = 0.94). Faculty evaluation by students was equally high in both groups (7 vs 7; P = 0.65). A pediatric acute care simulation by remote facilitation significantly improved students' performance. In this pilot study, remote facilitation seems as effective as a traditional, locally facilitated simulation. The remote simulation can be a strong alternative method, especially where experienced facilitators are limited.

  12. Colloid-Facilitated Transport of Radionuclides through the Vadose Zone

    International Nuclear Information System (INIS)

    Flury, Markus; Harsh, James B.; Zachara, John M.; McCarthy, John F.; Lichtner, Peter C.

    2006-01-01

    This project seeks to improve the basic understanding of the role of colloids in facilitating the transport of contaminants in the vadose zone. We focus on three major thrusts: (1) thermodynamic stability and mobility of colloids formed by reactions of sediments with highly alkaline tank waste solutions, (2) colloid-contaminant interactions, and (3) in-situ colloid mobilization and colloid facilitated contaminant transport occurring in both contaminated and uncontaminated Hanford sediments

  13. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  14. The Facilitator. Technical Note No. 11.

    Science.gov (United States)

    Barriga, Patricio; And Others

    This paper describes the concept, training, and experiences of community facilitators as change agents in a nonformal education project in rural Ecuador. Presently, the social, economic, and political context of the rural Ecuadorian consists of poverty, racial prejudice, economic exploitation, and psychological dependency. The project attempted to…

  15. Global bioethics and human rights in an African context: A reformed theological discourse on global bioethics as a new human rights ethos

    Directory of Open Access Journals (Sweden)

    A.L. Rheeder

    2016-09-01

    Full Text Available The 2005 UNESCO Universal Declaration of Bioethics and Human Rights (UDBHR is specifically aimed at Africa and developing countries from other regions. The acceptance of this UNESCO instrument shows that global bioethics and human rights have become part of the bioethics discourse of today. It is clear that there is a certain affinity between human rights and bioethics, which makes such a link desirable. The value of this link lies in the fact that human rights facilitate a normative universal expansion of bioethical principles. The human rights framework provides bioethical principles with some authority and political influence, an instrument that can protect people in our broken context. Human rights practice and a reformed understanding of natural law both show that humanity can reach consensus on ethical principles such as those found in the UDBHR. Consensus on the theoretical foundation of human rights is not a prerequisite for the successful utilisation of these principles.

  16. A taxonomy for human reliability analysis

    International Nuclear Information System (INIS)

    Beattie, J.D.; Iwasa-Madge, K.M.

    1984-01-01

    A human interaction taxonomy (classification scheme) was developed to facilitate human reliability analysis in a probabilistic safety evaluation of a nuclear power plant, being performed at Ontario Hydro. A human interaction occurs, by definition, when operators or maintainers manipulate, or respond to indication from, a plant component or system. The taxonomy aids the fault tree analyst by acting as a heuristic device. It helps define the range and type of human errors to be identified in the construction of fault trees, while keeping the identification by different analysts consistent. It decreases the workload associated with preliminary quantification of the large number of identified interactions by including a category called 'simple interactions'. Fault tree analysts quantify these according to a procedure developed by a team of human reliability specialists. The interactions which do not fit into this category are called 'complex' and are quantified by the human reliability team. The taxonomy is currently being used in fault tree construction in a probabilistic safety evaluation. As far as can be determined at this early stage, the potential benefits of consistency and completeness in identifying human interactions and streamlining the initial quantification are being realized

  17. Intramuscular ketamine to facilitate pediatric central vascular access.

    Science.gov (United States)

    Denmark, T Kent; Hargrove, Jenny R; Brown, Lance

    2004-07-01

    Obtaining prompt vascular access in young children presenting to the emergency department (ED) is frequently both necessary and technically challenging. The objective of our study was to describe our experience using intramuscular (IM) ketamine to facilitate the placement of central venous catheters in children presenting to our ED needing vascular access in a timely fashion. We performed a retrospective medical record review of all pediatric patients central venous catheter facilitated by the use of IM ketamine. Eleven children met our inclusion criteria. Most of the children were young and medically complicated. The children ranged in age from 6 months to 8 years. The only complication identified was vomiting experienced by an 8-year-old boy. Emergency physicians successfully obtained central venous access in all subjects in the case series. The use of IM ketamine to facilitate the placement of central venous catheters in children who do not have peripheral venous access appears to be helpful. Emergency physicians may find it useful to be familiar with this use of IM ketamine.

  18. An Interagency Collaboration to Facilitate Development of Filovirus Medical Countermeasures

    Directory of Open Access Journals (Sweden)

    Edwin O. Nuzum

    2012-10-01

    Full Text Available The Filovirus Animal Non-Clinical Group (FANG is a US interdepartmental and interagency group established to support and facilitate the advanced development of filovirus Medical Countermeasures (MCM, both vaccines and therapeutics. It is co-led by one representative from the Department of Defense (DoD, the first author, and one from the Department of Health and Human Services (HHS, the second author. The FANG membership includes operational level program staff and Subject Matter Experts (SME from performing organizations as well as scientific staff and program managers from DoD and HHS funding and regulatory agencies. Focus areas include animal models, assays, reagents, product manufacture and characterization, and other interagency product development issues that will support Food and Drug Administration (FDA licensure of safe and effective filovirus MCMs. The FANG continues to develop strategies to address broadly applicable and interagency product development challenges relevant to filovirus MCM development. This paper summarizes FANG structure and accomplishments and is meant to heighten community awareness of this government-led collaborative effort.

  19. Mycobacterium smegmatis Lhr Is a DNA-dependent ATPase and a 3'-to-5' DNA translocase and helicase that prefers to unwind 3'-tailed RNA:DNA hybrids.

    Science.gov (United States)

    Ordonez, Heather; Shuman, Stewart

    2013-05-17

    We are interested in the distinctive roster of helicases of Mycobacterium, a genus of the phylum Actinobacteria that includes the human pathogen Mycobacterium tuberculosis and its avirulent relative Mycobacterium smegmatis. Here, we identify and characterize M. smegmatis Lhr as the exemplar of a novel clade of superfamily II helicases, by virtue of its biochemical specificities and signature domain organization. Lhr is a 1507-amino acid monomeric nucleic acid-dependent ATPase that uses the energy of ATP hydrolysis to drive unidirectional 3'-to-5' translocation along single strand DNA and to unwind duplexes en route. The ATPase is more active in the presence of calcium than magnesium. ATP hydrolysis is triggered by either single strand DNA or single strand RNA, yet the apparent affinity for a DNA activator is 11-fold higher than for an RNA strand of identical size and nucleobase sequence. Lhr is 8-fold better at unwinding an RNA:DNA hybrid than it is at displacing a DNA:DNA duplex of identical nucleobase sequence. The truncated derivative Lhr-(1-856) is an autonomous ATPase, 3'-to-5' translocase, and RNA:DNA helicase. Lhr-(1-856) is 100-fold better RNA:DNA helicase than DNA:DNA helicase. Lhr homologs are found in bacteria representing eight different phyla, being especially prevalent in Actinobacteria (including M. tuberculosis) and Proteobacteria (including Escherichia coli).

  20. Connecting today's climates to future climate analogs to facilitate movement of species under climate change.

    Science.gov (United States)

    Littlefield, Caitlin E; McRae, Brad H; Michalak, Julia L; Lawler, Joshua J; Carroll, Carlos

    2017-12-01

    Increasing connectivity is an important strategy for facilitating species range shifts and maintaining biodiversity in the face of climate change. To date, however, few researchers have included future climate projections in efforts to prioritize areas for increasing connectivity. We identified key areas likely to facilitate climate-induced species' movement across western North America. Using historical climate data sets and future climate projections, we mapped potential species' movement routes that link current climate conditions to analogous climate conditions in the future (i.e., future climate analogs) with a novel moving-window analysis based on electrical circuit theory. In addition to tracing shifting climates, the approach accounted for landscape permeability and empirically derived species' dispersal capabilities. We compared connectivity maps generated with our climate-change-informed approach with maps of connectivity based solely on the degree of human modification of the landscape. Including future climate projections in connectivity models substantially shifted and constrained priority areas for movement to a smaller proportion of the landscape than when climate projections were not considered. Potential movement, measured as current flow, decreased in all ecoregions when climate projections were included, particularly when dispersal was limited, which made climate analogs inaccessible. Many areas emerged as important for connectivity only when climate change was modeled in 2 time steps rather than in a single time step. Our results illustrate that movement routes needed to track changing climatic conditions may differ from those that connect present-day landscapes. Incorporating future climate projections into connectivity modeling is an important step toward facilitating successful species movement and population persistence in a changing climate. © 2017 Society for Conservation Biology.

  1. Orthographic facilitation in oral vocabulary acquisition.

    Science.gov (United States)

    Ricketts, Jessie; Bishop, Dorothy V M; Nation, Kate

    2009-10-01

    An experiment investigated whether exposure to orthography facilitates oral vocabulary learning. A total of 58 typically developing children aged 8-9 years were taught 12 nonwords. Children were trained to associate novel phonological forms with pictures of novel objects. Pictures were used as referents to represent novel word meanings. For half of the nonwords children were additionally exposed to orthography, although they were not alerted to its presence, nor were they instructed to use it. After this training phase a nonword-picture matching posttest was used to assess learning of nonword meaning, and a spelling posttest was used to assess learning of nonword orthography. Children showed robust learning for novel spelling patterns after incidental exposure to orthography. Further, we observed stronger learning for nonword-referent pairings trained with orthography. The degree of orthographic facilitation observed in posttests was related to children's reading levels, with more advanced readers showing more benefit from the presence of orthography.

  2. Facilitation of speech repetition accuracy by theta burst stimulation of the left posterior inferior frontal gyrus.

    Science.gov (United States)

    Restle, Julia; Murakami, Takenobu; Ziemann, Ulf

    2012-07-01

    The posterior part of the inferior frontal gyrus (pIFG) in the left hemisphere is thought to form part of the putative human mirror neuron system and is assigned a key role in mapping sensory perception onto motor action. Accordingly, the pIFG is involved in motor imitation of the observed actions of others but it is not known to what extent speech repetition of auditory-presented sentences is also a function of the pIFG. Here we applied fMRI-guided facilitating intermittent theta burst transcranial magnetic stimulation (iTBS), or depressant continuous TBS (cTBS), or intermediate TBS (imTBS) over the left pIFG of healthy subjects and compared speech repetition accuracy of foreign Japanese sentences before and after TBS. We found that repetition accuracy improved after iTBS and, to a lesser extent, after imTBS, but remained unchanged after cTBS. In a control experiment, iTBS was applied over the left middle occipital gyrus (MOG), a region not involved in sensorimotor processing of auditory-presented speech. Repetition accuracy remained unchanged after iTBS of MOG. We argue that the stimulation type and stimulation site specific facilitating effect of iTBS over left pIFG on speech repetition accuracy indicates a causal role of the human left-hemispheric pIFG in the translation of phonological perception to motor articulatory output for repetition of speech. This effect may prove useful in rehabilitation strategies that combine repetitive speech training with iTBS of the left pIFG in speech disorders, such as aphasia after cerebral stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Architectural space characteristics facilitating teaching and apprenticeship

    Directory of Open Access Journals (Sweden)

    Maria do Carmo de Lima Bezerra

    2016-06-01

    Full Text Available The article discusses the relevance of the architectural space as a facilitator of teaching and learning processes. It adopts an analytical methodology based on the architecture and pedagogy literature to know the view of these areas on the subject, and identifies relevant spatial attributes to facilitate education. Research has shown that there are recurrences pointing disciplinary fields of environmental comfort, ergonomics and environmental psychology, which were the subject of this conceptual research about the positive and negative impacts on the school design facility by each attribute of these disciplines. As result, it presents a framework of attributes, characteristics and relevance to teaching and learning to be used as support to the space needs assessment, ie: during the first stage of an architectural design process.

  4. POSITIVE LIFE CHANGE AFTER CANCER: THE KEY INGREDIENTS TO FACILITATE IT AND EFFECTS ON WELL-BEING

    Directory of Open Access Journals (Sweden)

    Cristian Ochoa Arnedo

    2017-01-01

    Full Text Available Over the last decades, Positive Psychology (PP has promoted the scientific study of positive life changes in the aftermath of cancer. These have been integrated within negative life changes, based on the same human experience framework. Innovative interventions have been designed, prioritizing the pathways to the reduction of emotional distress and psychopathology in cancer, through the facilitation of positive psychological functioning. These interventions have achieved promising results. A theoretical and integrative review of the PP-related constructs was performed in the relevant databases (PsycINFO, PubMed, Web of Science, Scopus, etc.. These constructs have been linked to positive life changes after cancer and their therapeutic potential. Finally, we provide a summary of a positive psychotherapy program for cancer survivors, indicating the therapeutic strategies that facilitate positive life changes in the aftermath of cancer. Positive life changes after suffering cancer are more the norm than the exception. These changes play an important role in psychosocial adjustment, adherence to cancer treatments, well-being and quality of life. Psychological treatment programs based on PP achieve promising results with cancer. These programs are capable of complementing and improving the outcomes achieved by traditional stress-management programs.

  5. If a Student Takes Control: Facilitator's Tasks and Responsibilities

    Science.gov (United States)

    Väljataga, Terje

    This paper presents initial research results of an intervention into higher educational teaching and studying practices from facilitators‘ point of view. The intervention was implemented into an international Master’s level online course mediated by landscapes of social media tools and services. In this course more emphasis was put on a shift of control from a facilitator to a student or a group of students in the following aspects: setting up one’s study goals, choosing activities, selecting appropriate resources, including technology and defining one’s evaluation criteria. The initial analysis showed that the facilitators gained a lot in terms of understanding the benefits of exploiting social media tools and services for their teaching practices, perceiving a need of having a different role as well as the shortages and problems while being a facilitator in such a course.

  6. A Critique on the Effectiveness of Current Human Reliability Analysis Approach for the Human-Machine Interface Design in Nuclear Power Plants

    International Nuclear Information System (INIS)

    Lee, Yong Hee

    2010-01-01

    Human Reliability Analysis (HRA) in cooperation of PSA has been conducted to evaluate the safety of a system and the validity of a system design. HRA has been believed to provide a quantitative value of human error potential and the safety level of a design alternative in Nuclear Power Plants (NPPs). However, it becomes doubtful that current HRA is worth to conduct to evaluate the human factors of NPP design, since there have been many critiques upon the virtue of HRA. Inevitably, the newer the technology becomes, the larger endeavors bound for the new facilitated methods. This paper describes the limitations and the obsolescence of the current HRA, especially for the design evaluation of Human-Machine Interface (HMI) utilizing the recent digital technologies. An alternative approach to the assessment of the human error potential of HMI design is proposed

  7. Facilitated transport of copper with hydroxyapatite nanoparticles in saturated sand

    Science.gov (United States)

    Saturated packed column experiments were conducted to investigate the facilitated transport of Cu with hydroxyapatite nanoparticles (nHAP) at different pore water velocities (0.22-2.2 cm min–1), solution pH (6.2-9.0), and fraction of Fe oxide coating on grain surfaces (', 0-0.36). The facilitated tr...

  8. Human-machine interface upgrade

    International Nuclear Information System (INIS)

    Kropik, M.; Matejka, K.; Sklenka, L.; Chab, V.

    2002-01-01

    The article describes a new human-machine interface that was installed at the VR-1 training reactor. The human-machine interface upgrade was completed in the summer 2001. The interface was designed with respect to functional, ergonomic and aesthetic requirements. The interface is based on a personal computer equipped with two displays. One display enables alphanumeric communication between the reactor operator and the nuclear reactor I and C. The second display is a graphical one. It presents the status of the reactor, principal parameters (as power, period), control rods positions, course of the reactor power. Furthermore, it is possible to set parameters, to show the active core configuration, to perform reactivity calculations, etc. The software for the new human-machine interface was produced with the InTouch developing tool of the Wonder-Ware Company. It is possible to switch the language of the interface between Czech and English because of many foreign students and visitors to the reactor. Microcomputer based communication units with proper software were developed to connect the new human-machine interface with the present reactor I and C. The new human-machine interface at the VR-1 training reactor improves the comfort and safety of the reactor utilisation, facilitates experiments and training, and provides better support for foreign visitors. (orig.)

  9. Structural and electronic properties of barbituric acid and melamine-containing ribonucleosides as plausible components of prebiotic RNA: implications for prebiotic self-assembly.

    Science.gov (United States)

    Kaur, Sarabjeet; Sharma, Purshotam; Wetmore, Stacey D

    2017-11-22

    The RNA world hypothesis assumes that RNA was the first informational polymer that originated from prebiotic chemical soup. However, since the reaction of d-ribose with canonical nucleobases (A, C, G and U) fails to yield ribonucleosides (rNs) in substantial amounts, the spontaneous origin of rNs and the subsequent synthesis of RNA remains an unsolved mystery. To this end, it has been suggested that RNA may have evolved from primitive genetic material (preRNA) composed of simpler prebiotic heterocycles that spontaneously form glycosidic bonds with ribose. As an effort toward evaluating this hypothesis, the present study uses density functional theory (DFT) to assess the suitability of barbituric acid (BA) and melamine (MM) to act as prebiotic nucleobases, both of which have recently been shown to spontaneously form a glycosidic bond with ribose and organize into supramolecular assemblies in solution. The significant strength of hydrogen bonds involving BA and MM indicates that such interactions may have played a crucial role in their preferential selection over competing heterocycles that interact solely through stacking interactions from the primordial soup during the early phase of evolution. However, the greater stability of stacked dimers involving BA or MM and the canonical nucleobases compared to those consisting solely of BA and/or MM points towards the possible evolution of intermediate informational polymers consisting of prebiotic and canonical nucleobases, which could have eventually evolved into RNA. Analysis of the associated rNs reveals an anti conformational preference for the biologically-relevant β-anomer of both BA and MM rNs, which will allow complementary WC-like hydrogen bonding that can stabilize preRNA polymers. Large calculated deglycosylation barriers suggest BA rNs containing C-C glycosidic bonds are relevant in challenging prebiotic environments such as volcanic geotherms, while lower barriers indicate the MM rNs containing C

  10. Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Liin, Sara I; Karlsson, Urban; Bentzen, Bo Hjorth

    2016-01-01

    the threshold current to evoke action potentials in dorsal root ganglion neurons. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes......, by shifting the conductance-versus-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μM). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. CONCLUSIONS: These findings suggest that circulating...... polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty...

  11. Behavioural responses to human-induced environmental change.

    Science.gov (United States)

    Tuomainen, Ulla; Candolin, Ulrika

    2011-08-01

    The initial response of individuals to human-induced environmental change is often behavioural. This can improve the performance of individuals under sudden, large-scale perturbations and maintain viable populations. The response can also give additional time for genetic changes to arise and, hence, facilitate adaptation to new conditions. On the other hand, maladaptive responses, which reduce individual fitness, may occur when individuals encounter conditions that the population has not experienced during its evolutionary history, which can decrease population viability. A growing number of studies find human disturbances to induce behavioural responses, both directly and by altering factors that influence fitness. Common causes of behavioural responses are changes in the transmission of information, the concentration of endocrine disrupters, the availability of resources, the possibility of dispersal, and the abundance of interacting species. Frequent responses are alterations in habitat choice, movements, foraging, social behaviour and reproductive behaviour. Behavioural responses depend on the genetically determined reaction norm of the individuals, which evolves over generations. Populations first respond with individual behavioural plasticity, whereafter changes may arise through innovations and the social transmission of behavioural patterns within and across generations, and, finally, by evolution of the behavioural response over generations. Only a restricted number of species show behavioural adaptations that make them thrive in severely disturbed environments. Hence, rapid human-induced disturbances often decrease the diversity of native species, while facilitating the spread of invasive species with highly plastic behaviours. Consequently, behavioural responses to human-induced environmental change can have profound effects on the distribution, adaptation, speciation and extinction of populations and, hence, on biodiversity. A better understanding of

  12. Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

    Science.gov (United States)

    Malan-Müller, Stefanie; Fairbairn, Lorren; Daniels, Willie M U; Dashti, Mahjoubeh Jalali Sefid; Oakeley, Edward J; Altorfer, Marc; Kidd, Martin; Seedat, Soraya; Gamieldien, Junaid; Hemmings, Sîan Megan Joanna

    2016-02-01

    D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction.

  13. Anhydrous crystals of DNA bases are wide gap semiconductors.

    Science.gov (United States)

    Maia, F F; Freire, V N; Caetano, E W S; Azevedo, D L; Sales, F A M; Albuquerque, E L

    2011-05-07

    We present the structural, electronic, and optical properties of anhydrous crystals of DNA nucleobases (guanine, adenine, cytosine, and thymine) found after DFT (Density Functional Theory) calculations within the local density approximation, as well as experimental measurements of optical absorption for powders of these crystals. Guanine and cytosine (adenine and thymine) anhydrous crystals are predicted from the DFT simulations to be direct (indirect) band gap semiconductors, with values 2.68 eV and 3.30 eV (2.83 eV and 3.22 eV), respectively, while the experimentally estimated band gaps we have measured are 3.83 eV and 3.84 eV (3.89 eV and 4.07 eV), in the same order. The electronic effective masses we have obtained at band extremes show that, at low temperatures, these crystals behave like wide gap semiconductors for electrons moving along the nucleobases stacking direction, while the hole transport are somewhat limited. Lastly, the calculated electronic dielectric functions of DNA nucleobases crystals in the parallel and perpendicular directions to the stacking planes exhibit a high degree of anisotropy (except cytosine), in agreement with published experimental results.

  14. Facilitation of Retention by White Noise

    Science.gov (United States)

    Baumeister, Alfred A.; Kistler, Doris

    1975-01-01

    This study attempted to determine if white noise (an arousing stimulus), when presented at the time of recall, facilitates performance of second and fifth grade students, and if this effect generalizes across different kinds of learning tasks. Findings indicate that white noise produces improvements in performance in both age groups. (GO)

  15. Facilitating Team Learning through Transformational Leadership

    Science.gov (United States)

    Raes, Elisabeth; Decuyper, Stefan; Lismont, Bart; Van den Bossche, Piet; Kyndt, Eva; Demeyere, Sybille; Dochy, Filip

    2013-01-01

    This article investigates when and how teams engage in team learning behaviours (TLB). More specifically, it looks into how different leadership styles facilitate TLB by influencing the social conditions that proceed them. 498 healthcare workers from 28 nursery teams filled out a questionnaire measuring the concepts leadership style, TLB, social…

  16. FIRE (facilitating implementation of research evidence: a study protocol

    Directory of Open Access Journals (Sweden)

    Seers Kate

    2012-03-01

    Full Text Available Abstract Background Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids. Objectives This study aims to advance understanding about the contribution facilitation can make to implementing research findings into practice via: extending current knowledge of facilitation as a process for translating research evidence into practice; evaluating the feasibility, effectiveness, and cost-effectiveness of two different models of facilitation in promoting the uptake of research evidence on continence management; assessing the impact of contextual factors on the processes and outcomes of implementation; and implementing a pro-active knowledge transfer and dissemination strategy to diffuse study findings to a wide policy and practice community. Setting and sample Four European countries, each with six long-term nursing care sites (total 24 sites for people aged 60 years and over with documented urinary incontinence Methods and design Pragmatic randomised controlled trial with three arms (standard dissemination and two different programmes of facilitation, with embedded process and economic evaluation. The primary outcome is compliance with the continence recommendations. Secondary outcomes include proportion of residents with incontinence, incidence of incontinence-related dermatitis, urinary tract infections, and quality of life. Outcomes are assessed at baseline

  17. Incorporating Ecosystem Processes Controlling Carbon Balance Into Models of Coupled Human-Natural Systems

    Science.gov (United States)

    Currie, W.; Brown, D. G.; Brunner, A.; Fouladbash, L.; Hadzick, Z.; Hutchins, M.; Kiger, S. E.; Makino, Y.; Nassauer, J. I.; Robinson, D. T.; Riolo, R. L.; Sun, S.

    2012-12-01

    A key element in the study of coupled human-natural systems is the interactions of human populations with vegetation and soils. In human-dominated landscapes, vegetation production and change results from a combination of ecological processes and human decision-making and behavior. Vegetation is often dramatically altered, whether to produce food for humans and livestock, to harvest fiber for construction and other materials, to harvest fuel wood or feedstock for biofuels, or simply for cultural preferences as in the case of residential lawns with sparse trees in the exurban landscape. This alteration of vegetation and its management has a substantial impact on the landscape carbon balance. Models can be used to simulate scenarios in human-natural systems and to examine the integration of processes that determine future trajectories of carbon balance. However, most models of human-natural systems include little integration of the human alteration of vegetation with the ecosystem processes that regulate carbon balance. Here we illustrate a few case studies of pilot-study models that strive for this integration from our research across various types of landscapes. We focus greater detail on a fully developed research model linked to a field study of vegetation and soils in the exurban residential landscape of Southeastern Michigan, USA. The field study characterized vegetation and soil carbon storage in 5 types of ecological zones. Field-observed carbon storage in the vegetation in these zones ranged widely, from 150 g C/m2 in turfgrass zones, to 6,000 g C/m2 in zones defined as turfgrass with sparse woody vegetation, to 16,000 g C/m2 in a zone defined as dense trees and shrubs. Use of these zones facilitated the scaling of carbon pools to the landscape, where the areal mixtures of zone types had a significant impact on landscape C storage. Use of these zones also facilitated the use of the ecosystem process model Biome-BGC to simulate C trajectories and also

  18. Tactile-dependant corticomotor facilitation is influenced by discrimination performance in seniors

    Directory of Open Access Journals (Sweden)

    Tremblay François

    2010-03-01

    Full Text Available Abstract Background Active contraction leads to facilitation of motor responses evoked by transcranial magnetic stimulation (TMS. In small hand muscles, motor facilitation is known to be also influenced by the nature of the task. Recently, we showed that corticomotor facilitation was selectively enhanced when young participants actively discriminated tactile symbols with the tip of their index or little finger. This tactile-dependant motor facilitation reflected, for the large part, attentional influences associated with performing tactile discrimination, since execution of a concomitant distraction task abolished facilitation. In the present report, we extend these observations to examine the influence of age on the ability to produce extra motor facilitation when the hand is used for sensory exploration. Methods Corticomotor excitability was tested in 16 healthy seniors (58-83 years while they actively moved their right index finger over a surface under two task conditions. In the tactile discrimination (TD condition, participants attended to the spatial location of two tactile symbols on the explored surface, while in the non discrimination (ND condition, participants simply moved their finger over a blank surface. Changes in amplitude, in latency and in the silent period (SP duration were measured from recordings of motor evoked potentials (MEP in the right first dorsal interosseous muscle in response to TMS of the left motor cortex. Results Healthy seniors exhibited widely varying levels of performance with the TD task, older age being associated with lower accuracy and vice-versa. Large inter-individual variations were also observed in terms of tactile-specific corticomotor facilitation. Regrouping seniors into higher (n = 6 and lower performance groups (n = 10 revealed a significant task by performance interaction. This latter interaction reflected differences between higher and lower performance groups; tactile-related facilitation being

  19. Voice congruency facilitates word recognition.

    Science.gov (United States)

    Campeanu, Sandra; Craik, Fergus I M; Alain, Claude

    2013-01-01

    Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs) while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent) varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  20. Voice congruency facilitates word recognition.

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    Sandra Campeanu

    Full Text Available Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.