Regulation of exocytosis by the exocyst subunit Sec6 and the SM protein Sec1.

PubMed

Morgera, Francesca; Sallah, Margaret R; Dubuke, Michelle L; Gandhi, Pallavi; Brewer, Daniel N; Carr, Chavela M; Munson, Mary

2012-01-01

Trafficking of protein and lipid cargo through the secretory pathway in eukaryotic cells is mediated by membrane-bound vesicles. Secretory vesicle targeting and fusion require a conserved multisubunit protein complex termed the exocyst, which has been implicated in specific tethering of vesicles to sites of polarized exocytosis. The exocyst is directly involved in regulating soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) complexes and membrane fusion through interactions between the Sec6 subunit and the plasma membrane SNARE protein Sec9. Here we show another facet of Sec6 function-it directly binds Sec1, another SNARE regulator, but of the Sec1/Munc18 family. The Sec6-Sec1 interaction is exclusive of Sec6-Sec9 but compatible with Sec6-exocyst assembly. In contrast, the Sec6-exocyst interaction is incompatible with Sec6-Sec9. Therefore, upon vesicle arrival, Sec6 is proposed to release Sec9 in favor of Sec6-exocyst assembly and to simultaneously recruit Sec1 to sites of secretion for coordinated SNARE complex formation and membrane fusion.

Proteins on exocytic vesicles mediate calcium-triggered fusion.

PubMed Central

Vogel, S S; Zimmerberg, J

1992-01-01

In many exocytic systems, micromolar concentrations of intracellular Ca2+ trigger fusion. We find that aggregates of secretory granules isolated from sea urchin eggs fuse together when perfused with greater than or equal to 10 microM free Ca2+. Mixing of membrane components was demonstrated by transfer of fluorescent lipophilic dye, and melding of granule contents was seen with differential interference microscopy. A technique based upon light scattering was developed to conveniently detect fusion. Two protein modifiers, trypsin and N-ethylmaleimide, inhibit granule-granule fusion at concentrations similar to those that inhibit granule-plasma membrane fusion. We suggest that molecular machinery sufficient for Ca(2+)-triggered fusion resides on secretory granules as purified and that at least some of these essential components are proteinaceous. Images PMID:1584814

Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses

PubMed Central

Sinha, Raunak; Ahmed, Saheeb; Jahn, Reinhard; Klingauf, Jurgen

2011-01-01

Exocytosis of synaptic vesicles (SVs) during fast synaptic transmission is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly formed by the coil-coiling of three members of this protein family: vesicle SNARE protein, synaptobrevin 2 (syb2), and the presynaptic membrane SNAREs syntaxin-1A and SNAP-25. However, it is controversially debated how many SNARE complexes are minimally needed for SV priming and fusion. To quantify this effective number, we measured the fluorescence responses from single fusing vesicles expressing pHluorin (pHl), a pH-sensitive variant of GFP, fused to the luminal domain of the vesicular SNARE syb2 (spH) in cultured hippocampal neurons lacking endogenous syb2. Fluorescence responses were quantal, with the unitary signals precisely corresponding to single pHluorin molecules. Using this approach we found that two copies of spH per SV fully rescued evoked fusion whereas SVs expressing only one spH were unable to rapidly fuse upon stimulation. Thus, two syb2 molecules and likely two SNARE complexes are necessary and sufficient for SV fusion during fast synaptic transmission. PMID:21844343

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

NASA Astrophysics Data System (ADS)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

PubMed

Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

2013-12-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

Regulation of platelet granule exocytosis by S-nitrosylation

PubMed Central

Morrell, Craig N.; Matsushita, Kenji; Chiles, Kelly; Scharpf, Robert B.; Yamakuchi, Munekazu; Mason, Rebecca J. A.; Bergmeier, Wolfgang; Mankowski, Joseph L.; Baldwin, William M.; Faraday, Nauder; Lowenstein, Charles J.

2005-01-01

Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and α-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis. PMID:15738422

Vesicle Adhesion and Fusion Studied by Small-Angle X-Ray Scattering.

PubMed

Komorowski, Karlo; Salditt, Annalena; Xu, Yihui; Yavuz, Halenur; Brennich, Martha; Jahn, Reinhard; Salditt, Tim

2018-04-24

We have studied the adhesion state (also denoted by docking state) of lipid vesicles as induced by the divalent ions Ca 2+ or Mg 2+ at well-controlled ion concentration, lipid composition, and charge density. The bilayer structure and the interbilayer distance in the docking state were analyzed by small-angle x-ray scattering. A strong adhesion state was observed for DOPC:DOPS vesicles, indicating like-charge attraction resulting from ion correlations. The observed interbilayer separations of ∼1.6 nm agree quantitatively with the predictions of electrostatics in the strong coupling regime. Although this phenomenon was observed when mixing anionic and zwitterionic (or neutral) lipids, pure anionic membranes (DOPS) with highest charge density σ resulted in a direct phase transition to a multilamellar state, which must be accompanied by rupture and fusion of vesicles. To extend the structural assay toward protein-controlled docking and fusion, we have characterized reconstituted N-ethylmaleimide-sensitive factor attachment protein receptors in controlled proteoliposome suspensions by small-angle x-ray scattering. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases soluble N-ethylmaleimide-sensitive factor attachment receptor protein expression within neuronal perikarya.

PubMed

McGorum, B C; Scholes, S; Milne, E M; Eaton, S L; Wishart, T M; Poxton, I R; Moss, S; Wernery, U; Davey, T; Harris, J B; Pirie, R S

2016-11-01

Equine grass sickness (EGS) is of unknown aetiology. Despite some evidence suggesting that it represents a toxico-infection with Clostridium botulinum types C and/or D, the effect of EGS on the functional targets of botulinum neurotoxins, namely the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, is unknown. Further, while it is commonly stated that, unlike EGS, equine botulism is not associated with autonomic and enteric neurodegeneration, this has not been definitively assessed. To determine: 1) whether botulism causes autonomic and enteric neurodegeneration; and 2) the effect of EGS on the expression of SNARE proteins within cranial cervical ganglion (CCG) and enteric neuronal perikarya. Descriptive study. Light microscopy was used to compare the morphology of neurons in haematoxylin-eosin stained sections of CCG and ileum from 6 EGS horses, 5 botulism horses and 6 control horses. Immunohistochemistry was used to compare the expression of synaptosomal-associated protein-25, synaptobrevin (Syb) and syntaxin within CCG neurons, and of Syb in enteric neurons, from horses with EGS, horses with botulism and control horses. The concentrations of these SNARE proteins in extracts of CCG from EGS and control horses were compared using quantitative fluorescent western blotting. EGS, but not botulism, was associated with autonomic and enteric neurodegeneration and with increased immunoreactivity for SNARE proteins within neuronal perikarya. Quantitative fluorescent western blotting confirmed increased concentrations of synaptosomal-associated protein-25, Syb and syntaxin within CCG extracts from EGS vs. control horses, with the increases in the latter 2 proteins being statistically significant. The occurrence of autonomic and enteric neurodegeneration, and increased expression of SNARE proteins within neuronal perikarya, in EGS but not botulism, suggests that EGS may not be caused by botulinum neurotoxins. Further investigation of the

Effect of N-Ethylmaleimide as a Blocker of Disulfide Crosslinks Formation on the Alkali-Cold Gelation of Whey Proteins

PubMed Central

Lei, Zhao; Chen, Xiao Dong

2016-01-01

N-ethylmaleimide (NEM) was used to verify that no new disulfide crosslinks were formed during the fascinating rheology of the alkali cold-gelation of whey proteins, which show Sol-Gel-Sol transitions with time at pH > 11.5. These dynamic transitions involve the formation and subsequent destruction of non-covalent interactions between soluble whey aggregates. Therefore, incubation of aggregates with NEM was expected not to affect much the rheology. Experiments show that very little additions of NEM, such as 0.5 mol per mol of protein, delayed and significantly strengthened the metastable gels formed. Interactions between whey protein aggregates were surprisingly enhanced during incubation with NEM as inferred from oscillatory rheometry at different protein concentrations, dynamic swelling, Trp fluorescence and SDS-PAGE measurements. PMID:27732644

ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.

PubMed

Diao, Jiajie; Liu, Rong; Rong, Yueguang; Zhao, Minglei; Zhang, Jing; Lai, Ying; Zhou, Qiangjun; Wilz, Livia M; Li, Jianxu; Vivona, Sandro; Pfuetzner, Richard A; Brunger, Axel T; Zhong, Qing

2015-04-23

Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.

SNARE-mediated rapid lysosome fusion in membrane raft clustering and dysfunction of bovine coronary arterial endothelium

PubMed Central

Han, Wei-Qing; Xia, Min; Zhang, Chun; Zhang, Fan; Xu, Ming; Li, Ning-Jun

2011-01-01

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP-2, vesicle-SNAREs) were found to be abundantly expressed in the endothelium of bovine coronary arteries. Direct lysosome fusion monitoring by N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyridinium dibromide (FM1-43) quenching demonstrated that the inhibition of VAMP-2 with tetanus toxin or specific small interfering ribonucleic acid (siRNA) almost completely blocked lysosome fusion to plasma membrane induced by Fas ligand (FasL), a well-known MR clustering stimulator. The involvement of SNAREs was further confirmed by an increased interaction of VAMP-2 with a target-SNARE protein syntaxin-4 after FasL stimulation in coimmunoprecipitation analysis. Also, the inhibition of VAMP-2 with tetanus toxin or VAMP-2 siRNA abolished FasL-induced MR clustering, its colocalization with a NADPH oxidase unit gp91phox, and increased superoxide production. Finally, FasL-induced impairment of endothelium-dependent vasodilation was reversed by the treatment of bovine coronary arteries with tetanus toxin or VAMP-2 siRNA. VAMP-2 is critical to lysosome fusion in MR clustering, and this VAMP-2-mediated lysosome-MR signalosomes contribute to redox regulation of coronary endothelial function. PMID:21926345

Disease resistance through impairment of α-SNAP–NSF interaction and vesicular trafficking by soybean Rhg1

PubMed Central

Bayless, Adam M.; Smith, John M.; Song, Junqi; McMinn, Patrick H.; Teillet, Alice; August, Benjamin K.

2016-01-01

α-SNAP [soluble NSF (N-ethylmaleimide–sensitive factor) attachment protein] and NSF proteins are conserved across eukaryotes and sustain cellular vesicle trafficking by mediating disassembly and reuse of SNARE protein complexes, which facilitate fusion of vesicles to target membranes. However, certain haplotypes of the Rhg1 (resistance to Heterodera glycines 1) locus of soybean possess multiple repeat copies of an α-SNAP gene (Glyma.18G022500) that encodes atypical amino acids at a highly conserved functional site. These Rhg1 loci mediate resistance to soybean cyst nematode (SCN; H. glycines), the most economically damaging pathogen of soybeans worldwide. Rhg1 is widely used in agriculture, but the mechanisms of Rhg1 disease resistance have remained unclear. In the present study, we found that the resistance-type Rhg1 α-SNAP is defective in interaction with NSF. Elevated in planta expression of resistance-type Rhg1 α-SNAPs depleted the abundance of SNARE-recycling 20S complexes, disrupted vesicle trafficking, induced elevated abundance of NSF, and caused cytotoxicity. Soybean, due to ancient genome duplication events, carries other loci that encode canonical (wild-type) α-SNAPs. Expression of these α-SNAPs counteracted the cytotoxicity of resistance-type Rhg1 α-SNAPs. For successful growth and reproduction, SCN dramatically reprograms a set of plant root cells and must sustain this sedentary feeding site for 2–4 weeks. Immunoblots and electron microscopy immunolocalization revealed that resistance-type α-SNAPs specifically hyperaccumulate relative to wild-type α-SNAPs at the nematode feeding site, promoting the demise of this biotrophic interface. The paradigm of disease resistance through a dysfunctional variant of an essential gene may be applicable to other plant–pathogen interactions. PMID:27821740

Redox agents and N-ethylmaleimide affect protein polymerization during laboratory scale dry pasta production and cooking.

PubMed

Bruneel, Charlotte; Buggenhout, Joke; Lagrain, Bert; Brijs, Kristof; Delcour, Jan A

2016-04-01

Durum wheat (Triticum durum Desf.) semolina gluten proteins consist of monomeric gliadin and polymeric glutenin and determine the quality of pasta products made therefrom. During pasta drying, glutenin starts polymerizing already below 60 °C (65% relative humidity (RH)), whereas gliadin only is incorporated in the protein network at temperatures exceeding 68 °C (68% RH) through thiol (SH)/disulfide (SS) exchange reactions. Removal of free SH groups in glutenin by adding 2.3 μmol KBrO3 or KIO3 per g dry matter semolina protein (g protein) or 13.8 μmol N-ethylmaleimide/g protein reduces gliadin-glutenin cross-linking during pasta drying and/or cooking and yields cooked pasta of high quality. Introducing free SH groups by adding 13.8 μmol glutathione/g protein increases gliadin-glutenin cross-linking during pasta processing, resulting in cooked pasta of lower quality. We hypothesize that too much gliadin incorporation in the glutenin network during pasta processing tightens the protein network and results in lower cooking quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae.

PubMed

Rogers, Jason V; Rose, Mark D

2014-12-02

During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p's functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion. Copyright © 2015 Rogers and Rose.

Synaptotagmin C2B Domain Regulates Ca2+-triggered Fusion in Vitro

PubMed Central

Gaffaney, Jon D.; Dunning, F. Mark; Wang, Zhao; Hui, Enfu; Chapman, Edwin R.

2008-01-01

Synaptotagmin (syt) 1 is localized to synaptic vesicles, binds Ca2+, and regulates neuronal exocytosis. Syt 1 harbors two Ca2+-binding motifs referred to as C2A and C2B. In this study we examine the function of the isolated C2 domains of Syt 1 using a reconstituted, SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor)-mediated, fusion assay. We report that inclusion of phosphatidylethanolamine into reconstituted SNARE vesicles enabled isolated C2B, but not C2A, to regulate Ca2+-triggered fusion. The isolated C2B domain had a 6-fold lower EC for Ca2+ 50-activated fusion than the intact cytosolic domain of Syt 1 (C2AB). Phosphatidylethanolamine increased both the rate and efficiency of C2AB- and C2B-regulated fusion without affecting their abilities to bind membrane-embedded syntaxin-SNAP-25 (t-SNARE) complexes. At equimolar concentrations, the isolated C2A domain was an effective inhibitor of C2B-, but not C2AB-regulated fusion; hence, C2A has markedly different effects in the fusion assay depending on whether it is tethered to C2B. Finally, scanning alanine mutagenesis of C2AB revealed four distinct groups of mutations within the C2B domain that play roles in the regulation of SNARE-mediated fusion. Surprisingly, substitution of Arg-398 with alanine, which lies on the opposite end of C2B from the Ca2+/membrane-binding loops, decreases C2AB t-SNARE binding and Ca2+-triggered fusion in vitro without affecting Ca2+-triggered interactions with phosphatidylserine or vesicle aggregation. In addition, some mutations uncouple the clamping and stimulatory functions of syt 1, suggesting that these two activities are mediated by distinct structural determinants in C2B. PMID:18784080

State-of-the-Art Fusion-Finder Algorithms Sensitivity and Specificity

PubMed Central

Carrara, Matteo; Beccuti, Marco; Lazzarato, Fulvio; Cavallo, Federica; Cordero, Francesca; Donatelli, Susanna; Calogero, Raffaele A.

2013-01-01

Background. Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way. Results. We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions. Conclusions. The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms. PMID:23555082

Green fluorescence protein-based content-mixing assay of SNARE-driven membrane fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heo, Paul; Kong, Byoungjae; Jung, Young-Hun

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediate intracellular membrane fusion by forming a ternary SNARE complex. A minimalist approach utilizing proteoliposomes with reconstituted SNARE proteins yielded a wealth of information pinpointing the molecular mechanism of SNARE-mediated fusion and its regulation by accessory proteins. Two important attributes of a membrane fusion are lipid-mixing and the formation of an aqueous passage between apposing membranes. These two attributes are typically observed by using various fluorescent dyes. Currently available in vitro assay systems for observing fusion pore opening have several weaknesses such as cargo-bleeding, incomplete removal of unencapsulated dyes, and inadequate information regardingmore » the size of the fusion pore, limiting measurements of the final stage of membrane fusion. In the present study, we used a biotinylated green fluorescence protein and streptavidin conjugated with Dylight 594 (DyStrp) as a Föster resonance energy transfer (FRET) donor and acceptor, respectively. This FRET pair encapsulated in each v-vesicle containing synaptobrevin and t-vesicle containing a binary acceptor complex of syntaxin 1a and synaptosomal-associated protein 25 revealed the opening of a large fusion pore of more than 5 nm, without the unwanted signals from unencapsulated dyes or leakage. This system enabled determination of the stoichiometry of the merging vesicles because the FRET efficiency of the FRET pair depended on the molar ratio between dyes. Here, we report a robust and informative assay for SNARE-mediated fusion pore opening. - Highlights: • SNARE proteins drive membrane fusion and open a pore for cargo release. • Biotinylated GFP and DyStrp was used as the reporter pair of fusion pore opening. • Procedure for efficient SNARE reconstitution and reporter encapsulation was established. • The FRET pair reported opening of a large fusion pore bigger than 5�

The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing.

PubMed

Kou, Xiaoxing; Xu, Xingtian; Chen, Chider; Sanmillan, Maria Laura; Cai, Tao; Zhou, Yanheng; Giraudo, Claudio; Le, Anh; Shi, Songtao

2018-03-14

Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-α (TNF-α) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor κB pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A Critical Role for Protein Degradation in the Nucleus Accumbens Core in Cocaine Reward Memory

PubMed Central

Ren, Zhen-Yu; Liu, Meng-Meng; Xue, Yan-Xue; Ding, Zeng-Bo; Xue, Li-Fen; Zhai, Suo-Di; Lu, Lin

2013-01-01

The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli contribute to cocaine seeking and relapse. Previous studies have shown impairment in cocaine reward memories by manipulating a labile state induced by memory retrieval, but the mechanisms that underlie the destabilization of cocaine reward memory are unknown. In this study, using a Pavlovian cocaine-induced conditioned place preference (CPP) procedure in rats, we tested the contribution of ubiquitin-proteasome system-dependent protein degradation in destabilization of cocaine reward memory. First, we found that polyubiquitinated protein expression levels and polyubiquitinated N-ethylmaleimide-sensitive fusion (NSF) markedly increased 15 min after retrieval while NSF protein levels decreased 1 h after retrieval in the synaptosomal membrane fraction in the nucleus accumbens (NAc) core. We then found that infusion of the proteasome inhibitor lactacystin into the NAc core prevented the impairment of memory reconsolidation induced by the protein synthesis inhibitor anisomycin and reversed the effects of anisomycin on NSF and glutamate receptor 2 (GluR2) protein levels in the synaptosomal membrane fraction in the NAc core. We also found that lactacystin infusion into the NAc core but not into the shell immediately after extinction training sessions inhibited CPP extinction and reversed the extinction training-induced decrease in NSF and GluR2 in the synaptosomal membrane fraction in the NAc core. Finally, infusions of lactacystin by itself into the NAc core immediately after each training session or before the CPP retrieval test had no effect on the consolidation and retrieval of cocaine reward memory. These findings suggest that ubiquitin-proteasome system-dependent protein degradation is critical for retrieval-induced memory destabilization. PMID:23303053

BKV Agnoprotein Interacts with α-Soluble N-Ethylmaleimide-Sensitive Fusion Attachment Protein, and Negatively Influences Transport of VSVG-EGFP

PubMed Central

Johannessen, Mona; Walquist, Mari; Gerits, Nancy; Dragset, Marte; Spang, Anne; Moens, Ugo

2011-01-01

Background The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. Principal Findings As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them α-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and α-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and α-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with α-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. Conclusions We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with α-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter. PMID:21931730

Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool.

PubMed

Haglerød, C; Hussain, S; Nakamura, Y; Xia, J; Haug, F-M S; Ottersen, O P; Henley, J M; Davanger, S

2017-03-06

Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus. Furthermore, we show that GluA2 and protein interacting with C kinase 1 (PICK1) are colocalized at presynaptic vesicles. Similar to postsynaptic mechanisms, overexpression of either PICK1 or pep2m, which inhibit the N-ethylmaleimide sensitive fusion protein (NSF)-GluA2 interaction, decreases the concentration of GluA2 in the presynaptic active zone membrane. These data suggest that the interacting proteins PICK1 and NSF act as regulators of presynaptic GluA2-containing AMPAR trafficking between the active zone and a vesicle pool that may provide the basis of presynaptic components of synaptic plasticity. Copyright © 2017 IBRO. All rights reserved.

NSF appointment

NASA Astrophysics Data System (ADS)

President Ronald Reagan has announced his intention to nominate Richard S. Nicholson as assistant director of the National Science Foundation (NSF) for mathematical and physical sciences. Nicholson has been acting deputy director and staff director of NSF since 1983.A research chemist by training, Nicholson was an associate professor of chemistry at Michigan State University before joining NSF in 1970. He served in a number of capacities at NSF, including executive director of the National Science Board commission on precollege education in mathematics, science, and technology, deputy assistant director for the mathematical and physical sciences, and senior planning officer for mathematical and physical sciences. The nomination is subject to Senate confirmation.

pH-Sensitive Liposomes: Acid-Induced Liposome Fusion

NASA Astrophysics Data System (ADS)

Connor, Jerome; Yatvin, Milton B.; Huang, Leaf

1984-03-01

Sonicated unilamellar liposomes containing phosphatidylethanolamine and palmitoylhomocysteine fuse rapidly when the medium pH is lowered from 7 to 5. Liposome fusion was demonstrated by (i) mixing of the liposomal lipids as shown by resonance energy transfer, (ii) gel filtration, and (iii) electron microscopy. The pH-sensitive fusion of liposomes was observed only when palmitoylhomocysteine (>= 20 mol%) was present in the liposomes. The presence of phosphatidyl-ethanolamine in the liposomes greatly enhanced fusion whereas the presence of phosphatidylcholine inhibited fusion. During fusion of liposomes containing phosphatidylethanolamine and palmitoylhomocysteine (8:2, mol/mol), almost all of the encapsulated calcein was released. Inclusion of cholesterol (40 mol%) in the liposomes substantially decreased leakage without impairing fusion.

Progress in understanding the neuronal SNARE function and its regulation.

PubMed

Yoon, T-Y; Shin, Y-K

2009-02-01

Vesicle budding and fusion underlies many essential biochemical deliveries in eukaryotic cells, and its core fusion machinery is thought to be built on one protein family named soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE). Recent technical advances based on site-directed fluorescence labelling and nano-scale detection down to the single-molecule level rapidly unveiled the protein and the lipid intermediates along the fusion pathway as well as the molecular actions of fusion effectors. Here we summarize these new exciting findings in context with a new mechanistic model that reconciles two existing fusion models: the proteinaceous pore model and the hemifusion model. Further, we attempt to locate the points of action for the fusion effectors along the fusion pathway and to delineate the energetic interplay between the SNARE complexes and the fusion effectors.

NSF's Career-Life Balance Initiative and the NSF Astronomy and Astrophysics Postdoctoral Fellowships

NASA Astrophysics Data System (ADS)

Ajhar, Edward A.

2013-01-01

In the fall of 2011, the National Science Foundation (NSF) began the Career-Life Balance Initiative to support graduate students, postdoctoral students, and early-career researchers in STEM fields. NSF is focusing first on its most prestigious programs for early-career scientists---the CAREER program and the postdoctoral programs, including the NSF Astronomy and Astrophysics Postdoctoral Fellowships (AAPF)---where career-life balance opportunities can help retain a significant fraction of early career talent. Subject to budget constraints, NSF plans to further integrate and enhance career-life balance opportunities over time through other programs, like the Graduate Research Fellowships Program and ADVANCE, and subsequently through the broader portfolio of NSF activities. In addition, to comply with Title IX, NSF has regulations to ensure that educational programs that receive NSF funds are free of gender discrimination and harassment. A primary goal of this presentation is to put facts about NSF into the hands of students, faculty, staff, administrators and other policy makers to benefit the advancement of career-life balance in the astronomical community. The presentation focus areas will (1) address common misconceptions about NSF rules regarding parental leave; (2) discuss benefits already available through the AAPF program, Graduate Research Fellowships, and other programs; and (3) listen to community concerns and issues to bring these back to the foundation for consideration. Did you know that NSF allows paid parental leave under many circumstances? For example, the AAPF program currently allows two months of paid parental leave during the fellow's tenure. What are the rules for NSF Graduate Research Fellowships? Come to the session and find out; the answers to such questions might surprise you.

Septin dynamics are essential for exocytosis.

PubMed

Tokhtaeva, Elmira; Capri, Joe; Marcus, Elizabeth A; Whitelegge, Julian P; Khuzakhmetova, Venera; Bukharaeva, Ellya; Deiss-Yehiely, Nimrod; Dada, Laura A; Sachs, George; Fernandez-Salas, Ester; Vagin, Olga

2015-02-27

Septins are a family of 14 cytoskeletal proteins that dynamically form hetero-oligomers and organize membrane microdomains for protein complexes. The previously reported interactions with SNARE proteins suggested the involvement of septins in exocytosis. However, the contradictory results of up- or down-regulation of septin-5 in various cells and mouse models or septin-4 in mice suggested either an inhibitory or a stimulatory role for these septins in exocytosis. The involvement of the ubiquitously expressed septin-2 or general septin polymerization in exocytosis has not been explored to date. Here, by nano-LC with tandem MS and immunoblot analyses of the septin-2 interactome in mouse brain, we identified not only SNARE proteins but also Munc-18-1 (stabilizes assembled SNARE complexes), N-ethylmaleimide-sensitive factor (NSF) (disassembles SNARE complexes after each membrane fusion event), and the chaperones Hsc70 and synucleins (maintain functional conformation of SNARE proteins after complex disassembly). Importantly, α-soluble NSF attachment protein (SNAP), the adaptor protein that mediates NSF binding to the SNARE complex, did not interact with septin-2, indicating that septins undergo reorganization during each exocytosis cycle. Partial depletion of septin-2 by siRNA or impairment of septin dynamics by forchlorfenuron inhibited constitutive and stimulated exocytosis of secreted and transmembrane proteins in various cell types. Forchlorfenuron impaired the interaction between SNAP-25 and its chaperone Hsc70, decreasing SNAP-25 levels in cultured neuroendocrine cells, and inhibited both spontaneous and stimulated acetylcholine secretion in mouse motor neurons. The results demonstrate a stimulatory role of septin-2 and the dynamic reorganization of septin oligomers in exocytosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs.

PubMed

Gerlach, Thomas; Hensen, Luca; Matrosovich, Tatyana; Bergmann, Janina; Winkler, Michael; Peteranderl, Christin; Klenk, Hans-Dieter; Weber, Friedemann; Herold, Susanne; Pöhlmann, Stefan; Matrosovich, Mikhail

2017-06-01

The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins. IMPORTANCE The IFN system constitutes an important innate defense against viral infection. Substantial information is available on how IAVs avoid detection by sensors of the IFN system and disable IFN signaling pathways. Much less is known about the ability of IAVs to tolerate the antiviral activity of IFN

pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs

PubMed Central

Gerlach, Thomas; Hensen, Luca; Matrosovich, Tatyana; Bergmann, Janina; Winkler, Michael; Peteranderl, Christin; Klenk, Hans-Dieter; Herold, Susanne

2017-01-01

ABSTRACT The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity was confirmed by using HA point mutants of A/Hong Kong/1/1968-PR8 that differed solely by their fusion properties. Furthermore, similar effects of the viral fusion pH on IFN sensitivity were observed in experiments with (i) primary human type II alveolar epithelial cells and differentiated cultures of human airway epithelial cells, (ii) nonrecombinant zoonotic and pandemic IAVs, and (iii) preparations of IFN-α and IFN-λ1. A higher pH of membrane fusion and reduced sensitivity to IFN correlated with lower restriction of the viruses in MDCK cells stably expressing the IFN-inducible transmembrane proteins IFITM2 and IFITM3, which are known to inhibit viral fusion. Our results reveal that the pH optimum of HA-driven membrane fusion of IAVs is a determinant of their sensitivity to IFN and IFITM proteins. IMPORTANCE The IFN system constitutes an important innate defense against viral infection. Substantial information is available on how IAVs avoid detection by sensors of the IFN system and disable IFN signaling pathways. Much less is known about the ability of IAVs to tolerate the antiviral activity of

Binding of SEC11 Indicates Its Role in SNARE Recycling after Vesicle Fusion and Identifies Two Pathways for Vesicular Traffic to the Plasma Membrane[OPEN

PubMed Central

Karnik, Rucha; Zhang, Ben; Waghmare, Sakharam; Aderhold, Christin; Grefen, Christopher; Blatt, Michael R.

2015-01-01

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins drive vesicle fusion in all eukaryotes and contribute to homeostasis, pathogen defense, cell expansion, and growth in plants. Two homologous SNAREs, SYP121 (=SYR1/PEN1) and SYP122, dominate secretory traffic to the Arabidopsis thaliana plasma membrane. Although these proteins overlap functionally, differences between SYP121 and SYP122 have surfaced, suggesting that they mark two discrete pathways for vesicular traffic. The SNAREs share primary cognate partners, which has made separating their respective control mechanisms difficult. Here, we show that the regulatory protein SEC11 (=KEULE) binds selectively with SYP121 to affect secretory traffic mediated by this SNARE. SEC11 rescued traffic block by dominant-negative (inhibitory) fragments of both SNAREs, but only in plants expressing the native SYP121. Traffic and its rescue were sensitive to mutations affecting SEC11 interaction with the N terminus of SYP121. Furthermore, the domain of SEC11 that bound the SYP121 N terminus was itself able to block secretory traffic in the wild type and syp122 but not in syp121 mutant Arabidopsis. Thus, SEC11 binds and selectively regulates secretory traffic mediated by SYP121 and is important for recycling of the SNARE and its cognate partners. PMID:25747882

The uncharacterized transcription factor YdhM is the regulator of the nemA gene, encoding N-ethylmaleimide reductase.

PubMed

Umezawa, Yoshimasa; Shimada, Tomohiro; Kori, Ayako; Yamada, Kayoko; Ishihama, Akira

2008-09-01

N-ethylmaleimide (NEM) has been used as a specific reagent of Cys modification in proteins and thus is toxic for cell growth. On the Escherichia coli genome, the nemA gene coding for NEM reductase is located downstream of the gene encoding an as-yet-uncharacterized transcription factor, YdhM. Disruption of the ydhM gene results in reduction of nemA expression even in the induced state, indicating that the two genes form a single operon. After in vitro genomic SELEX screening, one of the target recognition sequences for YdhM was identified within the promoter region for this ydhM-nemA operon. Both YdhM binding in vitro to the ydhM promoter region and transcription repression in vivo of the ydhM-nemA operon by YdhM were markedly reduced by the addition of NEM. Taken together, we propose that YdhM is the repressor for the nemA gene, thus hereafter designated NemR. The repressor function of NemR was inactivated by the addition of not only NEM but also other Cys modification reagents, implying that Cys modification of NemR renders it inactive. This is an addition to the mode of controlling activity of transcription factors by alkylation with chemical agents.

A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang

2010-01-22

To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potentialmore » entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.« less

Targeting Chronic and Neuropathic Pain: The N-type Calcium Channel Comes of Age

PubMed Central

Snutch, Terrance P.

2005-01-01

Summary: The rapid entry of calcium into cells through activation of voltage-gated calcium channels directly affects membrane potential and contributes to electrical excitability, repetitive firing patterns, excitation-contraction coupling, and gene expression. At presynaptic nerve terminals, calcium entry is the initial trigger mediating the release of neurotransmitters via the calcium-dependent fusion of synaptic vesicles and involves interactions with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex of synaptic release proteins. Physiological factors or drugs that affect either presynaptic calcium channel activity or the efficacy of calcium-dependent vesicle fusion have dramatic consequences on synaptic transmission, including that mediating pain signaling. The N-type calcium channel exhibits a number of characteristics that make it an attractive target for therapeutic intervention concerning chronic and neuropathic pain conditions. Within the past year, both U.S. and European regulatory agencies have approved the use of the cationic peptide Prialt for the treatment of intractable pain. Prialt is the first N-type calcium channel blocker approved for clinical use and represents the first new proven mechanism of action for chronic pain intervention in many years. The present review discusses the rationale behind targeting the N-type calcium channel, some of the limitations confronting the widespread clinical application of Prialt, and outlines possible strategies to improve upon Prialt's relatively narrow therapeutic window. PMID:16489373

SNARE-encoding genes VdSec22 and VdSso1 mediate protein secretion required for full virulence in Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Proteins that mediate cellular and subcellular membrane fusion are key factors in vesicular trafficking in all eukaryotic cells, including the secretion and transport of plant pathogen virulence factors. In this study, we identified vesicle fusion components that included 22 soluble N-ethylmaleimide...

Nominations for NSF, NSB

NASA Astrophysics Data System (ADS)

President Ronald Reagan plans to nominate William J. Merrell, Jr., to be assistant director of the National Science Foundation (NSF) for Astronomical, Atmospheric, Earth, and Ocean Sciences (AAEO), according to an announcement by NSF. The President also has announced his intention to nominate Craig C. Black and Charles L. Hosier to the National Science Board (NSB), NSF said. The president's nominations are subject to Senate confirmation.

Loss of a membrane trafficking protein αSNAP induces non-canonical autophagy in human epithelia

PubMed Central

Naydenov, Nayden G.; Harris, Gianni; Morales, Victor; Ivanov, Andrei I.

2012-01-01

Autophagy is a catabolic process that sequesters intracellular proteins and organelles within membrane vesicles called autophagosomes with their subsequent delivery to lyzosomes for degradation. This process involves multiple fusions of autophagosomal membranes with different vesicular compartments; however, the role of vesicle fusion in autophagosomal biogenesis remains poorly understood. This study addresses the role of a key vesicle fusion regulator, soluble N-ethylmaleimide-sensitive factor attachment protein α (αSNAP), in autophagy. Small interfering RNA-mediated downregulation of αSNAP expression in cultured epithelial cells stimulated the autophagic flux, which was manifested by increased conjugation of microtubule-associated protein light chain 3 (LC3-II) and accumulation of LC3-positive autophagosomes. This enhanced autophagy developed via a non-canonical mechanism that did not require beclin1-p150-dependent nucleation, but involved Atg5 and Atg7-mediated elongation of autophagosomal membranes. Induction of autophagy in αSNAP-depleted cells was accompanied by decreased mTOR signaling but appeared to be independent of αSNAP-binding partners, N-ethylmaleimide-sensitive factor and BNIP1. Loss of αSNAP caused fragmentation of the Golgi and downregulation of the Golgi-specific GTP exchange factors, GBF1, BIG1 and BIG2. Pharmacological disruption of the Golgi and genetic inhibition of GBF1 recreated the effects of αSNAP depletion on the autophagic flux. Our study revealed a novel role for αSNAP as a negative regulator of autophagy that acts by enhancing mTOR signaling and regulating the integrity of the Golgi complex. PMID:23187805

NSF Commits to Supercomputers.

ERIC Educational Resources Information Center

Waldrop, M. Mitchell

1985-01-01

The National Science Foundation (NSF) has allocated at least $200 million over the next five years to support four new supercomputer centers. Issues and trends related to this NSF initiative are examined. (JN)

NSF Director Bloch Stresses Effectiveness and Efficiency.

ERIC Educational Resources Information Center

Lepkowski, Wil

1985-01-01

The text of an interview with Erich Bloch, National Science Foundation (NSF) director, is provided. Among the topics/issues explored are NSF's role in policy research, mission and goals of NSF, establishment of NSF Engineering Research Centers, and national security issues involving access to supercomputers in universities that NSF is funding. (JN)

NSF Director to resign

NASA Astrophysics Data System (ADS)

Richman, Barbara T.

Edward A. Knapp, director of the National Science Foundation (NSF) since late 1982, will resign his post later this year to return to research at the Los Alamos National Laboratory. President Ronald Reagan has announced his intention to nominate Erich Bloch, vice president for technical personnel development at the IBM Corp., as Knapp's successor.Following formal nomination by President Reagan, the Senate must confirm Bloch as NSF director. If Bloch is confirmed, he is likely to bring to NSF the greater emphasis on engineering that the agency has sought in response to requests from Congress and the engineering community during the last year.

Hybrid- and complex-type N-glycans are not essential for Newcastle disease virus infection and fusion of host cells.

PubMed

Sun, Qing; Zhao, Lixiang; Song, Qingqing; Wang, Zheng; Qiu, Xusheng; Zhang, Wenjun; Zhao, Mingjun; Zhao, Guo; Liu, Wenbo; Liu, Haiyan; Li, Yunsen; Liu, Xiufan

2012-03-01

N-linked glycans are composed of three major types: high-mannose (Man), hybrid or complex. The functional role of hybrid- and complex-type N-glycans in Newcastle disease virus (NDV) infection and fusion was examined in N-acetylglucosaminyltransferase I (GnT I)-deficient Lec1 cells, a mutant Chinese hamster ovary (CHO) cell incapable of synthesizing hybrid- and complex-type N-glycans. We used recombinant NDV expressing green fluorescence protein or red fluorescence protein to monitor NDV infection, syncytium formation and viral yield. Flow cytometry showed that CHO-K1 and Lec1 cells had essentially the same degree of NDV infection. In contrast, Lec2 cells were found to be resistant to NDV infection. Compared with CHO-K1 cells, Lec1 cells were shown to more sensitive to fusion induced by NDV. Viral attachment was found to be comparable in both lines. We found that there were no significant differences in the yield of progeny virus produced by both CHO-K1 and Lec1 cells. Quantitative analysis revealed that NDV infection and fusion in Lec1 cells were also inhibited by treatment with sialidase. Pretreatment of Lec1 cells with Galanthus nivalis agglutinin specific for terminal α1-3-linked Man prior to inoculation with NDV rendered Lec1 cells less sensitive to cell-to-cell fusion compared with mock-treated Lec1 cells. Treatment of CHO-K1 and Lec1 cells with tunicamycin, an inhibitor of N-glycosylation, significantly blocked fusion and infection. In conclusion, our results suggest that hybrid- and complex-type N-glycans are not required for NDV infection and fusion. We propose that high-Man-type N-glycans could play an important role in the cell-to-cell fusion induced by NDV.

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins.

PubMed

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented.

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins

PubMed Central

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented. PMID:24848368

Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1.

PubMed

Varodayan, F P; Pignataro, L; Harrison, N L

2011-10-13

Many synapses within the central nervous system are sensitive to ethanol. Although alcohol is known to affect the probability of neurotransmitter release in specific brain regions, the effects of alcohol on the underlying synaptic vesicle fusion machinery have been little studied. To identify a potential pathway by which ethanol can regulate neurotransmitter release, we investigated the effects of acute alcohol exposure (1-24 h) on the expression of the gene encoding synaptotagmin 1 (Syt1), a synaptic protein that binds calcium to directly trigger vesicle fusion. Syt1 was identified in a microarray screen as a gene that may be sensitive to alcohol and heat shock. We found that Syt1 mRNA and protein expression are rapidly and robustly up-regulated by ethanol in mouse cortical neurons, and that the distribution of Syt1 protein along neuronal processes is also altered. Syt1 mRNA up-regulation is dependent on the activation of the transcription factor heat shock factor 1 (HSF1). The transfection of a constitutively active Hsf1 construct into neurons stimulates Syt1 transcription, while transfection of Hsf1 small interfering RNA (siRNA) or a constitutively inactive Hsf1 construct into neurons attenuates the induction of Syt1 by ethanol. This suggests that the activation of HSF1 can induce Syt1 expression and that this may be a mechanism by which alcohol regulates neurotransmitter release during brief exposures. Further analysis revealed that a subset of the genes encoding the core synaptic vesicle fusion (soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor; SNARE) proteins share this property of induction by ethanol, suggesting that alcohol may trigger a specific coordinated adaptation in synaptic function. This molecular mechanism could explain some of the changes in synaptic function that occur following alcohol administration and may be an important step in the process of neuronal adaptation to alcohol. Copyright © 2011 IBRO. Published by

Knapp confirmed as NSF Director

NASA Astrophysics Data System (ADS)

Edward A. Knapp was confirmed by the Senate in a voice vote on April 15 as the director of the National Science Foundation (NSF). The Senate vote followed a confirmation hearing by the Senate Labor and Human Resources Committee. Knapp, who was nominated by President Reagan to head the foundation in November, had been assistant director for NSF's mathematical and physical sciences (MPS) directorate since July 1982.Allegations that he has been politicizing NSF have beleaguered Knapp since he asked for resignations or firm commitments to leave from three NSF top administrators in December (two of these administrators had been planning to leave, though no resignation dates had been set). Knapp assured the Senate committee during the April 13 confirmation hearings that he made the decision to ask for the resignations and that, although he had discussed his plan with Office of Science and Technology Policy officials, they did not request that certain people be removed in exchange for particular increases in the NSF budget. Knapp consistently has defended himself against the allegations by saying that he wants his own team at the agency.

Information Technology Research and Education at NSF

NASA Astrophysics Data System (ADS)

Wink, Donald J.

2000-11-01

The NSF has been a leader in the development of new information technologies, including support for work in education and technology. Often, opportunities for educators are found in larger efforts. This is the case for the Information Technology Research (ITR) program. It has now been extended to education areas, as announced in NSF Publication 00-126. Links to the program announcement in multiple formats are found at http://www.nsf.gov/cgi-bin/getpub?nsf00126.

Research Funding Set for NSF, NASA, EPA.

ERIC Educational Resources Information Center

Chemical and Engineering News, 1982

1982-01-01

Funds (1983) for National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), and Environmental Protection Agency (EPA) research programs include $1,092,200,000 (NSF), $5.5 billion (NASA), and $119 million (EPA). NSF's science education activities were raised to $30 million in spite of the Administration's plan to phase…

The Rab3A-22A Chimera Prevents Sperm Exocytosis by Stabilizing Open Fusion Pores*

PubMed Central

Quevedo, María F.; Lucchesi, Ornella; Bustos, Matías A.; Pocognoni, Cristian A.; De la Iglesia, Paola X.

2016-01-01

At the final stage of exocytotis, a fusion pore opens between the plasma and a secretory vesicle membranes; typically, when the pore dilates the vesicle releases its cargo. Sperm contain a large dense-core secretory granule (the acrosome) whose contents are secreted by regulated exocytosis at fertilization. Minutes after the arrival of the triggering signal, the acrosomal and plasma membranes dock at multiple sites and fusion pores open at the contact points. It is believed that immediately afterward, fusion pores dilate spontaneously. Rab3A is an essential component of human sperm exocytotic machinery. Yet, recombinant, persistently active Rab3A halts calcium-triggered secretion when introduced after docking into streptolysin O-permeabilized cells; so does a Rab3A-22A chimera. Here, we applied functional assays, electron and confocal microscopy to show that the secretion blockage is due to the stabilization of open fusion pores. Other novel findings are that sperm SNAREs engage in α-SNAP/NSF-sensitive complexes at a post-fusion stage. Complexes are disentangled by these chaperons to achieve vesiculation and acrosomal contents release. Thus, post-fusion regulation of the pores determines their expansion and the success of the acrosome reaction. PMID:27613869

Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles.

PubMed

Woo, Sang Su; James, Declan J; Martin, Thomas F J

2017-03-15

Munc13-4 is a Ca 2+ -dependent SNARE (soluble N -ethylmaleimide-sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca 2+ -evoked secretion in various secretory cells. Studies in mast cell-like RBL-2H3 cells provide direct evidence that Munc13-4 with its two Ca 2+ -binding C2 domains functions as a Ca 2+ sensor for SG exocytosis. Unexpectedly, Ca 2+ stimulation also generated large (>2.4 μm in diameter) Munc13-4 + /Rab7 + /Rab11 + endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4 + /Rab7 + SGs, followed by a merge with Rab11 + endosomes, and depended on Ca 2+ binding to Munc13-4. Munc13-4 promoted the Ca 2+ -stimulated fusion of VAMP8-containing liposomes with liposomes containing exocytic or endosomal Q-SNAREs and directly interacted with late endosomal SNARE complexes. Thus Munc13-4 is a tethering/priming factor and Ca 2+ sensor for both heterotypic SG-plasma membrane and homotypic SG-SG fusion. Total internal reflection fluorescence microscopy imaging revealed that vacuoles were exocytic and mediated secretion of β-hexosaminidase and cytokines accompanied by Munc13-4 diffusion onto the plasma membrane. The results provide new molecular insights into the mechanism of multigranular compound exocytosis commonly observed in various secretory cells. © 2017 Woo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

PubMed

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

48 CFR 2515.215-70 - NSF negotiation authorities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NSF negotiation authorities... CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Negotiation Authorities 2515.215-70 NSF negotiation authorities. (a) Authorities. Citation: 42 U.S.C. 1870(c). (b) Application. When an NSF contract...

Uncertainty-Sensitive Heterogeneous Information Fusion: Assessing Threat with Soft, Uncertain, and Conflicting Evidence

DTIC Science & Technology

2016-01-01

planning exercises and wargaming. Initial Experimentation Late in the research , the prototype platform and the various fusion methods came together. This...Chapter Four points to prior research 2 Uncertainty-Sensitive Heterogeneous Information Fusion in mind multimethod fusing of complex information...our research is assessing the threat of terrorism posed by individuals or groups under scrutiny. Broadly, the ultimate objec- tives, which go well

Scripps museum receives NSF grant

NASA Astrophysics Data System (ADS)

Scripps Institution of Oceanography has been awarded a $500,000 grant from the National Science Foundation for a 37,000-square-foot museum exhibition on ocean sciences entitled “Exploring the Blue Planet.” The exhibition will be installed in the Scripps Hall of Oceanography of the new Stephen Birch Aquarium-Museum. The facility is under construction at the University of California, San Diego, and is scheduled to open in fall 1992.NSF is providing approximately half of the funds required for “Exploring the Blue Planet,” which is designed to help visitors explore the many fields of oceanography. “This NSF grant will fund interactive exhibits and changing displays featuring the latest Scripps research that will allow children and adults to experience science as an approachable, creative process that can be used to understand the changing world,” said Luther Williams, NSF Assistant Director for Education and Human Resources.

The Rab3A-22A Chimera Prevents Sperm Exocytosis by Stabilizing Open Fusion Pores.

PubMed

Quevedo, María F; Lucchesi, Ornella; Bustos, Matías A; Pocognoni, Cristian A; De la Iglesia, Paola X; Tomes, Claudia N

2016-10-28

At the final stage of exocytotis, a fusion pore opens between the plasma and a secretory vesicle membranes; typically, when the pore dilates the vesicle releases its cargo. Sperm contain a large dense-core secretory granule (the acrosome) whose contents are secreted by regulated exocytosis at fertilization. Minutes after the arrival of the triggering signal, the acrosomal and plasma membranes dock at multiple sites and fusion pores open at the contact points. It is believed that immediately afterward, fusion pores dilate spontaneously. Rab3A is an essential component of human sperm exocytotic machinery. Yet, recombinant, persistently active Rab3A halts calcium-triggered secretion when introduced after docking into streptolysin O-permeabilized cells; so does a Rab3A-22A chimera. Here, we applied functional assays, electron and confocal microscopy to show that the secretion blockage is due to the stabilization of open fusion pores. Other novel findings are that sperm SNAREs engage in α-SNAP/NSF-sensitive complexes at a post-fusion stage. Complexes are disentangled by these chaperons to achieve vesiculation and acrosomal contents release. Thus, post-fusion regulation of the pores determines their expansion and the success of the acrosome reaction. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Trafficking of presynaptic AMPA receptors mediating neurotransmitter release: neuronal selectivity and relationships with sensitivity to cyclothiazide.

PubMed

Pittaluga, Anna; Feligioni, Marco; Longordo, Fabio; Luccini, Elisa; Raiteri, Maurizio

2006-03-01

Postsynaptic glutamate AMPA receptors (AMPARs) can recycle between plasma membrane and intracellular pools. In contrast, trafficking of presynaptic AMPARs has not been investigated. AMPAR surface expression involves interactions between the GluR2 carboxy tail and various proteins including glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), protein interacting with C kinase 1 (PICK1), N-ethyl-maleimide-sensitive fusion protein (NSF). Here, peptides known to selectively block the above interactions were entrapped into synaptosomes to study the effects on the AMPA-evoked release of [3H]noradrenaline ([3H]NA) and [3H]acetylcholine ([3H]ACh) from rat hippocampal and cortical synaptosomes, respectively. Internalization of pep2-SVKI to prevent GluR2-GRIP/ABP/PICK1 interactions potentiated the AMPA-evoked release of [3H]NA but left unmodified that of [3H]ACh. Similar potentiation was caused by pep2-AVKI, the blocker of GluR2-PICK1 interaction. Conversely, a decrease in the AMPA-evoked release of [3H]NA, but not of [3H]ACh, was caused by pep2m, a selective blocker of the GluR2-NSF interaction. In the presence of pep2-SVKI the presynaptic AMPARs on noradrenergic terminals lost sensitivity to cyclothiazide. AMPARs releasing [3H]ACh, but not those releasing [3H]NA, were sensitive to spermine, suggesting that they are GluR2-lacking AMPARs. To conclude: (i) release-regulating presynaptic AMPARs constitutively cycle in isolated nerve terminals; (ii) the process exhibits neuronal selectivity; (iii) AMPAR trafficking and desensitization may be interrelated.

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE PAGES

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.; ...

2017-08-16

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The NSF and the geosciences community: Rotating program officers

NASA Astrophysics Data System (ADS)

Batiza, Rodey; Rea, David K.; Rumble, Douglas, III

The National Science Foundation (NSF) is a federal agency charged with the care and feeding of basic scientific research in U.S. colleges and universities. NSF is a major contributor toward the support of research in Earth, ocean, and atmospheric sciences, disciplines of great importance to AGU members.NSF makes a regular practice of employing scientists from universities, nonprofit research organizations, industry, and state or local governments as temporary program officers (“rotators”) with terms of service from 1 to 2 years. There are several reasons for the use of rotators: It brings to NSF people who have firsthand, recent knowledge of "what it is really like" beyond the Washington, D.C. beltway. Knowledge of new ideas, recent graduates, and a fresh look at the system are worth considerably more than the problems that arise owing to inexperienced program officers.It sheds some sunshine on internal NSF procedures when the rotator returns with his tales to his home institution.It provides NSF management with considerable flexibility in coping with changing staff requirements.

Sensitivity Changes over the Course of Infection Increases the Likelihood of Resistance Against Fusion but Not CCR5 Receptor Blockers

PubMed Central

Chatziandreou, Nikolaos; Arauz, Ana Belen; Freitas, Ines; Nyein, Phyu Hninn; Fenton, Gregory; Mehta, Shruti H.; Kirk, Gregory D.

2012-01-01

Abstract As HIV-1 evolves over the course of infection, resistance against antiretrovirals may arise in the absence of drug pressure, especially against receptor and fusion blockers because of the extensive changes observed in the envelope glycoprotein. Here we show that viruses from the chronic phase of disease are significantly less sensitive to CCR5 receptor and fusion blockers compared to early infection variants. Differences in susceptibility to CCR5 antagonists were observed in spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity differences were observed to another entry blocker, soluble CD4, or to reverse transcriptase, protease, or integrase inhibitors. Chronic as compared to early phase variants demonstrated greater replication when passaged in the presence of subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion antagonist resistance, however, emerged from only one chronic phase virus culture. Because sensitivity to receptor and fusion antagonists is correlated with receptor affinity and fusion capacity, respectively, changes that occur in the envelope glycoprotein over the course of infection confer greater ability to use the CCR5 receptor and increased fusion ability. Our in vitro passage studies suggest that these evolving phenotypes increase the likelihood of resistance against fusion but not CCR5 receptor blockers. PMID:22650962

POCA Update: An NSF PAARE Project

NASA Astrophysics Data System (ADS)

Walter, Donald K.; Brittain, S. D.; Cash, J. L.; Hartmann, D. H.; Howell, S. B.; King, J. R.; Leising, M. D.; Mayo, E. A.; Mighell, K. J.; Smith, D. M., Jr.

2011-01-01

We report on the status of "A Partnership in Observational and Computational Astronomy (POCA)” under the NSF's "Partnerships in Astronomy and Astrophysics Research and Education (PAARE)" program. This partnership includes South Carolina State University (a Historically Black College/University), Clemson University (a Ph.D. granting institution) and the National Optical Astronomy Observatory. We have reached the midpoint of this 5-year award and discuss the successes, challenges and obstacles encountered to date. Included is a summary of our summer REU program, the POCA graduate fellowship program, faculty research capacity building, outreach activities, increased use of NSF facilities and shared resources. Additional POCA research presentations by the authors are described elsewhere in these proceedings. Support for this work was provided by the NSF PAARE program to South Carolina State University under award AST-0750814 as well as resources and support provided by Clemson University and the National Optical Astronomy Observatory.

The Evolving Evaluation Process for NSF Broader Impacts

NASA Astrophysics Data System (ADS)

Straub, J. A.; Lawrence, J. E.

2016-12-01

The National Science Foundation (NSF) supports basic research in all non-medical fields of fundamental science that benefit society. To pursue this goal, NSF uses two merit review criteria: intellectual merit and broader impacts. As defined by NSF, intellectual merit "encompasses the potential to advance knowledge," while broader impacts "encompasses the potential to benefit society and contribute to the achievement of specific, desired societal outcomes." Articulating compelling broader impacts is increasingly critical as limited available funding means that both sets of criteria will impact the final proposal outcome. Although societal relevance has been valued by NSF since the foundation was established, recent events have placed increased emphasis on its importance: the America COMPETES Act encouraged increased efforts across agencies in educating the future STEM workforce (2007); NSF prioritized broader STEM participation (2008); the Obama administration issued a memo on transparency and open government (2009); and the National Science Board revised the NSF merit review criteria to emphasize that the same five elements should be considered for both merit review criteria (2012). Principal Investigators, reviewers (including panelists), and Program Officers are being asked to justify how the broader impacts contribute significantly to the project. As broader impacts become increasingly emphasized in the merit review process, it is important to understand not only how Principal Investigators are responding, but how reviewers are evaluating this aspect of proposals. To examine how reviewers are responding to this change in NSF's evaluation policy, an assessment of broader impacts in the Division of Earth Sciences is being conducted. The data were analyzed to see how reviewers have shifted their feedback in the last ten years. Data so far suggest that policy changes to the Grant Proposal Guide in 2012 have caused a notable shift to reviewers being more evaluative

Enemy at the gates: traffic at the plant cell pathogen interface.

PubMed

Hoefle, Caroline; Hückelhoven, Ralph

2008-12-01

The plant apoplast constitutes a space for early recognition of potentially harmful non-self. Basal pathogen recognition operates via dynamic sensing of conserved microbial patterns by pattern recognition receptors or of elicitor-active molecules released from plant cell walls during infection. Recognition elicits defence reactions depending on cellular export via SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex-mediated vesicle fusion or plasma membrane transporter activity. Lipid rafts appear also involved in focusing immunity-associated proteins to the site of pathogen contact. Simultaneously, pathogen effectors target recognition, apoplastic host proteins and transport for cell wall-associated defence. This microreview highlights most recent reports on the arms race for plant disease and immunity at the cell surface.

International Opportunities and Programs at NSF

NASA Astrophysics Data System (ADS)

Wodarczyk, F.

2006-05-01

The National Science Foundation's Office of International Science and Engineering (OISE) promotes the development of an integrated, Foundation-wide international strategy for international science and engineering activities both inside and outside NSF and manages international programs that are innovative, catalytic, and responsive to a broad range of NSF interests. Specifically, OISE supports programs to expand and enhance leading-edge international research and education opportunities for U.S. scientists and engineers, especially at the early career stage. It works to build and strengthen effective institutional partnerships throughout the global science and engineering research and education community, and it supports international collaborations in NSF's priority research areas. This talk will highlight opportunities for international collaboration for individuals at all levels of their careers, from student to established researcher, with examples of supported programs. Some recent activities focus on bringing together researchers in scientific disciplines and experts in cyberinfrastructure to promote and enable international data collection, manipulation, storage, and sharing via high-speed networks.

Study of the plant COPII vesicle coat subunits by functional complementation of yeast Saccharomyces cerevisiae mutants.

PubMed

De Craene, Johan-Owen; Courte, Fanny; Rinaldi, Bruno; Fitterer, Chantal; Herranz, Mari Carmen; Schmitt-Keichinger, Corinne; Ritzenthaler, Christophe; Friant, Sylvie

2014-01-01

The formation and budding of endoplasmic reticulum ER-derived vesicles depends on the COPII coat protein complex that was first identified in yeast Saccharomyces cerevisiae. The ER-associated Sec12 and the Sar1 GTPase initiate the COPII coat formation by recruiting the Sec23-Sec24 heterodimer following the subsequent recruitment of the Sec13-Sec31 heterotetramer. In yeast, there is usually one gene encoding each COPII protein and these proteins are essential for yeast viability, whereas the plant genome encodes multiple isoforms of all COPII subunits. Here, we used a systematic yeast complementation assay to assess the functionality of Arabidopsis thaliana COPII proteins. In this study, the different plant COPII subunits were expressed in their corresponding temperature-sensitive yeast mutant strain to complement their thermosensitivity and secretion phenotypes. Secretion was assessed using two different yeast cargos: the soluble α-factor pheromone and the membranous v-SNARE (vesicle-soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor) Snc1 involved in the fusion of the secretory vesicles with the plasma membrane. This complementation study allowed the identification of functional A. thaliana COPII proteins for the Sec12, Sar1, Sec24 and Sec13 subunits that could represent an active COPII complex in plant cells. Moreover, we found that AtSec12 and AtSec23 were co-immunoprecipitated with AtSar1 in total cell extract of 15 day-old seedlings of A. thaliana. This demonstrates that AtSar1, AtSec12 and AtSec23 can form a protein complex that might represent an active COPII complex in plant cells.

48 CFR 2515.215-70 - NSF negotiation authorities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false NSF negotiation... FOUNDATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Negotiation Authorities 2515.215-70 NSF negotiation authorities. (a) Authorities. Citation: 42 U.S.C. 1870(c). (b) Application. When...

48 CFR 2515.215-70 - NSF negotiation authorities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false NSF negotiation... FOUNDATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Negotiation Authorities 2515.215-70 NSF negotiation authorities. (a) Authorities. Citation: 42 U.S.C. 1870(c). (b) Application. When...

48 CFR 2515.215-70 - NSF negotiation authorities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false NSF negotiation... FOUNDATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Negotiation Authorities 2515.215-70 NSF negotiation authorities. (a) Authorities. Citation: 42 U.S.C. 1870(c). (b) Application. When...

48 CFR 2515.215-70 - NSF negotiation authorities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false NSF negotiation... FOUNDATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Negotiation Authorities 2515.215-70 NSF negotiation authorities. (a) Authorities. Citation: 42 U.S.C. 1870(c). (b) Application. When...

Fusion-neutron-yield, activation measurements at the Z accelerator: design, analysis, and sensitivity.

PubMed

Hahn, K D; Cooper, G W; Ruiz, C L; Fehl, D L; Chandler, G A; Knapp, P F; Leeper, R J; Nelson, A J; Smelser, R M; Torres, J A

2014-04-01

We present a general methodology to determine the diagnostic sensitivity that is directly applicable to neutron-activation diagnostics fielded on a wide variety of neutron-producing experiments, which include inertial-confinement fusion (ICF), dense plasma focus, and ion beam-driven concepts. This approach includes a combination of several effects: (1) non-isotropic neutron emission; (2) the 1/r(2) decrease in neutron fluence in the activation material; (3) the spatially distributed neutron scattering, attenuation, and energy losses due to the fielding environment and activation material itself; and (4) temporally varying neutron emission. As an example, we describe the copper-activation diagnostic used to measure secondary deuterium-tritium fusion-neutron yields on ICF experiments conducted on the pulsed-power Z Accelerator at Sandia National Laboratories. Using this methodology along with results from absolute calibrations and Monte Carlo simulations, we find that for the diagnostic configuration on Z, the diagnostic sensitivity is 0.037% ± 17% counts/neutron per cm(2) and is ∼ 40% less sensitive than it would be in an ideal geometry due to neutron attenuation, scattering, and energy-loss effects.

NSF Geosciences Committee Focuses on Program and Budget Issues

NASA Astrophysics Data System (ADS)

Showstack, Randy

2014-04-01

The spring meeting of the National Science Foundation's (NSF) Advisory Committee for the Geosciences (AC GEO), held on 3-4 April, was filled with firsts. It was the first time that AC GEO met as a body after merging with NSF's polar advisory committee in 2012. In addition, it was the first time that France Córdova, sworn in as the new NSF director on 31 March and sworn in again during a special ceremony in the atrium at NSF headquarters on 3 April, met with AC GEO in her new capacity. Córdova, who is president emerita of Purdue University, previously was a distinguished professor of physics and astronomy at the University of California, Riverside, and NASA chief scientist.

NSF Factbook. Guide to National Science Foundation Programs and Activities.

ERIC Educational Resources Information Center

Renetzky, Alvin, Ed.; Flynn, Barbara J., Ed.

This publication is a thorough guide to National Science Foundation (NSF) programs and activities. Research activities and science education programs supported by NSF during the fiscal year 1970 are reviewed in part one of this volume. Comprehensive listings of NSF grants and awards are presented in the second section which includes a list of…

45 CFR 689.5 - Initial NSF handling of misconduct matters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Initial NSF handling of misconduct matters. 689.5... FOUNDATION RESEARCH MISCONDUCT § 689.5 Initial NSF handling of misconduct matters. (a) NSF staff who learn of alleged misconduct will promptly and discreetly inform OIG or refer informants to OIG. (b) The identity of...

45 CFR 689.5 - Initial NSF handling of misconduct matters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Initial NSF handling of misconduct matters. 689.5... FOUNDATION RESEARCH MISCONDUCT § 689.5 Initial NSF handling of misconduct matters. (a) NSF staff who learn of alleged misconduct will promptly and discreetly inform OIG or refer informants to OIG. (b) The identity of...

45 CFR 689.5 - Initial NSF handling of misconduct matters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Initial NSF handling of misconduct matters. 689.5... FOUNDATION RESEARCH MISCONDUCT § 689.5 Initial NSF handling of misconduct matters. (a) NSF staff who learn of alleged misconduct will promptly and discreetly inform OIG or refer informants to OIG. (b) The identity of...

45 CFR 689.5 - Initial NSF handling of misconduct matters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Initial NSF handling of misconduct matters. 689.5... FOUNDATION RESEARCH MISCONDUCT § 689.5 Initial NSF handling of misconduct matters. (a) NSF staff who learn of alleged misconduct will promptly and discreetly inform OIG or refer informants to OIG. (b) The identity of...

45 CFR 689.5 - Initial NSF handling of misconduct matters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Initial NSF handling of misconduct matters. 689.5... FOUNDATION RESEARCH MISCONDUCT § 689.5 Initial NSF handling of misconduct matters. (a) NSF staff who learn of alleged misconduct will promptly and discreetly inform OIG or refer informants to OIG. (b) The identity of...

A Guide to NSF Science/Engineering Resources Data.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC. Directorate for Scientific, Technological and International Affairs.

The National Science Foundation (NSF) Division of Science Resources Services designs and conducts surveys related to, and supports other data collection activities dealing with, science resources. The data from these surveys and data collection efforts are used by NSF and others to analyze various research and development (R&D) funding and…

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136(T).

PubMed

Naqvi, Kubra F; Patin, Delphine; Wheatley, Matthew S; Savka, Michael A; Dobson, Renwick C J; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/C Vs ) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44-46°C. Its apparent K m values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum.

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136T

PubMed Central

Naqvi, Kubra F.; Patin, Delphine; Wheatley, Matthew S.; Savka, Michael A.; Dobson, Renwick C. J.; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O.

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/CVs) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44–46°C. Its apparent Km values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum. PMID:27047475

Polar advisory committee focuses on NSF realignment

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-11-01

With the U.S. National Science Foundation's (NSF) realignment that moves the agency's Office of Polar Programs (OPP) back to the Directorate for Geosciences (GEO), "the emphasis on the importance of the polar program at NSF doesn't change," NSF director Subra Suresh reassured members of the federal Advisory Committee on Polar Programs during a committee meeting on 5 November. "The polar program in its entirety stays as the same entity. Nothing changes," he told committee members, regarding the realignment that began on 1 October (see Eos, 93(43), 427, doi:10.1029/2012EO430003). "Nothing changes in terms of our commitment to the polar program. Nothing changes in terms of infrastructure support. Nothing changes in terms of people in the polar program speaking for the polar program to the external world and internally. And nothing changes in terms of how individual scientists interact with the polar program."

Astrophysicist nominated to head NSF

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2013-09-01

US president Barack Obama has nominated astrophysicist France Córdova as the next director of the National Science Foundation (NSF) - the country's biggest funder of basic research with an annual budget of 7bn.

77 FR 51791 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Department of Energy.../NSF Nuclear Science Advisory Committee (NSAC). The Federal Advisory Committee Act (Pub. L. 92-463, 86... on scientific priorities within the field of basic nuclear science research. Tentative Agenda: Agenda...

75 FR 6651 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Department of Energy.../NSF Nuclear Science Advisory Committee (NSAC). Federal Advisory Committee Act (Pub. L. 92- 463, 86... on scientific priorities within the field of basic nuclear science research. Tentative Agenda: Agenda...

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding

PubMed Central

Ikin, Annat F; Causevic, Mirsada; Pedrini, Steve; Benson, Lyndsey S; Buxbaum, Joseph D; Suzuki, Toshiharu; Lovestone, Simon; Higashiyama, Shigeki; Mustelin, Tomas; Burgoyne, Robert D; Gandy, Sam

2007-01-01

Background Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Results Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα. Conclusion Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP. PMID:18067682

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding.

PubMed

Ikin, Annat F; Causevic, Mirsada; Pedrini, Steve; Benson, Lyndsey S; Buxbaum, Joseph D; Suzuki, Toshiharu; Lovestone, Simon; Higashiyama, Shigeki; Mustelin, Tomas; Burgoyne, Robert D; Gandy, Sam

2007-12-09

Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Rossner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPalpha. Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

76 FR 31945 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Department of Energy.../NSF Nuclear Science Advisory Committee (NSAC). The Federal Advisory Committee Act (Pub. L. 92-463, 86... the field of basic nuclear science research. Tentative Agenda: Agenda will include discussions of the...

78 FR 716 - DOE/NSF Nuclear Science Advisory Committee

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2013-01-04

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Office of Science, DOE. ACTION: Notice of open meeting. SUMMARY: This notice announces a meeting of the DOE/NSF Nuclear Science... Energy and the National Science Foundation on scientific priorities within the field of basic nuclear...

78 FR 62609 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... Secretariat, General Services Administration, notice is hereby given that the DOE/NSF Nuclear Science Advisory Committee (NSAC) will be renewed for a two-year period. The Committee will provide advice and... research. Additionally, the renewal of the DOE/NSF Nuclear Science Advisory Committee has been determined...

76 FR 62050 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Department of Energy, Office of Science. ACTION: Notice of renewal. SUMMARY: Pursuant to Section 14(a)(2)(A) of the Federal... Services Administration, notice is hereby given that the DOE/NSF Nuclear Science Advisory Committee (NSAC...

Rolling blackout is required for synaptic vesicle exocytosis.

PubMed

Huang, Fu-De; Woodruff, Elvin; Mohrmann, Ralf; Broadie, Kendal

2006-03-01

Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate-diacylglycerol signaling in Drosophila neurons. Conditional temperature-sensitive (TS) rbo mutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, and rbo TS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adult rbo TS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction between rbo and syntaxin1A TS mutants, suggesting that RBO is required in the mechanism of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. The rbo TS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion.

Perhaps the NSF Is a Model, but Perhaps Not ... .

ERIC Educational Resources Information Center

Glidden, Robert

1990-01-01

Responds to Charles Fowler's article, "Arts Education and the NEA: Does the National Science Foundation Point the Way?" Recommends that the National Science Foundation (NSF) and the National Endowment for the Arts (NEA) work together to promote intellectual values in schooling. Suggests that the NEA follow the NSF in its commitment to…

NCALM: NSF Supported Center for Airborne Laser Mapping

NASA Astrophysics Data System (ADS)

Shrestha, R. L.; Carter, W. E.; Dietrich, W. E.

2003-12-01

The National Science Foundation (NSF) recently awarded a grant to create a research center to support the use of airborne laser mapping technology in the scientific community. The NSF supported Center for Airborne Laser Mapping (NCALM) will be operated jointly by the Department of Civil & Coastal Engineering, College of Engineering, University of Florida (UF) and the Department of Earth and Planetary Science, University of California-Berkeley (UCB). NCALM will use the Airborne Laser Swath Mapping (ALSM) system jointly owned by UF and Florida International University (FIU), based at the UF Geosensing Engineering and Mapping (GEM) Research Center. The state-of-the-art laser surveying instrumentation, GPS systems, which are installed in a Cessna 337 Skymaster aircraft, will collect research grade data in areas selected through the competitive NSF grant review process. The ALSM observations will be analyzed both at UF and UCB, and made available to the PI through an archiving and distribution center at UCB-building upon the Berkeley Seismological Laboratory (BSL) Northern California Earthquake Data Center system. The purpose of NCALM is to provide research grade data from ALSM technology to NSF supported research studies in geosciences. The Center will also contribute to software development that will increase the processing speed and data accuracy. This presentation will discuss NCALM operation and the process of submitting proposals to NSF. In addition, it will outline the process to request available NCALM seed project funds to help jump-start small scientific research studies. Funds are also available for travel by academic researchers and students for hands-on knowledge and experience in ALSM technology at UF and UCB.

Connecting NSF funding to patent innovation in nanotechnology (2001-2004)

NASA Astrophysics Data System (ADS)

Huang, Zan; Chen, Hsinchun; Li, Xin; Roco, Mihail C.

2006-12-01

Nanotechnology research has experienced growth rapid in knowledge and innovations; it also attracted significant public funding in recent years. Several countries have recognized nanotechnology as a critical research domain that promises to revolutionize a wide range of fields of applications. In this paper, we present an analysis of the funding for nanoscale science and engineering (NSE) at the National Science Foundation (NSF) and its implications on technological innovation (number of patents) in this field from 2001 to 2004. Using a combination of basic bibliometric analysis and content visualization tools, we identify growth trends, research topic distribution, and the evolution in NSF funding and commercial patenting activities recorded at the United States Patent Office (USPTO). The patent citations are used to compare the impact of the NSF-funded research on nanotechnology development with research supported by other sources in the United States and abroad. The analysis shows that the NSF-funded researchers and patents authored by them have significantly higher impact based on patent citation measures in the four-year period than other comparison groups. The NSF-authored patent impact is growing faster with the lifetime of a patent, indicating the long-term importance of fundamental research.

45 CFR 674.6 - Submission of information to NSF.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Submission of information to NSF. 674.6 Section 674.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION ANTARCTIC METEORITES § 674.6 Submission of information to NSF. A copy of the written procedures developed by expedition organizers pursuant to § 674.5(...

45 CFR 674.6 - Submission of information to NSF.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Submission of information to NSF. 674.6 Section 674.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION ANTARCTIC METEORITES § 674.6 Submission of information to NSF. A copy of the written procedures developed by expedition organizers pursuant to § 674.5(...

45 CFR 674.6 - Submission of information to NSF.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Submission of information to NSF. 674.6 Section 674.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION ANTARCTIC METEORITES § 674.6 Submission of information to NSF. A copy of the written procedures developed by expedition organizers pursuant to § 674.5(...

45 CFR 674.6 - Submission of information to NSF.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Submission of information to NSF. 674.6 Section 674.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION ANTARCTIC METEORITES § 674.6 Submission of information to NSF. A copy of the written procedures developed by expedition organizers pursuant to § 674.5(...

Congressional hearing reviews NSF major research and facilities projects

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-03-01

An 8 March congressional hearing about the U.S. National Science Foundation's Major Research Equipment and Facilities Construction (NSF MREFC) account focused on fiscal management and accountability of projects in that account and reviewed concerns raised by NSF's Office of Inspector General (OIG). NSF established the MREFC account in 1995 to better plan and manage investments in major equipment and facilities projects, which can cost from tens of millions to hundreds of millions of dollars, and the foundation has funded 17 MREFC projects since then. The Obama administration's proposed fiscal year (FY) 2013 budget includes funding for four MREFC projects: Advanced Laser Gravitational-Wave Observatory (AdvLIGO), Advanced Technology Solar Telescope (ATST), National Ecological Observatory (NEON), and Ocean Observatories Initiative (OOI). The hearing, held by a subcommittee of the House of Representatives' Committee on Science, Space, and Technology, reviewed management oversight throughout the life cycles of MREFC projects and concerns raised in recent OIG reports about the use of budget contingency funds. NSF's February 2012 manual called "Risk management guide for large facilities" states that cost contingency is "that portion of the project budget required to cover `known unknowns,'" such as planning and estimating errors and omissions, minor labor or material price fluctuations, and design developments and changes within the project scope. Committee members acknowledged measures that NSF has made to improve the MREFC oversight process, but they also urged the agency to continue to take steps to ensure better project management.

75 FR 63450 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). Federal Advisory Committee Act (Pub. L. 92-463, 86... 20852. FOR FURTHER INFORMATION CONTACT: John Kogut, Executive Secretary; High Energy Physics Advisory...

NSF announces diversity programme

NASA Astrophysics Data System (ADS)

Kruesi, Liz

2016-04-01

The US National Science Foundation (NSF) has initiated a new funding programme that will create schemes to increase diversity in science, technology, engineering and mathematics (STEM). The initiative - Inclusion across the Nation of Communities of Learners of Underrepresented Discoverers in Engineering and Science (INCLUDES) - aims to increase the participation of women, those with a low socioeconomic status, people with disabilities and those from minority racial backgrounds.

Gallium arsenide-gallium nitride wafer fusion and the n-aluminum gallium arsenide/p-gallium arsenide/n-gallium nitride double heterojunction bipolar transistor

NASA Astrophysics Data System (ADS)

Estrada, Sarah M.

This dissertation describes the n-AlGaAs/p-GaAs/n-GaN heterojunction bipolar transistor (HBT), the first transistor formed via wafer fusion. The fusion process was developed as a way to combine lattice-mismatched materials for high-performance electronic devices, not obtainable via conventional all-epitaxial formation methods. Despite the many challenges of wafer fusion, successful transistors were demonstrated and improved, via the optimization of material structure and fusion process conditions. Thus, this project demonstrated the integration of disparate device materials, chosen for their optimal electronic properties, unrestricted by the conventional (and very limiting) requirement of lattice-matching. By combining an AlGaAs-GaAs emitter-base with a GaN collector, the HBT benefited from the high breakdown voltage of GaN, and from the high emitter injection efficiency and low base transit time of AlGaAs-GaAs. Because the GaAs-GaN lattice mismatch precluded an all-epitaxial formation of the HBT, the GaAs-GaN heterostructure was formed via fusion. This project began with the development of a fusion process that formed mechanically robust and electrically active GaAs-GaN heterojunctions. During the correlation of device electrical performance with a systematic variation of fusion conditions over a wide range (500--750°C, 0.5--2hours), a mid-range fusion temperature was found to induce optimal HBT electrical performance. Transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS) were used to assess possible reasons for the variations observed in device electrical performance. Fusion process conditions were correlated with electrical (I-V), structural (TEM), and chemical (SIMS) analyses of the resulting heterojunctions, in order to investigate the trade-off between increased interfacial disorder (TEM) with low fusion temperature and increased diffusion (SIMS) with high fusion temperature. The best do device results (IC ˜ 2.9 kA/cm2 and beta �

76 FR 19986 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-11

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). The Federal Advisory Committee Act (Pub. L. 92-463, 86... FURTHER INFORMATION CONTACT: John Kogut, Executive Secretary; High Energy Physics Advisory Panel; U.S...

News Focus: NSF Director Erich Bloch Discusses Foundation's Problems, Outlook.

ERIC Educational Resources Information Center

Chemical and Engineering News, 1987

1987-01-01

Relates the comments offered in an interview with Erich Bloch, the National Science Foundation (NSF) Director. Discusses issues related to NSF and its funding, engineering research centers, involvement with industry, concern for science education, computer centers, and its affiliation with the social sciences. (ML)

Administration's Proposed NSF Budget Includes a 5.5% Increase for Geosciences

NASA Astrophysics Data System (ADS)

Showstack, Randy

2013-04-01

The fiscal year (FY) 2014 proposed federal budget for the U.S. National Science Foundation (NSF) is $7.63 billion, 7.3% above the FY 2012 actual amount. NSF acting director Cora Marrett said the budget reflects the administration's recognition of NSF and the importance of funding basic research. "We are pleased about where we stand and hope that Congress will be just as pleased with the budget proposal and will help move things forward," she said during a meeting of the NSF Advisory Committee for Geosciences on 11 April. Budget comparisons are to FY 2012 because the 2013 appropriations were enacted at the end of March, less than 2 weeks before President Barack Obama sent the proposed budget to Congress.

Analysis of Chinese women with primary ovarian insufficiency by high resolution array-comparative genomic hybridization.

PubMed

Liao, Can; Fu, Fang; Yang, Xin; Sun, Yi-Min; Li, Dong-Zhi

2011-06-01

Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years. The etiology of primary ovarian insufficiency in human female patients is still unclear. The purpose of this study is to investigate the potential genetic causes in primary amenorrhea patients by high resolution array based comparative genomic hybridization (array-CGH) analysis. Following the standard karyotyping analysis, genomic DNA from whole blood of 15 primary amenorrhea patients and 15 normal control women was hybridized with Affymetrix cytogenetic 2.7M arrays following the standard protocol. Copy number variations identified by array-CGH were confirmed by real time polymerase chain reaction. All the 30 samples were negative by conventional karyotyping analysis. Microdeletions on chromosome 17q21.31-q21.32 with approximately 1.3 Mb were identified in four patients by high resolution array-CGH analysis. This included the female reproductive secretory pathway related factor N-ethylmaleimide-sensitive factor (NSF) gene. The results of the present study suggest that there may be critical regions regulating primary ovarian insufficiency in women with a 17q21.31-q21.32 microdeletion. This effect might be due to the loss of function of the NSF gene/genes within the deleted region or to effects on contiguous genes.

77 FR 4027 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). The Federal Advisory Committee Act (Pub. L. 92-463, 86... Secretary; High Energy Physics Advisory Panel; U.S. Department of Energy; SC-25/ Germantown Building, 1000...

76 FR 8358 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). Federal Advisory Committee Act (Pub. L. 92-463, 86... Secretary; High Energy Physics Advisory Panel; U.S. Department of Energy; SC-25/ Germantown Building, 1000...

75 FR 57463 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). Federal Advisory Committee Act (Pub. L. 92-463, 86... Secretary; High Energy Physics Advisory Panel; U.S. Department of Energy; SC-25/ Germantown Building, 1000...

78 FR 69839 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). The Federal Advisory Committee Act (Pub. L. 92-463, 86... CONTACT: John Kogut, Executive Secretary; High Energy Physics Advisory Panel; U.S. Department of Energy...

76 FR 41234 - DOE/NSF High Energy Physics Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Department of Energy.../NSF High Energy Physics Advisory Panel (HEPAP). The Federal Advisory Committee Act (Pub. L. 92-463, 86... Secretary; High Energy Physics Advisory Panel; U.S. Department of Energy; SC-25/ Germantown Building, 1000...

Fusion of Positive Energy Representations of LSpin(2n)

NASA Astrophysics Data System (ADS)

Toledano-Laredo, V.

2004-09-01

Building upon the Jones-Wassermann program of studying Conformal Field Theory using operator algebraic tools, and the work of A. Wassermann on the loop group of LSU(n) (Invent. Math. 133 (1998), 467-538), we give a solution to the problem of fusion for the loop group of Spin(2n). Our approach relies on the use of A. Connes' tensor product of bimodules over a von Neumann algebra to define a multiplicative operation (Connes fusion) on the (integrable) positive energy representations of a given level. The notion of bimodules arises by restricting these representations to loops with support contained in an interval I of the circle or its complement. We study the corresponding Grothendieck ring and show that fusion with the vector representation is given by the Verlinde rules. The computation rests on 1) the solution of a 6-parameter family of Knizhnik-Zamolodchikhov equations and the determination of its monodromy, 2) the explicit construction of the primary fields of the theory, which allows to prove that they define operator-valued distributions and 3) the algebraic theory of superselection sectors developed by Doplicher-Haag-Roberts.

Wakimoto discusses role as NSF's incoming assistant director of geosciences

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-12-01

Roger Wakimoto's adrenaline “is starting to pump,” the incoming assistant director for geosciences (GEO) at the U.S. National Science Foundation (NSF) told Eos during an exclusive interview at this month's AGU Fall Meeting in San Francisco. Wakimoto, whose scientific expertise is in extreme weather, is scheduled to take charge as head of the NSF directorate for geosciences starting in February 2013. During his 4-year appointment at NSF, Wakimoto, 59 and an avowed workaholic, will head up the GEO directorate, which has about an $880 million annual funding portfolio and provides about 55% of federal funding for geosciences basic research at U.S. academic institutions. The directorate currently includes the divisions of atmospheric and geospace sciences, Earth sciences, and ocean sciences. In addition, NSF's Office of Polar Programs is slated to become a GEO division under a realignment plan announced on 7 September; Wakimoto said that shift had “no bearing” on his decision to accept the position.

The pollen-specific R-SNARE/longin PiVAMP726 mediates fusion of endo- and exocytic compartments in pollen tube tip growth

PubMed Central

Guo, Feng; McCubbin, Andrew G.

2012-01-01

The growing pollen tube apex is dedicated to balancing exo- and endocytic processes to form a rapidly extending tube. As perturbation of either tends to cause a morphological phenotype, this system provides tractable model for studying these processes. Vesicle-associated membrane protein 7s (VAMP7s) are members of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family that mediate cognate membrane fusion but their role in pollen tube growth has not been investigated. This manuscript identifies PiVAMP726 of Petunia inflata as a pollen-specific VAMP7 that localizes to the inverted cone of transport vesicles at the pollen tube tip. The endocytic marker FM4-64 was found to colocalize with yellow fluorescent protein (YFP)-PiVAMP726, which is consistent with PiVAMP726 containing an amino-acid motif implicated in endosomal localization, At high overexpression levels, YFP- PiVAMP726 inhibited growth and caused the formation of novel membrane compartments within the pollen tube tip. Functional dissection of PiVAMP726 implicated the N-terminal longin domain in negative regulation of the SNARE activity, but not localization of PiVAMP726. Expression of the constitutively active C-terminal SNARE domain alone, in pollen tubes, generated similar phenotypes to the full-length protein, but the truncated domain was more potent than the wild-type protein at both inhibiting growth and forming the novel membrane compartments. Both endo- and exocytic markers localized to these compartments in addition to YFP-PiVAMP726, leading to the speculation that PiVAMP726 might be involved in the recycling of endocytic vesicles in tip growth. PMID:22345643

Research Misconduct: Policy and Practice at the NSF

NASA Astrophysics Data System (ADS)

Manka, Aaron

2004-03-01

Under NSF's Office of Inspector General mandate to prevent fraud, waste, abuse, or mismanagement involving NSF's proposals and awards, our office also investigates allegations of research misconduct. I will discuss our office's handling of such matters, focusing on the ethical and legal obligations of proposal submitters and awardees and the role of the scientific community. To illustrate some other points that are of interest to the physics community, I will also discuss some of our investigative activities relevant to: duplicate funding, the accuracy of information in proposals, and collaborations.

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.

PubMed

Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail

2016-02-01

The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased

H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion

PubMed Central

Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter

2015-01-01

ABSTRACT The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions—T492S, N722D, R752K, and S1132F—were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. IMPORTANCE Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in

45 CFR 681.6 - When may NSF issue a complaint?

Code of Federal Regulations, 2010 CFR

2010-10-01

... may NSF issue a complaint? NSF may issue a complaint: (a) If the Attorney General (or designee) approves the referral of the allegations for adjudication; and (b) In a case of submission of false claims, if the amount of money or the value of property or services demanded or requested in a false claim...

Nuclear fusion and genome encounter during yeast zygote formation.

PubMed

Tartakoff, Alan Michael; Jaiswal, Purnima

2009-06-01

When haploid cells of Saccharomyces cerevisiae are crossed, parental nuclei congress and fuse with each other. To investigate underlying mechanisms, we have developed assays that evaluate the impact of drugs and mutations. Nuclear congression is inhibited by drugs that perturb the actin and tubulin cytoskeletons. Nuclear envelope (NE) fusion consists of at least five steps in which preliminary modifications are followed by controlled flux of first outer and then inner membrane proteins, all before visible dilation of the waist of the nucleus or coalescence of the parental spindle pole bodies. Flux of nuclear pore complexes occurs after dilation. Karyogamy requires both the Sec18p/NSF ATPase and ER/NE luminal homeostasis. After fusion, chromosome tethering keeps tagged parental genomes separate from each other. The process of NE fusion and evidence of genome independence in yeast provide a prototype for understanding related events in higher eukaryotes.

Role of the Simian Virus 5 Fusion Protein N-Terminal Coiled-Coil Domain in Folding and Promotion of Membrane Fusion

PubMed Central

West, Dava S.; Sheehan, Michael S.; Segeleon, Patrick K.; Dutch, Rebecca Ellis

2005-01-01

Formation of a six-helix bundle comprised of three C-terminal heptad repeat regions in antiparallel orientation in the grooves of an N-terminal coiled-coil is critical for promotion of membrane fusion by paramyxovirus fusion (F) proteins. We have examined the effect of mutations in four residues of the N-terminal heptad repeat in the simian virus 5 (SV5) F protein on protein folding, transport, and fusogenic activity. The residues chosen have previously been shown from study of isolated peptides to have differing effects on stability of the N-terminal coiled-coil and six-helix bundle (R. E. Dutch, G. P. Leser, and R. A. Lamb, Virology 254:147-159, 1999). The mutant V154M showed reduced proteolytic cleavage and surface expression, indicating a defect in intracellular transport, though this mutation had no effect when studied in isolated peptides. The mutation I137M, previously shown to lower thermostability of the six-helix bundle, resulted in an F protein which was properly processed and transported to the cell surface but which had reduced fusogenic activity. Finally, mutations at L140M and L161M, previously shown to disrupt α-helix formation of isolated N-1 peptides but not to affect six-helix bundle formation, resulted in F proteins that were properly processed. Interestingly, the L161M mutant showed increased syncytium formation and promoted fusion at lower temperatures than the wild-type F protein. These results indicate that interactions separate from formation of an N-terminal coiled-coil or six-helix bundle are important in the initial folding and transport of the SV5 F protein and that mutations that destabilize the N-terminal coiled-coil can result in stimulation of membrane fusion. PMID:15650180

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer.

PubMed

Lu, Hengyu; Villafane, Nicole; Dogruluk, Turgut; Grzeskowiak, Caitlin L; Kong, Kathleen; Tsang, Yiu Huen; Zagorodna, Oksana; Pantazi, Angeliki; Yang, Lixing; Neill, Nicholas J; Kim, Young Won; Creighton, Chad J; Verhaak, Roel G; Mills, Gordon B; Park, Peter J; Kucherlapati, Raju; Scott, Kenneth L

2017-07-01

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK , and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in The Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2 , and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors. Our fusion construction strategy also enabled domain-function studies of BRAF fusion genes. Our results confirmed other reports that the transforming activity of BRAF fusions results from truncation-mediated loss of inhibitory domains within the N-terminus of the BRAF protein. BRAF mutations residing within this inhibitory region may provide a means for BRAF activation in cancer, therefore we leveraged the modular design of our fusion gene construction methodology to screen N-terminal domain mutations discovered in tumors that are wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools will facilitate rapid fusion gene construction for subsequent functional characterization and translation into personalized treatment strategies. Cancer Res; 77(13); 3502-12. ©2017 AACR . ©2017 American Association for Cancer Research.

Strategic Research Partnerships: Proceedings from an NSF Workshop (Washington, D.C., October 13, 2000). Special Report.

ERIC Educational Resources Information Center

Jankowski, John E.; Link, Albert N.; Vonortas, Nicholas S.

This document contains the proceedings from the National Science Foundation (NSF) Workshop on Strategic Research Partnerships. Papers include: (1) "Strategic Research Partnerships: Results of the Workshop" (Albert N. Link and Nicholas S. Vonortas); (2) "Strategic Research Partnerships: Evidence and Analysis" (Stephen Martin);…

NSF-Sponsored Biological and Chemical Oceanography Data Management Office

NASA Astrophysics Data System (ADS)

Allison, M. D.; Chandler, C. L.; Copley, N.; Galvarino, C.; Gegg, S. R.; Glover, D. M.; Groman, R. C.; Wiebe, P. H.; Work, T. T.; Biological; Chemical Oceanography Data Management Office

2010-12-01

Ocean biogeochemistry and marine ecosystem research projects are inherently interdisciplinary and benefit from improved access to well-documented data. Improved data sharing practices are important to the continued exploration of research themes that are a central focus of the ocean science community and are essential to interdisciplinary and international collaborations that address complex, global research themes. In 2006, the National Science Foundation Division of Ocean Sciences (NSF OCE) funded the Biological and Chemical Oceanography Data Management Office (BCO-DMO) to serve the data management requirements of scientific investigators funded by the National Science Foundation’s Biological and Chemical Oceanography Sections. BCO-DMO staff members work with investigators to manage marine biogeochemical, ecological, and oceanographic data and information developed in the course of scientific research. These valuable data sets are documented, stored, disseminated, and protected over short and intermediate time frames. One of the goals of the BCO-DMO is to facilitate regional, national, and international data and information exchange through improved data discovery, access, display, downloading, and interoperability. In May 2010, NSF released a statement to the effect that in October 2010, it is planning to require that all proposals include a data management plan in the form of a two-page supplementary document. The data management plan would be an element of the merit review process. NSF has long been committed to making data from NSF-funded research publicly available and the new policy will strengthen this commitment. BCO-DMO is poised to assist in creating the data management plans and in ultimately serving the data and information resulting from NSF OCE funded research. We will present an overview of the data management system capabilities including: geospatial and text-based data discovery and access systems; recent enhancements to data search tools; data

CAREER opportunities at the Condensed Matter Physics Program, NSF/DMR

NASA Astrophysics Data System (ADS)

Durakiewicz, Tomasz

The Faculty Early Career Development (CAREER) Program is a Foundation-wide activity, offering prestigious awards in support of junior faculty. Awards are expected to build the careers of teacher-scholars through outstanding research, excellent education and the integration of education and research. Condensed Matter Physics Program receives between 35 and 45 CAREER proposals each year, in areas related to fundamental research of phenomena exhibited by condensed matter systems. Proposal processing, merit review process, funding levels and success rates will be discussed in the presentation. NSF encourages submission of CAREER proposals from junior faculty members from CAREER-eligible organizations and encourages women, members of underrepresented minority groups, and persons with disabilities to apply. NSF/DMR/CMP homepage: https://www.nsf.gov/funding/pgm_summ.jsp?pims_id=5666

Critical time for NSF, NASA funding bills

NASA Astrophysics Data System (ADS)

Jones, Richard

Although the new fiscal year does not start until October, the next few weeks will be critical in determining the amount of money which the National Science Foundation and the National Aeronautics and Space Administration receive. Scientists who want to communicate their views to key representatives and senators about these agencies should do so now.Every year Congress must pass new funding, or appropriations, legislation. Both NSF and NASA funding come under the jurisdiction of the House and Senate appropriations subcommittees for the Veterans Administration, Department of Housing and Urban Development, and Independent Agencies. These two subcommittees have already heard from NSF officials, and will wrap-up official NASA testimony this week. Several days of hearings from public witnesses are also scheduled.

78 FR 14087 - DOE/NSF High Energy Physics Advisory Panel: Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel: Correction AGENCY: Office of..., the Department of Energy (DOE) published a notice of open meeting for the DOE/NSF High Energy Physics... FURTHER INFORMATION CONTACT: John Kogut, Executive Secretary; High Energy Physics Advisory Panel; U.S...

Report on the Partnership for Excellence in Teacher Education: An NSF Funded Project (NSF DUE-9343612).

ERIC Educational Resources Information Center

Blake, Sally; Tchoshanov, Mourat; Della-Piana, Connie Kubo; Pacheco, Arturo; Brady, Tom

2001-01-01

Reports on the Partnership for Excellence in Teacher Education (PETE), an NSF-funded project to promote reform in mathematics and science teacher preparation that features the redesign of teacher preparation to reflect current research on learning and teaching. Concludes that new tools of technology have the potential for enhancing education but…

Inhibition of the ATPase from Halobacterium Saccharovorum by Thiol Inhibitors: Evidence for the Presence of More Than One Essential Cysteinyl Residue

NASA Technical Reports Server (NTRS)

Hochstein, Lawrence I.; Emrich, Errol; Stan-Lotter, Helga; DeVincenzi, Donald L. (Technical Monitor)

1995-01-01

The vacuolar-like ATPase from Halobacterium saccha vorum is inhibited by N-ethylmaleimide and p-chloromercudphenylsulfonate. The failure of adenine nucleotides to protect against p-chloromercuriphenyisulfonate inhibition, of p-chloromercuriphenylsulfonate to protect against N-ethylmaleimide inhibition, and the difference in the temperature dependence of inactivation infers that the enzyme contains at least two thiols that are essential for enzyme activity. CNBr cleavage of C-14-N-ethylmaleimide labeled subunit results in two radioactive peptides that locates the N-ethylmaleimide-reactive cysteinyl residue as cysteine-262 in the H. salinarium sequence.

Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion.

PubMed

James, Declan J; Khodthong, Chuenchanok; Kowalchyk, Judith A; Martin, Thomas F J

2008-07-28

Phosphatidylinositol 4,5-bisphosphate (PI 4,5-P(2)) on the plasma membrane is essential for vesicle exocytosis but its role in membrane fusion has not been determined. Here, we quantify the concentration of PI 4,5-P(2) as approximately 6 mol% in the cytoplasmic leaflet of plasma membrane microdomains at sites of docked vesicles. At this concentration of PI 4,5-P(2) soluble NSF attachment protein receptor (SNARE)-dependent liposome fusion is inhibited. Inhibition by PI 4,5-P(2) likely results from its intrinsic positive curvature-promoting properties that inhibit formation of high negative curvature membrane fusion intermediates. Mutation of juxtamembrane basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggesting that syntaxin sequesters PI 4,5-P(2) to alleviate inhibition. To define an essential rather than inhibitory role for PI 4,5-P(2), we test a PI 4,5-P(2)-binding priming factor required for vesicle exocytosis. Ca(2+)-dependent activator protein for secretion promotes increased rates of SNARE-dependent fusion that are PI 4,5-P(2) dependent. These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion.

A botulinum neurotoxin-like function of Potentilla chinensis extract that inhibits neuronal SNARE complex formation, membrane fusion, neuroexocytosis, and muscle contraction.

PubMed

Jung, Chang-Hwa; Choi, Jin-Kyu; Yang, Yoosoo; Koh, Hyun-Ju; Heo, Paul; Yoon, Kee-Jung; Kim, Sehyun; Park, Won-Seok; Shing, Hong-Ju; Kweon, Dae-Hyuk

2012-09-01

Botulinum neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis. In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated. After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined. The extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 μg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca²⁺-channel blocker verapamil and BoNT type A. While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the Potentilla chinensis extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics.

NSF Support for Physics at the Undergraduate Level: A View from Inside

NASA Astrophysics Data System (ADS)

McBride, Duncan

2015-03-01

NSF has supported a wide range of projects in physics that involve undergraduate students. These projects include NSF research grants in which undergraduates participate; Research Experiences for Undergraduates (REU) centers and supplements; and education grants that range from upper-division labs that may include research, to curriculum development for upper- and lower-level courses and labs, to courses for non-majors, to Physics Education Research (PER). The NSF Divisions of Physics, Materials Research, and Astronomy provide most of the disciplinary research support, with some from other parts of NSF. I recently retired as the permanent physicist in NSF's Division of Undergraduate Education (DUE), which supports the education grants. I was responsible for a majority of DUE's physics grants and was involved with others overseen by a series of physics rotators. There I worked in programs entitled Instrumentation and Laboratory Improvement (ILI); Course and Curriculum Development (CCD); Course, Curriculum, and Laboratory Improvement (CCLI); Transforming Undergraduate STEM Education (TUES); and Improving Undergraduate STEM Education (IUSE). NSF support has enabled physics Principal Investigators to change and improve substantially the way physics is taught and the way students learn physics. The most important changes are increased undergraduate participation in physics research; more teaching using interactive engagement methods in classes; and growth of PER as a legitimate field of physics research as well as outcomes from PER that guide physics teaching. In turn these have led, along with other factors, to students who are better-prepared for graduate school and work, and to increases in the number of undergraduate physics majors. In addition, students in disciplines that physics directly supports, notably engineering and chemistry, and increasingly biology, are better and more broadly prepared to use their physics education in these fields. I will describe NSF

[Expression of AMPA receptors and related protein in immobilization stressed rats and effect of Xiaoyaosan].

PubMed

Yue, Guang-Xin; Wang, Zhu-Feng; Zhang, Qiao-Li; Zhao, Xin; Yue, Li-Feng; Ding, Jie; Chen, Jia-Xu

2008-05-01

To observe protein expression changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and related regulatory protein in the hippocampus and amygdala in chronic immobilization stressed rat and Xiaoyaosan's regulatory effect. Rats were tied 3 h per day to establish immobilization stress condition and treatment with Xiaoyaosan. After 7 days and 21 days stress, the protein expression of AMPA receptor subunit (GluR2/3), N-ethylmaleimide sensitive factor (NSF) and protein interacting with C-kinase 1 (PICK1) in hippocampus and amygdala were detected by using Western blot techniques. The expression of GluR2/3, NSF in dentate gyrus (DG) and amygdala were markedly attenuated (P < 0.05) and PICK1 in CA1 region were significantly increased (P < 0.05) in 7 d immobilization stressed rats while 7 days xiaoyaosan treatment showed an effective regulatory result to PICK1's changes. Under 21 days immobilization stressed condition, the expression of GluR2/3, NSF in CA1 region showed an increasing trend, and GluR2/3 showed a markedly increase (P < 0.01), but showed an significantly decreased trend in amygdala, Xiaoyaosan showed an effective result to such changes above (P < 0.05). The expression of PICK1 showed increasing trend in amygdala and xiaoyaosan could lower its expression (P < 0.05). There are different trends of the expression of AMPA receptor in repeat short-term stress versus chronic immobilization stress, and in hippocampal CA1 region versus amygdala. Xiaoyaosan has better regulation effect on the expression of AMPA receptors in the condition of chronic immobilization stress than those of repeat shortterm stress.

Detecting protein-protein interactions using Renilla luciferase fusion proteins.

PubMed

Burbelo, Peter D; Kisailus, Adam E; Peck, Jeremy W

2002-11-01

We have developed a novel system designated the luciferase assay for protein detection (LAPD) to study protein-protein interactions. This method involves two protein fusions, a soluble reporter fusion and a fusion for immobilizing the target protein. The soluble reporter is an N-terminal Renilla luciferase fusion protein that exhibits high Renilla luciferase activity. Crude cleared lysates from transfected Cos1 cells that express the Renilla luciferase fusion protein can be used in binding assays with immobilized target proteins. Following incubation and washing, target-bound Renilla luciferase fusion proteins produce light from the coelenterazine substrate, indicating an interaction between the two proteins of interest. As proof of the principle, we reproduced known, transient protein-protein interactions between the Cdc42 GTPase and its effector proteins. GTPase Renilla fusion proteins produced in Cos1 cells were tested with immobilized recombinant GST-N-WASP and CEP5 effector proteins. Using this assay, we could detect specific interactions of Cdc42 with these effector proteins in approximately 50 min. The specificity of these interactions was demonstrated by showing that they were GTPase-specific and GTP-dependent and not seen with other unrelated target proteins. These results suggest that the LAPD method, which is both rapid and sensitive, may have research and practical applications.

45 CFR 650.14 - Request for conveyance of title to NSF.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Request for conveyance of title to NSF. 650.14 Section 650.14 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.14 Request for conveyance of title to NSF. (a) The procedures established by this...

45 CFR 650.14 - Request for conveyance of title to NSF.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Request for conveyance of title to NSF. 650.14 Section 650.14 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.14 Request for conveyance of title to NSF. (a) The procedures established by this...

45 CFR 650.14 - Request for conveyance of title to NSF.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Request for conveyance of title to NSF. 650.14 Section 650.14 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.14 Request for conveyance of title to NSF. (a) The procedures established by this...

Determinants of Broader Impacts Activities: A Survey of NSF-Funded Investigators

ERIC Educational Resources Information Center

Nagy, Dianne

2016-01-01

This study investigated the factors that shape the broader impacts activities of NSF grant recipients. A random sample of NSF grantees was surveyed about the type and quality of their broader impacts activities, their views on knowledge production and the democratization of science, their experience and training, and the existence of a supportive…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yoosoo; Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791; Kim, Se-Hyun

Highlights: • Membrane fusion driven by SNARE complex is hindered by several polyphenols. • Distinctive inhibitory effect of each polyphenol on SNARE zippering in neuron was examined. • FRET between fluorescence protein-tagged SNAREs probed well SNARE zippering in PC12 cells. • Delphinidin and cyanidin inhibit N-terminal SNARE nucleation in Ca{sup 2+}-independent manner. • Myricetin inhibits Ca{sup 2+}-dependent transmembrane association of SNARE complex. - Abstract: Fusion of synaptic vesicles with the presynaptic plasma membrane in the neuron is mediated by soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor (SNARE) proteins. SNARE complex formation is a zippering-like process which initiates at the N-terminus andmore » proceeds to the C-terminal membrane-proximal region. Previously, we showed that this zippering-like process is regulated by several polyphenols, leading to the arrest of membrane fusion and the inhibition of neuroexocytosis. In vitro studies using purified SNARE proteins reconstituted in liposomes revealed that each polyphenol uniquely regulates SNARE zippering. However, the unique regulatory effect of each polyphenol in cells has not yet been examined. In the present study, we observed SNARE zippering in neuronal PC12 cells by measuring the fluorescence resonance energy transfer (FRET) changes of a cyan fluorescence protein (CFP) and a yellow fluorescence protein (YFP) fused to the N-termini or C-termini of SNARE proteins. We show that delphinidin and cyanidin inhibit the initial N-terminal nucleation of SNARE complex formation in a Ca{sup 2+}-independent manner, while myricetin inhibits Ca{sup 2+}-dependent transmembrane domain association of the SNARE complex in the cell. This result explains how polyphenols exhibit botulinum neurotoxin-like activity in vivo.« less

Comprehensive sets of 124Xe(n ,γ )125Xe and 124Xe(n ,2 n )123Xe cross-section data for assessment of inertial-confinement deuterium-tritium fusion plasma

NASA Astrophysics Data System (ADS)

Bhike, Megha; Fallin, B.; Gooden, M. E.; Ludin, N.; Tornow, W.

2015-01-01

Measurements of the neutron radiative-capture cross section of 124Xe have been performed for the first time for neutron energies above 100 keV. In addition, data for the 124Xe(n ,2 n )123Xe reaction cross section have been obtained from threshold to 14.8 MeV to cover the entire energy range of interest, while previous data existed only at around 14 MeV. The results of these measurements provide the basis for an alternative and sensitive diagnostic tool for investigating properties of the inertial confinement fusion plasma in deuterium-tritium (DT) capsules at the National Ignition Facility located at Lawrence Livermore National Laboratory. Here, areal density ρ R (density × radius) of the fuel, burn asymmetry, and fuel-ablator mix are of special interest. The 124Xe(n ,γ )125Xe reaction probes the down-scattered neutrons, while the 124Xe(n ,2 n )123Xe reaction provides a measure of the 14 MeV direct neutrons.

Central Sensitization Inventory as a Predictor of Worse Quality of Life Measures and Increased Length of Stay Following Spinal Fusion.

PubMed

Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A

2017-08-01

Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers.

PubMed

Zhang, Yongli

2017-07-01

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion. A long-standing hypothesis suggests that SNAREs act like a zipper to draw the two membranes into proximity and thereby force them to fuse. However, a quantitative test of this SNARE zippering hypothesis was hindered by difficulties to determine the energetics and kinetics of SNARE assembly and to identify the relevant folding intermediates. Here, we first review different approaches that have been applied to study SNARE assembly and then focus on high-resolution optical tweezers. We summarize the folding energies, kinetics, and pathways of both wild-type and mutant SNARE complexes derived from this new approach. These results show that synaptic SNAREs assemble in four distinct stages with different functions: slow N-terminal domain association initiates SNARE assembly; a middle domain suspends and controls SNARE assembly; and rapid sequential zippering of the C-terminal domain and the linker domain directly drive membrane fusion. In addition, the kinetics and pathway of the stagewise assembly are shared by other SNARE complexes. These measurements prove the SNARE zippering hypothesis and suggest new mechanisms for SNARE assembly regulated by other proteins. © 2017 The Protein Society.

Linking the GLOBE Program With NASA and NSF Large-Scale Experiments

NASA Astrophysics Data System (ADS)

Filmer, P. E.

2005-12-01

NASA and the NSF, the sponsoring Federal agencies for the GLOBE Program, are seeking the participation of science teams who are working at the cutting edge of Earth systems science in large integrated Earth systems science programs. Connecting the GLOBE concept and structure with NASA and NSF's leading Earth systems science programs will give GLOBE schools and students access to top scientists, and expose them to programs that have been designated as scientific priorities. Students, teachers, parents, and their communities will be able to see how scientists of many disciplines work together to learn about the Earth system. The GLOBE solicitation released by the NSF targets partnerships between GLOBE and NSF/NASA-funded integrated Earth systems science programs. This presentation will focus on the goals and requirements of the NSF solicitation. Proponents will be expected to provide ways for the GLOBE community to interact with a group of scientists from their science programs as part of a wider joint Earth systems science educational strategy (the sponsoring agencies', GLOBE's, and the proposing programs'). Teams proposing to this solicitation must demonstrate: - A focus on direct connections with major NSF Geosciences and/or Polar Programs and/or NASA Earth-Sun research programs that are related to Earth systems science; - A demonstrable benefit to GLOBE and to NSF Geosciences and/or Polar Programs or NASA Earth-Sun education goals (providing access to program researchers and data, working with GLOBE in setting up campaigns where possible, using tested GLOBE or non-GLOBE protocols to the greatest extent possible, actively participating in the wider GLOBE community including schools, among other goals); - An international component; - How the existing educational efforts of the large science program will coordinate with GLOBE; - An Earth systems science education focus, rather than a GLOBE protocol-support focus; - A rigorous evaluation and assessment component

Congressional geohazards showcase presented by NSF and AGU

NASA Astrophysics Data System (ADS)

Uhlenbrock, Kristan

2011-10-01

On Wednesday, 7 September 2011, two weeks after the magnitude 5.8 earthquake in Mineral, Va., and a week after Hurricane Irene struck the U.S. East Coast, AGU cosponsored a showcase of National Science Foundation (NSF)—funded hazards research in recognition of National Preparedness Month. This annual event highlights NSF—funded hazards research from all over the United States, with more than 30 exhibitors demonstrating the latest research and technology on hurricanes, earthquakes, tornadoes, volcanoes, tsunamis, and oil spills, as well as emergency and social responses to these events. The event took place at the Hart Senate Office Building, where many members of Congress and their staff could attend and discuss the importance of hazards research with the researchers and NSF staff. Sen. Bill Nelson (D-Fla.) kicked off with a panel of speakers, which included remarks by Mary Voytek, a member of the AGU Board of Directors, and Subra Suresh, director of NSF. Expert presentations were also given on hazard prediction, human safety, and social response. Following the event, Senate Majority Leader Harry Reid (D-Nev.) hosted a small event to meet directly with a few of the exhibitors to discuss the importance of investment in scientific research and development.

CDCC calculations of fusion of 6Li with targets 144Sm and 154Sm: effect of resonance states

NASA Astrophysics Data System (ADS)

Gómez Camacho, A.; Lubian, J.; Zhang, H. Q.; Zhou, Shan-Gui

2017-12-01

Continuum Discretized Coupled-Channel (CDCC) model calculations of total, complete and incomplete fusion cross sections for reactions of the weakly bound 6Li with 144,154Sm targets at energies around the Coulomb barrier are presented. In the cluster structure frame of 6Li→α+d, short-range absorption potentials are considered for the interactions between the ground state of the projectile 6Li and α-d fragments with the target. In order to separately calculate complete and incomplete fusion and to reduce double-counting, the corresponding absorption potentials are chosen to be of different range. Couplings to low-lying excited states 2+, 3- of 144Sm and 2+, 4+ of 154Sm are included. So, the effect on total fusion from the excited states of the target is investigated. Similarly, the effect on fusion due to couplings to resonance breakup states of 6Li, namely, l=2, J π =3+,2+,1+ is also calculated. The latter effect is determined by using two approaches, (a) by considering only resonance state couplings and (b) by omitting these states from the full discretized energy space. Among other things, it is found that both resonance and non-resonance continuum breakup couplings produce fusion suppression at all the energies considered. A. Gómez Camacho from CONACYT, México, J. Lubian from CNPq, FAPERJ, Pronex, Brazil. S.G.Z was partly supported by the NSF of China (11120101005, 11275248, 11525524, 11621131001, 11647601, 11711540016), 973 Program of China (2013CB834400) and the Key Research Program of Frontier Sciences of CAS. H.Q.Z. from NSF China (11375266)

Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay.

PubMed

Rho, Jin Kyung; Lee, Hyangsin; Park, Chan-Sik; Choi, Chang-Min; Lee, Jae Cheol

2013-09-01

EML4-ALK fusion oncogene has emerged as a novel molecular target in non-small cell lung cancer (NSCLC). Although break-apart fluorescent in situ hybridization (FISH) is the standard method for diagnosis, it is expensive, not readily available and sometimes difficult to interpret. In addition, ALK immunohistochemistry (IHC) may miss the diagnosis because of relatively low level of ALK transcription. In situ proximity ligation assay (PLA) originally developed for precise detection and quantification of proteins by dual recognition and amplification process was used for sensitive detection of EML4-ALK fusion oncoprotein in NSCLC cell lines (ALK negative cell: PC-9 and H460, ALK positive cell: H3122 and H2228). EML4-ALK oncogene and protein in lung cancer cells were confirmed by multiplex RT-PCR and Western blots. We detected 117 kDa variant 1 of EML4-ALK in H3122 and 90 kDa variant 3 of EML4-ALK in H2228. These cells were more sensitive to crizotinib, an ALK inhibitor compared with PC-9 and H460 cells without EML4-ALK rearrangement. After fixing on glass slides by cytospin centrifuge, in situ PLA test was performed. Among four cell lines, distinct, tiny spots were visible only in H3122 and H2228 cell lines with ALK rearrangement. The same results were also obtained when paraffin-embedded cell blocks were used. Highly specific and sensitive detection of EML4-ALK fusion oncoprotein is possible by in situ PLA method suggesting its clinical application.

Report: NSF Instrumentation and Laboratory Improvement Grants in Chemistry

NASA Astrophysics Data System (ADS)

1997-01-01

The 1996 awards in chemistry under the Instrumentation and Laboratory Improvement Program (ILI) of the Division of Undergraduate Education (DUE) have been announced and are listed below. The ILI program provides matching funds in the range of 5,000 to 100,000 for purchasing equipment for laboratory improvement. Since the recipient institution must provide matching funds equaling or exceeding the NSF award, the supported projects range in cost from 10,000 to over 200,000. The 311 chemistry proposals requesting 13 million constituted 21% of the total number of proposals submitted to the ILI program. A total of 3.9 million was awarded in support of 110 projects in chemistry. The instruments requested most frequently were high field NMRs, GC/MS instruments, computers for data analysis, and FT-IRs; next most commonly requested were UV-vis spectrophotometers, followed by HPLCs, lasers, computers for molecular modeling, AAs, and GCs. In addition, one award was made this year in chemistry within the Leadership in Laboratory Development category. The next deadline for submission of ILI proposals is November 14, 1997. Guidelines for the preparation of proposals are found in the DUE Program Announcement (NSF 96-10), which may be obtained by calling (703) 306-1666 or by e-mail: undergrad@nsf.gov. Other information about DUE programs and activities and abstracts of the funded proposals can be found on the DUE Home Page at http://www.ehr.nsf.gov/EHR/DUE/start.htm. We thank Sandra D. Nelson, Science Education Analyst in DUE, for assistance in data gathering.

Calculation of Excitation Function of Some Structural Fusion Material for (n, p) Reactions up to 25 MeV

NASA Astrophysics Data System (ADS)

Reshid, Tarik S.

2013-04-01

Fusion serves an inexhaustible energy for humankind. Although there have been significant research and development studies on the inertial and magnetic fusion reactor technology, Furthermore, there are not radioactive nuclear waste problems in the fusion reactors. In this study, (n, p) reactions for some structural fusion materials such as 27Al, 51V, 52Cr, 55Mn and 56Fe have been investigated. The new calculations on the excitation functions of 27 Al(n, p) 27 Mg, 51 V(n, p) 51 Ti, 52 Cr(n, p) 52 V, 55 Mn(n, p) 55 Cr and 56 Fe(n, p) 56 Mn reactions have been carried out up to 30 MeV incident neutron energy. Statistical model calculations, based on the Hauser-Feshbach formalism, have been carried out using the TALYS-1.0 and were compared with available experimental data in the literature and with ENDF/B-VII, T = 300 K; JENDL-3.3, T = 300 K and JEFF-3.1, T = 300 K evaluated libraries.

Simultaneous determination of azathioprine and 6-mercaptopurine in serum by reversed-phase high-performance liquid chromatography.

PubMed

Tsutsumi, K; Otsuki, Y; Kinoshita, T

1982-09-10

The simultaneous determination of azathioprine and its metabolite 6-mercaptopurine in serum by reversed-phase high-performance liquid chromatography is described. 6-Mercaptopurine was converted to a derivative, 6-mercaptopurine-N-ethylmaleimide, which is stable against autoxidation, on reaction with N-ethylmaleimide. Since the N-ethylmaleimide derivative was more hydrophobic than the parent compound, it could be extracted into ethyl acetate together with azathioprine and the derivative was retained on the reversed-phase column better than 6-mercaptopurine. In addition, 6-mercaptopurine-N-ethylmaleimide absorbed at the same wavelength (280 nm) as azathioprine. Consequently, this derivatization procedure enabled the simultaneous extraction, separation, and detection of these compounds.

High-Sensitivity GaN Microchemical Sensors

NASA Technical Reports Server (NTRS)

Son, Kyung-ah; Yang, Baohua; Liao, Anna; Moon, Jeongsun; Prokopuk, Nicholas

2009-01-01

Systematic studies have been performed on the sensitivity of GaN HEMT (high electron mobility transistor) sensors using various gate electrode designs and operational parameters. The results here show that a higher sensitivity can be achieved with a larger W/L ratio (W = gate width, L = gate length) at a given D (D = source-drain distance), and multi-finger gate electrodes offer a higher sensitivity than a one-finger gate electrode. In terms of operating conditions, sensor sensitivity is strongly dependent on transconductance of the sensor. The highest sensitivity can be achieved at the gate voltage where the slope of the transconductance curve is the largest. This work provides critical information about how the gate electrode of a GaN HEMT, which has been identified as the most sensitive among GaN microsensors, needs to be designed, and what operation parameters should be used for high sensitivity detection.

48 CFR 2527.7002 - NSF patent policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NSF patent policy. 2527.7002 Section 2527.7002 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL... Department of Commerce in all its funding agreements for the performance of experimental, developmental, or...

48 CFR 2527.7002 - NSF patent policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

....7002 Section 2527.7002 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7002 NSF patent policy. As authorized by the National Science Board at its 230th meeting, October 15-16, 1981, the...

48 CFR 2527.7002 - NSF patent policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

....7002 Section 2527.7002 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7002 NSF patent policy. As authorized by the National Science Board at its 230th meeting, October 15-16, 1981, the...

48 CFR 2527.7002 - NSF patent policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

....7002 Section 2527.7002 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7002 NSF patent policy. As authorized by the National Science Board at its 230th meeting, October 15-16, 1981, the...

48 CFR 2527.7002 - NSF patent policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

....7002 Section 2527.7002 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Disposition of Rights in Inventions 2527.7002 NSF patent policy. As authorized by the National Science Board at its 230th meeting, October 15-16, 1981, the...

Pionic Fusion of 4He +12 C

NASA Astrophysics Data System (ADS)

Zarrella, Andrew; Yennello, Sherry

2017-09-01

Pionic fusion is the process by which two nuclei fuse and then deexcite by the exclusive emission of a pion. These reactions represent the most extreme examples of deep subthreshold pion production and provide evidence for an unknown, collective mechanism for pion production. An experiment was performed at the Texas A&M University Cyclotron Institute to measure the cross section of the 4He +12 C -> 16N +π+ reaction. The Momentum Achromat Recoil Spectrometer (MARS) was used to separate and identify the 16N fusion residues and the newly constructed Partial Truncated Icosahedron (ParTI) phoswich array was used to identify charged pions. The detector responses for each phoswich unit were recorded using fast-sampling ADCs which allow all light charged particles in the ParTI phoswiches to be identified using ``fast vs. slow'' pulse shape discrimination. By writing the waveform responses, pions can also be identified by the presence of a characteristic muon decay pulse. The combination of the residue-pion coincidence and the two independent pion identification techniques represent a highly sensitive experimental design for studying pionic fusion reactions.

Low-energy nuclear reaction of the 14N+169Tm system: Incomplete fusion

NASA Astrophysics Data System (ADS)

Kumar, R.; Sharma, Vijay R.; Yadav, Abhishek; Singh, Pushpendra P.; Agarwal, Avinash; Appannababu, S.; Mukherjee, S.; Singh, B. P.; Ali, R.; Bhowmik, R. K.

2017-11-01

Excitation functions of reaction residues produced in the 14N+169Tm system have been measured to high precision at energies above the fusion barrier, ranging from 1.04 VB to 1.30 VB , and analyzed in the framework of the statistical model code pace4. Analysis of α -emitting channels points toward the onset of incomplete fusion even at slightly above-barrier energies where complete fusion is supposed to be one of the dominant processes. The onset and strength of incomplete fusion have been deduced and studied in terms of various entrance channel parameters. Present results together with the reanalysis of existing data for various projectile-target combinations conclusively suggest strong influence of projectile structure on the onset of incomplete fusion. Also, a strong dependence on the Coulomb effect (ZPZT) has been observed for the present system along with different projectile-target combinations available in the literature. It is concluded that the fraction of incomplete fusion linearly increases with ZPZT and is found to be more for larger ZPZT values, indicating significantly important linear systematics.

National Science Foundation Fiscal Year 1986 Awards (by State and NSF Directorate).

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC.

Provided is a listing of National Science Foundation (NSF) program grants and contracts awarded in Fiscal Year 1986. Data, current as of Feburary 13, 1987, are arranged as follows: (1) by state, with totals for each state (foreign countries are alphabetized with states); (2) by NSF Directorate, with award and dollar totals for each NSF…

In vitro effects of platinum compounds on renal cellular respiration in mice.

PubMed

Almarzooqi, Saeeda-S; Alfazari, Ali-S; Abdul-Kader, Hidaya-M; Saraswathiamma, Dhanya; Albawardi, Alia-S; Souid, Abdul-Kader

2015-01-01

Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.

Improved Access to NSF Funded Ocean Research Data

NASA Astrophysics Data System (ADS)

Chandler, C. L.; Groman, R. C.; Kinkade, D.; Shepherd, A.; Rauch, S.; Allison, M. D.; Gegg, S. R.; Wiebe, P. H.; Glover, D. M.

2015-12-01

Data from NSF-funded, hypothesis-driven research comprise an essential part of the research results upon which we base our knowledge and improved understanding of the impacts of climate change. Initially funded in 2006, the Biological and Chemical Oceanography Data Management Office (BCO-DMO) works with marine scientists to ensure that data from NSF-funded ocean research programs are fully documented and freely available for future use. BCO-DMO works in partnership with information technology professionals, other marine data repositories and national data archive centers to ensure long-term preservation of these valuable environmental research data. Data contributed to BCO-DMO by the original investigators are enhanced with sufficient discipline-specific documentation and published in a variety of standards-compliant forms designed to enable discovery and support accurate re-use.

Fusion information entropy method of rolling bearing fault diagnosis based on n-dimensional characteristic parameter distance

NASA Astrophysics Data System (ADS)

Ai, Yan-Ting; Guan, Jiao-Yue; Fei, Cheng-Wei; Tian, Jing; Zhang, Feng-Ling

2017-05-01

To monitor rolling bearing operating status with casings in real time efficiently and accurately, a fusion method based on n-dimensional characteristic parameters distance (n-DCPD) was proposed for rolling bearing fault diagnosis with two types of signals including vibration signal and acoustic emission signals. The n-DCPD was investigated based on four information entropies (singular spectrum entropy in time domain, power spectrum entropy in frequency domain, wavelet space characteristic spectrum entropy and wavelet energy spectrum entropy in time-frequency domain) and the basic thought of fusion information entropy fault diagnosis method with n-DCPD was given. Through rotor simulation test rig, the vibration and acoustic emission signals of six rolling bearing faults (ball fault, inner race fault, outer race fault, inner-ball faults, inner-outer faults and normal) are collected under different operation conditions with the emphasis on the rotation speed from 800 rpm to 2000 rpm. In the light of the proposed fusion information entropy method with n-DCPD, the diagnosis of rolling bearing faults was completed. The fault diagnosis results show that the fusion entropy method holds high precision in the recognition of rolling bearing faults. The efforts of this study provide a novel and useful methodology for the fault diagnosis of an aeroengine rolling bearing.

NSF Establishes First Four National Supercomputer Centers.

ERIC Educational Resources Information Center

Lepkowski, Wil

1985-01-01

The National Science Foundation (NSF) has awarded support for supercomputer centers at Cornell University, Princeton University, University of California (San Diego), and University of Illinois. These centers are to be the nucleus of a national academic network for use by scientists and engineers throughout the United States. (DH)

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

Hsieh, Gillian; Bierman, Rob; Szabo, Linda; Lee, Alex Gia; Freeman, Donald E.; Watson, Nathaniel; Sweet-Cordero, E. Alejandro

2017-01-01

Abstract Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors. PMID:28541529

Discovery of the First Germline-Restricted Gene by Subtractive Transcriptomic Analysis in the Zebra Finch, Taeniopygia guttata.

PubMed

Biederman, Michelle K; Nelson, Megan M; Asalone, Kathryn C; Pedersen, Alyssa L; Saldanha, Colin J; Bracht, John R

2018-05-21

Developmentally programmed genome rearrangements are rare in vertebrates, but have been reported in scattered lineages including the bandicoot, hagfish, lamprey, and zebra finch (Taeniopygia guttata) [1]. In the finch, a well-studied animal model for neuroendocrinology and vocal learning [2], one such programmed genome rearrangement involves a germline-restricted chromosome, or GRC, which is found in germlines of both sexes but eliminated from mature sperm [3, 4]. Transmitted only through the oocyte, it displays uniparental female-driven inheritance, and early in embryonic development is apparently eliminated from all somatic tissue in both sexes [3, 4]. The GRC comprises the longest finch chromosome at over 120 million base pairs [3], and previously the only known GRC-derived sequence was repetitive and non-coding [5]. Because the zebra finch genome project was sourced from male muscle (somatic) tissue [6], the remaining genomic sequence and protein-coding content of the GRC remain unknown. Here we report the first protein-coding gene from the GRC: a member of the α-soluble N-ethylmaleimide sensitive fusion protein (NSF) attachment protein (α-SNAP) family hitherto missing from zebra finch gene annotations. In addition to the GRC-encoded α-SNAP, we find an additional paralogous α-SNAP residing in the somatic genome (a somatolog)-making the zebra finch the first example in which α-SNAP is not a single-copy gene. We show divergent, sex-biased expression for the paralogs and also that positive selection is detectable across the bird α-SNAP lineage, including the GRC-encoded α-SNAP. This study presents the identification and evolutionary characterization of the first protein-coding GRC gene in any organism. Copyright © 2018 Elsevier Ltd. All rights reserved.

The NSF/RANN FY 1975 program for geothermal resources research and technology

NASA Technical Reports Server (NTRS)

Kruger, P.

1974-01-01

The specific goal of the NSF geothermal program is the rapid development by industry of the nation's geothermal resources that can be demonstrated to be commercially, environmentally and socially acceptable as alternate energy sources. NSF, as the lead agency for the federal geothermal energy research program, is expediting a program which encompasses the objectives necessary for significant utilization. These include: acceleration of exploration and assessment methods to identify commercial geothermal resources; development of innovative and improved technology to achieve economic feasibility; evaluation of policy options to resolve environmental, legal, and institutional problems; and support of experimental research facilities for each type of geothermal resource. Specific projects in each of these four objective areas are part of the NSF program for fiscal year 1975.

New directions at NSF

NASA Astrophysics Data System (ADS)

Harvey, Albert B.

1995-10-01

The mission and scope of the National Science Foundation (NSF) and lightwave technology will be very briefly discussed. The focus of the presentation will be directed toward changes in research support that are taking place and the opportunities we have for aiming our research to meet the challenges and needs that face the nation. In the USA it is very clear that defense oriented research is downsizing and is being redirected into economy driven aresas, such as manufacturing, business, and industry. For those researchers who are willing to move into these areas and find a niche, the rewards may be very great. Industrial research partners should also seize these opportunities to enhance their resources in an otherwise bleak future for industrial support of basic research in lightwave technology and many other reserach disciplines. These activities of bringing together industry and academia will have the value added benefit of providing increased job opportunities for students. An outline of some of these opportunities and incentives will be presented. On the international front, there has never been a better time for the encouragement of joint research and collaboration across borders. The economic potential for involvement in Eastern Europe and Asia are enormous. Agencies like ourselves are open to help support of visiting scientist/engineer exchange, international conferences and forums and support of innovative ideas to help further enhance economic developemnt of the world and hence the quality of life. The presence of the Russian delegation here at these SPIE meetings in in part the result of NSF support. Concomitant with these changes is a growing interest in education. Academia is gradually realizing that education includes training for students to acquire jobs and hence we complete the cycle of the importance of interacting with industry. At the NSF a major new initiative is being introduced in Optical Science and Engineering (OSE). This effort has been

NSF's Handling of Allegations of Misconduct in Science

NASA Astrophysics Data System (ADS)

Manka, Aaron

2000-03-01

Under NSF's Office of Inspector General mandate to prevent fraud, waste, abuse, or mismanagement involving NSF's proposals and awards, our office is unique in that it also investigates allegations of misconduct in science. I will discuss our office's handling of such matters, focusing on the ethical and legal obligations of proposal submitters and awardees and the role of the scientific community. To illustrate some of these points that are of interest to the physics community, I will discuss some of our investigative activities relevant to: duplicate funding, cost sharing, and the accuracy of information in proposals. If the OSTP policy on research misconduct has been released for public comment, I will briefly discuss this policy, which is meant to be adopted by all federal funding agencies, and what it will mean for us and the community we serve.

NSF budget clears Senate hurdle

NASA Astrophysics Data System (ADS)

Jones, Richard

At one of the two most important hearings on the National Science Foundation's budget request for FY 1992, held April 24, there was little to suggest that the Senate VA, HUD, and Independent Agencies subcommittee—chaired by Barbara Mikulski (D-Md.)—will make any dramatic changes in the agency's allotment.NSF director Walter Massey reviewed the foundation's budget request, up 17.5% over this year's, but he provoked little discussion about the portions for research and related activities. Mikulski was particularly interested in indirect cost rates and in facility modernization, especially at smaller colleges.

v-SNAREs control exocytosis of vesicles from priming to fusion.

PubMed

Borisovska, Maria; Zhao, Ying; Tsytsyura, Yaroslav; Glyvuk, Nataliya; Takamori, Shigeo; Matti, Ulf; Rettig, Jens; Südhof, Thomas; Bruns, Dieter

2005-06-15

SNARE proteins (soluble NSF-attachment protein receptors) are thought to be central components of the exocytotic mechanism in neurosecretory cells, but their precise function remained unclear. Here, we show that each of the vesicle-associated SNARE proteins (v-SNARE) of a chromaffin granule, synaptobrevin II or cellubrevin, is sufficient to support Ca(2+)-dependent exocytosis and to establish a pool of primed, readily releasable vesicles. In the absence of both proteins, secretion is abolished, without affecting biogenesis or docking of granules indicating that v-SNAREs are absolutely required for granule exocytosis. We find that synaptobrevin II and cellubrevin differentially control the pool of readily releasable vesicles and show that the v-SNARE's amino terminus regulates the vesicle's primed state. We demonstrate that dynamics of fusion pore dilation are regulated by v-SNAREs, indicating their action throughout exocytosis from priming to fusion of vesicles.

Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion.

PubMed

Peacock, Thomas P; Benton, Donald J; Sadeyen, Jean-Remy; Chang, Pengxiang; Sealy, Joshua E; Bryant, Juliet E; Martin, Stephen R; Shelton, Holly; McCauley, John W; Barclay, Wendy S; Iqbal, Munir

2017-03-22

H9N2 avian influenza viruses are primarily a disease of poultry; however, they occasionally infect humans and are considered a potential pandemic threat. Little work has been performed to assess the intrinsic biochemical properties related to zoonotic potential of H9N2 viruses. The objective of this study, therefore, was to investigate H9N2 haemagglutinins (HAs) using two well-known correlates for human adaption: receptor-binding avidity and pH of fusion. Receptor binding was characterized using bio-layer interferometry to measure virus binding to human and avian-like receptor analogues and the pH of fusion was assayed by syncytium formation in virus-infected cells at different pHs. We characterized contemporary H9N2 viruses of the zoonotic G1 lineage, as well as representative viruses of the zoonotic BJ94 lineage. We found that most contemporary H9N2 viruses show a preference for sulphated avian-like receptor analogues. However, the 'Eastern' G1 H9N2 viruses displayed a consistent preference in binding to a human-like receptor analogue. We demonstrate that the presence of leucine at position 226 of the HA receptor-binding site correlated poorly with the ability to bind a human-like sialic acid receptor. H9N2 HAs also display variability in their pH of fusion, ranging between pH 5.4 and 5.85 which is similar to that of the first wave of human H1N1pdm09 viruses but lower than the pH of fusion seen in zoonotic H5N1 and H7N9 viruses. Our results suggest possible molecular mechanisms that may underlie the relatively high prevalence of human zoonotic infection by particular H9N2 virus lineages.

Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion

PubMed Central

Peacock, Thomas P; Benton, Donald J; Sadeyen, Jean-Remy; Chang, Pengxiang; Sealy, Joshua E; Bryant, Juliet E; Martin, Stephen R; Shelton, Holly; McCauley, John W; Barclay, Wendy S; Iqbal, Munir

2017-01-01

H9N2 avian influenza viruses are primarily a disease of poultry; however, they occasionally infect humans and are considered a potential pandemic threat. Little work has been performed to assess the intrinsic biochemical properties related to zoonotic potential of H9N2 viruses. The objective of this study, therefore, was to investigate H9N2 haemagglutinins (HAs) using two well-known correlates for human adaption: receptor-binding avidity and pH of fusion. Receptor binding was characterized using bio-layer interferometry to measure virus binding to human and avian-like receptor analogues and the pH of fusion was assayed by syncytium formation in virus-infected cells at different pHs. We characterized contemporary H9N2 viruses of the zoonotic G1 lineage, as well as representative viruses of the zoonotic BJ94 lineage. We found that most contemporary H9N2 viruses show a preference for sulphated avian-like receptor analogues. However, the ‘Eastern' G1 H9N2 viruses displayed a consistent preference in binding to a human-like receptor analogue. We demonstrate that the presence of leucine at position 226 of the HA receptor-binding site correlated poorly with the ability to bind a human-like sialic acid receptor. H9N2 HAs also display variability in their pH of fusion, ranging between pH 5.4 and 5.85 which is similar to that of the first wave of human H1N1pdm09 viruses but lower than the pH of fusion seen in zoonotic H5N1 and H7N9 viruses. Our results suggest possible molecular mechanisms that may underlie the relatively high prevalence of human zoonotic infection by particular H9N2 virus lineages. PMID:28325922

Integrating Research and Education in NSF's Office of Polar Programs

NASA Astrophysics Data System (ADS)

Wharton, R. A.; Crain, R. D.

2003-12-01

The National Science Foundation invests in activities that integrate research and education, and that develop reward systems to support teaching, mentoring and outreach. Effective integration of research and education at all levels can infuse learning with the excitement of discovery. It can also ensure that the findings and methods of research are quickly and effectively communicated in a broader context and to a larger audience. This strategy is vital to the accomplishment of NSF's strategic goals of ensuring a world-class science and engineering workforce, new knowledge across the frontiers of science and engineering, and the tools to get the job done efficiently and effectively. The NSF's Office of Polar Programs sponsors educational projects at all levels of learning, making full use of the variety of disciplinary and interdisciplinary studies in the polar regions to attract and invigorate students. An array of efforts from the Arctic and Antarctic scientific communities link research activities with education. There has been an advance from the beneficial but isolated impacts of individual researcher visits to K-12 classrooms to large-scale developments, such as field research experiences for teachers and undergraduate students, online sharing of polar field experiences with rural classrooms, the institution of interdisciplinary graduate research programs through NSF initiatives, and opportunities for minority and underrepresented groups in polar sciences. The NSF's criterion for evaluating proposals based upon the broader impacts of the research activity has strengthened efforts to link research and education, resulting in partnerships and innovations that infuse research into education from kindergarten through postdoctoral studies and reaching out to the general public. In addition, the Office of Polar Programs partners with other directorates at NSF to broaden OPP's efforts and benefit from resources and experience in the Education and Human Resources

Communicating Science Broadly: An NSF Point of View

NASA Astrophysics Data System (ADS)

Leinen, M. S.

2006-12-01

In the view of NSF, communicating about both the process of doing science and about scientific results are of paramount importance. But those of us in the agency are not the ones who do the science or generate the results. Thus, our policy is to encourage the community we fund to communicate their results as broadly as possible. Why does NSF feel so strongly about communicating scientific results? First, science only moves forward when there is free and open debate about scientific results through public mechanisms in which there is an opportunity for thorough analysis (e.g. scientific literature, professional meetings and workshops). Second, the research we support is done for the good of the public and should be communicated to the public. Third, scientific results are critical to many important decision-making processes and policy-making processes. Democracies thrive when an informed public is engaged, so communicating science broadly to the lay public is important. Why does NSF feel so strongly about communicating about the process of science? Science is a habit of mind; an orderly process for testing ideas. But many do not understand how science is done, the difference between fact and conjecture, why speculation, hypotheses and theory are critical to progress, or why the culture of constructive criticism is essential to progress. Without this context, science can be misunderstood as magic, opinion, or argument. Thus the efforts that we fund to enhance scientific education and outreach are critical to having discourse about scientific results.

The mediating role of disgust sensitivity and thought-action fusion between religiosity and obsessive compulsive symptoms.

PubMed

Inozu, Mujgan; Ulukut, Fulya Ozcanli; Ergun, Gokce; Alcolado, Gillian M

2014-10-01

Psychological theories of obsessions and compulsions have long recognised that strict religious codes and moral standards might promote thought-action fusion (TAF) appraisals. These appraisals have been implicated in the transformation of normally occurring intrusions into clinically distressing obsessions. Furthermore, increased disgust sensitivity has also been reported to be associated with obsessive compulsive (OC) symptoms. No research, however, has investigated the mediating roles of TAF and disgust sensitivity between religiosity and OC symptoms. This study was composed of 244 undergraduate students who completed measures of OC symptoms, TAF, disgust sensitivity, religiosity and negative effect. Analyses revealed that the relationship between religiosity and OC symptoms was mediated by TAF and disgust sensitivity. More importantly, the mediating role of TAF was not different across OC symptom subtypes, whereas the mediating role of disgust sensitivity showed different patterns across OC symptom subtypes. These findings indicate that the tendency for highly religious Muslims to experience greater OC symptoms is related to their heightened beliefs about disgust sensitivity and the importance of thoughts. © 2014 International Union of Psychological Science.

NSF Perspective on Engaging the NRC and the Community in Developing Priorities

NASA Astrophysics Data System (ADS)

Wakimoto, R. M.

2015-12-01

NSF pursued a new strategy to assess the balance between funding for core research and infrastructure in a time of limited budgets in the Division of Ocean Sciences (OCE). The latter constraint uniquely distinguished this report from previous community attempts to define future research priorities. The process that ultimately led to "Sea Change: 2015-2025: Decadal Survey of Ocean Sciences" report was closely monitored by Congress, OMB/OSTP, the National Science Board, NSF Senior Management, and the community. The Sea Change recommendations were specific and difficult but highly strategic. They also recommended immediate implementation. NSF and GEO were pleased with the outcome of a process that was initially viewed with some trepidation. Additional thoughts on the report and the process will be presented as well as future plans to engage the NAS and community in defining research priorities.

Sensitivity of low-energy incomplete fusion to various entrance-channel parameters

NASA Astrophysics Data System (ADS)

Kumar, Harish; Tali, Suhail A.; Afzal Ansari, M.; Singh, D.; Ali, Rahbar; Kumar, Kamal; Sathik, N. P. M.; Ali, Asif; Parashari, Siddharth; Dubey, R.; Bala, Indu; Kumar, R.; Singh, R. P.; Muralithar, S.

2018-03-01

The disentangling of incomplete fusion dependence on various entrance channel parameters has been made from the forward recoil range distribution measurement for the 12C+175Lu system at ≈ 88 MeV energy. It gives the direct measure of full and/or partial linear momentum transfer from the projectile to the target nucleus. The comparison of observed recoil ranges with theoretical ranges calculated using the code SRIM infers the production of evaporation residues via complete and/or incomplete fusion process. Present results show that incomplete fusion process contributes significantly in the production of α xn and 2α xn emission channels. The deduced incomplete fusion probability (F_{ICF}) is compared with that obtained for systems available in the literature. An interesting behavior of F_{ICF} with ZP ZT is observed in the reinvestigation of incomplete fusion dependency with the Coulomb factor (ZPZT), contrary to the recent observations. The present results based on (ZPZT) are found in good agreement with recent observations of our group. A larger F_{ICF} value for 12C induced reactions is found than that for 13C, although both have the same ZPZT. A nonsystematic behavior of the incomplete fusion process with the target deformation parameter (β2) is observed, which is further correlated with a new parameter (ZP ZT . β2). The projectile α -Q-value is found to explain more clearly the discrepancy observed in incomplete fusion dependency with parameters ( ZPZT) and (ZP ZT . β2). It may be pointed out that any single entrance channel parameter (mass-asymmetry or (ZPZT) or β2 or projectile α-Q-value) may not be able to explain completely the incomplete fusion process.

[Radiological study on the n-HA/PA66 cage used in the transforaminal lumbar interbody fusion].

PubMed

Sang, Pei-ming; Zhang, Ming; Chen, Bin-hui; Cai, Chang; Gu, Shi-rong; Zhou, Min

2014-08-01

To explore the effects of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage on recovering and maintaining lumbar curvature, lumbar heights and fusion rate when used in the transforaminal lumbar interbody fusion. From February to July 2012, 50 patients with degenerative lumbar disease(lumbar disc herniation in 32 cases and lumbar spondylolisthesis in 18 cases) were treated with transforaminal lumbar interbody fusion using the n-HA/PA66 cage, and their preoperative and postoperative clinical outcomes were analyzed. The patients were followed up for 2, 4, 6 and 8 months after operation, during which the CR and CT film of lumbar vertebra were checked to get relative height of vertebral space, Taillard index,index of lumbar spinal curvature,angle of segmental and full lumbar lordosis. The data were analyzed respectively with pair t-test, analysis of variance or LSD-t-test. All the patients were followed up, and the duraion ranged from 8 to 13 months, with a mean of 11.32 months. There were significant differences in relative height of vertebral space, Taillard index, index of lumbar spinal curvature, angle of segmental and full lumbar lordosis after surgery, but there were no significant differences in different periods after operation. The fusion time of lumbar ranged from 4 to 8 months. The n-HA/PA66 cage can recover and maintain lumbar normal stability with higher rate of fusion and less complications.

Functional Analyses of NSF1 in Wine Yeast Using Interconnected Correlation Clustering and Molecular Analyses

PubMed Central

Bessonov, Kyrylo; Walkey, Christopher J.; Shelp, Barry J.; van Vuuren, Hennie J. J.; Chiu, David; van der Merwe, George

2013-01-01

Analyzing time-course expression data captured in microarray datasets is a complex undertaking as the vast and complex data space is represented by a relatively low number of samples as compared to thousands of available genes. Here, we developed the Interdependent Correlation Clustering (ICC) method to analyze relationships that exist among genes conditioned on the expression of a specific target gene in microarray data. Based on Correlation Clustering, the ICC method analyzes a large set of correlation values related to gene expression profiles extracted from given microarray datasets. ICC can be applied to any microarray dataset and any target gene. We applied this method to microarray data generated from wine fermentations and selected NSF1, which encodes a C2H2 zinc finger-type transcription factor, as the target gene. The validity of the method was verified by accurate identifications of the previously known functional roles of NSF1. In addition, we identified and verified potential new functions for this gene; specifically, NSF1 is a negative regulator for the expression of sulfur metabolism genes, the nuclear localization of Nsf1 protein (Nsf1p) is controlled in a sulfur-dependent manner, and the transcription of NSF1 is regulated by Met4p, an important transcriptional activator of sulfur metabolism genes. The inter-disciplinary approach adopted here highlighted the accuracy and relevancy of the ICC method in mining for novel gene functions using complex microarray datasets with a limited number of samples. PMID:24130853

Cornell Center for Materials Research - An NSF MRSEC

Science.gov Websites

Cornell Center for Materials Research Cornell Center for Materials Research | An NSF MRSEC Search Research Atomic Membranes for 3D Systems Structured Materials for Strong Light-Matter Interactions Mechanisms, Materials, and Devices for Spin Manipulation Seed Projects - Exploratory Research Acknowledging

Educational Outreach by the NSF Polymers Program

NASA Astrophysics Data System (ADS)

Lovinger, Andrew J.

2002-03-01

Education and outreach have been NSF priority areas over the last few years. Reviewers of all proposals are explicitly asked to evaluate not only the "intellectual merit" of a research proposal but also its "broader impacts", including specifically "integration of research and education". The NSF Polymers Program has strongly emphasized these areas and has initiated and supported a wide variety of outreach activities designed to bring out the importance of polymeric materials to diverse communities and to encourage young students to develop interests in this area. Specific activities have included: Workshops and their broad dissemination through the media; press releases on important polymer-related developments; interviews to the scientific and popular press; outreach to Congress; establishment of widely publicized and broadly attended lecture series; funding and support of conferences, symposia, and workshops aimed at students and teachers from kindergarten to graduate school; support of web-based educational projects aimed at the general public and schoolchildren; participation in web-based "ask-the-experts" resources to answer science questions from children or the general public; and personal outreach to middle- and high-schools through talks and demonstrations on polymers and plastics, participation at science fairs, career days, etc.

Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion.

PubMed

Peisajovich, S G; Samuel, O; Shai, Y

2000-03-10

Viral fusion proteins contain a highly hydrophobic segment, named the fusion peptide, which is thought to be responsible for the merging of the cellular and viral membranes. Paramyxoviruses are believed to contain a single fusion peptide at the N terminus of the F1 protein. However, here we identified an additional internal segment in the Sendai virus F1 protein (amino acids 214-226) highly homologous to the fusion peptides of HIV-1 and RSV. A synthetic peptide, which includes this region, was found to induce membrane fusion of large unilamellar vesicles, at concentrations where the known N-terminal fusion peptide is not effective. A scrambled peptide as well as several peptides from other regions of the F1 protein, which strongly bind to membranes, are not fusogenic. The functional and structural characterization of this active segment suggest that the F1 protein has an additional internal fusion peptide that could participate in the actual fusion event. The presence of homologous regions in other members of the same family suggests that the concerted action of two fusion peptides, one N-terminal and the other internal, is a general feature of paramyxoviruses. Copyright 2000 Academic Press.

NSF Anticipates Pushing Boundaries on Open-Access Plan

ERIC Educational Resources Information Center

Basken, Paul

2013-01-01

The National Science Foundation (NSF), in carrying out the Obama administration's new push for greater public access to research published in scientific journals, will consider exclusivity periods shorter than the 12-month standard in the White House directive, as well as trade-offs involving data-sharing and considerations of publishers'…

Calculations of Excitation Functions of Some Structural Fusion Materials for ( n, t) Reactions up to 50 MeV Energy

NASA Astrophysics Data System (ADS)

Tel, E.; Durgu, C.; Aktı, N. N.; Okuducu, Ş.

2010-06-01

Fusion serves an inexhaustible energy for humankind. Although there have been significant research and development studies on the inertial and magnetic fusion reactor technology, there is still a long way to go to penetrate commercial fusion reactors to the energy market. Tritium self-sufficiency must be maintained for a commercial power plant. For self-sustaining (D-T) fusion driver tritium breeding ratio should be greater than 1.05. So, the working out the systematics of ( n, t) reaction cross sections is of great importance for the definition of the excitation function character for the given reaction taking place on various nuclei at different energies. In this study, ( n, t) reactions for some structural fusion materials such as 27Al, 51V, 52Cr, 55Mn, and 56Fe have been investigated. The new calculations on the excitation functions of 27Al( n, t)25Mg, 51V( n, t)49Ti, 52Cr( n, t)50V, 55Mn( n, t)53Cr and 56Fe( n, t)54Mn reactions have been carried out up to 50 MeV incident neutron energy. In these calculations, the pre-equilibrium and equilibrium effects have been investigated. The pre-equilibrium calculations involve the new evaluated the geometry dependent hybrid model, hybrid model and the cascade exciton model. Equilibrium effects are calculated according to the Weisskopf-Ewing model. Also in the present work, we have calculated ( n, t) reaction cross-sections by using new evaluated semi-empirical formulas developed by Tel et al. at 14-15 MeV energy. The calculated results are discussed and compared with the experimental data taken from the literature.

[Tartrate-sensitive and tartrate-resistant acid phosphatases in Amoeba proteus].

PubMed

Sopina, V A; Beliaeva, T N

2000-01-01

In free-living Amoeba proteus (strain B), acid phosphatase (AcP) was examined by disc-electrophoresis in polyacrylamide gel. The tartrate-sensitive amebian AcP was greatly inhibited by dithiothreitol and Cu2+, and only partly inhibited by sodium orthovanadate, ammonium molybdate, EDTA, disodium salt and Mg2+, Ca2+, Zn2+ and Mn2+. On the contrary, it appeared to be resistant to sulfhydryl reagents--4(hydroxymercury) benzoic acid, sodium salt and N-ethylmaleimide. Unlike the tartrate-sensitive enzyme, the tartrate-resistant AcP was greatly inhibited by EDTA and partly inhibited by dithiothreitol, Mg2+ and Cu2+ (Mn2+ > Cu2+), being activated by orthovanadate, molybdate, sulfhydryl reagents, Mg2+, Ca2+ and Zn2+. Both tartrate-sensitive and tartrate-resistant AcPs lack apparently free SH-groups necessary for their catalytic activities. Using 2-naphthyl phosphate as a substrate at pH 4.5, six AcP electromorphs were revealed in cytosol and sediment, four of these being most frequently localized in the former, and two in the latter. Two other AcP electromorphs were confined to the sediment only. Depending on the quantity of sedimented amoebae making a homogenate (0.5 or 2.0 cm3), that was added to Percoll solution, the lysosomal AcP fraction in polyacrylamide gel was represented by one or two tartrate-sensitive electromorphs. Therefore, tartrate-resistant AcP in A. proteus may be a lysosomal enzyme, while tartrate-resistant AcP may correspond to serine/threonine protein phosphatase.

Summary Report of the NSF/EPA WATERS Network Workshop

EPA Science Inventory

The National Science Foundation (NSF) and The U.S. Environmental Protection Agency (EPA) organized a workshop to support The WATer and Environmental Research Systems (WATERS) Network project. The WATERS Network is a new joint initiative of the environmental engineering and hydrol...

Molecular characterization of the staphylococcal multidrug resistance export protein QacC.

PubMed Central

Paulsen, I T; Brown, M H; Dunstan, S J; Skurray, R A

1995-01-01

The QacC polypeptide is a member of a family of small membrane proteins which confer resistance to toxic compounds. The staphylococcal qacC gene confers resistance to toxic organic cations via proton-dependent export. The membrane topology of the QacC polypeptide was investigated by constructing and analyzing a series of qacC-phoA and qacC-lacZ fusions. From these analyses, most of the predicted features of the QacC protein were verified, although data regarding the possible orientation of the COOH region were not conclusive. The role of the sole cysteine residue, Cys-42, in QacC was studied by using the sulfhydryl reagent N-ethylmaleimide and site-directed mutagenesis. N-Ethylmaleimide was shown to inhibit qacC-mediated ethidium export. Multiple amino acid substitutions were made for Cys-42, and mutations at this location had various effects on resistance specificity. This suggests that the Cys-42 residue may be located near a region of QacC that is involved in substrate recognition. Mutagenesis of conserved residues in QacC indicated that Tyr-59 and Trp-62 also play an essential structural or functional role in QacC. PMID:7751293

Design and synthesis study of the thermo-sensitive poly (N-vinylpyrrolidone-b- N, N-diethylacrylamide).

PubMed

Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen

2018-01-01

The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

Diagnostic Value of Software-Based Image Fusion of Computed Tomography and F18-FDG PET Scans in Patients with Malignant Lymphoma

PubMed Central

Henninger, B.; Putzer, D.; Kendler, D.; Uprimny, C.; Virgolini, I.; Gunsilius, E.; Bale, R.

2012-01-01

Aim. The purpose of this study was to evaluate the accuracy of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET), computed tomography (CT), and software-based image fusion of both modalities in the imaging of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). Methods. 77 patients with NHL (n = 58) or HD (n = 19) underwent a FDG PET scan, a contrast-enhanced CT, and a subsequent digital image fusion during initial staging or followup. 109 examinations of each modality were evaluated and compared to each other. Conventional staging procedures, other imaging techniques, laboratory screening, and follow-up data constituted the reference standard for comparison with image fusion. Sensitivity and specificity were calculated for CT and PET separately. Results. Sensitivity and specificity for detecting malignant lymphoma were 90% and 76% for CT and 94% and 91% for PET, respectively. A lymph node region-based analysis (comprising 14 defined anatomical regions) revealed a sensitivity of 81% and a specificity of 97% for CT and 96% and 99% for FDG PET, respectively. Only three of 109 image fusion findings needed further evaluation (false positive). Conclusion. Digital fusion of PET and CT improves the accuracy of staging, restaging, and therapy monitoring in patients with malignant lymphoma and may reduce the need for invasive diagnostic procedures. PMID:22654631

5 CFR 5301.104 - Participation in NSF-supported conferences.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Participation in NSF-supported conferences. 5301.104 Section 5301.104 Administrative Personnel NATIONAL SCIENCE FOUNDATION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE NATIONAL SCIENCE FOUNDATION § 5301.104 Participation in...

5 CFR 5301.104 - Participation in NSF-supported conferences.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Participation in NSF-supported conferences. 5301.104 Section 5301.104 Administrative Personnel NATIONAL SCIENCE FOUNDATION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE NATIONAL SCIENCE FOUNDATION § 5301.104 Participation in...

5 CFR 5301.104 - Participation in NSF-supported conferences.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Participation in NSF-supported conferences. 5301.104 Section 5301.104 Administrative Personnel NATIONAL SCIENCE FOUNDATION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE NATIONAL SCIENCE FOUNDATION § 5301.104 Participation in...

5 CFR 5301.104 - Participation in NSF-supported conferences.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Participation in NSF-supported conferences. 5301.104 Section 5301.104 Administrative Personnel NATIONAL SCIENCE FOUNDATION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE NATIONAL SCIENCE FOUNDATION § 5301.104 Participation in...

5 CFR 5301.104 - Participation in NSF-supported conferences.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Participation in NSF-supported conferences. 5301.104 Section 5301.104 Administrative Personnel NATIONAL SCIENCE FOUNDATION SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE NATIONAL SCIENCE FOUNDATION § 5301.104 Participation in...

Energetics and Kinetics of trans-SNARE Zippering

NASA Astrophysics Data System (ADS)

Rebane, Aleksander A.; Shu, Tong; Krishnakumar, Shyam; Rothman, James E.; Zhang, Yongli

Synaptic exocytosis relies on assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins into a four-helix bundle to drive membrane fusion. Complementary SNAREs anchored to the synaptic vesicle (v-SNARE) and the plasma membrane (t-SNARE) associate from their N-termini, transiting a half-assembled intermediate (trans-SNARE), and ending at their C-termini with a rapid power stroke that leads to membrane fusion. Although cytosolic SNARE assembly has been characterized, it remains unknown how membranes modulate the energetics and kinetics of SNARE assembly. Here, we present optical tweezers measurements on folding of single membrane proteins in phospholipid bilayers. To our knowledge, this is the first such report. We measured the energetics, kinetics, and assembly intermediates of trans-SNAREs formed between a t-SNARE inserted into a bead-supported bilayer and a v-SNARE in a nanodisc. We found that the repulsive force of the apposed membranes increases the lifetime of the half-assembled intermediate. Our findings provide a single-molecule platform to study the regulation of trans-SNARE assembly by proteins that act on the half-assembled state, and thus reveal the mechanistic basis of the speed and high fidelity of synaptic transmission. This work was supported by US National Institutes of Health Grants F31 GM119312-01 (to A.A.R) and R01 GM093341 (to Y.Z.).

78 FR 58569 - Notice of Meeting; NSF Synchrotron Subcommittee of the Advisory Committee for Mathematical and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... NATIONAL SCIENCE FOUNDATION Notice of Meeting; NSF Synchrotron Subcommittee of the Advisory Committee for Mathematical and Physical Sciences The National Science Foundation (NSF) announces the...--Patricia Dehmer, DOE 3. Biology/biomaterials talk--importance of materials research facilities--Pupa...

Bill sets NSF on path to double its budget

NASA Astrophysics Data System (ADS)

Showstack, Randy

The US. National Science Foundation (NSF) is one step closer to having its budget more than doubled over the next five years, thanks to legislation approved 14 November by both houses of Congress.President George W. Bush is expected to sign the bill into law.

78 FR 12044 - DOE/NSF Nuclear Science Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... DEPARTMENT OF ENERGY DOE/NSF Nuclear Science Advisory Committee AGENCY: Office of Science... Nuclear Science Advisory Committee (NSAC). The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat... Energy and the National Science Foundation on scientific priorities within the field of basic nuclear...

Fusions between green fluorescent protein and beta-glucuronidase as sensitive and vital bifunctional reporters in plants.

PubMed

Quaedvlieg, N E; Schlaman, H R; Admiraal, P C; Wijting, S E; Stougaard, J; Spaink, H P

1998-07-01

By fusing the genes encoding green fluorescent protein (GFP) and beta-glucuronidase (GUS) we have created a set of bifunctional reporter constructs which are optimized for use in transient and stable expression studies in plants. This approach makes it possible to combine the advantage of GUS, its high sensitivity in histochemical staining, with the advantages of GFP as a vital marker. The fusion proteins were functional in transient expression studies in tobacco using either DNA bombardment or potato virus X as a vector, and in stably transformed Arabidopsis thaliana and Lotus japonicus plants. The results show that high level of expression does not interfere with efficient stable transformation in A. thaliana and L. japonicus. Using confocal laser scanning microscopy we show that the fusion constructs are very suitable for promoter expression studies in all organs of living plants, including root nodules. The use of these reporter constructs in the model legume L. japonicus offers exciting new possibilities for the study of the root nodulation process.

Fusions between green fluorescent protein and beta-glucuronidase as sensitive and vital bifunctional reporters in plants.

PubMed

Quaedvlieg, N E; Schlaman, H R; Admiraal, P C; Wijting, S E; Stougaard, J; Spaink, H P

1998-11-01

By fusing the genes encoding green fluorescent protein (GFP) and beta-glucuronidase (GUS) we have created a set of bifunctional reporter constructs which are optimized for use in transient and stable expression studies in plants. This approach makes it possible to combine the advantage of GUS, its high sensitivity in histochemical staining, with the advantages of GFP as a vital marker. The fusion proteins were functional in transient expression studies in tobacco using either DNA bombardment or potato virus X as a vector, and in stably transformed Arabidopsis thaliana and Lotus japonicus plants. The results show that high level of expression does not interfere with efficient stable transformation in A. thaliana and L. japonicus. Using confocal laser scanning microscopy we show that the fusion constructs are very suitable for promoter expression studies in all organs of living plants, including root nodules. The use of these reporter constructs in the model legume L. japonicus offers exciting new possibilities for the study of the root nodulation process.

NSF's Perspective on Space Weather Research for Building Forecasting Capabilities

NASA Astrophysics Data System (ADS)

Bisi, M. M.; Pulkkinen, A. A.; Bisi, M. M.; Pulkkinen, A. A.; Webb, D. F.; Oughton, E. J.; Azeem, S. I.

2017-12-01

Space weather research at the National Science Foundation (NSF) is focused on scientific discovery and on deepening knowledge of the Sun-Geospace system. The process of maturation of knowledge base is a requirement for the development of improved space weather forecast models and for the accurate assessment of potential mitigation strategies. Progress in space weather forecasting requires advancing in-depth understanding of the underlying physical processes, developing better instrumentation and measurement techniques, and capturing the advancements in understanding in large-scale physics based models that span the entire chain of events from the Sun to the Earth. This presentation will provide an overview of current and planned programs pertaining to space weather research at NSF and discuss the recommendations of the Geospace Section portfolio review panel within the context of space weather forecasting capabilities.

The 1983-1984 NSF Chautauqua-Type Short Course Program.

ERIC Educational Resources Information Center

Zeitler, William R.; Ogletree, Owen, Jr.

1984-01-01

National Science Foundation (NSF) Chautauqua-type short courses offer undergraduate science teachers the opportunity to absorbe new ideas from highly respected scholars. A complete list of courses, course directors, locations, dates, and registration fees for the 1983-84 program is provided. Subject areas include: instructional composting, cells…

Development of Sintered Si3N4 for High Performance Thermomechanical Applications.

DTIC Science & Technology

1984-01-01

noted( 17) that final grain size of sintered Si3 N4 is quite sensitive to both temperature and time at temperature. The sintering of Si NI containing...Characterization of Ube-SN-E0 Si3 N4 Chemical Analysis Lot A-10 Lot A-18 N (alkali fusion) wt . % 38 38 0 (inert gas fusion) wt . % 1.2 1.4 C (inert gas fusion) wt ...temperature stutral applications except for the high creep rate, Which is of the ame order a NC-13. The sintering of -qfiN4ontaning 5 wt % LiAIq0 1and

45 CFR 674.6 - Submission of information to NSF.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Submission of information to NSF. 674.6 Section 674.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION... expedition organizers pursuant to § 674.5(b) shall be furnished to the National Science Foundation's Office...

Different Effects of NSF and PCE Superplasticizer on Adsorption, Dynamic Yield Stress and Thixotropy of Cement Pastes

PubMed Central

2018-01-01

This study compares the differences and similarities of two types of superplasticizers—NSF (Naphthalene Sulfonate Formaldehyde) and PCE (PolyCarboxylate Ester)—in fresh cement paste systems, in terms of adsorption, dynamic yield stress, and thixotropic index. Results show that with either NSF or PCE addition, the more superplasticizer is added, the more it is adsorbed and the more it remains in the interstitial pore solution. The dynamic yield stress and thixotropic index also decrease with increasing addition the amount of either superplasticizer. However, NSF is less efficient in decreasing the dynamic yield stress than PCE. More importantly, the decreasing patterns of dynamic yield stress and thixotropic index are different with NSF and PCE additions; this is tied to the adsorption and dispersing mechanisms of these two types of superplasticizers. PMID:29710782

SNARE interactions in membrane trafficking: a perspective from mammalian central synapses.

PubMed

Kavalali, Ege T

2002-10-01

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock-and-key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as the synaptic core complex, is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non-cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short-term synaptic plasticity. Copyright 2002 Wiley Periodicals, Inc.

Higgs boson gluon-fusion production beyond threshold in N 3LO QCD

DOE PAGES

Anastasiou, Charalampos; Duhr, Claude; Dulat, Falko; ...

2015-03-18

In this study, we compute the gluon fusion Higgs boson cross-section at N 3LO through the second term in the threshold expansion. This calculation constitutes a major milestone towards the full N 3LO cross section. Our result has the best formal accuracy in the threshold expansion currently available, and includes contributions from collinear regions besides subleading corrections from soft and hard regions, as well as certain logarithmically enhanced contributions for general kinematics. We use our results to perform a critical appraisal of the validity of the threshold approximation at N 3LO in perturbative QCD.

Positional effects of fusion partners on the yield and solubility of MBP fusion proteins

PubMed Central

Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S.

2015-01-01

Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that 1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and 2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. PMID:25782741

The NSF Cybersecurity Center of Excellence: Translating Identity Management and Cybersecurity into Scientific Collaboration

NASA Astrophysics Data System (ADS)

Welch, V.

2016-12-01

Scientists care deeply about their collaborations: who is a member, who can access, produce, and correct data, and manager instruments critical to their science missions. The communities of cybersecurity and identity management professionals develop tools to support collaborations and the undertaking of trustworthy science, but there are large cultural and linguistic gaps between these communities and the scientists they service. The National Science Foundation has recently funded a NSF Cybersecurity Center of Excellence to help its community of projects by providing leadership and addressing the challenges of trustworthy science. A key goal of this NSF Center has been translating between the goals of the science community into requirements and risks understood by identity management and cybersecurity communities. This talk will give an update on the Center's efforts and other services it provides to the NSF community to bridge these cultures.

Optical Science and Engineering. New Directions and Opportunities in Research and Education. NSF Workshop (Arlington, VA, May 23-24, 1994).

ERIC Educational Resources Information Center

National Science Foundation, Arlington, VA.

The National Science Foundation (NSF) workshop on Optical Science and Engineering was organized to examine approaches NSF could use to identify opportunities in optical science, engineering, and education that meet both the mission of NSF and its broader national goals. The workshop participants identified opportunities where optical science and…

Detection of EML4-ALK fusion gene in Chinese non-small cell lung cancer by using a sensitive quantitative real-time reverse transcriptase PCR technique.

PubMed

Fu, Sha; Wang, Fang; Shao, Qiong; Zhang, Xu; Duan, Li-Ping; Zhang, Xiao; Zhang, Li; Shao, Jian-Yong

2015-04-01

Anaplastic lymphoma kinase (ALK) rearrangement is present in approximately 5% of lung adenocarcinoma. Clinical trials on ALK inhibitor phase I to III have shown an interesting disease control rate and acceptable tolerability in ALK rearrangement patients. In clinical application, the precise diagnostic strategy for identifying ALK rearrangements remains to be determined. In this study, ALK rearrangement was screened by using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), direct sequencing, 2 fluorescence in situ hybridization (FISH) assays, and immunohistochemistry in 173 lung adenocarcinomas. We identified 18 cases (10.4%) with EML4-ALK fusion-positive by qRT-PCR, and all were positive for EML4-ALK fusion gene validated by direct sequencing. The result was consistent with that of other methods. Furthermore, of the 18 EML4-ALK fusion-positive cases, 16 (9.2%) were positive by using EML4-ALK fusion probe FISH, and 15 (8.7%) were positive by using ALK break-apart probe FISH and immunohistochemistry staining. Of the 18 ALK fusion-positive lung adenocarcinomas, 8 cases (44.4%) were histologically diagnosed as subtypes of cribriform adenocarcinoma, 7 cases (38.9%) as cribriform adenocarcinoma mixed with papillary and/or mucinous pattern, 2 cases (11.1%) as papillary adenocarcinoma, and 1 case (5.6%) as mucinous adenocarcinoma. In the present study, the ALK rearrangement frequency detected by qRT-PCR in Chinese NSCLC patients was higher than that in the western populations. QRT-PCR is a rapid, sensitive technology that could be used as a screening tool for identifying EML4-ALK fusion-positive NSCLC patients who would be sensitive for receiving ALK inhibitor therapy.

Fusion Products of { s} { l} N Symmetric Power Representations and Kostka Polynomials

NASA Astrophysics Data System (ADS)

Kedem, Rinat

2004-10-01

We explain the relation between the Feigin-Loktev fusion product and the graded multiplicities of Specht modules in the integer cohomology ring of the GLN generalized flag manifold. We use only very basic notions, most notably the Schur-Weyl duality and the description of the cohomology ring as a quotient of the polynomial ring in N variables.

High Sensitive pH Sensor Based on AlInN/GaN Heterostructure Transistor.

PubMed

Dong, Yan; Son, Dong-Hyeok; Dai, Quan; Lee, Jun-Hyeok; Won, Chul-Ho; Kim, Jeong-Gil; Chen, Dunjun; Lee, Jung-Hee; Lu, Hai; Zhang, Rong; Zheng, Youdou

2018-04-24

The AlInN/GaN high-electron-mobility-transistor (HEMT) indicates better performances compared with the traditional AlGaN/GaN HEMTs. The present work investigated the pH sensor functionality of an analogous HEMT AlInN/GaN device with an open gate. It was shown that the Al 0.83 In 0.17 N/GaN device demonstrates excellent pH sense functionality in aqueous solutions, exhibiting higher sensitivity (−30.83 μA/pH for AlInN/GaN and −4.6 μA/pH for AlGaN/GaN) and a faster response time, lower degradation and good stability with respect to the AlGaN/GaN device, which is attributed to higher two-dimensional electron gas (2DEG) density and a thinner barrier layer in Al 0.83 In 0.17 N/GaN owning to lattice matching. On the other hand, the open gate geometry was found to affect the pH sensitivity obviously. Properly increasing the width and shortening the length of the open gate area could enhance the sensitivity. However, when the open gate width is too larger or too small, the pH sensitivity would be suppressed conversely. Designing an optimal ratio of the width to the length is important for achieving high sensitivity. This work suggests that the AlInN/GaN-based 2DEG carrier modulated devices would be good candidates for high-performance pH sensors and other related applications.

Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal Assembly.

PubMed

Rebane, Aleksander A; Wang, Bigeng; Ma, Lu; Qu, Hong; Coleman, Jeff; Krishnakumar, Shyam; Rothman, James E; Zhang, Yongli

2018-02-16

Synaptic exocytosis relies on assembly of three soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins into a parallel four-helix bundle to drive membrane fusion. SNARE assembly occurs by stepwise zippering of the vesicle-associated SNARE (v-SNARE) onto a binary SNARE complex on the target plasma membrane (t-SNARE). Zippering begins with slow N-terminal association followed by rapid C-terminal zippering, which serves as a power stroke to drive membrane fusion. SNARE mutations have been associated with numerous diseases, especially neurological disorders. It remains unclear how these mutations affect SNARE zippering, partly due to difficulties to quantify the energetics and kinetics of SNARE assembly. Here, we used single-molecule optical tweezers to measure the assembly energy and kinetics of SNARE complexes containing single mutations I67T/N in neuronal SNARE synaptosomal-associated protein of 25kDa (SNAP-25B), which disrupt neurotransmitter release and have been implicated in neurological disorders. We found that both mutations significantly reduced the energy of C-terminal zippering by ~10 k B T, but did not affect N-terminal assembly. In addition, we observed that both mutations lead to unfolding of the C-terminal region in the t-SNARE complex. Our findings suggest that both SNAP-25B mutations impair synaptic exocytosis by destabilizing SNARE assembly, rather than stabilizing SNARE assembly as previously proposed. Therefore, our measurements provide insights into the molecular mechanism of the disease caused by SNARE mutations. Copyright © 2017 Elsevier Ltd. All rights reserved.

45 CFR 680.12 - One-year NSF post-employment restrictions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 680.12 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION NATIONAL SCIENCE FOUNDATION RULES OF PRACTICE AND STATUTORY CONFLICT-OF-INTEREST EXEMPTIONS Rules of Practice for the National Science Foundation § 680.12 One-year NSF post-employment restrictions...

Dr. Tulga Ersal at NSF Workshop Accessible Remote Testbeds ART'15

Science.gov Websites

;Enabling High-Fidelity Closed-Loop Integration of Remotely Accessible Testbeds" at the NSF Sponsored project (2010-2013) "Internet-Distributed Hardware-in-the-Loop Simulation". Sponsored by U.S

Fusion Power measurement at ITER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertalot, L.; Barnsley, R.; Krasilnikov, V.

2015-07-01

Nuclear fusion research aims to provide energy for the future in a sustainable way and the ITER project scope is to demonstrate the feasibility of nuclear fusion energy. ITER is a nuclear experimental reactor based on a large scale fusion plasma (tokamak type) device generating Deuterium - Tritium (DT) fusion reactions with emission of 14 MeV neutrons producing up to 700 MW fusion power. The measurement of fusion power, i.e. total neutron emissivity, will play an important role for achieving ITER goals, in particular the fusion gain factor Q related to the reactor performance. Particular attention is given also tomore » the development of the neutron calibration strategy whose main scope is to achieve the required accuracy of 10% for the measurement of fusion power. Neutron Flux Monitors located in diagnostic ports and inside the vacuum vessel will measure ITER total neutron emissivity, expected to range from 1014 n/s in Deuterium - Deuterium (DD) plasmas up to almost 10{sup 21} n/s in DT plasmas. The neutron detection systems as well all other ITER diagnostics have to withstand high nuclear radiation and electromagnetic fields as well ultrahigh vacuum and thermal loads. (authors)« less

Global nanotechnology development from 1991 to 2012: patents, scientific publications, and effect of NSF funding

NASA Astrophysics Data System (ADS)

Chen, Hsinchun; Roco, Mihail C.; Son, Jaebong; Jiang, Shan; Larson, Catherine A.; Gao, Qiang

2013-09-01

In a relatively short interval for an emerging technology, nanotechnology has made a significant economic impact in numerous sectors including semiconductor manufacturing, catalysts, medicine, agriculture, and energy production. A part of the United States (US) government investment in basic research has been realized in the last two decades through the National Science Foundation (NSF), beginning with the nanoparticle research initiative in 1991 and continuing with support from the National Nanotechnology Initiative after fiscal year 2001. This paper has two main goals: (a) present a longitudinal analysis of the global nanotechnology development as reflected in the United States Patent and Trade Office (USPTO) patents and Web of Science (WoS) publications in nanoscale science and engineering (NSE) for the interval 1991-2012; and (b) identify the effect of basic research funded by NSF on both indicators. The interval has been separated into three parts for comparison purposes: 1991-2000, 2001-2010, and 2011-2012. The global trends of patents and scientific publications are presented. Bibliometric analysis, topic analysis, and citation network analysis methods are used to rank countries, institutions, technology subfields, and inventors contributing to nanotechnology development. We then, examined how these entities were affected by NSF funding and how they evolved over the past two decades. Results show that dedicated NSF funding used to support nanotechnology R&D was followed by an increased number of relevant patents and scientific publications, a greater diversity of technology topics, and a significant increase of citations. The NSF played important roles in the inventor community and served as a major contributor to numerous nanotechnology subfields.

78 FR 46330 - DOE/NSF High Energy Physics Advisory Panel

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Positional effects of fusion partners on the yield and solubility of MBP fusion proteins.

PubMed

Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S

2015-06-01

Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that (1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and (2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. Published by Elsevier Inc.

Advancing Capabilities for Understanding the Earth System Through Intelligent Systems, the NSF Perspective

NASA Astrophysics Data System (ADS)

Gil, Y.; Zanzerkia, E. E.; Munoz-Avila, H.

2015-12-01

The National Science Foundation (NSF) Directorate for Geosciences (GEO) and Directorate for Computer and Information Science (CISE) acknowledge the significant scientific challenges required to understand the fundamental processes of the Earth system, within the atmospheric and geospace, Earth, ocean and polar sciences, and across those boundaries. A broad view of the opportunities and directions for GEO are described in the report "Dynamic Earth: GEO imperative and Frontiers 2015-2020." Many of the aspects of geosciences research, highlighted both in this document and other community grand challenges, pose novel problems for researchers in intelligent systems. Geosciences research will require solutions for data-intensive science, advanced computational capabilities, and transformative concepts for visualizing, using, analyzing and understanding geo phenomena and data. Opportunities for the scientific community to engage in addressing these challenges are available and being developed through NSF's portfolio of investments and activities. The NSF-wide initiative, Cyberinfrastructure Framework for 21st Century Science and Engineering (CIF21), looks to accelerate research and education through new capabilities in data, computation, software and other aspects of cyberinfrastructure. EarthCube, a joint program between GEO and the Advanced Cyberinfrastructure Division, aims to create a well-connected and facile environment to share data and knowledge in an open, transparent, and inclusive manner, thus accelerating our ability to understand and predict the Earth system. EarthCube's mission opens an opportunity for collaborative research on novel information systems enhancing and supporting geosciences research efforts. NSF encourages true, collaborative partnerships between scientists in computer sciences and the geosciences to meet these challenges.

The life cycle of platelet granules.

PubMed

Sharda, Anish; Flaumenhaft, Robert

2018-01-01

Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

Our Story | Materials Research Laboratory at UCSB: an NSF MRSEC

Science.gov Websites

this site Materials Research Laboratory at UCSB: an NSF MRSEC logo Materials Research Laboratory at & Workshops Visitor Info Research IRG-1: Magnetic Intermetallic Mesostructures IRG 2: Polymeric Seminars Publications MRL Calendar Facilities Computing Energy Research Facility Microscopy &

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... DEPARTMENT OF ENERGY DOE/NSF High Energy Physics Advisory Panel AGENCY: Office of Science... High Energy Physics Advisory Panel (HEPAP). The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat... INFORMATION CONTACT: John Kogut, Executive Secretary; High Energy Physics Advisory Panel; U.S. Department of...

Release of kinesin from vesicles by hsc70 and regulation of fast axonal transport

NASA Technical Reports Server (NTRS)

Tsai, M. Y.; Morfini, G.; Szebenyi, G.; Brady, S. T.

2000-01-01

The nature of kinesin interactions with membrane-bound organelles and mechanisms for regulation of kinesin-based motility have both been surprisingly difficult to define. Most kinesin is recovered in supernatants with standard protocols for purification of motor proteins, but kinesin recovered on membrane-bound organelles is tightly bound. Partitioning of kinesin between vesicle and cytosolic fractions is highly sensitive to buffer composition. Addition of either N-ethylmaleimide or EDTA to homogenization buffers significantly increased the fraction of kinesin bound to organelles. Given that an antibody against kinesin light chain tandem repeats also releases kinesin from vesicles, these observations indicated that specific cytoplasmic factors may regulate kinesin release from membranes. Kinesin light tandem repeats contain DnaJ-like motifs, so the effects of hsp70 chaperones were evaluated. Hsc70 released kinesin from vesicles in an MgATP-dependent and N-ethylmaleimide-sensitive manner. Recombinant kinesin light chains inhibited kinesin release by hsc70 and stimulated the hsc70 ATPase. Hsc70 actions may provide a mechanism to regulate kinesin function by releasing kinesin from cargo in specific subcellular domains, thereby effecting delivery of axonally transported materials.

DUX4 Immunohistochemistry Is a Highly Sensitive and Specific Marker for CIC-DUX4 Fusion-positive Round Cell Tumor.

PubMed

Siegele, Bradford; Roberts, Jon; Black, Jennifer O; Rudzinski, Erin; Vargas, Sara O; Galambos, Csaba

2017-03-01

The histologic differential diagnosis of pediatric and adult round cell tumors is vast and includes the recently recognized entity CIC-DUX4 fusion-positive round cell tumor. The diagnosis of CIC-DUX4 tumor can be suggested by light microscopic and immunohistochemical features, but currently, definitive diagnosis requires ancillary genetic testing such as conventional karyotyping, fluorescence in situ hybridization, or molecular methods. We sought to determine whether DUX4 expression would serve as a fusion-specific immunohistochemical marker distinguishing CIC-DUX4 tumor from potential histologic mimics. A cohort of CIC-DUX4 fusion-positive round cell tumors harboring t(4;19)(q35;q13) and t(10;19)(q26;q13) translocations was designed, with additional inclusion of a case with a translocation confirmed to involve the CIC gene without delineation of the partner. Round cell tumors with potentially overlapping histologic features were also collected. Staining with a monoclonal antibody raised against the C-terminus of the DUX4 protein was applied to all cases. DUX4 immunohistochemistry exhibited diffuse, crisp, strong nuclear staining in all CIC-DUX4 fusion-positive round cell tumors (5/5, 100% sensitivity), and exhibited negative staining in nuclei of all of the other tested round cell tumors, including 20 Ewing sarcomas, 1 Ewing-like sarcoma, 11 alveolar rhabdomyosarcomas, 9 embryonal rhabdomyosarcomas, 12 synovial sarcomas, 7 desmoplastic small round cell tumors, 3 malignant rhabdoid tumors, 9 neuroblastomas, and 4 clear cell sarcomas (0/76, 100% specificity). Thus, in our experience, DUX4 immunostaining distinguishes CIC-DUX4 tumors from other round cell mimics. We recommend its use when CIC-DUX4 fusion-positive round cell tumor enters the histologic differential diagnosis.

Fusion-neutron measurements for magnetized liner inertial fusion experiments on the Z accelerator

DOE PAGES

Hahn, K. D.; Chandler, G. A.; Ruiz, C. L.; ...

2016-05-26

Several magnetized liner inertial fusion (MagLIF) experiments have been conducted on the Z accelerator at Sandia National Laboratories since late 2013. Measurements of the primary DD (2.45 MeV) neutrons for these experiments suggest that the neutron production is thermonuclear. Primary DD yields up to 3e12 with ion temperatures ~2-3 keV have been achieved. Measurements of the secondary DT (14 MeV) neutrons indicate that the fuel is significantly magnetized. Measurements of down-scattered neutrons from the beryllium liner suggest ρR liner ~ 1g/cm 2. Neutron bang times, estimated from neutron time-of-flight (nTOF) measurements, coincide with peak x-ray production. Furthermore, plans to improvemore » and expand the Z neutron diagnostic suite include neutron burn-history diagnostics, increased sensitivity and higher precision nTOF detectors, and neutron recoil-based yield and spectral measurements.« less

Fusion-neutron measurements for magnetized liner inertial fusion experiments on the Z accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, K. D.; Chandler, G. A.; Ruiz, C. L.

Several magnetized liner inertial fusion (MagLIF) experiments have been conducted on the Z accelerator at Sandia National Laboratories since late 2013. Measurements of the primary DD (2.45 MeV) neutrons for these experiments suggest that the neutron production is thermonuclear. Primary DD yields up to 3e12 with ion temperatures ~2-3 keV have been achieved. Measurements of the secondary DT (14 MeV) neutrons indicate that the fuel is significantly magnetized. Measurements of down-scattered neutrons from the beryllium liner suggest ρR liner ~ 1g/cm 2. Neutron bang times, estimated from neutron time-of-flight (nTOF) measurements, coincide with peak x-ray production. Furthermore, plans to improvemore » and expand the Z neutron diagnostic suite include neutron burn-history diagnostics, increased sensitivity and higher precision nTOF detectors, and neutron recoil-based yield and spectral measurements.« less

The SC State NSF PAARE Program

NASA Astrophysics Data System (ADS)

Walter, Donald; Ajello, Marco; Brittain, Sean; Cash, Jennifer; Fogle, Bryan; Hartmann, Dieter; Ho, Shirley; Howell, Steve; King, Jeremy; Leising, Mark; Smith, Daniel

2018-01-01

We report on the activities of our NSF PAARE program during Year 3 of the project. Our partnership under this award includes South Carolina State University (a Historically Black College/University), Clemson University (a Ph.D. granting institution) and individual investigators at NASA Ames and elsewhere. Our partnership with the Citizen CATE Experiment and involvement in the total solar eclipse which passed through our campus on August 21, 2017, will be discussed. The PAARE project continues to strengthen our partnership with Clemson. We are close to completing a memorandum of agreement between the two institutions that will allow for the seamless transfer of an undergraduate from SC State to Clemson’s graduate program in physics and astronomy. Additionally, we have worked together under the Citizen CATE project and through other research activities. SC State is a member of the National Astronomy Consortium (NAC) and participates through its faculty and undergraduates, one of whom (Wesley Red) is reporting on his summer internship at this conference. We also served as the state coordinator for South Carolina for the Citizen CATE Experiment. The August 21st path of totality crossed through our campus and the campus of our partner Clemson University. Additional colleges, universities and citizen scientist groups partnered with us to provide 7 sites of coverage across South Carolina from the foothills of the Appalachian mountains to the Atlantic Ocean near the site of departure of the shadow from the continental U.S. Support for this work includes our NSF PAARE award AST-1358913 as well as resources and support provided by Clemson University and the National Optical Astronomy Observatory. CATE work has been supported by NASA SMD award NNX16AB92A to the National Solar Observatory. Additional details can be found at: http://physics.scsu.edu

Nuclear science experiments with a bright neutron source from fusion reactions on the OMEGA Laser System

NASA Astrophysics Data System (ADS)

Forrest, C. J.; Knauer, J. P.; Schroeder, W. U.; Glebov, V. Yu.; Radha, P. B.; Regan, S. P.; Sangster, T. C.; Sickles, M.; Stoeckl, C.; Szczepanski, J.

2018-04-01

Subnanosecond impulses of 1013 to 1014 neutrons, produced in direct-drive laser inertial confinement fusion implosions, have been used to irradiate deuterated targets at the OMEGA Laser System (Boehly et al., 1997). The target compounds include heavy water (D2O) and deuterated benzene (C6D6). Yields and energy spectra of neutrons from D(n,2n)p to study the breakup reaction have been measured at a forward angle of θlab = 3 .5∘ ± 3.5° with a sensitive, high-dynamic-range neutron time-of-flight spectrometer to infer the double-differential breakup cross section d2 σ/dE d Ω for 14-MeV D-T fusion neutrons.

45 CFR 680.11 - Staff involvement with NSF proposals and awards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... teaching careers to spend a year or two at NSF and then return to research and teaching, usually at the... investigator and his or her laboratory or group (if any) in the same general field of science, engineering, or...

Dissection of the Role of the Stable Signal Peptide of the Arenavirus Envelope Glycoprotein in Membrane Fusion

PubMed Central

Messina, Emily L.; York, Joanne

2012-01-01

The arenavirus envelope glycoprotein (GPC) retains a stable signal peptide (SSP) as an essential subunit in the mature complex. The 58-amino-acid residue SSP comprises two membrane-spanning hydrophobic regions separated by a short ectodomain loop that interacts with the G2 fusion subunit to promote pH-dependent membrane fusion. Small-molecule compounds that target this unique SSP-G2 interaction prevent arenavirus entry and infection. The interaction between SSP and G2 is sensitive to the phylogenetic distance between New World (Junín) and Old World (Lassa) arenaviruses. For example, heterotypic GPC complexes are unable to support virion entry. In this report, we demonstrate that the hybrid GPC complexes are properly assembled, proteolytically cleaved, and transported to the cell surface but are specifically defective in their membrane fusion activity. Chimeric SSP constructs reveal that this incompatibility is localized to the first transmembrane segment of SSP (TM1). Genetic changes in TM1 also affect sensitivity to small-molecule fusion inhibitors, generating resistance in some cases and inhibitor dependence in others. Our studies suggest that interactions of SSP TM1 with the transmembrane domain of G2 may be important for GPC-mediated membrane fusion and its inhibition. PMID:22438561

Normal myoblast fusion requires myoferlin

PubMed Central

Doherty, Katherine R.; Cave, Andrew; Davis, Dawn Belt; Delmonte, Anthony J.; Posey, Avery; Earley, Judy U.; Hadhazy, Michele; McNally, Elizabeth M.

2014-01-01

Summary Muscle growth occurs during embryonic development and continues in adult life as regeneration. During embryonic muscle growth and regeneration in mature muscle, singly nucleated myoblasts fuse to each other to form myotubes. In muscle growth, singly nucleated myoblasts can also fuse to existing large, syncytial myofibers as a mechanism of increasing muscle mass without increasing myofiber number. Myoblast fusion requires the alignment and fusion of two apposed lipid bilayers. The repair of muscle plasma membrane disruptions also relies on the fusion of two apposed lipid bilayers. The protein dysferlin, the product of the Limb Girdle Muscular Dystrophy type 2 locus, has been shown to be necessary for efficient, calcium-sensitive, membrane resealing. We now show that the related protein myoferlin is highly expressed in myoblasts undergoing fusion, and is expressed at the site of myoblasts fusing to myotubes. Like dysferlin, we found that myoferlin binds phospholipids in a calcium-sensitive manner that requires the first C2A domain. We generated mice with a null allele of myoferlin. Myoferlin null myoblasts undergo initial fusion events, but they form large myotubes less efficiently in vitro, consistent with a defect in a later stage of myogenesis. In vivo, myoferlin null mice have smaller muscles than controls do, and myoferlin null muscle lacks large diameter myofibers. Additionally, myoferlin null muscle does not regenerate as well as wild-type muscle does, and instead displays a dystrophic phenotype. These data support a role for myoferlin in the maturation of myotubes and the formation of large myotubes that arise from the fusion of myoblasts to multinucleate myotubes. PMID:16280346

Burn Control in Fusion Reactors via Isotopic Fuel Tailoring

NASA Astrophysics Data System (ADS)

Boyer, Mark D.; Schuster, Eugenio

2011-10-01

The control of plasma density and temperature are among the most fundamental problems in fusion reactors and will be critical to the success of burning plasma experiments like ITER. Economic and technological constraints may require future commercial reactors to operate with low temperature, high-density plasma, for which the burn condition may be unstable. An active control system will be essential for stabilizing such operating points. In this work, a volume-averaged transport model for the energy and the densities of deuterium and tritium fuel ions, as well as the alpha particles, is used to synthesize a nonlinear feedback controller for stabilizing the burn condition. The controller makes use of ITER's planned isotopic fueling capability and controls the densities of these ions separately. The ability to modulate the DT fuel mix is exploited in order to reduce the fusion power during thermal excursions without the need for impurity injection. By moving the isotopic mix in the plasma away from the optimal 50:50 mix, the reaction rate is slowed and the alpha-particle heating is reduced to desired levels. Supported by the NSF CAREER award program (ECCS-0645086).

Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.

PubMed

Malli, Theodora; Buxhofer-Ausch, Veronika; Rammer, Melanie; Erdel, Martin; Kranewitter, Wolfgang; Rumpold, Holger; Marschon, Renate; Deutschbauer, Sabine; Simonitsch-Klupp, Ingrid; Valent, Peter; Muellner-Ammer, Kirsten; Sebesta, Christian; Birkner, Thomas; Webersinke, Gerald

2016-01-01

Myeloid and lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) abnormalities, also known as 8p11 myeloproliferative syndrome (EMS), represent rare and aggressive disorders, associated with chromosomal aberrations that lead to the fusion of FGFR1 to different partner genes. We report on a third patient with a fusion of the translocated promoter region (TPR) gene, a component of the nuclear pore complex, to FGFR1 due to a novel ins(1;8)(q25;p11p23). The fact that this fusion is a rare but recurrent event in EMS prompted us to examine the localization and transforming potential of the chimeric protein. TPR-FGFR1 localizes in the cytoplasm, although the nuclear pore localization signal of TPR is retained in the fusion protein. Furthermore, TPR-FGFR1 enables cytokine-independent survival, proliferation, and granulocytic differentiation of the interleukin-3 dependent myeloid progenitor cell line 32Dcl3, reflecting the chronic phase of EMS characterized by myeloid hyperplasia. 32Dcl3 cells transformed with the TPR-FGFR1 fusion and treated with increasing concentrations of the tyrosine kinase inhibitors ponatinib (AP24534) and infigratinib (NVP-BGJ398) displayed reduced survival and proliferation with IC50 values of 49.8 and 7.7 nM, respectively. Ponatinib, a multitargeted tyrosine kinase inhibitor, is already shown to be effective against several FGFR1-fusion kinases. Infigratinib, tested only against FGFR1OP2-FGFR1 to date, is also efficient against TPR-FGFR1. Taking its high specificity for FGFRs into account, infigratinib could be beneficial for EMS patients and should be further investigated for the treatment of myeloproliferative neoplasms with FGFR1 abnormalities. © 2015 Wiley Periodicals, Inc.

Breakup and n -transfer effects on the fusion reactions Li,76+Sn,119120 around the Coulomb barrier

NASA Astrophysics Data System (ADS)

Fisichella, M.; Shotter, A. C.; Figuera, P.; Lubian, J.; Di Pietro, A.; Fernandez-Garcia, J. P.; Ferreira, J. L.; Lattuada, M.; Lotti, P.; Musumarra, A.; Pellegriti, M. G.; Ruiz, C.; Scuderi, V.; Strano, E.; Torresi, D.; Zadro, M.

2017-03-01

This paper presents values of complete fusion cross sections deduced from activation measurements for the reactions 6Li+120Sn and 7Li+119Sn , and for a projectile energy range from 17.5 to 28 MeV in the center-of-mass system. A new deconvolution analysis technique is used to link the basic activation data to the actual fusion excitation function. The complete fusion cross sections above the barrier are suppressed by about 70 % and 85 % with respect to the universal fusion function, used as a standard reference, in the 6Li and 7Li induced reactions, respectively. From a comparison of the excitation functions of the two systems at energies below the barrier, no significant differences can be observed, despite the two systems have different n -transfer Q values. This observation is supported by the results of coupled reaction channels (CRC) calculations.

Modeled cost-effectiveness of transforaminal lumbar interbody fusion compared with posterolateral fusion for spondylolisthesis using N(2)QOD data.

PubMed

Carreon, Leah Y; Glassman, Steven D; Ghogawala, Zoher; Mummaneni, Praveen V; McGirt, Matthew J; Asher, Anthony L

2016-06-01

OBJECTIVE Transforaminal lumbar interbody fusion (TLIF) has become the most commonly used fusion technique for lumbar degenerative disorders. This suggests an expectation of better clinical outcomes with this technique, but this has not been validated consistently. How surgical variables and choice of health utility measures drive the cost-effectiveness of TLIF relative to posterolateral fusion (PSF) has not been established. The authors used health utility values derived from Short Form-6D (SF-6D) and EQ-5D and different cost-effectiveness thresholds to evaluate the relative cost-effectiveness of TLIF compared with PSF. METHODS From the National Neurosurgery Quality and Outcomes Database (N(2)QOD), 101 patients with spondylolisthesis who underwent PSF were propensity matched to patients who underwent TLIF. Health-related quality of life measures and perioperative parameters were compared. Because health utility values derived from the SF-6D and EQ-5D questionnaires have been shown to vary in patients with low-back pain, quality-adjusted life years (QALYs) were derived from both measures. On the basis of these matched cases, a sensitivity analysis for the relative cost per QALY of TLIF versus PSF was performed in a series of cost-assumption models. RESULTS Operative time, blood loss, hospital stay, and 30-day and 90-day readmission rates were similar for the TLIF and PSF groups. Both TLIF and PSF significantly improved back and leg pain, Oswestry Disability Index (ODI) scores, and EQ-5D and SF-6D scores at 3 and 12 months postoperatively. At 12 months postoperatively, patients who had undergone TLIF had greater improvements in mean ODI scores (30.4 vs 21.1, p = 0.001) and mean SF-6D scores (0.16 vs 0.11, p = 0.001) but similar improvements in mean EQ-5D scores (0.25 vs 0.22, p = 0.415) as patients treated with PSF. At a cost per QALY threshold of $100,000 and using SF-6D-based QALYs, the authors found that TLIF would be cost-prohibitive compared with PSF at a

124Xe(n,γ)125Xe and 124Xe(n,2n)123Xe measurements for National Ignition Facility

NASA Astrophysics Data System (ADS)

Bhike, Megha; Ludin, Nurin; Tornow, Werner

2015-05-01

The cross section for the 124Xe(n,γ)125Xe reaction has been measured for the first time for neutron energies above 100 keV. In addition, the 124Xe(n,2n)123Xe reaction has been studied between threshold and 14.8 MeV. The results of these measurements provide sensitive diagnostic tools for investigating properties of the inertial confinement fusion plasma in Deuterium-Tritium (DT) capsules at the National Ignition Facility (NIF) located at Lawrence Livermore National Laboratory.

Current trends on 2D materials for photonics devices: an NSF perspective (Conference Presentation)

NASA Astrophysics Data System (ADS)

Fallahi, Mahmoud

2017-05-01

Recent advancements in two-dimensional (2D) materials have opened significant research opportunities in optics and photonics. While the initial focus on 2D materials was on Graphene, new generation of 2D materials such as hexagonal boron nitride (h-BN), transition metal dichalcogenides (TMDCs), monolayer black phosphorous (BP) and other monolayer structures have shown unique electrical and optical properties. For example, h-BN is an insulator, while monolayers of some TMDCs such as MoS2 and WSe2 are direct band-gap semiconductors. Depending on the choice of material compositional and layer variations their optical properties can be engineered, making them particularly attractive as novel light sources, photodetectors, modulators and photovoltaic components, in particular for few photon applications. Plasmonic properties of 2D materials make them suitable for nanophotonics and monolithic integration with other conventional materials. The National Science Foundation (NSF) is a US federal agency dedicated to promote progress of science and engineering. NSF is the funding source for approximately 24 percent of all federally supported basic research conducted by America's colleges and universities. NSF has recently supported several initiatives related to novel 2D material and device research. In this talk, I will first give an overview of the NSF programs and funding opportunities. The second part of the talk will be focused on the programs related to 2D materials for photonic devices and program specific initiatives. Several highlights of the recent achievements and awards in the field of 2D materials for photonic devices will be presented.

Interrelationships between mitochondrial fusion, energy metabolism and oxidative stress during development in Caenorhabditis elegans.

PubMed

Yasuda, Kayo; Hartman, Philip S; Ishii, Takamasa; Suda, Hitoshi; Akatsuka, Akira; Shoyama, Tetsuji; Miyazawa, Masaki; Ishii, Naoaki

2011-01-21

Mitochondria are known to be dynamic structures with the energetically and enzymatically mediated processes of fusion and fission responsible for maintaining a constant flux. Mitochondria also play a role of reactive oxygen species production as a byproduct of energy metabolism. In the current study, interrelationships between mitochondrial fusion, energy metabolism and oxidative stress on development were explored using a fzo-1 mutant defective in the fusion process and a mev-1 mutant overproducing superoxide from mitochondrial electron transport complex II of Caenorhabditis elegans. While growth and development of both single mutants was slightly delayed relative to the wild type, the fzo-1;mev-1 double mutant experienced considerable delay. Oxygen sensitivity during larval development, superoxide production and carbonyl protein accumulation of the fzo-1 mutant were similar to wild type. fzo-1 animals had significantly lower metabolism than did N2 and mev-1. These data indicate that mitochondrial fusion can profoundly affect energy metabolism and development. Copyright © 2010 Elsevier Inc. All rights reserved.

NSF Geosciences Initiatives and Plans Reviewed at Advisory Committee Meeting

NASA Astrophysics Data System (ADS)

Showstack, Randy

2010-10-01

In its semiannual meeting on 6-7 October, the U.S. National Science Foundation's (NSF) Advisory Committee for Geosciences (GEO) reviewed GEO initiatives, programs, and plans, including the GEO directorate's fast and significant response to support research related to various aspects of the Deepwater Horizon oil spill in the Gulf of Mexico through Rapid Response Research (RAPID) awards and other measures. An undercurrent during the meeting was concern about workload stress among GEO staff. Assistant director of geosciences Tim Killeen noted that the proposed budget for fiscal year (FY) 2011, which began on 1 October, would increase directorate funding 7.4% over FY 2010, if the budget is approved by Congress. A continuing resolution in Congress maintains FY 2010 funding levels until at least 3 December. Killeen said NSF's budget request for FY 2012 has been submitted to the White House Office of Management and Budget, adding that although he cannot discuss details of that budget yet, GEO Vision, a long­range strategy document for the directorate released in October 2009, “is reflected in our thinking going forward.”

Career Achievements of NSF Graduate Fellows: The Awardees of 1952-1972.

ERIC Educational Resources Information Center

Harmon, Lindsey R.

The National Science Foundation (NSF) Graduate Fellows of calendar years 1952-1972 were followed up in this study to determine their subsequent career achievements. Career achievements of these individuals are discussed in terms of the following criteria: doctorate attainment, postdoctoral fellowship awards, faculty membership, dissertation…

Evaluation of NSF's International Research Fellowship Program: Final Report

ERIC Educational Resources Information Center

Martinez, Alina; Epstein, Carter; Parsad, Amanda; Whittaker, Karla

2012-01-01

Among the National Science Foundation's (NSF) postdoctoral programs, the International Research Fellowship Program (IRFP) is unique in its emphasis on providing postdoctoral fellows with international research experiences. Established in 1992, IRFP provides financial support to postdoctoral scientists for a research experience abroad lasting…

Optimization of the Efficiency of a Neutron Detector to Measure (α, n) Reaction Cross-Section

NASA Astrophysics Data System (ADS)

Perello, Jesus; Montes, Fernando; Ahn, Tony; Meisel, Zach; Joint InstituteNuclear Astrophysics Team

2015-04-01

Nucleosynthesis, the origin of elements, is one of the greatest mysteries in physics. A recent particular nucleosynthesis process of interest is the charge-particle process (cpp). In the cpp, elements form by nuclear fusion reactions during supernovae. This process of nuclear fusion, (α,n), will be studied by colliding beam elements produced and accelerated at the National Superconducting Cyclotron Laboratory (NSCL) to a helium-filled cell target. The elements will fuse with α (helium nuclei) and emit neutrons during the reaction. The neutrons will be detected for a count of fused-elements, thus providing us the probability of such reactions. The neutrons will be detected using the Neutron Emission Ratio Observer (NERO). Currently, NERO's efficiency varies for neutrons at the expected energy range (0-12 MeV). To study (α,n), NERO's efficiency must be near-constant at these energies. Monte-Carlo N-Particle Transport Code (MCNP6), a software package that simulates nuclear processes, was used to optimize NERO configuration for the experiment. MCNP6 was used to simulate neutron interaction with different NERO configurations at the expected neutron energies. By adding additional 3He detectors and polyethylene, a near-constant efficiency at these energies was obtained in the simulations. With the new NERO configuration, study of the (α,n) reactions can begin, which may explain how elements are formed in the cpp. SROP MSU, NSF, JINA, McNair Society.

Surface sensitization mechanism on negative electron affinity p-GaN nanowires

NASA Astrophysics Data System (ADS)

Diao, Yu; Liu, Lei; Xia, Sihao; Feng, Shu; Lu, Feifei

2018-03-01

The surface sensitization is the key to prepare negative electron affinity photocathode. The thesis emphasizes on the study of surface sensitization mechanism of p-type doping GaN nanowires utilizing first principles based on density function theory. The adsorption energy, work function, dipole moment, geometry structure, electronic structure and optical properties of Mg-doped GaN nanowires surfaces with various coverages of Cs atoms are investigated. The GaN nanowire with Mg doped in core position is taken as the sensitization base. At the initial stage of sensitization, the best adsorption site for Cs atom on GaN nanowire surface is BN, the bridge site of two adjacent N atoms. Surface sensitization generates a p-type internal surface with an n-type surface state, introducing a band bending region which can help reduce surface barrier and work function. With increasing Cs coverage, work functions decrease monotonously and the "Cs-kill" phenomenon disappears. For Cs coverage of 0.75 ML and 1 ML, the corresponding sensitization systems reach negative electron affinity state. Through surface sensitization, the absorption curves are red shifted and the absorption coefficient is cut down. All theoretical calculations can guide the design of negative electron affinity Mg doped GaN nanowires photocathode.

45 CFR 680.11 - Staff involvement with NSF proposals and awards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SCIENCE FOUNDATION NATIONAL SCIENCE FOUNDATION RULES OF PRACTICE Rules of Practice for the National Science Foundation § 680.11 Staff involvement with NSF proposals and awards. (a)(1) Many scientists... field of science, engineering, or education, notwithstanding that the focus of the work may change in...

45 CFR 680.11 - Staff involvement with NSF proposals and awards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SCIENCE FOUNDATION NATIONAL SCIENCE FOUNDATION RULES OF PRACTICE Rules of Practice for the National Science Foundation § 680.11 Staff involvement with NSF proposals and awards. (a)(1) Many scientists... field of science, engineering, or education, notwithstanding that the focus of the work may change in...

45 CFR 680.11 - Staff involvement with NSF proposals and awards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SCIENCE FOUNDATION NATIONAL SCIENCE FOUNDATION RULES OF PRACTICE Rules of Practice for the National Science Foundation § 680.11 Staff involvement with NSF proposals and awards. (a)(1) Many scientists... field of science, engineering, or education, notwithstanding that the focus of the work may change in...

45 CFR 680.11 - Staff involvement with NSF proposals and awards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SCIENCE FOUNDATION NATIONAL SCIENCE FOUNDATION RULES OF PRACTICE Rules of Practice for the National Science Foundation § 680.11 Staff involvement with NSF proposals and awards. (a)(1) Many scientists... field of science, engineering, or education, notwithstanding that the focus of the work may change in...

Comparison of instrumented anterior interbody fusion with instrumented circumferential lumbar fusion.

PubMed

Madan, S S; Boeree, N R

2003-12-01

Posterior lumbar interbody fusion (PLIF) restores disc height, the load bearing ability of anterior ligaments and muscles, root canal dimensions, and spinal balance. It immobilizes the painful degenerate spinal segment and decompresses the nerve roots. Anterior lumbar interbody fusion (ALIF) does the same, but could have complications of graft extrusion, compression and instability contributing to pseudarthrosis in the absence of instrumentation. The purpose of this study was to assess and compare the outcome of instrumented circumferential fusion through a posterior approach [PLIF and posterolateral fusion (PLF)] with instrumented ALIF using the Hartshill horseshoe cage, for comparable degrees of internal disc disruption and clinical disability. It was designed as a prospective study, comparing the outcome of two methods of instrumented interbody fusion for internal disc disruption. Between April 1994 and June 1998, the senior author (N.R.B.) performed 39 instrumented ALIF procedures and 35 instrumented circumferential fusion with PLIF procedures. The second author, an independent assessor (S.M.), performed the entire review. Preoperative radiographic assessment included plain radiographs, magnetic resonance imaging (MRI) and provocative discography in all the patients. The outcome in the two groups was compared in terms of radiological improvement and clinical improvement, measured on the basis of improvement of back pain and work capacity. Preoperatively, patients were asked to fill out a questionnaire giving their demographic details, maximum walking distance and current employment status in order to establish the comparability of the two groups. Patient assessment was with the Oswestry Disability Index, quality of life questionnaire (subjective), pain drawing, visual analogue scale, disability benefit, compensation status, and psychological profile. The results of the study showed a satisfactory outcome (score< or =30) on the subjective (quality of life

Cells with dysfunctional telomeres are susceptible to reactive oxygen species hydrogen peroxide via generation of multichromosomal fusions and chromosomal fragments bearing telomeres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woo, Seon Rang; Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705; Park, Jeong-Eun

2012-01-06

Highlights: Black-Right-Pointing-Pointer Under conditions of telomere erosion, cells become extremely sensitive to H{sub 2}O{sub 2}. Black-Right-Pointing-Pointer Chromosomal regions adjacent to telomeres are cleaved by H{sub 2}O{sub 2} under such conditions. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} thus causes multichromosomal fusions and generation of small chromosomal fragments. Black-Right-Pointing-Pointer N-acetylcysteine prevents H{sub 2}O{sub 2}-induced chromosomal aberrations. -- Abstract: During genotoxic stress, reactive oxygen species hydrogen peroxide (H{sub 2}O{sub 2}) is a prime mediator of the DNA damage response. Telomeres function both to assist in DNA damage repair and to inhibit chromosomal end-to-end fusion. Here, we show that telomere dysfunction renders cells susceptible to H{submore » 2}O{sub 2}, via generation of multichromosomal fusion and chromosomal fragments. H{sub 2}O{sub 2} caused formation of multichromosomal end-to-end fusions involving more than three chromosomes, preferentially when telomeres were erosive. Interestingly, extensive chromosomal fragmentation (yielding small-sized fragments) occurred only in cells exhibiting such multichromosomal fusions. Telomeres were absent from fusion points, being rather present in the small fragments, indicating that H{sub 2}O{sub 2} cleaves chromosomal regions adjacent to telomeres. Restoration of telomere function or addition of the antioxidant N-acetylcysteine prevented development of chromosomal aberrations and rescued the observed hypersensitivity to H{sub 2}O{sub 2}. Thus, chromosomal regions adjacent to telomeres become sensitive to reactive oxygen species hydrogen peroxide when telomeres are dysfunctional, and are cleaved to produce multichromosomal fusions and small chromosomal fragments bearing the telomeres.« less

Sensitivity of the fusion cross section to the density dependence of the symmetry energy

NASA Astrophysics Data System (ADS)

Reinhard, P.-G.; Umar, A. S.; Stevenson, P. D.; Piekarewicz, J.; Oberacker, V. E.; Maruhn, J. A.

2016-04-01

Background: The study of the nuclear equation of state (EOS) and the behavior of nuclear matter under extreme conditions is crucial to our understanding of many nuclear and astrophysical phenomena. Nuclear reactions serve as one of the means for studying the EOS. Purpose: It is the aim of this paper to discuss the impact of nuclear fusion on the EOS. This is a timely subject given the expected availability of increasingly exotic beams at rare isotope facilities [A. B. Balantekin et al., Mod. Phys. Lett. A 29, 1430010 (2014), 10.1142/S0217732314300109]. In practice, we focus on 48Ca+48Ca fusion. Method: We employ three different approaches to calculate fusion cross sections for a set of energy density functionals with systematically varying nuclear matter properties. Fusion calculations are performed using frozen densities, using a dynamic microscopic method based on density-constrained time-dependent Hartree-Fock (DC-TDHF) approach, as well as direct TDHF study of above barrier cross sections. For these studies, we employ a family of Skyrme parametrizations with systematically varied nuclear matter properties. Results: The folding-potential model provides a reasonable first estimate of cross sections. DC-TDHF, which includes dynamical polarization, reduces the fusion barriers and delivers much better cross sections. Full TDHF near the barrier agrees nicely with DC-TDHF. Most of the Skyrme forces which we used deliver, on the average, fusion cross sections in good agreement with the data. Trying to read off a trend in the results, we find a slight preference for forces which deliver a slope of symmetry energy of L ≈50 MeV that corresponds to a neutron-skin thickness of 48Ca of Rskin=(0.180 -0.210 ) fm. Conclusions: Fusion reactions in the barrier and sub-barrier region can be a tool to study the EOS and the neutron skin of nuclei. The success of the approach will depend on reduced experimental uncertainties of fusion data as well as the development of fusion

Cluster-impact fusion, or beam-contaminant fusion? (abstract)a),b)

NASA Astrophysics Data System (ADS)

Lo, Daniel H.; Petrasso, Richard D.; Wenzel, Kevin W.

1992-10-01

Beuhler, Friedlander, and Friedman (BFF) reported anomalously huge D-D fusion rates while bombarding deuterated targets with (D2O)N+ clusters (N˜25-1000) accelerated to ≊325 keV [R. J. Beuhler et al., Phys. Rev. Lett. 63, 1292 (1989); R. J. Beuhler et al., J. Phys. Chem. 94, 7665 (1990)] [i.e., ≊0.3 keV lab energy for D in (D2O)100+]. However, from our analysis of BFF's fusion product spectra, we conclude that their D lab energy was ˜50 keV. Therefore, no gross anomalies exist. Also, from our analysis of the BFF beam-ranging experiments through 500 μg/cm2 of Au, we conclude that light-ion-beam contaminants (e.g., D+ of order 100 keV) have not been ruled out, and are the probable cause of their fusion reactions. This work was supported by LLNL Subcontract B116798, Department of Energy (DOE) Grant No. DE-FG02-91ER54109, DOE Magnetic Fusion Energy Technology Fellowship Program (D. H. Lo), and DOE Fusion Energy Postdoctoral Research Program (Kevin W. Wenzel).

Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora.

PubMed

Traeger, Stefanie; Nowrousian, Minou

2015-04-14

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. Copyright © 2015 Traeger and Nowrousian.

Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora

PubMed Central

Traeger, Stefanie; Nowrousian, Minou

2015-01-01

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. PMID:25873638

Building Bridges Between EPO Professionals Across Scientific Disciplines: Partnerships with NSF Centers (First Steps)

NASA Astrophysics Data System (ADS)

Steinberg, D.; Black, K.; Schultz, S.

2010-08-01

NASA, NSF and other funding organizations support science education and outreach to achieve their broader impact goals. Organizations like ASP and the NSF Research Centers Educators Network (NRCEN) are building networks of education and public outreach (EPO) professionals to enhance programmatic success in reaching these goals. As the professionals who provide these programs to the various scientific communities, we are often the key connectors between investigators at cutting-edge research centers, the education world and the public. However, our profession does not have strong ties for sharing best practices across the different scientific disciplines. To develop those ties, we need to identify our common interests and build on them by sharing lessons learned and best practices. We will use the technique of concept mapping to develop a schematic of how each of us addresses our broader impact goals and discuss the common and divergent features. We will also present the education and outreach logic model that was recently developed by the 27 Education Directors of NSF-funded Materials Research Science and Engineering Centers (MRSEC). Building on this information, we will collaboratively develop a list of key areas of similar interest between ASP and NRCEN EPO professionals.

Córdova to Be Nominated as New Head of NSF

NASA Astrophysics Data System (ADS)

Showstack, Randy

2013-08-01

President Barack Obama announced on 31 July that he intends to nominate France Anne Córdova to become the next director of the National Science Foundation (NSF). Córdova was president of Purdue University from 2007 to 2012 and has been a professor of physics and astronomy there. Previously, Córdova was chancellor of the University of California, Riverside from 1996 to 2002.

NSF in a Changing World: The National Science Foundation's Strategic Plan.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC.

The National Science Foundation's (NSF) role as a leader and steward of the Nation's science and engineering enterprise faces new tests--promoting new approaches to research, education, and workforce training that reach all Americans; responding to the increased importance of science and engineering in many aspects of daily life; modernizing the…

Development of a Consensus Standard for School Equipment: NSF/NSSEA 380

ERIC Educational Resources Information Center

Breitner, Ashlee

2011-01-01

For many years, the school supplies and equipment industry has investigated methods to ensure product safety and compliance across all its product categories. In early 2010, NSF International and the National School Supply and Equipment Association (NSSEA) came together to develop quality standards for products and equipment designed for use in…

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating

PubMed Central

Rogers, Jason V.; Arlow, Tim; Inkellis, Elizabeth R.; Koo, Timothy S.; Rose, Mark D.

2013-01-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide–sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway. PMID:24152736

BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum

PubMed Central

Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

2015-01-01

Abstract Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Adam J.; Brown, Melissa N.; Black, Margaret E., E-mail: blackm@vetmed.wsu.edu

2011-12-09

Highlights: Black-Right-Pointing-Pointer Goal was to enhance dFdC cytotoxicity by the creation of a UCMK/dCK fusion enzyme. Black-Right-Pointing-Pointer The UCMK/dCK fusion enzyme possesses both native activities. Black-Right-Pointing-Pointer The fusion renders cells equally sensitive to dFdC relative to dCK expression alone. Black-Right-Pointing-Pointer Dual activities of fusion not sufficient to augment cell dFdC sensitivity in vitro. Black-Right-Pointing-Pointer Data may warrant the implementation of UCMK mutagenesis studies. -- Abstract: While gemcitabine (2 Prime -2 Prime -difluoro-2 Prime -deoxycytidine, dFdC) displays wide-ranging antineoplastic activity as a single agent, variable response rates and poor intracellular metabolism often limit its clinical efficacy. In an effort to enhancemore » dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide. Our goal was to evaluate whether the created fusion could induce beneficial, functional changes toward dFdC, expedite dFdC conversion to its active antimetabolites and consequently amplify cell dFdC sensitivity. While kinetic analyses revealed the UCMK/dCK fusion enzyme to possess both native activities, the fusion rendered cells sensitive to the cytotoxic effects of dFdC at the same level as dCK expression alone. These results suggest that increased wild-type UCMK expression does not provide a significant enhancement in dFdC-mediated cytotoxicity and may warrant the implementation of studies aimed at engineering UCMK variants with improved activity toward gemcitabine monophosphate.« less

Eliciting an antibody response against a recombinant TSH containing fusion protein.

PubMed

Mard-Soltani, Maysam; Rasaee, Mohamad Javad; Sheikhi, AbdolKarim; Hedayati, Mehdi

2017-01-01

Designing novel antigens to rise specific antibodies for Thyroid Stimulating Hormone (TSH) detection is of great significance. A novel fusion protein consisting of the C termini sequence of TSH beta subunit and a fusion sequence was designed and produced for rabbit immunization. Thereafter, the produced antibodies were purified and characterized for TSH detection. Our results indicate that the produced antibody is capable of sensitive and specific detection of TSH with low cross reactivity. This study underscores the applicability of designed fusion protein for specific and sensitive polyclonal antibody production and the importance of selecting an amenable region of the TSH for immunization.

Leveraging the NSF Broader-Impacts Criterion for Change in STEM Education

ERIC Educational Resources Information Center

Mathieu, Robert D.; Pfund, Christine; Gillian-Daniel, Don

2009-01-01

In an attempt to move, if not balance, the scales of activity toward increasing scientific capability across a diverse national population, U.S. federal funding agencies are purposefully linking research funding to broad national impact. Among United States federal agencies, the National Science Foundation (NSF) has led the way in the integration…

Gold nanoprobe functionalized with specific fusion protein selection from phage display and its application in rapid, selective and sensitive colorimetric biosensing of Staphylococcus aureus.

PubMed

Liu, Pei; Han, Lei; Wang, Fei; Petrenko, Valery A; Liu, Aihua

2016-08-15

Staphylococcus aureus (S. aureus) is one of the most ubiquitous pathogens in public healthcare worldwide. It holds great insterest in establishing robust analytical method for S. aureus. Herein, we report a S. aureus-specific recognition element, isolated from phage monoclone GQTTLTTS, which was selected from f8/8 landscape phage library against S. aureus in a high-throughput way. By functionalizing cysteamine (CS)-stabilized gold nanoparticles (CS-AuNPs) with S. aureus-specific pVIII fusion protein (fusion-pVIII), a bifunctional nanoprobe (CS-AuNPs@fusion-pVIII) for S. aureus was developed. In this strategy, the CS-AuNPs@fusion-pVIII could be induced to aggregate quickly in the presence of target S. aureus, resulting in a rapid colorimetric response of gold nanoparticles. More importantly, the as-designed probe exhibited excellent selectivity over other bacteria. Thus, the CS-AuNPs@fusion-pVIII could be used as the indicator of target S. aureus. This assay can detect as low as 19CFUmL(-1)S. aureus within 30min. Further, this approach can be applicable to detect S. aureus in real water samples. Due to its sensitivity, specificity and rapidness, this proposed method is promising for on-site testing of S. aureus without using any costly instruments. Copyright © 2016 Elsevier B.V. All rights reserved.

Immobilization of the N-terminal helix stabilizes prefusion paramyxovirus fusion proteins

PubMed Central

Song, Albert S.; Poor, Taylor A.; Abriata, Luciano A.; Jardetzky, Theodore S.; Dal Peraro, Matteo; Lamb, Robert A.

2016-01-01

Parainfluenza virus 5 (PIV5) is an enveloped, single-stranded, negative-sense RNA virus of the Paramyxoviridae family. PIV5 fusion and entry are mediated by the coordinated action of the receptor-binding protein, hemagglutinin–neuraminidase (HN), and the fusion protein (F). Upon triggering by HN, F undergoes an irreversible ATP- and pH-independent conformational change, going down an energy gradient from a metastable prefusion state to a highly stable postfusion state. Previous studies have highlighted key conformational changes in the F-protein refolding pathway, but a detailed understanding of prefusion F-protein metastability remains elusive. Here, using two previously described F-protein mutations (S443D or P22L), we examine the capacity to modulate PIV5 F stability and the mechanisms by which these point mutants act. The S443D mutation destabilizes prefusion F proteins by disrupting a hydrogen bond network at the base of the F-protein globular head. The introduction of a P22L mutation robustly rescues destabilized F proteins through a local hydrophobic interaction between the N-terminal helix and a hydrophobic pocket. Prefusion stabilization conferred by a P22L-homologous mutation is demonstrated in the F protein of Newcastle disease virus, a paramyxovirus of a different genus, suggesting a conserved stabilizing structural element within the paramyxovirus family. Taken together, the available data suggest that movement of the N-terminal helix is a necessary early step for paramyxovirus F-protein refolding and presents a novel target for structure-based drug design. PMID:27335462

Immobilization of the N-terminal helix stabilizes prefusion paramyxovirus fusion proteins.

PubMed

Song, Albert S; Poor, Taylor A; Abriata, Luciano A; Jardetzky, Theodore S; Dal Peraro, Matteo; Lamb, Robert A

2016-07-05

Parainfluenza virus 5 (PIV5) is an enveloped, single-stranded, negative-sense RNA virus of the Paramyxoviridae family. PIV5 fusion and entry are mediated by the coordinated action of the receptor-binding protein, hemagglutinin-neuraminidase (HN), and the fusion protein (F). Upon triggering by HN, F undergoes an irreversible ATP- and pH-independent conformational change, going down an energy gradient from a metastable prefusion state to a highly stable postfusion state. Previous studies have highlighted key conformational changes in the F-protein refolding pathway, but a detailed understanding of prefusion F-protein metastability remains elusive. Here, using two previously described F-protein mutations (S443D or P22L), we examine the capacity to modulate PIV5 F stability and the mechanisms by which these point mutants act. The S443D mutation destabilizes prefusion F proteins by disrupting a hydrogen bond network at the base of the F-protein globular head. The introduction of a P22L mutation robustly rescues destabilized F proteins through a local hydrophobic interaction between the N-terminal helix and a hydrophobic pocket. Prefusion stabilization conferred by a P22L-homologous mutation is demonstrated in the F protein of Newcastle disease virus, a paramyxovirus of a different genus, suggesting a conserved stabilizing structural element within the paramyxovirus family. Taken together, the available data suggest that movement of the N-terminal helix is a necessary early step for paramyxovirus F-protein refolding and presents a novel target for structure-based drug design.

NSF Lower Atmospheric Observing Facilities (LAOF) in support of science and education

NASA Astrophysics Data System (ADS)

Baeuerle, B.; Rockwell, A.

2012-12-01

Researchers, students and teachers who want to understand and describe the Earth System require high quality observations of the atmosphere, ocean, and biosphere. Making these observations requires state-of-the-art instruments and systems, often carried on highly capable research platforms. To support this need of the geosciences community, the National Science Foundation's (NSF) Division of Atmospheric and Geospace Sciences (AGS) provides multi-user national facilities through its Lower Atmospheric Observing Facilities (LAOF) Program at no cost to the investigator. These facilities, which include research aircraft, radars, lidars, and surface and sounding systems, receive NSF financial support and are eligible for deployment funding. The facilities are managed and operated by five LAOF partner organizations: the National Center for Atmospheric Research (NCAR); Colorado State University (CSU); the University of Wyoming (UWY); the Center for Severe Weather Research (CSWR); and the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS). These observational facilities are available on a competitive basis to all qualified researchers from US universities, requiring the platforms and associated services to carry out various research objectives. The deployment of all facilities is driven by scientific merit, capabilities of a specific facility to carry out the proposed observations, and scheduling for the requested time. The process for considering requests and setting priorities is determined on the basis of the complexity of a field campaign. The poster will describe available observing facilities and associated services, and explain the request process researchers have to follow to secure access to these platforms for scientific as well as educational deployments. NSF/NCAR GV Aircraft

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

DOE PAGES

McDermott, Samuel D.

2018-06-01

Here, we suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v n~(10 –(2–3)) n, where n=1, 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ~0.1–1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ~O(100 MeV). Darkmore » fusion firmly predicts constant σv below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Samuel D.

2017-11-02

We suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v^n ~ [10^{-(2-3)}]^n, where n=1,2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be sigma ~ 0.1-1 barn, moderately larger than for Standard Model deuteron fusion, indicating a dark nuclear scale Lambda ~ O(100 MeV).more » Dark fusion firmly predicts constant sigma v below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometer per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Samuel D.

Here, we suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v n~(10 –(2–3)) n, where n=1, 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ~0.1–1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ~O(100 MeV). Darkmore » fusion firmly predicts constant σv below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

FUSION-Guided Hypothesis Development Leads to the Identification of N6,N6-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor

PubMed Central

Vaden, Rachel M.; Oswald, Nathaniel W.; Potts, Malia B.; MacMillan, John B.; White, Michael A.

2017-01-01

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism. Using Functional Signature Ontology (FUSION), we report the parallel isolation and characterization of a marine-derived natural product, N6,N6-dimethyladenosine, that robustly inhibits AKT signaling in a variety of non-small cell lung cancer cell lines. Upon validation of the elucidated structure by comparison with a commercially available sample, experiments were initiated to understand the small molecule’s breadth of effect in a biological setting. One such experiment, a reverse phase protein array (RPPA) analysis of >50 kinases, indicated a specific cellular response to treatment. In all, leveraging the FUSION platform allowed for the rapid generation and validation of a biological mechanism of action hypothesis for an unknown natural product and permitted accelerated purification of the bioactive component from a chemically complex fraction. PMID:28294973

ESO and NSF Sign Agreement on ALMA

NASA Astrophysics Data System (ADS)

2003-02-01

Green Light for World's Most Powerful Radio Observatory On February 25, 2003, the European Southern Observatory (ESO) and the US National Science Foundation (NSF) are signing a historic agreement to construct and operate the world's largest and most powerful radio telescope, operating at millimeter and sub-millimeter wavelength. The Director General of ESO, Dr. Catherine Cesarsky, and the Director of the NSF, Dr. Rita Colwell, act for their respective organizations. Known as the Atacama Large Millimeter Array (ALMA), the future facility will encompass sixty-four interconnected 12-meter antennae at a unique, high-altitude site at Chajnantor in the Atacama region of northern Chile. ALMA is a joint project between Europe and North America. In Europe, ESO is leading on behalf of its ten member countries and Spain. In North America, the NSF also acts for the National Research Council of Canada and executes the project through the National Radio Astronomy Observatory (NRAO) operated by Associated Universities, Inc. (AUI). The conclusion of the ESO-NSF Agreement now gives the final green light for the ALMA project. The total cost of approximately 650 million Euro (or US Dollars) is shared equally between the two partners. Dr. Cesarsky is excited: "This agreement signifies the start of a great project of contemporary astronomy and astrophysics. Representing Europe, and in collaboration with many laboratories and institutes on this continent, we together look forward towards wonderful research projects. With ALMA we may learn how the earliest galaxies in the Universe really looked like, to mention but one of the many eagerly awaited opportunities with this marvellous facility". "With this agreement, we usher in a new age of research in astronomy" says Dr. Colwell. "By working together in this truly global partnership, the international astronomy community will be able to ensure the research capabilities needed to meet the long-term demands of our scientific enterprise, and

Enhancement of Skin Penetration of Hydrophilic and Lipophilic Compounds by pH-sensitive Liposomes.

PubMed

Tokudome, Yoshihiro; Nakamura, Kaoru; Itaya, Yurina; Hashimoto, Fumie

2015-01-01

Enhance skin penetration of hydrophilic and lipophilic compounds using liposomes that are responsible to the pH of the skin surface. pH-sensitive liposomes were prepared by a thin layer and freeze-thaw method with dioleoyl phosphatidyl ethanolamine and cholesteryl hemisuccinate. Liposomal fusion with stratum corneum lipid liposomes was measured using fluorescence resonance energy transfer. Particle diameter and zeta potential of the liposomes after fusion were measured by dynamic light scattering and electrophoresis. Under neutral pH conditions, the diameter of the pH-sensitive liposomes was 130 nm and their zeta potential was -70 mV. In weakly acidic conditions, the diameter was larger than 3,000 nm and the zeta potential was -50 mV. In contrast, the particle diameter and the zeta potential of the non-pH-sensitive liposomes remained constant under various pH conditions. A skin penetration study was performed on hairless mice skin using vertical diffusion cells, showing that the fusion ability of pH-sensitive liposomes was higher than that of non-pH-sensitive liposomes. In the skin penetration study was carried out using hydrophilic (calcein) and lipophilic (N-(7-nitrobenz- 2-oxa-1,3-diazol-4yl)-PE) (NBD-PE) model compounds which were applied to the skin with pH-sensitive liposomes as carrier. The fluorescent compounds contained within the pH-sensitive liposomes permeated the skin more effectively than those within non-pH-sensitive liposomes, and this ability was further enhanced with the lipophilic compound. These studies suggest that pH-sensitive liposomes have potential as an important tool for delivery of compounds into the skin.

Regulation of Exocytotic Fusion Pores by SNARE Protein Transmembrane Domains

PubMed Central

Wu, Zhenyong; Thiyagarajan, Sathish; O’Shaughnessy, Ben; Karatekin, Erdem

2017-01-01

Calcium-triggered exocytotic release of neurotransmitters and hormones from neurons and neuroendocrine cells underlies neuronal communication, motor activity and endocrine functions. The core of the neuronal exocytotic machinery is composed of soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs). Formation of complexes between vesicle-attached v- and plasma-membrane anchored t-SNAREs in a highly regulated fashion brings the membranes into close apposition. Small, soluble proteins called Complexins (Cpx) and calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium concentrations, but trigger release upon calcium increase. A growing body of evidence suggests that the transmembrane domains (TMDs) of SNARE proteins play important roles in regulating the processes of fusion and release, but the mechanisms involved are only starting to be uncovered. Here we review recent evidence that SNARE TMDs exert influence by regulating the dynamics of the fusion pore, the initial aqueous connection between the vesicular lumen and the extracellular space. Even after the fusion pore is established, hormone release by neuroendocrine cells is tightly controlled, and the same may be true of neurotransmitter release by neurons. The dynamics of the fusion pore can regulate the kinetics of cargo release and the net amount released, and can determine the mode of vesicle recycling. Manipulations of SNARE TMDs were found to affect fusion pore properties profoundly, both during exocytosis and in biochemical reconstitutions. To explain these effects, TMD flexibility, and interactions among TMDs or between TMDs and lipids have been invoked. Exocytosis has provided the best setting in which to unravel the underlying mechanisms, being unique among membrane fusion reactions in that single fusion pores can be probed using high-resolution methods. An important role will likely be played by methods that can probe single fusion pores in a biochemically

EDITORIAL: The Nuclear Fusion Award The Nuclear Fusion Award

NASA Astrophysics Data System (ADS)

Kikuchi, M.

2011-01-01

Explanation of the JET n = 0 chirping mode Nucl. Fusion 46 S888-97 Urano H. et al 2006 Confinement degradation with beta for ELMy HH-mode plasmas in JT-60U tokamak Nucl. Fusion 46 781-7 Izzo V.A. et al 2006 A numerical investigation of the effects of impurity penetration depth on disruption mitigation by massive high-pressure gas jet Nucl. Fusion 46 541-7 Inagaki S. et al 2006 Comparison of transient electron heat transport in LHD helical and JT-60U tokamak plasmas Nucl. Fusion 46 133-41 Watanabe T.-H. et al 2006 Velocity-space structures of distribution function in toroidal ion temperature gradient turbulence Nucl. Fusion 46 24-32 2010 Nuclear Fusion Award nominees For the 2010 award, the papers published in the 2007 volume were assessed and the following papers were nominated, all of which are magnetic confinement experiments and theory. Rice J.E. et al 2007 Inter-machine comparison of intrinsic toroidal rotation in tokamaks Nucl. Fusion 47 1618-24 Lipschultz B. et al 2007 Plasma-surface interaction, scrape-off layer and divertor physics: implications for ITER Nucl. Fusion 47 1189-205 Loarer T. et al 2007 Gas balance and fuel retention in fusion devices Nucl. Fusion 47 1112-20 Garcia O.E et al 2007 Fluctuations and transport in the TCV scrape-off layer Nucl. Fusion 47 667-76 Zonca F. et al 2007 Electron fishbones: theory and experimental evidence Nucl. Fusion 47 1588-97 Maggi C.F. et al 2007 Characteristics of the H-mode pedestal in improved confinement scenarios in ASDEX Upgrade, DIII-D, JET and JT-60U Nucl. Fusion 47 535-51 Yoshida M. et al 2007 Momentum transport and plasma rotation profile in toroidal direction in JT-60U L-mode plasmas Nucl. Fusion 47 856-63 Zohm H. et al 2007 Control of MHD instabilities by ECCD: ASDEX Upgrade results and implications for ITER Nucl. Fusion 47 228-32 Snyder P.B. et al 2007 Stability and dynamics of the edge pedestal in the low collisionality regime: physics mechanisms for steady-state ELM-free operation Nucl. Fusion 47 961-8 Urano H. et

Cost-effectiveness of minimally invasive sacroiliac joint fusion.

PubMed

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée Jg; Polly, David W

2016-01-01

Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. To determine the cost-effectiveness of minimally invasive SIJ fusion. Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162-$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption.

Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model.

PubMed

Jain, Nikhil; Himed, Khaled; Toth, Jeffrey M; Briley, Karen C; Phillips, Frank M; Khan, Safdar N

2018-04-19

Opioid use is prevalent for management of pre- and post-operative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in-vitro, and one previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. To study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. Pre-clinical animal study. 24 adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received four-weeks pre-operative and six-weeks post-operative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and four-weeks post-operatively to ensure adequate levels. The control group (n=12) received only peri-operative pain control as necessary. All animals received a bilateral L5-L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the six-week post-operative time point, and assessment of fusion was done by manual palpation, plain radiographs, micro-computed tomography (microCT), and histology. 12 animals in control group and 11 animals in the opioid group were available for analysis at the end of six weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=0.09), lower trabecular number (p=0.02) and higher trabecular separation (p=0.02) as compared to control. Histological analysis

NRAO Response to NSF Senior Review of Astronomy Facilities

NASA Astrophysics Data System (ADS)

2006-11-01

The National Science Foundation's (NSF) Astronomy Senior Review Committee report (pdf file), released today, made major recommendations for restructuring the NSF's ground-based astronomy efforts, including significant changes for the National Radio Astronomy Observatory (NRAO). The committee's report urged that leadership in radio astronomy, including millimeter- and submillimeter-wave observatories, "remain centered at NRAO as it is, by far, the largest radio astronomy organization in the world." The report praised the record of management of NRAO and the scientific capabilities of the Atacama Large Millimeter/submillimeter Array (ALMA), the Expanded Very Large Array (EVLA), the Robert C. Byrd Green Bank Telescope (GBT), and the Very Long Baseline Array (VLBA). However, the report also recommended that some reductions and changes occur at the NRAO by 2011. Specifically, the report recommended that: (a) VLBA operations make a transition to a significant reliance on international funding or risk closure; (b) GBT operations costs be reduced; and (c) NRAO scientific staff costs be reduced. "The Senior Review Committee had the very difficult task of reconciling the needs of current facilities and funding new facilities for the future of astronomy. We appreciate their efforts and look forward to working with the NSF to ensure that the valuable and unique research capabilities of our NRAO telescopes continue to serve the astronomical community," said Dr. Fred K.Y. Lo, NRAO Director. The VLBA provides the greatest angular resolution, or ability to see fine detail, of any telescope in the world, greatly exceeding the capabilities of the Hubble Space Telescope and the future Square Kilometre Array. The committee recognized that, "if the VLBA is closed, a unique capability would likely be lost for decades." "The VLBA is used by scientists from around the world because of its unique capabilities. It has produced landmark research milestones and the committee recognized in its

NCLscan: accurate identification of non-co-linear transcripts (fusion, trans-splicing and circular RNA) with a good balance between sensitivity and precision.

PubMed

Chuang, Trees-Juen; Wu, Chan-Shuo; Chen, Chia-Ying; Hung, Li-Yuan; Chiang, Tai-Wei; Yang, Min-Yu

2016-02-18

Analysis of RNA-seq data often detects numerous 'non-co-linear' (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts (trans-spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method ('NCLscan'), which utilized a stepwise alignment strategy to almost completely eliminate false calls (>98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans-spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans-spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Theoretical quantification of shock-timing sensitivities for direct-drive inertial confinement fusion implosions on OMEGA

NASA Astrophysics Data System (ADS)

Cao, D.; Boehly, T. R.; Gregor, M. C.; Polsin, D. N.; Davis, A. K.; Radha, P. B.; Regan, S. P.; Goncharov, V. N.

2018-05-01

Using temporally shaped laser pulses, multiple shocks can be launched in direct-drive inertial confinement fusion implosion experiments to set the shell on a desired isentrope or adiabat. The velocity of the first shock and the times at which subsequent shocks catch up to it are measured through the velocity interferometry system for any reflector diagnostic [T. R. Boehly et al., Phys. Plasmas 18, 092706 (2011)] on OMEGA [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. Simulations reproduce these velocity and shock-merger time measurements when using laser pulses designed for setting mid-adiabat (α ˜ 3) implosions, but agreement degrades for lower-adiabat (α ˜ 1) designs. Simulation results indicate that the shock timing discrepancy is most sensitive to details of the density and temperature profiles in the coronal plasma, which influences the laser energy coupled into the target, and only marginally sensitive to the target offset and beam power imbalance. To aid in verifying the coronal profile's influence, a new technique under development to infer coronal profiles using x-ray self-emission imaging [A. K. Davis et al., Bull. Am. Phys. Soc. 61, BAPS.2016.DPP.NO8.7 (2016)] can be applied to the pulse shapes used in shock-timing experiments.

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Rui; Xu, Kai; Zhou, Tongqing

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. In this paper, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showedmore » that the N-terminal portion of the fusion peptide can be solvent-exposed. Finally, these results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.« less

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

DOE PAGES

Kong, Rui; Xu, Kai; Zhou, Tongqing; ...

2016-05-13

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. In this paper, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showedmore » that the N-terminal portion of the fusion peptide can be solvent-exposed. Finally, these results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.« less

Multitude of core-localized shear Alfvén waves in a high-temperature fusion plasma.

PubMed

Nazikian, R; Berk, H L; Budny, R V; Burrell, K H; Doyle, E J; Fonck, R J; Gorelenkov, N N; Holcomb, C; Kramer, G J; Jayakumar, R J; La Haye, R J; McKee, G R; Makowski, M A; Peebles, W A; Rhodes, T L; Solomon, W M; Strait, E J; Vanzeeland, M A; Zeng, L

2006-03-17

Evidence is presented for a multitude of discrete frequency Alfvén waves in the core of magnetically confined high-temperature fusion plasmas. Multiple diagnostic instruments confirm wave excitation over a wide spatial range from the device size at the longest wavelengths down to the thermal ion Larmor radius. At the shortest scales, the poloidal wavelengths are comparable to the scale length of electrostatic drift wave turbulence. Theoretical analysis confirms a dominant interaction of the modes with particles in the thermal ion distribution traveling well below the Alfvén velocity.

Cost-effectiveness of minimally invasive sacroiliac joint fusion

PubMed Central

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée JG; Polly, David W

2016-01-01

Background Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. Objective To determine the cost-effectiveness of minimally invasive SIJ fusion. Methods Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. Results SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162–$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Conclusion Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption. PMID:26719717

How does the stimulus define exocytosis in adrenal chromaffin cells?

PubMed

Marengo, Fernando D; Cárdenas, Ana M

2018-01-01

The extent and type of hormones and active peptides secreted by the chromaffin cells of the adrenal medulla have to be adjusted to physiological requirements. The chromaffin cell secretory activity is controlled by the splanchnic nerve firing frequency, which goes from approximately 0.5 Hz in basal conditions to more than 15 Hz in stress. Thus, these neuroendocrine cells maintain a tonic release of catecholamines under resting conditions, massively discharge intravesicular transmitters in response to stress, or adequately respond to moderate stimuli. In order to adjust the secretory response to the stimulus, the adrenal chromaffin cells have an appropriate organization of Ca 2+ channels, secretory granules pools, and sets of proteins dedicated to selectively control different steps of the secretion process, such as the traffic, docking, priming and fusion of the chromaffin granules. Among the molecules implicated in such events are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Ca 2+ sensors like Munc13 and synaptotagmin-1, chaperon proteins such as Munc18, and the actomyosin complex. In the present review, we discuss how these different actors contribute to the extent and maintenance of the stimulus-dependent exocytosis in the adrenal chromaffin cells.

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

NASA Astrophysics Data System (ADS)

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-08-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

PubMed Central

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-01-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view. PMID:27493064

Is the Paracoccus halodenitrificans ATPase a chimeric enzyme?

NASA Technical Reports Server (NTRS)

Hochstein, L. I.

1996-01-01

Membranes from Paracoccus halodenitrificans contain an ATPase that is most active in the absence of NaCl. The most unusual characteristic of the enzyme is its pattern of sensitivity to various inhibitors. Azide and rhodamine 6G, inhibitors of F1F0-ATPases, inhibit ATP hydrolysis as do bafilomycin A1, concanamycin A (folimycin), N-ethylmaleimide, and p-chloromercuriphenylsulfonate which are inhibitors of vacuolar ATPases. This indiscriminate sensitivity suggests that this ATPase may be a hybrid and that caution should be exercised when using inhibition as a diagnostic for distinguishing between F1F0-ATPases and vacuolar ATPases.

Fast degradable citrate-based bone scaffold promotes spinal fusion.

PubMed

Tang, Jiajun; Guo, Jinshan; Li, Zhen; Yang, Cheng; Xie, Denghui; Chen, Jian; Li, Shengfa; Li, Shaolin; Kim, Gloria B; Bai, Xiaochun; Zhang, Zhongmin; Yang, Jian

2015-07-21

It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications.

Evaluation of the NSF Industry/University Cooperative Research Centers: Descriptive and Correlative Findings.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC. Directorate for Engineering.

This report presents results of a survey of participants in the National Science Foundation (NSF) Industry-University Cooperative Research Centers program. The program promotes more rapid technological innovation by creating linkages between industry and university scientists. The Centers function as university research groups, with partial…

NSF ADVANCE: Institutional Transformation to Achieve Faculty Diversity

NASA Astrophysics Data System (ADS)

Anthony, E. Y.

2004-12-01

The NSF ADVANCE initiative is designed to enhance gender equity in academic science and engineering faculty. One of its components - Institutional Transformation - has the goal of establishing strategies and policies that will revolutionize institutional climate so that diverse faculty flourish. The University of Texas at El Paso is one of 19 institutions to currently hold a 5-year grant under the Institutional Transformation program. This poster presentation highlights practices from the participating institutions. Two general aspects of the program are: 1) co-principal investigators are a blend of administrators and active researchers. This blend ensures a bottom-up, top-down approach to presenting gender equity to faculty. 2) Many of the investigators have diversity as their research focus, which is intended to result in rigorous, peer-reviewed dissemination of institutional results. Specific effors for all institutions relate to recruitment, retention, and advancement of female faculty and, by establishing equitable conditions, to improvement of the workplace for all faculty. To aid recruitment, institutions have committed faculty involved in the search process, including training of search committees in diversity strategies and interaction with candidates. A close working relationship with the campus EO officer is essential. Retention strategies center on mentoring, monetary support for research, and policy implementation. Policies focus on work-family balance. Advancement of females to important administrative and non-administrative leadership roles is the third focus. Workshops and seminars on leadership skills are common in the various institutions. Finally, a central theme of the program is that, in addition to specific strategies, institutions must articulate diversity as a core value and reflect on the means to actualize this value. More information on the NSF ADVANCE program, including links to the Institutional Transformation grantees, may be found on

Tensor functors between Morita duals of fusion categories

NASA Astrophysics Data System (ADS)

Galindo, César; Plavnik, Julia Yael

2017-03-01

Given a fusion category C and an indecomposable C -module category M , the fusion category C^*_{_{M}} of C-module endofunctors of M is called the (Morita) dual fusion category of C with respect to M . We describe tensor functors between two arbitrary duals C^*_{_{M}} and D^*_N in terms of data associated to C and D . We apply the results to G-equivariantizations of fusion categories and group-theoretical fusion categories. We describe the orbits of the action of the Brauer-Picard group on the set of module categories and we propose a categorification of the Rosenberg-Zelinsky sequence for fusion categories.

Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity.

PubMed

McCoy, Andrea J; Maurelli, Anthony T

2005-07-01

Recent characterization of chlamydial genes encoding functional peptidoglycan (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to synthesize PG yet biochemical evidence for the synthesis of PG has yet to be demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria. Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D-alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we undertook a genetics-based approach to demonstrate and characterize the D-Ala-D-Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC. The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was cloned and placed under the control of the arabinose-inducible ara promoter and transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing deletions of both the ddlA and ddlB genes. Viability of the E. coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide became dependent on the expression of the chlamydial murC-ddl thus demonstrating functional ligase activity. Domain mapping of the full-length fusion protein and site-directed mutagenesis of the MurC domain revealed that the structure of the full fusion protein but not MurC enzymatic activity was required for ligase activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala. Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity. In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D-Ala-D-Ala. Together, these findings further support our hypothesis that PG is synthesized by members of the Chlamydiaceae family and suggest that D-amino acids, specifically D-Ala, are present in chlamydial PG.

2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation.

PubMed

Lai, Jeffrey K F; Sam, I-Ching; Verlhac, Pauline; Baguet, Joël; Eskelinen, Eeva-Liisa; Faure, Mathias; Chan, Yoke Fun

2017-07-04

Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation. Yeast 2-hybrid and co-affinity purification assays showed that 2BC physically and specifically interacted with a N -ethylmaleimide-sensitive factor attachment receptor (SNARE) protein, syntaxin-17 (STX17). Co-immunoprecipitation assay further showed that 2BC binds to SNARE proteins, STX17 and synaptosome associated protein 29 (SNAP29). Transient knockdown of STX17, SNAP29, and microtubule-associated protein 1 light chain 3B (LC3B), crucial proteins in the fusion between autophagosomes and lysosomes) as well as the lysosomal-associated membrane protein 1 (LAMP1) impaired production of infectious EV-A71 in RD cells. Collectively, these results demonstrate that the generation of autolysosomes triggered by the 2BC non-structural protein is important for EV-A71 replication, revealing a potential molecular pathway targeted by the virus to exploit autophagy. This study opens the possibility for the development of novel antivirals that specifically target 2BC to inhibit formation of autolysosomes during EV-A71 infection.

The Arctic Cooperative Data and Information System: Data Management Support for the NSF Arctic Research Program (Invited)

NASA Astrophysics Data System (ADS)

Moore, J.; Serreze, M. C.; Middleton, D.; Ramamurthy, M. K.; Yarmey, L.

2013-12-01

The NSF funds the Advanced Cooperative Arctic Data and Information System (ACADIS), url: (http://www.aoncadis.org/). It serves the growing and increasingly diverse data management needs of NSF's arctic research community. The ACADIS investigator team combines experienced data managers, curators and software engineers from the NSIDC, UCAR and NCAR. ACADIS fosters scientific synthesis and discovery by providing a secure long-term data archive to NSF investigators. The system provides discovery and access to arctic related data from this and other archives. This paper updates the technical components of ACADIS, the implementation of best practices, the value of ACADIS to the community and the major challenges facing this archive for the future in handling the diverse data coming from NSF Arctic investigators. ACADIS provides sustainable data management, data stewardship services and leadership for the NSF Arctic research community through open data sharing, adherence to best practices and standards, capitalizing on appropriate evolving technologies, community support and engagement. ACADIS leverages other pertinent projects, capitalizing on appropriate emerging technologies and participating in emerging cyberinfrastructure initiatives. The key elements of ACADIS user services to the NSF Arctic community include: data and metadata upload; support for datasets with special requirements; metadata and documentation generation; interoperability and initiatives with other archives; and science support to investigators and the community. Providing a self-service data publishing platform requiring minimal curation oversight while maintaining rich metadata for discovery, access and preservation is challenging. Implementing metadata standards are a first step towards consistent content. The ACADIS Gateway and ADE offer users choices for data discovery and access with the clear objective of increasing discovery and use of all Arctic data especially for analysis activities

[Experience of Fusion image guided system in endonasal endoscopic surgery].

PubMed

Wen, Jingying; Zhen, Hongtao; Shi, Lili; Cao, Pingping; Cui, Yonghua

2015-08-01

To review endonasal endoscopic surgeries aided by Fusion image guided system, and to explore the application value of Fusion image guided system in endonasal endoscopic surgeries. Retrospective research. Sixty cases of endonasal endoscopic surgeries aided by Fusion image guided system were analysed including chronic rhinosinusitis with polyp (n = 10), fungus sinusitis (n = 5), endoscopic optic nerve decompression (n = 16), inverted papilloma of the paranasal sinus (n = 9), ossifying fibroma of sphenoid bone (n = 1), malignance of the paranasal sinus (n = 9), cerebrospinal fluid leak (n = 5), hemangioma of orbital apex (n = 2) and orbital reconstruction (n = 3). Sixty cases of endonasal endoscopic surgeries completed successfully without any complications. Fusion image guided system can help to identify the ostium of paranasal sinus, lamina papyracea and skull base. Fused CT-CTA images, or fused MR-MRA images can help to localize the optic nerve or internal carotid arteiy . Fused CT-MR images can help to detect the range of the tumor. It spent (7.13 ± 1.358) minutes for image guided system to do preoperative preparation and the surgical navigation accuracy reached less than 1mm after proficient. There was no device localization problem because of block or head set loosed. Fusion image guided system make endonasal endoscopic surgery to be a true microinvasive and exact surgery. It spends less preoperative preparation time, has high surgical navigation accuracy, improves the surgical safety and reduces the surgical complications.

Enhanced pH sensitivity of AlGaN/GaN ion-sensitive field effect transistor with Al2O3 synthesized by atomic layer deposition

NASA Astrophysics Data System (ADS)

Wang, Lei; Li, Liuan; Zhang, Tong; Liu, Xinke; Ao, Jin-Ping

2018-01-01

In this study, we evaluated the pH sensitivity enhancement of AlGaN/GaN ion-sensitive field-effect transistor (ISFET) coated by Al2O3 film on the sensing area utilizing atomic layer deposition (ALD). The presence of the Al2O3 film leads to an obvious reduction of surface state density as well as leakage current in the solution, which is beneficial for improving the stability of the ISFET. Furthermore, the sensitivity of the ISFET was improved to 57.8 mV/pH, which is very close to the Nernstian limit at room temperature. The pH sensitivity enhancement can be explained by the higher density of sensing site as well as better surface hydrophilicity.

Position Paper. Cutting the NSF-OSIS Budget: Potential Disaster for Information Science and Technology

ERIC Educational Resources Information Center

Smith, Joshua I.

1974-01-01

A statement submitted on behalf of ASIS to the Subcommitte on Science Research and Development of the Committee on Science and Astronautics of the U.S. House of Representatives on the NSF Authorization Act 1975, HR 12816. (Author/JB)

Fast degradable citrate-based bone scaffold promotes spinal fusion

PubMed Central

Tang, Jiajun; Guo, Jinshan; Li, Zhen; Yang, Cheng; Xie, Denghui; Chen, Jian; Li, Shengfa; Li, Shaolin; Kim, Gloria B.; Bai, Xiaochun; Zhang, Zhongmin; Yang, Jian

2015-01-01

It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications. PMID:26213625

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

NASA Astrophysics Data System (ADS)

McDermott, Samuel D.

2018-06-01

We suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than vn˜(10-(2 -3 ))n , where n =1 , 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ˜0.1 - 1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ ˜O (100 MeV ) . Dark fusion firmly predicts constant σ v below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.

Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses.

PubMed

Sakai-Tagawa, Yuko; Ozawa, Makoto; Tamura, Daisuke; Le, Mai thi Quynh; Nidom, Chairul A; Sugaya, Norio; Kawaoka, Yoshihiro

2010-08-01

Simple and rapid diagnosis of influenza is useful for making treatment decisions in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine origin pandemic (H1N1) 2009 virus, remains largely unknown. Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.

Single residues in the surface subunits of oncogenic sheep retrovirus envelopes distinguish receptor-mediated triggering for fusion at low pH and infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cote, Marceline; Zheng, Yi-Min; Albritton, Lorraine M.

2011-12-20

Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are two closely related oncogenic retroviruses that share the same cellular receptor yet exhibit distinct fusogenicity and infectivity. Here, we find that the low fusogenicity of ENTV envelope protein (Env) is not because of receptor binding, but lies in its intrinsic insensitivity to receptor-mediated triggering for fusion at low pH. Distinct from JSRV, shedding of ENTV surface (SU) subunit into culture medium was not enhanced by a soluble form of receptor, Hyal2 (sHyal2), and sHyal2 was unable to effectively inactivate the ENTV pseudovirions. Remarkably, replacing either of the two aminomore » acid residues, N191 or S195, located in the ENTV SU with the corresponding JSRV residues, H191 or G195, markedly increased the Env-mediated membrane fusion activity and infection. Reciprocal amino acid substitutions also partly switched the sensitivities of ENTV and JSRV pseudovirions to sHyal2-mediated SU shedding and inactivation. While N191 is responsible for an extra N-linked glycosylation of ENTV SU relative to that of JSRV, S195 possibly forms a hydrogen bond with a surrounding amino acid residue. Molecular modeling of the pre-fusion structure of JSRV Env predicts that the segment of SU that contains H191 to G195 contacts the fusion peptide and suggests that the H191N and G195S changes seen in ENTV may stabilize its pre-fusion structure against receptor priming and therefore modulate fusion activation by Hyal2. In summary, our study reveals critical determinants in the SU subunits of JSRV and ENTV Env proteins that likely regulate their local structures and thereby differential receptor-mediated fusion activation at low pH, and these findings explain, at least in part, their distinct viral infectivity.« less

PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, So-Hee; Moon, Jeonghee; Lee, Myungkyu

2013-09-13

Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified asmore » a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1.« less

Effect of cholesterol depletion on exocytosis of alveolar type II cells.

PubMed

Chintagari, Narendranath Reddy; Jin, Nili; Wang, Pengcheng; Narasaraju, Telugu Akula; Chen, Jiwang; Liu, Lin

2006-06-01

Alveolar epithelial type II cells secrete lung surfactant via exocytosis. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) are implicated in this process. Lipid rafts, the cholesterol- and sphingolipid-rich microdomains, may offer a platform for protein organization on the cell membrane. We tested the hypothesis that lipid rafts organize exocytotic proteins in type II cells and are essential for the fusion of lamellar bodies, the secretory granules of type II cells, with the plasma membrane. The lipid rafts, isolated from type II cells using 1% Triton X-100 and a sucrose gradient centrifugation, contained the lipid raft markers, flotillin-1 and -2, whereas they excluded the nonraft marker, Na+-K+ ATPase. SNAP-23, syntaxin 2, and VAMP-2 were enriched in lipid rafts. When type II cells were depleted of cholesterol, the association of SNAREs with the lipid rafts was disrupted and the formation of fusion pore was inhibited. Furthermore, the cholesterol-depleted plasma membrane had less ability to fuse with lamellar bodies, a process mediated by annexin A2. The secretagogue-stimulated secretion of lung surfactant from type II cells was also reduced by methyl-beta-cyclodextrin. When the raft-associated cell surface protein, CD44, was cross-linked using anti-CD44 antibodies, the CD44 clusters were observed. Syntaxin 2, SNAP-23, and annexin A2 co-localized with the CD44 clusters, which were cholesterol dependent. Our results suggested that lipid rafts may form a functional platform for surfactant secretion in alveolar type II cells, and raft integrity was essential for the fusion between lamellar bodies with the plasma membrane.

Enterotoxigenic Escherichia coli heat-stable toxin and heat-labile toxin toxoid fusion 3xSTaN12S-dmLT induces neutralizing anti-STa antibodies in subcutaneously immunized mice.

PubMed

Nandre, Rahul; Ruan, Xiaosai; Duan, Qiangde; Zhang, Weiping

2016-11-02

Enterotoxigenic Escherichia coli (ETEC) bacteria producing heat-stable toxin (STa) and/or heat-labile toxin (LT) are among top causes of children's diarrhea and travelers' diarrhea. Currently no vaccines are available for ETEC associated diarrhea. A major challenge in developing ETEC vaccines is the inability to stimulate protective antibodies against the key STa toxin which is potently toxic and also poorly immunogenic. A recent study suggested toxoid fusion 3xSTa N12S -dmLT, which consists of a monomer LT toxoid (LT R192G/L211A ) and three copies of STa toxoid STa N12S , may represent an optimal immunogen inducing neutralizing antibodies against STa toxin [IAI 2014, 82(5):1823-32]. In this study, we immunized mice with this fusion protein following a different parenteral route and using different adjuvants to further characterize immunogenicity of this toxoid fusion. Data from this study showed that 3xSTa N12S -dmLT toxoid fusion induced neutralizing anti-STa antibodies in the mice following subcutaneous immunization, as effectively as in the mice under intraperitoneal route. Data also indicated that double mutant LT (dmLT) can be an effective adjuvant for this toxoid fusion in mice subcutaneous immunization. Results from this study affirmed that toxoid fusion 3xSTa N12S -dmLT induces neutralizing antibodies against STa toxin, suggesting this toxoid fusion is potentially a promising immunogen for ETEC vaccine development. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Theoretical quantification of shock-timing sensitivities for direct-drive inertial confinement fusion implosions on OMEGA

DOE PAGES

Cao, D.; Boehly, T. R.; Gregor, M. C.; ...

2018-05-16

Using temporally shaped laser pulses, multiple shocks can be launched in direct-drive inertial confinement fusion implosion experiments to set the shell on a desired isentrope or adiabat. The velocity of the first shock and the times at which subsequent shocks catch up to it are measured through the VISAR diagnostic on OMEGA. Simulations reproduce these velocity and shock-merger time measurements when using laser pulses designed for setting mid-adiabat (α ~ 3) implosions, but agreement degrades for lower-adiabat (α ~ 1) designs. Several possibilities for this difference are studied: errors in placing the target at the center of irradiation (target offset),more » variations in energy between the different incident beams (power imbalance), and errors in modeling the laser energy coupled into the capsule. Simulation results indicate that shock timing is most sensitive to details of the density and temperature profiles in the coronal plasma, which influences the laser energy coupled into the target, and only marginally sensitive to target offset and beam power imbalance. A new technique under development to infer coronal profiles using x-ray self-emission imaging can be applied to the pulse shapes used in shock-timing experiments. In conclusion, this will help identify improved physics models to implement in codes and consequently enhance shock-timing predictive capability for low-adiabat pulses.« less

Management and Stewardship of Airborne Observational Data for the NSF/NCAR HIAPER (GV) and NSF/NCAR C-130 at the National Center for Atmospheric Research (NCAR) Earth Observing Laboratory (EOL)

NASA Astrophysics Data System (ADS)

Aquino, J.

2014-12-01

The National Science Foundation (NSF) provides the National Center for Atmospheric Research (NCAR) Earth Observing Laboratory (EOL) funding for the operation, maintenance and upgrade of two research aircraft: the NSF/NCAR High-performance Instrumented Airborne Platform for Environmental Research (HIAPER) Gulfstream V and the NSF/NCAR Hercules C-130. A suite of in-situ and remote sensing airborne instruments housed at the EOL Research Aviation Facility (RAF) provide a basic set of measurements that are typically deployed on most airborne field campaigns. In addition, instruments to address more specific research requirements are provided by collaborating participants from universities, industry, NASA, NOAA or other agencies. The data collected are an important legacy of these field campaigns. A comprehensive metadata database and integrated cyber-infrastructure, along with a robust data workflow that begins during the field phase and extends to long-term archival (current aircraft data holdings go back to 1967), assures that: all data and associated software are safeguarded throughout the data handling process; community standards of practice for data stewardship and software version control are followed; simple and timely community access to collected data and associated software tools are provided; and the quality of the collected data is preserved, with the ultimate goal of supporting research and the reproducibility of published results. The components of this data system to be presented include: robust, searchable web access to data holdings; reliable, redundant data storage; web-based tools and scripts for efficient creation, maintenance and update of data holdings; access to supplemental data and documentation; storage of data in standardized data formats; comprehensive metadata collection; mature version control; human-discernable storage practices; and procedures to inform users of changes. In addition, lessons learned, shortcomings, and desired upgrades

Understanding the fusion cross section among light nuclei around the Coulomb barrier

NASA Astrophysics Data System (ADS)

Del Zoppo, Antonio; La Cognata, Marco

2017-11-01

In this work we investigate fusion induced by a radioactive 8Li projectile on a 4He gas target, at center-of-mass energies between 0.6 and 5 MeV. The main result is the tendency of the dimensionless fusion cross section to form well visible plateaus alternated to steep rises. This is likely to be the most genuine consequence of the discrete nature of the intervening angular momenta observed so far in fusion reactions right above the Coulomb barrier. A partial-wave analysis, exclusively based on a pure quantal penetration fusion model, identifies a remarkably low-height barrier. Indeed, these plateaus allow enhanced experimental sensitivity to the fusion barrier given that the most barrier-sensitive lowest partial waves are well separated. We expect that the present results for 8Li+4He will promote further investigations of the fusion reaction mechanism between very light ions at energies much below the interaction barrier. For the moment, we believe that understanding the plateau origin in the cross section above the barrier will almost certainly be useful to corroborate the extrapolation to the important astrophysical region below the Coulomb barrier, not only in the case of the 8Li+4He fusion but also for other systems, such as the 12C+12C.

Determination of the topology of endoplasmic reticulum membrane proteins using redox-sensitive green-fluorescence protein fusions.

PubMed

Tsachaki, Maria; Birk, Julia; Egert, Aurélie; Odermatt, Alex

2015-07-01

Membrane proteins of the endoplasmic reticulum (ER) are involved in a wide array of essential cellular functions. Identification of the topology of membrane proteins can provide significant insight into their mechanisms of action and biological roles. This is particularly important for membrane enzymes, since their topology determines the subcellular site where a biochemical reaction takes place and the dependence on luminal or cytosolic co-factor pools and substrates. The methods currently available for the determination of topology of proteins are rather laborious and require post-lysis or post-fixation manipulation of cells. In this work, we have developed a simple method for defining intracellular localization and topology of ER membrane proteins in living cells, based on the fusion of the respective protein with redox-sensitive green-fluorescent protein (roGFP). We validated the method and demonstrated that roGFP fusion proteins constitute a reliable tool for the study of ER membrane protein topology, using as control microsomal 11β-hydroxysteroid dehydrogenase (11β-HSD) proteins whose topology has been resolved, and comparing with an independent approach. We then implemented this method to determine the membrane topology of six microsomal members of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family. The results revealed a luminal orientation of the catalytic site for three enzymes, i.e. 17β-HSD6, 7 and 12. Knowledge of the intracellular location of the catalytic site of these enzymes will enable future studies on their biological functions and on the role of the luminal co-factor pool. Copyright © 2015 Elsevier B.V. All rights reserved.

HgNO3 sensitivity of AlGaN/GaN field effect transistors functionalized with phytochelating peptides

NASA Astrophysics Data System (ADS)

Rohrbaugh, Nathaniel; Hernandez-Balderrama, Luis; Kaess, Felix; Kirste, Ronny; Collazo, Ramon; Ivanisevic, Albena

2016-06-01

This study examined the conductance sensitivity of AlGaN/GaN field effect transistors in response to varying Hg/HNO3 solutions. FET surfaces were covalently functionalized with phytochelatin-5 peptides in order to detect Hg in solution. Results showed a resilience of peptide-AlGaN/GaN bonds in the presence of strong HNO3 aliquots, with significant degradation in FET ID signal. However, devices showed strong and varied response to Hg concentrations of 1, 10, 100, and 1000 ppm. The gathered statistically significant results indicate that peptide terminated AlGaN/GaN devices are capable of differentiating between Hg solutions and demonstrate device sensitivity.

S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers.

PubMed

Dutka, T L; Mollica, J P; Lamboley, C R; Weerakkody, V C; Greening, D W; Posterino, G S; Murphy, R M; Lamb, G D

2017-03-01

Nitric oxide is generated in skeletal muscle with activity and decreases Ca 2+ sensitivity of the contractile apparatus, putatively by S- nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca 2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S- glutathionylation of Cys134 on fast troponin I (TnI f ). Force-[Ca 2+ ] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca 2+ -buffered solutions. Treatment with S- nitrosylating agents, S- nitrosoglutathione (GSNO) or S- nitroso- N -acetyl-penicillamine (SNAP), decreased pCa 50 ( = -log 10 [Ca 2+ ] at half-maximal activation) by ~-0.07 pCa units in rat and human FT fibers without affecting maximum force, but had no effect on rat and human slow-twitch fibers or toad or chicken FT fibers, which all lack Cys134. The Ca 2+ sensitivity decrease was 1 ) fully reversed with dithiothreitol or reduced glutathione, 2 ) at least partially reversed with ascorbate, indicative of involvement of S-nitrosylation, and 3 ) irreversibly blocked by low concentration of the alkylating agent, N -ethylmaleimide (NEM). The biotin-switch assay showed that both GSNO and SNAP treatments caused S- nitrosylation of TnI f S- glutathionylation pretreatment blocked the effects of S- nitrosylation on Ca 2+ sensitivity, and vice-versa. S- nitrosylation pretreatment prevented NEM from irreversibly blocking S- glutathionylation of TnI f and its effects on Ca 2+ sensitivity, and likewise S- glutathionylation pretreatment prevented NEM block of S- nitrosylation. Following substitution of TnI f into rat slow-twitch fibers, S- nitrosylation treatment caused decreased Ca 2+ sensitivity. These findings demonstrate that S- nitrosylation and S- glutathionylation exert opposing effects on Ca 2+ sensitivity in mammalian FT muscle fibers, mediated by competitive actions on Cys134

Rubella virus: first calcium-requiring viral fusion protein.

PubMed

Dubé, Mathieu; Rey, Felix A; Kielian, Margaret

2014-12-01

Rubella virus (RuV) infection of pregnant women can cause fetal death, miscarriage, or severe fetal malformations, and remains a significant health problem in much of the underdeveloped world. RuV is a small enveloped RNA virus that infects target cells by receptor-mediated endocytosis and low pH-dependent membrane fusion. The structure of the RuV E1 fusion protein was recently solved in its postfusion conformation. RuV E1 is a member of the class II fusion proteins and is structurally related to the alphavirus and flavivirus fusion proteins. Unlike the other known class II fusion proteins, however, RuV E1 contains two fusion loops, with a metal ion complexed between them by the polar residues N88 and D136. Here we demonstrated that RuV infection specifically requires Ca(2+) during virus entry. Other tested cations did not substitute. Ca(2+) was not required for virus binding to cell surface receptors, endocytic uptake, or formation of the low pH-dependent E1 homotrimer. However, Ca(2+) was required for low pH-triggered E1 liposome insertion, virus fusion and infection. Alanine substitution of N88 or D136 was lethal. While the mutant viruses were efficiently assembled and endocytosed by host cells, E1-membrane insertion and fusion were specifically blocked. Together our data indicate that RuV E1 is the first example of a Ca(2+)-dependent viral fusion protein and has a unique membrane interaction mechanism.

NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion.

PubMed

Mahajan, Mukesh; Chatterjee, Deepak; Bhuvaneswari, Kannaian; Pillay, Shubhadra; Bhattacharjya, Surajit

2018-02-01

The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15 N{ 1 H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. Copyright © 2017 Elsevier B.V. All rights reserved.

Hyperpolarized 15N-pyridine Derivatives as pH-Sensitive MRI Agents

PubMed Central

Jiang, Weina; Lumata, Lloyd; Chen, Wei; Zhang, Shanrong; Kovacs, Zoltan; Sherry, A. Dean; Khemtong, Chalermchai

2015-01-01

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Δδ >90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values. PMID:25774436

Influence of nuclear data uncertainties on thorium fusion-fission hybrid blanket nucleonic performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, E.T.; Mathews, D.R.

1979-09-01

The fusion-fission hybrid blanket proposed for the Tandem Mirror Hybrid Reactor employs thorium metal as the fertile material. Based on the ENDF/B-IV nuclear data, the /sup 233/U and tritium production rate and blanket energy multiplication averaged over the blanket lifetime of about 9 MW-yr/m/sup 2/ are 0.76 and 1.12 per D-T neutron and 4.8, respectively. At the time of the blanket discharge, the /sup 233/U enrichment in the thorium metal is about 3%. The thorium cross sections given by the ENDF/B-IV and V were reviewed, and the important partial cross sections such as (n,2n), (n,3n), and (n,..gamma..) were found tomore » be known to +-10 to 20% in the respective energy range of interest. A sensitivity study showed that the /sup 233/U and tritium production rate and blanket energy multiplication are relatively sensitive to the thorium capture and fission cross section uncertainties. In order to predict the above parameters within +-1%, the Th(n,..gamma..) and Th(n,..nu..f) cross sections must be measured within about +-2% in the energy range 3 to 3000 keV and 13.5 to 15 MeV, respectively.« less

Sulphate transport by H+ symport and by the dicarboxylate carrier in mitochondria.

PubMed Central

Saris, N E

1980-01-01

1. Swelling of mitochondria was induced in non-respiring mitochondria by 30 mM or more Na2SO4 or by respiration in the presence of K2SO4. Respiration-drive swelling resulted in loss of respiratory control. Sulphate, when present at 10 mM concentration, promoted the release of accumulated Ca2+. 2. Swelling was prevented by N-ethylmaleimide and formaldehyde, known inhibitors of the phosphate carrier. Sulphate-induced swelling was more sensitive to the inhibitors than was phosphate-induced swelling. At lower concentration of sulphate, 5 mM, an alkalinisation of the medium was observed in addition of sulphate, indicating H+-sulphate symport. There was competition between sulphate and phosphate for transport by this mechanism. It is suggested that sulphate may be transported, though at a comparatively slow rate, by the phosphate carrier. 3. Uptake of sulphate was stimulated when preceded by energy-dependent accumulation of Ba2+, especially when acetate was also present, indicating precipitation of BaSO4 in the matrix. Using this system the influx of sulphate was studied at lower concentrations, 10 mM or less. the contributions of the H+ symporter (sensitive to N-ethylmaleimide) and the dicarboxylate carrier (sensitive to butylmalonate) could then be studied. The dicarboxylate carrier had a lower Km and was mainly responsible for sulphate transport at lower concentration range. At 10 mM-sulphate the transport rates by the two systems appeared to be similar; at still higher concentrations the H+ symporter may become more important. PMID:7236245

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes.

PubMed

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian; Kielian, Margaret

2016-07-15

The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes

PubMed Central

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian

2016-01-01

ABSTRACT The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. IMPORTANCE Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium

Fusion imaging: a novel staging modality in testis cancer.

PubMed

Sterbis, Joseph R; Rice, Kevin R; Javitt, Marcia C; Schenkman, Noah S; Brassell, Stephen A

2010-11-05

Computed tomography and chest radiographs provide the standard imaging for staging, treatment, and surveillance of testicular germ cell neoplasms. Positron emission tomography has recently been utilized for staging, but is somewhat limited in its ability to provide anatomic localization. Fusion imaging combines the metabolic information provided by positron emission tomography with the anatomic precision of computed tomography. To the best of our knowledge, this represents the first study of the effectiveness using fusion imaging in evaluation of patients with testis cancer. A prospective study of 49 patients presenting to Walter Reed Army Medical Center with testicular cancer from 2003 to 2009 was performed. Fusion imaging was compared with conventional imaging, tumor markers, pathologic results, and clinical follow-up. There were 14 true positives, 33 true negatives, 1 false positive, and 1 false negative. Sensitivity, specificity, positive predictive value, and negative predictive value were 93.3, 97.0, 93.3, and 97.0% respectively. In 11 patient scenarios, fusion imaging differed from conventional imaging. Utility was found in superior lesion detection compared to helical computed tomography due to anatomical/functional image co-registration, detection of micrometastasis in lymph nodes (pathologic nodes < 1cm), surveillance for recurrence post-chemotherapy, differentiating fibrosis from active disease in nodes < 2.5cm, and acting as a quality assurance measure to computed tomography alone. In addition to demonstrating a sensitivity and specificity comparable or superior to conventional imaging, fusion imaging shows promise in providing additive data that may assist in clinical decision-making.

Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis

PubMed Central

Erben, Philipp; Gosenca, Darko; Müller, Martin C.; Reinhard, Jelena; Score, Joannah; del Valle, Francesco; Walz, Christoph; Mix, Jürgen; Metzgeroth, Georgia; Ernst, Thomas; Haferlach, Claudia; Cross, Nicholas C.P.; Hochhaus, Andreas; Reiter, Andreas

2010-01-01

Background Rapid identification of diverse fusion genes with involvement of PDGFRA or PDGFRB in eosinophilia-associated myeloproliferative neoplasms is essential for adequate clinical management but is complicated by the multitude and heterogeneity of partner genes and breakpoints. Design and Methods We established a generic quantitative reverse transcriptase polymerase chain reaction to detect overexpression of the 3′-regions of PDGFRA or PDGFRB as a possible indicator of an underlying fusion. Results At diagnosis, all patients with known fusion genes involving PDGFRA (n=5; 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 versus 0.0066 versus 0.0064, P<0.0001; PDGFRB/ABL: 196 versus 3.8 versus 5.85, P<0.0001). The sensitivity and specificity of the activation screening test were, respectively, 100% and 88.4% for PDGFRA and 100% and 94% for PDGFRB. Furthermore, significant overexpression of PDGFRB was found in a patient with an eosinophilia-associated myeloproliferative neoplasm with uninformative cytogenetics and an excellent response to imatinib. Subsequently, a new SART3-PDGFRB fusion gene was identified by 5′-rapid amplification of cDNA ends polymerase chain reaction (5′-RACE-PCR). Conclusions Quantitative reverse transcriptase polymerase chain reaction analysis is a simple and useful adjunct to standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in eosinophilia-associated myeloproliferative neoplasms or related disorders. PMID:20107158

Multisensor Parallel Largest Ellipsoid Distributed Data Fusion with Unknown Cross-Covariances

PubMed Central

Liu, Baoyu; Zhan, Xingqun; Zhu, Zheng H.

2017-01-01

As the largest ellipsoid (LE) data fusion algorithm can only be applied to two-sensor system, in this contribution, parallel fusion structure is proposed to introduce the LE algorithm into a multisensor system with unknown cross-covariances, and three parallel fusion structures based on different estimate pairing methods are presented and analyzed. In order to assess the influence of fusion structure on fusion performance, two fusion performance assessment parameters are defined as Fusion Distance and Fusion Index. Moreover, the formula for calculating the upper bounds of actual fused error covariances of the presented multisensor LE fusers is also provided. Demonstrated with simulation examples, the Fusion Index indicates fuser’s actual fused accuracy and its sensitivity to the sensor orders, as well as its robustness to the accuracy of newly added sensors. Compared to the LE fuser with sequential structure, the LE fusers with proposed parallel structures not only significantly improve their properties in these aspects, but also embrace better performances in consistency and computation efficiency. The presented multisensor LE fusers generally have better accuracies than covariance intersection (CI) fusion algorithm and are consistent when the local estimates are weakly correlated. PMID:28661442

Anchoring antibodies to membranes using a diphtheria toxin T domain-ZZ fusion protein as a pH sensitive membrane anchor.

PubMed

Nizard, P; Liger, D; Gaillard, C; Gillet, D

1998-08-14

We have constructed a fusion protein, T-ZZ, in which the IgG-Fc binding protein ZZ was fused to the C-terminus of the diphtheria toxin transmembrane domain (T domain). While soluble at neutral pH, T-ZZ retained the capacity of the T domain to bind to phospholipid membranes at acidic pH. Once anchored to the membrane, the ZZ part of the protein was capable of binding mouse monoclonal or rabbit polyclonal IgG. Our results show that the T-ZZ protein can function as a pH sensitive membrane anchor for the linkage of IgG to the membrane of lipid vesicles, adherent and non-adherent cells.

Circumferential fusion is dominant over posterolateral fusion in a long-term perspective: cost-utility evaluation of a randomized controlled trial in severe, chronic low back pain.

PubMed

Soegaard, Rikke; Bünger, Cody E; Christiansen, Terkel; Høy, Kristian; Eiskjaer, Søren P; Christensen, Finn B

2007-10-15

Cost-utility evaluation of a randomized, controlled trial with a 4- to 8-year follow-up. To investigate the incremental cost per quality-adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral fusion in a long-term, societal perspective. The cost-effectiveness of circumferential fusion in a long-term perspective is uncertain but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical studies reported the effect of circumferential fusion superior to the effect of posterolateral fusion. A recent trial found no significant difference between posterolateral and circumferential fusion reporting cost-effectiveness from a 2-year viewpoint. A total of 146 patients were randomized to posterolateral or circumferential fusion and followed 4 to 8 years after surgery. The mean age of the cohort was 46 years (range, 20-65 years); 61% were females, 49% were smokers, 30% had primary diagnosis of isthmic spondylolisthesis, 35% had disc degeneration and no previous surgery, and 35% had disc degeneration and previous surgery. Eighty-two percent of patients have had symptoms for more than 2 years and 50% were out of the labor market due to sickness. The EQ-5D instrument was applied for the measurement of health-related quality of life and costs (2004 U.S. dollars) were measured in a full-scale societal perspective. Productivity costs were valued by the Friction Cost method, and both costs and effects were discounted. Arithmetic means and 95% bias-corrected, bootstrapped confidence intervals were reported. Nonparametric statistics were used for tests of statistical significance. Comprehensive sensitivity analysis was conducted and reported using cost-effectiveness acceptability curves. The circumferential group demonstrated clinical superiority over the posterolateral fusion group in functional outcome (P < 0.01), fusion rate (P < 0.04), and number of reoperations (P < 0.01) among others. Cost-utility analysis demonstrated circumferential fusion

Regulation of exocytotic fusion by cell inflation.

PubMed Central

Solsona, C; Innocenti, B; Fernández, J M

1998-01-01

We have inflated patch-clamped mast cells by 3.8 +/- 1.6 times their volume by applying a hydrostatic pressure of 5-15 cm H2O to the interior of the patch pipette. Inflation did not cause changes in the cell membrane conductance and caused only a small reversible change in the cell membrane capacitance (36 +/- 5 fF/cm H2O). The specific cell membrane capacitance of inflated cells was found to be 0.5 microF/cm2. High-resolution capacitance recordings showed that inflation reduced the frequency of exocytotic fusion events by approximately 70-fold, with the remaining fusion events showing an unusual time course. Shortly after the pressure was returned to 0 cm H2O, mast cells regained their normal size and appearance and degranulated completely, even after remaining inflated for up to 60 min. We interpret these observations as an indication that inflated mast cells reversibly disassemble the structures that regulate exocytotic fusion. Upon returning to its normal size, the cell cytosol reassembles the fusion pore scaffolds and allows exocytosis to proceed, suggesting that exocytotic fusion does not require soluble proteins. Reassembly of the fusion pore can be prevented by inflating the cells with solutions containing the protease pronase, which completely blocked exocytosis. We also interpret these results as evidence that the activity of the fusion pore is sensitive to the tension of the plasma membrane. PMID:9533718

Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

PubMed

Saligan, L N; Lukkahatai, N; Holder, G; Walitt, B; Machado-Vieira, R

2016-12-01

Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P < 0.001), indicating worsening fatigue. SNAPIN levels were associated with fatigue scores (r s = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

From the NSF: The National Science Foundation's Investments in Broadening Participation in Science, Technology, Engineering, and Mathematics Education through Research and Capacity Building

ERIC Educational Resources Information Center

James, Sylvia M.; Singer, Susan R.

2016-01-01

The National Science Foundation (NSF) has a long history of investment in broadening participation (BP) in science, technology, engineering, and mathematics (STEM) education. A review of past NSF BP efforts provides insights into how the portfolio of programs and activities has evolved and the broad array of innovative strategies that has been…

Neutron diffraction studies of viral fusion peptides

NASA Astrophysics Data System (ADS)

Bradshaw, Jeremy P.; J. M. Darkes, Malcolm; Katsaras, John; Epand, Richard M.

2000-03-01

Membrane fusion plays a vital role in a large and diverse number of essential biological processes. Despite this fact, the precise molecular events that occur during fusion are still not known. We are currently engaged on a study of membrane fusion as mediated by viral fusion peptides. These peptides are the N-terminal regions of certain viral envelope proteins that mediate the process of fusion between the viral envelope and the membranes of the host cell during the infection process. As part of this study, we have carried out neutron diffraction measurements at the ILL, BeNSC and Chalk River, on a range of viral fusion peptides. The peptides, from simian immunodeficiency virus (SIV), influenza A and feline leukaemia virus (FeLV), were incorporated into stacked phospholipid bilayers. Some of the peptides had been specifically deuterated at key amino acids. Lamellar diffraction data were collected and analysed to yield information on the peptide conformation, location and orientation relative to the bilayer.

Sensor fusion to enable next generation low cost Night Vision systems

NASA Astrophysics Data System (ADS)

Schweiger, R.; Franz, S.; Löhlein, O.; Ritter, W.; Källhammer, J.-E.; Franks, J.; Krekels, T.

2010-04-01

The next generation of automotive Night Vision Enhancement systems offers automatic pedestrian recognition with a performance beyond current Night Vision systems at a lower cost. This will allow high market penetration, covering the luxury as well as compact car segments. Improved performance can be achieved by fusing a Far Infrared (FIR) sensor with a Near Infrared (NIR) sensor. However, fusing with today's FIR systems will be too costly to get a high market penetration. The main cost drivers of the FIR system are its resolution and its sensitivity. Sensor cost is largely determined by sensor die size. Fewer and smaller pixels will reduce die size but also resolution and sensitivity. Sensitivity limits are mainly determined by inclement weather performance. Sensitivity requirements should be matched to the possibilities of low cost FIR optics, especially implications of molding of highly complex optical surfaces. As a FIR sensor specified for fusion can have lower resolution as well as lower sensitivity, fusing FIR and NIR can solve performance and cost problems. To allow compensation of FIR-sensor degradation on the pedestrian detection capabilities, a fusion approach called MultiSensorBoosting is presented that produces a classifier holding highly discriminative sub-pixel features from both sensors at once. The algorithm is applied on data with different resolution and on data obtained from cameras with varying optics to incorporate various sensor sensitivities. As it is not feasible to record representative data with all different sensor configurations, transformation routines on existing high resolution data recorded with high sensitivity cameras are investigated in order to determine the effects of lower resolution and lower sensitivity to the overall detection performance. This paper also gives an overview of the first results showing that a reduction of FIR sensor resolution can be compensated using fusion techniques and a reduction of sensitivity can be

Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

PubMed

Conlon, Kevin P; Basrur, Venkatesha; Rolland, Delphine; Wolfe, Thomas; Nesvizhskii, Alexey I; MacCoss, Michael J; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2013-10-01

Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cavrois, Marielle; Neidleman, Jason; Yonemoto, Wes

2004-10-15

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing {beta}-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of {beta}-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype andmore » Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.« less

Kar5p Is Required for Multiple Functions in Both Inner and Outer Nuclear Envelope Fusion in Saccharomyces cerevisiae

PubMed Central

Rogers, Jason V.; Rose, Mark D.

2014-01-01

During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide–sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p’s functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion. PMID:25467943

Top-Down, Routinized Reform in Low-Income, Rural Schools: NSF's Appalachian Rural Systemic Initiative.

ERIC Educational Resources Information Center

Bickel, Robert; Tomasek, Terry; Eagle, Teresa Hardman

2000-01-01

Describes and evaluates the Appalachian Rural Systemic Initiative, a six-state consortium for academic improvement supported by the National Science Foundation (NSF), that focuses on low-income rural schools. The 1-day, one-school site visits that constitute program reviews in this initiative are unlikely to enhance achievement in either science…

From the NSF: The National Science Foundation's Investments in Broadening Participation in Science, Technology, Engineering, and Mathematics Education through Research and Capacity Building.

PubMed

James, Sylvia M; Singer, Susan R

The National Science Foundation (NSF) has a long history of investment in broadening participation (BP) in science, technology, engineering, and mathematics (STEM) education. A review of past NSF BP efforts provides insights into how the portfolio of programs and activities has evolved and the broad array of innovative strategies that has been used to increase the participation of groups underrepresented in STEM, including women, minorities, and persons with disabilities. While many are familiar with these long-standing programmatic efforts, BP is also a key component of NSF's strategic plans, has been highlighted in National Science Board reports, and is the focus of ongoing outreach efforts. The majority of familiar BP programs, such as the Louis Stokes Alliances for Minority Participation (now 25 years old), are housed in the Directorate for Education and Human Resources. However, fellowship programs such as the Graduate Research Fellowships and Postdoctoral Research Fellowships under the Directorate for Biological Sciences (and parallel directorates in other STEM disciplines) are frequently used to address underrepresentation in STEM disciplines. The FY2016 and FY2017 budget requests incorporate funding for NSF INCLUDES, a new cross-agency BP initiative that will build on prior successes while addressing national BP challenges. NSF INCLUDES invites the use of innovative approaches for taking evidence-based best practices to scale, ushering in a new era in NSF BP advancement. © 2016 S. M. James and S. R. Singer. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Evolution of Elemental Composition and Morphology in Fusion Reactor's First Wall

NASA Astrophysics Data System (ADS)

Kim, Yong W.

2007-11-01

Forcing of a multi-element alloy by a gradient field can modify the spatial profile of its elemental composition. The gradient field may be in the imposed temperature or the flux of impinging particles. In a fusion device, both scenarios apply. The consequences must be well understood because they change the thermal transport properties as well as the strength, corrosion and wear characteristics of the first wall materials. Given the large number of directions material evolution can take, new robust methods of near-surface composition analyses are needed. This paper presents a new measurement methodology and requisite instrumentation, which can provide measures of local elemental composition and transport properties simultaneously by time-resolved spectroscopy of laser-produced plasma (LPP) plume emissions from the specimen surfaces. The studies to date show that the composition profiles can be modified thermally in a reproducible manner; disparate thermal transport of constituent atoms can incur modifications of near-surface composition profiles.[Y.W. Kim, Int. J. Thermophysics 28, 732 (2007)] Also, disparate fluxes of fuel particles, fusion products and impurities force the first walls in myriad ways. Repetitive application of the LPP analysis can resolve the near-surface composition profile as well as transport properties over several microns with depth resolutions to 20 nm. Work supported in part by NSF-DMR.

Molecular switch-modulated fluorescent copper nanoclusters for selective and sensitive detection of histidine and cysteine.

PubMed

Gu, Zefeng; Cao, Zhijuan

2018-06-07

A novel assay for histidine and cysteine has been constructed based on modulation of fluorescent copper nanoclusters (CuNCs) by molecular switches. In our previous work, a dumbbell DNA template with a poly-T (thymine) loop has been developed as an excellent template for the formation of strongly fluorescent CuNCs. Herein, for the first time, we established this biosensor for sensing two amino acids by using dumbbell DNA-templated CuNCs as the single probe. Among 20 natural amino acids, only histidine and cysteine can selectively quench fluorescence emission of CuNCs, because of the specific interaction of these compounds with copper ions. Furthermore, by using nickel ions (Ni 2+ ) and N-ethylmaleimide as the masking agents for histidine and cysteine respectively, an integrated logic gate system was designed by coupling with the fluorescent CuNCs and demonstrated selective and sensitive detection of cysteine and histidine. Under optimal conditions, cysteine can be detected in the concentration ranges of 0.01-10.0 μM with the detection limit (DL) of as low as 98 pM, while histidine can be detected in the ranges of 0.05-40.0 μM with DL of 1.6 nM. In addition, histidine and cysteine can be observed with the naked eye under a hand-held UV lamp (DL, 50 nM), which can be easily adapted to automated high-throughput screening. Finally, the strategy has been successfully utilized for biological fluids. The proposed system can be conducted in homogeneous solution, eliminating the need for organic cosolvents, separation processes of nanomaterials, or any chemical modifications. Overall, the assay provides an alternative method for simultaneous detection of cysteine and histidine by taking the advantages of high speed, no label and enzyme requirement, and good sensitivity and specificity, and will satisfy the great demand for determination of amino acids in fields such as food processing, biochemistry, pharmaceuticals, and clinical analysis. Graphical abstract.

Fusion Imaging: A Novel Staging Modality in Testis Cancer

PubMed Central

Sterbis, Joseph R.; Rice, Kevin R.; Javitt, Marcia C.; Schenkman, Noah S.; Brassell, Stephen A.

2010-01-01

Objective: Computed tomography and chest radiographs provide the standard imaging for staging, treatment, and surveillance of testicular germ cell neoplasms. Positron emission tomography has recently been utilized for staging, but is somewhat limited in its ability to provide anatomic localization. Fusion imaging combines the metabolic information provided by positron emission tomography with the anatomic precision of computed tomography. To the best of our knowledge, this represents the first study of the effectiveness using fusion imaging in evaluation of patients with testis cancer. Methods: A prospective study of 49 patients presenting to Walter Reed Army Medical Center with testicular cancer from 2003 to 2009 was performed. Fusion imaging was compared with conventional imaging, tumor markers, pathologic results, and clinical follow-up. Results: There were 14 true positives, 33 true negatives, 1 false positive, and 1 false negative. Sensitivity, specificity, positive predictive value, and negative predictive value were 93.3, 97.0, 93.3, and 97.0% respectively. In 11 patient scenarios, fusion imaging differed from conventional imaging. Utility was found in superior lesion detection compared to helical computed tomography due to anatomical/functional image co-registration, detection of micrometastasis in lymph nodes (pathologic nodes < 1cm), surveillance for recurrence post-chemotherapy, differentiating fibrosis from active disease in nodes < 2.5cm, and acting as a quality assurance measure to computed tomography alone. Conclusions: In addition to demonstrating a sensitivity and specificity comparable or superior to conventional imaging, fusion imaging shows promise in providing additive data that may assist in clinical decision-making. PMID:21103077

UNC-18 Promotes Both the Anterograde Trafficking and Synaptic Function of Syntaxin

PubMed Central

McEwen, Jason M.

2008-01-01

The SM protein UNC-18 has been proposed to regulate several aspects of secretion, including synaptic vesicle docking, priming, and fusion. Here, we show that UNC-18 has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1. In unc-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies. Colocalization studies and analysis of carbohydrate modifications both suggest that this accumulation occurs in the endoplasmic reticulum. This trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two active zone markers were unaffected. UNC-18 binds to Syntaxin through at least two mechanisms: binding to closed Syntaxin, or to the N terminus of Syntaxin. It is unclear which of these binding modes mediates UNC-18 function in neurons. The chaperone function of UNC-18 was eliminated in double mutants predicted to disrupt both modes of Syntaxin binding, but it was unaffected in single mutants. By contrast, mutations predicted to disrupt UNC-18 binding to the N terminus of Syntaxin caused significant defects in locomotion behavior and responsiveness to cholinesterase inhibitors. Collectively, these results demonstrate the UNC-18 acts as a molecular chaperone for Syntaxin transport in neurons and that the two modes of UNC-18 binding to Syntaxin are involved in different aspects of UNC-18 function. PMID:18596236

Hybrid organic/inorganic position-sensitive detectors based on PEDOT:PSS/n-Si

NASA Astrophysics Data System (ADS)

Javadi, Mohammad; Gholami, Mahdiyeh; Torbatiyan, Hadis; Abdi, Yaser

2018-03-01

Various configurations like p-n junctions, metal-semiconductor Schottky barriers, and metal-oxide-semiconductor structures have been widely used in position-sensitive detectors. In this report, we propose a PEDOT:PSS/n-Si heterojunction as a hybrid organic/inorganic configuration for position-sensitive detectors. The influence of the thickness of the PEDOT:PSS layer, the wavelength of incident light, and the intensity of illumination on the device performance are investigated. The hybrid PSD exhibits very high sensitivity (>100 mV/mm), excellent nonlinearity (<3%), and a response correlation coefficient (>0.995) with a response time of <4 ms to the inhomogeneous IR illumination. The presented hybrid configuration also benefits from a straightforward low-temperature fabrication process. These advantages of the PEDOT:PSS/n-Si heterojunction are very promising for developing a new class of position-sensitive detectors based on the hybrid organic/inorganic junctions.

Role of hexadecapole deformation of projectile 28Si in heavy-ion fusion reactions near the Coulomb barrier

NASA Astrophysics Data System (ADS)

Kaur, Gurpreet; Hagino, K.; Rowley, N.

2018-06-01

The vast knowledge regarding the strong influence of quadrupole deformation β2 of colliding nuclei in heavy-ion sub-barrier fusion reactions inspires a desire to quest the sensitivity of fusion dynamics to higher order deformations, such as β4 and β6 deformations. However, such studies have rarely been carried out, especially for deformation of projectile nuclei. In this article, we investigated the role of β4 of the projectile nucleus in the fusion of the 28Si+92Zr system. We demonstrated that the fusion barrier distribution is sensitive to the sign and value of the β4 parameter of the projectile, 28Si, and confirmed that the 28Si nucleus has a large positive β4. This study opens an indirect way to estimate deformation parameters of radioactive nuclei using fusion reactions, which is otherwise difficult because of experimental constraints.

Fusion 2.0: The Next Generation of Fusion in California: Aligning State and Regional Fusion Centers

DTIC Science & Technology

2010-03-01

bible ” for fusion center management, as evidenced by the theme of the 2009 National Fusion Center Conference; appropriately called “Achieving Baseline...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS FUSION 2.0: THE NEXT GENERATION OF FUSION IN CALIFORNIA: ALIGNING STATE AND...Master’s Thesis 4. TITLE AND SUBTITLE Fusion 2.0: The Next Generation of Fusion in California: Aligning State and Regional Fusion

The University of Minnesota Morris - N.S.F. REU Program: Twenty years of encouraging women to participate in the Geological Sciences

NASA Astrophysics Data System (ADS)

Cotter, J. F.

2009-12-01

support network that has developed among the UMM-REU alumni. Participants read publications by past UMM-REU researchers, they are encouraged to contact alumni for information and advice, and alumni are invited back to mentor participants, provide insights and interact socially. UMM-REU reunions are held on a regular basis. The UMM-REU network is growing. Ninety-three women from 30 institutions have participated in the UMM-REU program. Participants have published four papers and 75 abstracts. Initial career trajectories are good. Of the 80 UMM-REU alumni that have (to date) received a bachelor degree: 29 went directly into careers in the sciences or teaching and 46 enrolled in graduate (9 have completed Ph.D.s). Over the long term results are also good. Of the 93 UMM-REU participants only 13 are not now pursuing degrees or working in careers in the sciences. Research for this study was funded by a grant from the N.S.F.-R.E.U. Program, including NSF-EAR 9820249 and NSF-EAR 0640575.

From the NSF: The National Science Foundation’s Investments in Broadening Participation in Science, Technology, Engineering, and Mathematics Education through Research and Capacity Building

PubMed Central

James, Sylvia M.; Singer, Susan R.

2016-01-01

The National Science Foundation (NSF) has a long history of investment in broadening participation (BP) in science, technology, engineering, and mathematics (STEM) education. A review of past NSF BP efforts provides insights into how the portfolio of programs and activities has evolved and the broad array of innovative strategies that has been used to increase the participation of groups underrepresented in STEM, including women, minorities, and persons with disabilities. While many are familiar with these long-standing programmatic efforts, BP is also a key component of NSF’s strategic plans, has been highlighted in National Science Board reports, and is the focus of ongoing outreach efforts. The majority of familiar BP programs, such as the Louis Stokes Alliances for Minority Participation (now 25 years old), are housed in the Directorate for Education and Human Resources. However, fellowship programs such as the Graduate Research Fellowships and Postdoctoral Research Fellowships under the Directorate for Biological Sciences (and parallel directorates in other STEM disciplines) are frequently used to address underrepresentation in STEM disciplines. The FY2016 and FY2017 budget requests incorporate funding for NSF INCLUDES, a new cross-agency BP initiative that will build on prior successes while addressing national BP challenges. NSF INCLUDES invites the use of innovative approaches for taking evidence-based best practices to scale, ushering in a new era in NSF BP advancement. PMID:27587853

Theoretical quantification of shock-timing sensitivities for direct-drive inertial confinement fusion implosions on OMEGA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, D.; Boehly, T. R.; Gregor, M. C.

Using temporally shaped laser pulses, multiple shocks can be launched in direct-drive inertial confinement fusion implosion experiments to set the shell on a desired isentrope or adiabat. The velocity of the first shock and the times at which subsequent shocks catch up to it are measured through the VISAR diagnostic [T. R. Boehly et al., Phys. Plasmas 18, 092706 (2011)] on OMEGA [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. Simulations reproduce these velocity and shock-merger time measurements when using laser pulses designed for setting mid-adiabat (alpha ~ 3) implosions, but agreement degrades for lower-adiabat (alpha ~ 1)more » designs. Several possibilities for this difference are studied: (1) errors in placing the target at the center of irradiation (target offset), (2) variations in energy between the different incident beams (power imbalance), and (3) errors in modeling the laser energy coupled into the capsule. Simulation results indicate that shock timing is most sensitive to details of the density and temperature profiles in the coronal plasma, which influences the laser energy coupled into the target, and only marginally sensitive to target offset and beam power imbalance. A new technique under development to infer coronal profiles using x-ray self-emission imaging [A. K. Davis et al., Bull. Am. Phys. Soc. 61, BAPS.2016.DPP.NO8.7 (2016)] can be applied to the pulse shapes used in shock-timing experiments. This will help identify improved physics models to implement in codes and consequently enhance shock-timing predictive capability for low-adiabat pulses.« less

Dual wavelength imaging allows analysis of membrane fusion of influenza virus inside cells.

PubMed

Sakai, Tatsuya; Ohuchi, Masanobu; Imai, Masaki; Mizuno, Takafumi; Kawasaki, Kazunori; Kuroda, Kazumichi; Yamashina, Shohei

2006-02-01

Influenza virus hemagglutinin (HA) is a determinant of virus infectivity. Therefore, it is important to determine whether HA of a new influenza virus, which can potentially cause pandemics, is functional against human cells. The novel imaging technique reported here allows rapid analysis of HA function by visualizing viral fusion inside cells. This imaging was designed to detect fusion changing the spectrum of the fluorescence-labeled virus. Using this imaging, we detected the fusion between a virus and a very small endosome that could not be detected previously, indicating that the imaging allows highly sensitive detection of viral fusion.

Metal Hall sensors for the new generation fusion reactors of DEMO scale

NASA Astrophysics Data System (ADS)

Bolshakova, I.; Bulavin, M.; Kargin, N.; Kost, Ya.; Kuech, T.; Kulikov, S.; Radishevskiy, M.; Shurygin, F.; Strikhanov, M.; Vasil'evskii, I.; Vasyliev, A.

2017-11-01

For the first time, the results of on-line testing of metal Hall sensors based on nano-thickness (50-70) nm gold films, which was conducted under irradiation by high-energy neutrons up to the high fluences of 1 · 1024 n · m-2, are presented. The testing has been carried out in the IBR-2 fast pulsed reactor in the neutron flux with the intensity of 1.5 · 1017 n · m-2 · s-1 at the Joint Institute for Nuclear Research. The energy spectrum of neutron flux was very close to that expected for the ex-vessel sensors locations in the ITER experimental reactor. The magnetic field sensitivity of the gold sensors was stable within the whole fluence range under research. Also, sensitivity values at the start and at the end of irradiation session were equal within the measurement error (<1%). The results obtained make it possible to recommend gold sensors for magnetic diagnostics in the new generation fusion reactors of DEMO scale.

A flexible data fusion architecture for persistent surveillance using ultra-low-power wireless sensor networks

NASA Astrophysics Data System (ADS)

Hanson, Jeffrey A.; McLaughlin, Keith L.; Sereno, Thomas J.

2011-06-01

We have developed a flexible, target-driven, multi-modal, physics-based fusion architecture that efficiently searches sensor detections for targets and rejects clutter while controlling the combinatoric problems that commonly arise in datadriven fusion systems. The informational constraints imposed by long lifetime requirements make systems vulnerable to false alarms. We demonstrate that our data fusion system significantly reduces false alarms while maintaining high sensitivity to threats. In addition, mission goals can vary substantially in terms of targets-of-interest, required characterization, acceptable latency, and false alarm rates. Our fusion architecture provides the flexibility to match these trade-offs with mission requirements unlike many conventional systems that require significant modifications for each new mission. We illustrate our data fusion performance with case studies that span many of the potential mission scenarios including border surveillance, base security, and infrastructure protection. In these studies, we deployed multi-modal sensor nodes - including geophones, magnetometers, accelerometers and PIR sensors - with low-power processing algorithms and low-bandwidth wireless mesh networking to create networks capable of multi-year operation. The results show our data fusion architecture maintains high sensitivities while suppressing most false alarms for a variety of environments and targets.

2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation

PubMed Central

Lai, Jeffrey K. F.; Sam, I-Ching; Verlhac, Pauline; Baguet, Joël; Faure, Mathias

2017-01-01

Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation. Yeast 2-hybrid and co-affinity purification assays showed that 2BC physically and specifically interacted with a N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein, syntaxin-17 (STX17). Co-immunoprecipitation assay further showed that 2BC binds to SNARE proteins, STX17 and synaptosome associated protein 29 (SNAP29). Transient knockdown of STX17, SNAP29, and microtubule-associated protein 1 light chain 3B (LC3B), crucial proteins in the fusion between autophagosomes and lysosomes) as well as the lysosomal-associated membrane protein 1 (LAMP1) impaired production of infectious EV-A71 in RD cells. Collectively, these results demonstrate that the generation of autolysosomes triggered by the 2BC non-structural protein is important for EV-A71 replication, revealing a potential molecular pathway targeted by the virus to exploit autophagy. This study opens the possibility for the development of novel antivirals that specifically target 2BC to inhibit formation of autolysosomes during EV-A71 infection. PMID:28677644

Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.

PubMed

Jin, Rongsheng; Rummel, Andreas; Binz, Thomas; Brunger, Axel T

2006-12-21

Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the neuroparalytic syndrome of botulism. With a lethal dose of 1 ng kg(-1), they pose a biological hazard to humans and a serious potential bioweapon threat. BoNTs bind with high specificity at neuromuscular junctions and they impair exocytosis of synaptic vesicles containing acetylcholine through specific proteolysis of SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery. The molecular details of the toxin-cell recognition have been elusive. Here we report the structure of a BoNT in complex with its protein receptor: the receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound to the luminal domain of synaptotagmin II, determined at 2.15 A resolution. On binding, a helix is induced in the luminal domain which binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice is adjacent to the non-overlapping ganglioside-binding site of BoNT/B. Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at both neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies of structure-based mutations indicate high specificity and affinity of the interaction, and high selectivity of BoNT/B among synaptotagmin I and II isoforms. Synergistic binding of both synaptotagmin and ganglioside imposes geometric restrictions on the initiation of BoNT/B translocation after endocytosis. Our results provide the basis for the rational development of preventive vaccines or inhibitors against these neurotoxins.

NSF Policies on Software and Data Sharing and their Implementation

NASA Astrophysics Data System (ADS)

Katz, Daniel

2014-01-01

Since January 2011, the National Science Foundation has required a Data Management plan to be submitted with all proposals. This plan should include a description of how the proposers will share the products of the research (http://www.nsf.gov/bfa/dias/policy/dmp.jsp). What constitutes such data will be determined by the community of interest through the process of peer review and program management. This may include, but is not limited to: data, publications, samples, physical collections, software and models. In particular, “investigators and grantees are encouraged to share software and inventions created under an award or otherwise make them or their products widely available and usable.”

Calcium-dependent regulation of SNARE-mediated membrane fusion by calmodulin.

PubMed

Di Giovanni, Jerome; Iborra, Cécile; Maulet, Yves; Lévêque, Christian; El Far, Oussama; Seagar, Michael

2010-07-30

Neuroexocytosis requires SNARE proteins, which assemble into trans complexes at the synaptic vesicle/plasma membrane interface and mediate bilayer fusion. Ca(2+) sensitivity is thought to be conferred by synaptotagmin, although the ubiquitous Ca(2+)-effector calmodulin has also been implicated in SNARE-dependent membrane fusion. To examine the molecular mechanisms involved, we examined the direct action of calmodulin and synaptotagmin in vitro, using fluorescence resonance energy transfer to assay lipid mixing between target- and vesicle-SNARE liposomes. Ca(2+)/calmodulin inhibited SNARE assembly and membrane fusion by binding to two distinct motifs located in the membrane-proximal regions of VAMP2 (K(D) = 500 nm) and syntaxin 1 (K(D) = 2 microm). In contrast, fusion was increased by full-length synaptotagmin 1 anchored in vesicle-SNARE liposomes. When synaptotagmin and calmodulin were combined, synaptotagmin overcame the inhibitory effects of calmodulin. Furthermore, synaptotagmin displaced calmodulin binding to target-SNAREs. These findings suggest that two distinct Ca(2+) sensors act antagonistically in SNARE-mediated fusion.

Purification and Properties of an ATPase from Sulfolobus solfataricus

NASA Technical Reports Server (NTRS)

Hochstein, Lawrence I.; Stan-Lotter, Helga

1992-01-01

A sulfite-activated ATPase isolated from Sulfolobus solfataricus had a relative molecular mass of 370,000. It was composed of three subunits whose relative molecular masses were 63,000, 48,000, and 24,000. The enzyme was inhibited by the vacuolar ATPase inhibitors nitrate and N-ethylmaleimide; 4-chloro-7-nitrobenzo-furazan (NBD-Cl) was also inhibitory. N-Ethylmaleimide was predominately bound to the largest subunit while NBD-CL was bound to both subunits. ATPase activity was inhibited by low concentrations of p-chloromercuri-phenyl sulfonate and the inhibition was reversed by cysteine which suggested that thiol groups were essential for activity. While the ATPase from S. solfataricus shared several properties with the ATPase from S. acidocaldarius there were significant differences. The latter enzyme was activated by sulfate and chloride and was unaffected by N-ethylmaleimide, whereas the S. solfataricus ATPase was inhibited by these anions as well as N-ethyimaleimide. These differences as well as differences that occur in other vacuolar-like ATPases isolated from the methanogenic and the extremely halophilic bacteria suggest the existence of several types of archaeal ATPases, none of which have been demonstrated to synthesize ATP.

Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients.

PubMed

Hong, Shaodong; Chen, Nan; Fang, Wenfeng; Zhan, Jianhua; Liu, Qing; Kang, Shiyang; He, Xiaobo; Liu, Lin; Zhou, Ting; Huang, Jiaxing; Chen, Ying; Qin, Tao; Zhang, Yaxiong; Ma, Yuxiang; Yang, Yunpeng; Zhao, Yuanyuan; Huang, Yan; Zhang, Li

2016-03-01

Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice.

Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients

PubMed Central

Hong, Shaodong; Chen, Nan; Fang, Wenfeng; Zhan, Jianhua; Liu, Qing; Kang, Shiyang; He, Xiaobo; Liu, Lin; Zhou, Ting; Huang, Jiaxing; Chen, Ying; Qin, Tao; Zhang, Yaxiong; Ma, Yuxiang; Yang, Yunpeng; Zhao, Yuanyuan; Huang, Yan; Zhang, Li

2016-01-01

ABSTRACT Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice. PMID:27141355

Preparation of the cortical reaction: maturation-dependent migration of SNARE proteins, clathrin, and complexin to the porcine oocyte's surface blocks membrane traffic until fertilization.

PubMed

Tsai, Pei-Shiue; van Haeften, Theo; Gadella, Bart M

2011-02-01

The cortical reaction is a calcium-dependent exocytotic process in which the content of secretory granules is released into the perivitellin space immediately after fertilization, which serves to prevent polyspermic fertilization. In this study, we investigated the involvement and the organization of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins in the docking and fusion of the cortical granule membrane with the oolemma in porcine oocytes. During meiotic maturation, secretory vesicles that were labeled with a granule-specific binding lectin, peanut agglutinin (PNA), migrated toward the oocyte's surface. This surface-orientated redistribution behavior was also observed for the oocyte-specific SNARE proteins SNAP23 and VAMP1 that colocalized with the PNA-labeled structures in the cortex area just under the oolemma and with the exclusive localization area of complexin (a trans-SNARE complex-stabilizing protein). The coming together of these proteins serves to prevent the spontaneous secretion of the docked cortical granules and to prepare the oocyte's surface for the cortical reaction, which should probably be immediately compensated for by a clathrin-mediated endocytosis. In vitro fertilization resulted in the secretion of the cortical granule content and the concomitant release of complexin and clathrin into the oocyte's cytosol, and this is considered to stimulate the observed endocytosis of SNARE-containing membrane vesicles.

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

PubMed Central

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-01-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses. PMID:27752100

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

NASA Astrophysics Data System (ADS)

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-10-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.

Inhibition of Sendai virus fusion with phospholipid vesicles and human erythrocyte membranes by hydrophobic peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, D.R.; Flanagan, T.D.; Young, J.E.

1991-06-01

Hydrophobic di- and tripeptides which are capable of inhibiting enveloped virus infection of cells are also capable of inhibiting at least three different types of membrane fusion events. Large unilamellar vesicles (LUV) of N-methyl dioleoylphosphatidylethanolamine (N-methyl DOPE), containing encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and/or p-xylene bis(pyridinium bromide) (DPX), were formed by extrusion. Vesicle fusion and leakage were then monitored with the ANTS/DPX fluorescence assay. Sendai virus fusion with lipid vesicles and Sendai virus fusion with human erythrocyte membranes were measured by following the relief of fluorescence quenching of virus labeled with octadecylrhodamine B chloride (R18). This study found that the effectivenessmore » of the peptides carbobenzoxy-L-Phe-L-Phe (Z-L-Phe-L-Phe), Z-L-Phe, Z-D-Phe, and Z-Gly-L-Phe-L-Phe in inhibiting N-methyl DOPE LUV fusion or fusion of virus with N-methyl DOPE LUV also paralleled their reported ability to block viral infectivity. Furthermore, Z-D-Phe-L-PheGly and Z-Gly-L-Phe inhibited Sendai virus fusion with human erythrocyte membranes with the same relative potency with which they inhibited vesicle-vesicle and virus-vesicle fusion. The evidence suggests a mechanism by which these peptides exert their inhibition of plaque formation by enveloped viruses. This class of inhibitors apparently acts by inhibiting fusion of the viral envelope with the target cell membrane, thereby preventing viral infection. The physical pathway by which these peptides inhibit membrane fusion was investigated. {sup 31}P nuclear magnetic resonance (NMR) of proposed intermediates in the pathway for membrane fusion in LUV revealed that the potent fusion inhibitor Z-D-Phe-L-PheGly selectively altered the structure (or dynamics) of the hypothesized fusion intermediates and that the poor inhibitor Z-Gly-L-Phe did not.« less

Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein

PubMed Central

Zhu, Qiyun; Biering, Scott B.; Mirza, Anne M.; Grasseschi, Brittany A.; Mahon, Paul J.; Lee, Benhur; Aguilar, Hector C.

2013-01-01

The promotion of membrane fusion by most paramyxoviruses requires an interaction between the viral attachment and fusion (F) proteins to enable receptor binding by the former to trigger the activation of the latter for fusion. Numerous studies demonstrate that the F-interactive sites on the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) and measles virus (MV) hemagglutinin (H) proteins reside entirely within the stalk regions of those proteins. Indeed, stalk residues of NDV HN and MV H that likely mediate the F interaction have been identified. However, despite extensive efforts, the F-interactive site(s) on the Nipah virus (NiV) G attachment glycoprotein has not been identified. In this study, we have introduced individual N-linked glycosylation sites at several positions spaced at intervals along the stalk of the NiV G protein. Five of the seven introduced sites are utilized as established by a retardation of electrophoretic mobility. Despite surface expression, ephrinB2 binding, and oligomerization comparable to those of the wild-type protein, four of the five added N-glycans completely eliminate the ability of the G protein to complement the homologous F protein in the promotion of fusion. The most membrane-proximal added N-glycan reduces fusion by 80%. However, unlike similar NDV HN and MV H mutants, the NiV G glycosylation stalk mutants retain the ability to bind F, indicating that the fusion deficiency of these mutants is not due to prevention of the G-F interaction. These findings suggest that the G-F interaction is not mediated entirely by the stalk domain of G and may be more complex than that of HN/H-F. PMID:23283956

A small molecule fusion inhibitor of dengue virus.

PubMed

Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P; Ma, Ngai Ling; Smit, Jolanda M; Wilschut, Jan; Shi, Pei-Yong; Wenk, Markus R; Schul, Wouter

2009-12-01

The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside (betaOG). Compounds blocking the betaOG pocket are thought to interfere with conformational changes in the envelope protein that are essential for fusion. Two fusion assays were developed to examine the anti-fusion activities of compounds. The first assay measures the cellular internalization of propidium iodide upon membrane fusion. The second assay measures the protease activity of trypsin upon fusion between dengue virions and trypsin-containing liposomes. We performed an in silico virtual screening for small molecules that can potentially bind to the betaOG pocket and tested these candidate molecules in the two fusion assays. We identified one compound that inhibits dengue fusion in both assays with an IC(50) of 6.8 microM and reduces viral titers with an EC(50) of 9.8 microM. Time-of-addition experiments showed that the compound was only active when present during viral infection but not when added 1h later, in agreement with a mechanism of action through fusion inhibition.

Re-evaluation of the H+/site ratio of mitochondrial electron transport with the oxygen pulse technique.

PubMed

Brand, M D; Reynafarje, B; Lehninger, A L

1976-09-25

The number of protons ejected per pair of electrons passing each energy-conserving site in the electron transport chain (the H+/site ratio) has been investigated in rat liver mitochondria by means of the oxygen pulse technique introduced by Mitchell and Moyle (1967) (Biochem. J. 105, 1147-1162). The usual H+/site values of 2.0 observed by this method were found to be substantially underestimated as a result of the influx of phosphate into the mitochondria. This was shown by three different kinds of experiments. 1. Addition of N-ethylmaleimide or mersalyl, inhibitors of mitochondrial phosphate transport, increased the H+/site ratio from 2.0 to 3.0. The dependence of this effect on the concentration of either inhibitor was identical with that for inhibition of phosphate transport. Added phosphate diminished the H+/site ratio to values below 2.0 in the absence of N-ethylmaleimide. N-Ethylmaleimide protected the elevated H+/site ratio of 3.0 against the deleterious effect of added phosphate, but did not prevent a lowering effect of weak acid anions such as 3-hydroxybutyrate. 2. Prior washing of mitochondria to remove the endogenous phosphate that leaks out during the anaerobic preincubation led to H+/site ratios near 3.0, which were not increased by N-ethylmaleimide. Addition of low concentrations of phosphate to such phosphate-depleted mitochondria decreased the H+/site ratio to 2.0; addition of N-ethylmaleimide returned the ratio to 3.0. 3. Lowering the temperature to 5 degrees, which slows down phosphate transport, led to H+/site values of 3.0 even in the absence of N-ethylmaleimide. The H+/site ratio of 3.0 observed in the absence of phosphate movements was not dependent on any narrowly limited set of experimental conditions. It occurred with either Ca2+ or K+ (in the presence of valinomycin) as mobile permeant cation. It was independent of the concentration of succinate, oxygen, mitochondria, or rotenone, additions of Ca2+, Li+, or Na+ and was independent of

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter.

PubMed

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-11-02

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system's error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter

PubMed Central

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-01-01

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system’s error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the

Biosurfactant mannosyl-erythritol lipid inhibits secretion of inflammatory mediators from RBL-2H3 cells.

PubMed

Morita, Yosuke; Tadokoro, Satoshi; Sasai, Masao; Kitamoto, Dai; Hirashima, Naohide

2011-12-01

Biosurfactant mannosyl-erythritol lipids (MELs) are glycolipids produced by microbes that have various biological activities. It has been reported that MELs exhibit excellent surface-activity and also various bioactivities, such as induction of cell differentiation and apoptosis. However, little is known about their action related to drug discovery or drug seeds. We investigated the effects of MELs on the secretion of inflammatory mediators from mast cells that play a central role in allergic responses. Mast cells secrete three kinds of inflammatory mediators and we quantified these secreted mediators by photometer or ELISA. The action mechanisms of MELs were studied by Ca(2+)-sensitive fluorescence dye and Western blotting of phosphorylated proteins. MELs inhibited exocytotic release by antigen stimulation in a dose-dependent manner. We also found that MELs inhibited antigen-induced secretion of leukotriene C(4) and cytokine TNF-α (tumor necrosis factor-α). The inhibitory action of MELs on mediator secretion was mediated by inhibition of Ca(2+) increase, phosphorylation of MAP kinases and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) that serve as a molecular machinery for exocytotic membrane fusion. MELs have anti-inflammatory action inhibiting the secretion of inflammatory mediators from mast cells. MELs affects two of major intracellular signaling pathways including Ca(2+) increase and MAP kinases. MELs also inhibited the phosphorylation of SNARE proteins that is crucial for not only exocytosis but also intracellular vesicular trafficking. 2011 Elsevier B.V. All rights reserved.

The Integration of Science and Mathematics Education: Highlights from the NSF/SSMA Wingspread Conference Plenary Papers.

ERIC Educational Resources Information Center

Berlin, Donna F.

1994-01-01

Summarizes plenary papers presented at the NSF/SSMA Wingspread Conference to explore ways to improve science and mathematics education through integration. Themes included analysis of integration; divergence of mathematics education from science education; technological perspectives; promoting mathematical and scientific inquiry; and school…

Miniature fiber Fabry-Perot sensors based on fusion splicing

NASA Astrophysics Data System (ADS)

Zhu, Jia-li; Wang, Ming; Yang, Chun-di; Wang, Ting-ting

2013-03-01

Fiber-optic Fabry-Perot (F-P) sensors are widely investigated because they have several advantages over conventional sensors, such as immunity to electromagnetic interference, ability to operate under bad environments, high sensitivity and the potential for multiplexing. A new method to fabricate micro-cavity Fabry-Perot interferometer is introduced, which is fusion splicing a section of conventional single-mode fiber (SMF) and a section of hollow core or solid core photonic crystal fiber (PCF) together to form a micro-cavity at the splice joint. The technology of fusion splicing is discussed, and two miniature optical fiber sensors based on Fabry-Perot interference using fusion splicing are presented. The two sensors are completely made of fused silica, and have good high-temperature capability.

Complications with axial presacral lumbar interbody fusion: A 5-year postmarketing surveillance experience

PubMed Central

Gundanna, Mukund I.; Miller, Larry E.; Block, Jon E.

2011-01-01

Background Open and minimally invasive lumbar fusion procedures have inherent procedural risks, with posterior and transforaminal approaches resulting in significant soft-tissue injury and the anterior approach endangering organs and major blood vessels. An alternative lumbar fusion technique uses a small paracoccygeal incision and a presacral approach to the L5-S1 intervertebral space, which avoids critical structures and may result in a favorable safety profile versus open and other minimally invasive fusion techniques. The purpose of this study was to evaluate complications associated with axial interbody lumbar fusion procedures using the Axial Lumbar Interbody Fusion (AxiaLIF) System (TranS1, Wilmington, North Carolina) in the postmarketing period. Methods Between March 2005 and March 2010, 9,152 patients underwent interbody fusion with the AxiaLIF System through an axial presacral approach. A single-level L5-S1 fusion was performed in 8,034 patients (88%), and a 2-level (L4-S1) fusion was used in 1,118 (12%). A predefined database was designed to record device- or procedure-related complaints via spontaneous reporting. The complications that were recorded included bowel injury, superficial wound and systemic infections, transient intraoperative hypotension, migration, subsidence, presacral hematoma, sacral fracture, vascular injury, nerve injury, and ureter injury. Results Complications were reported in 120 of 9,152 patients (1.3%). The most commonly reported complications were bowel injury (n = 59, 0.6%) and transient intraoperative hypotension (n = 20, 0.2%). The overall complication rate was similar between single-level (n = 102, 1.3%) and 2-level (n = 18, 1.6%) fusion procedures, with no significant differences noted for any single complication. Conclusions The 5-year postmarketing surveillance experience with the AxiaLIF System suggests that axial interbody lumbar fusion through the presacral approach is associated with a low incidence of complications

Update on the NSF PAARE Program at SC State

NASA Astrophysics Data System (ADS)

Walter, Donald K.; Ajello, Marco; Brittain, Sean D.; Cash, Jennifer; Hartmann, Dieter; Ho, Shirley; Howell, Steve B.; King, Jeremy R.; Leising, Mark D.; Smith, Daniel M.

2017-01-01

We report on results from our NSF PAARE program during Year 2 of the project. Our partnership under this PAARE award includes South Carolina State University (a Historically Black College/University), Clemson University (a Ph.D. granting institution) as well as individual investigators at NASA Ames and Carnegie Mellon University. Our recent work on variable and peculiar stars, work with the Kepler Observatory and our educational products in cosmology for non-STEM majors will be presented. We have successfully piloted sharing our teaching resources by offering an upper-level astrophysics course taught at Clemson via video conferencing , allowing a graduating senior from SC State to take a course not available through his home institution. Additionally, we are working on a memorandum of agreement between the two institutions that will allow for the seamless transfer of an undergraduate from SC State to Clemson’s graduate program in physics and astronomy. Our curriculum work includes new web-based cosmology activities and laboratory experiments. SC State undergraduates are reporting at this conference on their work with the light curves of semiregular variables using Kepler data. Additionally, we are heavily involved in the Citizen CATE Experiment. A PAARE scholarship student from SC State and the PAARE PI traveled to Indonesia for the March 2016 solar eclipse. Their results are also being presented elsewhere at this conference (see Myles McKay’s poster). Support for this work includes our NSF PAARE award AST-1358913 as well as resources and support provided by Clemson University and the National Optical Astronomy Observatory. Additional support has been provided by the South Carolina Space Grant Consortium and from NASA to SC State under awards NNX11AB82G and NNX13AC24G. CATE work has been supported by NASA SMD award NNX16AB92A to the National Solar Observatory. Additional details can be found at: http://physics.scsu.edu

Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis.

PubMed

Khalid, Ruqyya; Afzal, Madeeha; Khurshid, Sana; Paracha, Rehan Zafar; Khan, Imran H; Akhtar, Muhammad Waheed

Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37°C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that α-helical and β-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli.

[Perceptual sharpness metric for visible and infrared color fusion images].

PubMed

Gao, Shao-Shu; Jin, Wei-Qi; Wang, Xia; Wang, Ling-Xue; Luo, Yuan

2012-12-01

For visible and infrared color fusion images, objective sharpness assessment model is proposed to measure the clarity of detail and edge definition of the fusion image. Firstly, the contrast sensitivity functions (CSF) of the human visual system is used to reduce insensitive frequency components under certain viewing conditions. Secondly, perceptual contrast model, which takes human luminance masking effect into account, is proposed based on local band-limited contrast model. Finally, the perceptual contrast is calculated in the region of interest (contains image details and edges) in the fusion image to evaluate image perceptual sharpness. Experimental results show that the proposed perceptual sharpness metrics provides better predictions, which are more closely matched to human perceptual evaluations, than five existing sharpness (blur) metrics for color images. The proposed perceptual sharpness metrics can evaluate the perceptual sharpness for color fusion images effectively.

Z-Pinch fusion-based nuclear propulsion

NASA Astrophysics Data System (ADS)

Miernik, J.; Statham, G.; Fabisinski, L.; Maples, C. D.; Adams, R.; Polsgrove, T.; Fincher, S.; Cassibry, J.; Cortez, R.; Turner, M.; Percy, T.

2013-02-01

Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Due to the great distances between the planets of our solar system and the harmful radiation environment of interplanetary space, high specific impulse (Isp) propulsion in vehicles with high payload mass fractions must be developed to provide practical and safe vehicles for human space flight missions. The Z-Pinch dense plasma focus method is a Magneto-Inertial Fusion (MIF) approach that may potentially lead to a small, low cost fusion reactor/engine assembly [1]. Recent advancements in experimental and theoretical understanding of this concept suggest favorable scaling of fusion power output yield [2]. The magnetic field resulting from the large current compresses the plasma to fusion conditions, and this process can be pulsed over short timescales (10-6 s). This type of plasma formation is widely used in the field of Nuclear Weapons Effects testing in the defense industry, as well as in fusion energy research. A Z-Pinch propulsion concept was designed for a vehicle based on a previous fusion vehicle study called "Human Outer Planet Exploration" (HOPE), which used Magnetized Target Fusion (MTF) [3] propulsion. The reference mission is the transport of crew and cargo to Mars and back, with a reusable vehicle. The analysis of the Z-Pinch MIF propulsion system concludes that a 40-fold increase of Isp over chemical propulsion is predicted. An Isp of 19,436 s and thrust of 3812 N s/pulse, along with nearly doubling the predicted payload mass fraction, warrants further development of enabling technologies.

Year 4 Of The NSF-funded PAARE Project At SC State

NASA Astrophysics Data System (ADS)

Walter, Donald K.; Brittain, S. D.; Cash, J. L.; Hartmann, D. H.; Howell, S. B.; King, J. R.; Leising, M. D.; Mayo, E. A.; Mighell, K. J.; Smith, D. M.

2012-01-01

We summarize the progress made through Year 4 of "A Partnership in Observational and Computational Astronomy (POCA)". This NSF-funded project is part of the "Partnerships in Astronomy and Astrophysics Research and Education (PAARE)" program. Our partnership includes South Carolina State University (a Historically Black College/University), Clemson University (a Ph.D. granting institution) and the National Optical Astronomy Observatory. Fellowships provided by POCA as well as recruitment efforts on the national level have resulted in enrolling a total of four underrepresented minorities into the Ph.D. program in astronomy at Clemson. We report on the success and challenges to recruiting students into the undergraduate physics major with astronomy option at SC State. Our summer REU program under POCA includes underrepresented students from across the country conducting research at each of our three institutions. Examples are given of our inquiry-based, laboratory exercises and web- based activities related to cosmology that have been developed with PAARE funding. We discuss our ground-based photometric and spectroscopic study of RV Tauri and Semi-Regular variables which has been expanded to include successful Cycle 2 Kepler observations of a dozen of these objects reported elsewhere at this conference (see D.K. Walter, et.al.). Support for the POCA project is provided by the NSF PAARE program to South Carolina State University under award AST-0750814 as well as resources and support provided by Clemson University and the National Optical Astronomy Observatory. Support for the Kepler observations is provided by NASA to South Carolina State University under award NNX11AB82G.

Geoscience Workforce Development at UNAVCO: Leveraging the NSF GAGE Facility

NASA Astrophysics Data System (ADS)

Morris, A. R.; Charlevoix, D. J.; Miller, M.

2013-12-01

Global economic development demands that the United States remain competitive in the STEM fields, and developing a forward-looking and well-trained geoscience workforce is imperative. According to the Bureau of Labor Statistics, the geosciences will experience a growth of 19% by 2016. Fifty percent of the current geoscience workforce is within 10-15 years of retirement, and as a result, the U.S. is facing a gap between the supply of prepared geoscientists and the demand for well-trained labor. Barring aggressive intervention, the imbalance in the geoscience workforce will continue to grow, leaving the increased demand unmet. UNAVCO, Inc. is well situated to prepare undergraduate students for placement in geoscience technical positions and advanced graduate study. UNAVCO is a university-governed consortium facilitating research and education in the geosciences and in addition UNAVCO manages the NSF Geodesy Advancing Geosciences and EarthScope (GAGE) facility. The GAGE facility supports many facets of geoscience research including instrumentation and infrastructure, data analysis, cyberinfrastructure, and broader impacts. UNAVCO supports the Research Experiences in the Solid Earth Sciences for Students (RESESS), an NSF-funded multiyear geoscience research internship, community support, and professional development program. The primary goal of the RESESS program is to increase the number of historically underrepresented students entering graduate school in the geosciences. RESESS has met with high success in the first 9 years of the program, as more than 75% of RESESS alumni are currently in Master's and PhD programs across the U.S. Building upon the successes of RESESS, UNAVCO is launching a comprehensive workforce development program that will network underrepresented groups in the geosciences to research and opportunities throughout the geosciences. This presentation will focus on the successes of the RESESS program and plans to expand on this success with broader

Quantifying Fusion Born Ion Populations in Magnetically Confined Plasmas using Ion Cyclotron Emission.

PubMed

Carbajal, L; Dendy, R O; Chapman, S C; Cook, J W S

2017-03-10

Ion cyclotron emission (ICE) offers a unique promise as a diagnostic of the fusion born alpha-particle population in magnetically confined plasmas. Pioneering observations from JET and TFTR found that ICE intensity P_{ICE} scales approximately linearly with the measured neutron flux from fusion reactions, and with the inferred concentration, n_{α}/n_{i}, of fusion born alpha particles confined within the plasma. We present fully nonlinear self-consistent kinetic simulations that reproduce this scaling for the first time. This resolves a long-standing question in the physics of fusion alpha-particle confinement and stability in magnetic confinement fusion plasmas. It confirms the magnetoacoustic cyclotron instability as the likely emission mechanism and greatly strengthens the basis for diagnostic exploitation of ICE in future burning plasmas.

Drosophila Cancer Models Identify Functional Differences between Ret Fusions.

PubMed

Levinson, Sarah; Cagan, Ross L

2016-09-13

We generated and compared Drosophila models of RET fusions CCDC6-RET and NCOA4-RET. Both RET fusions directed cells to migrate, delaminate, and undergo EMT, and both resulted in lethality when broadly expressed. In all phenotypes examined, NCOA4-RET was more severe than CCDC6-RET, mirroring their effects on patients. A functional screen against the Drosophila kinome and a library of cancer drugs found that CCDC6-RET and NCOA4-RET acted through different signaling networks and displayed distinct drug sensitivities. Combining data from the kinome and drug screens identified the WEE1 inhibitor AZD1775 plus the multi-kinase inhibitor sorafenib as a synergistic drug combination that is specific for NCOA4-RET. Our work emphasizes the importance of identifying and tailoring a patient's treatment to their specific RET fusion isoform and identifies a multi-targeted therapy that may prove effective against tumors containing the NCOA4-RET fusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Development and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumors.

PubMed

Winters, Jennifer L; Davila, Jaime I; McDonald, Amber M; Nair, Asha A; Fadra, Numrah; Wehrs, Rebecca N; Thomas, Brittany C; Balcom, Jessica R; Jin, Long; Wu, Xianglin; Voss, Jesse S; Klee, Eric W; Oliver, Gavin R; Graham, Rondell P; Neff, Jadee L; Rumilla, Kandelaria M; Aypar, Umut; Kipp, Benjamin R; Jenkins, Robert B; Jen, Jin; Halling, Kevin C

2018-06-13

We assessed the performance characteristics of an RNA sequencing (RNA-Seq) assay designed to detect gene fusions in 571 genes to help manage patients with cancer. Polyadenylated RNA was converted to cDNA, which was then used to prepare next-generation sequencing libraries that were sequenced on an Illumina HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. The assay identified 38 of 41 gene fusions detected by another method, such as fluorescence in situ hybridization or RT-PCR, for a sensitivity of 93%. No false-positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA sequencing or Mate Pair NGS (100% specificity). The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods. Eighteen of the 22 fusions had not previously been described. Good intra-assay and interassay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion-positive cases with fusion-negative RNA. Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. This assay can help identify fusions in patients with cancer; these patients may in turn benefit from both US Food and Drug Administration-approved and investigational targeted therapies. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Increasing Access for Economically Disadvantaged Students: The NSF/CSEM & S-STEM Programs at Louisiana State University

ERIC Educational Resources Information Center

Wilson, Zakiya S.; Iyengar, Sitharama S.; Pang, Su-Seng; Warner, Isiah M.; Luces, Candace A.

2012-01-01

Increasing college degree attainment for students from disadvantaged backgrounds is a prominent component of numerous state and federal legislation focused on higher education. In 1999, the National Science Foundation (NSF) instituted the "Computer Science, Engineering, and Mathematics Scholarships" (CSEMS) program; this initiative was designed to…

Fusion

NASA Astrophysics Data System (ADS)

Herman, Robin

1990-10-01

The book abounds with fascinating anecdotes about fusion's rocky path: the spurious claim by Argentine dictator Juan Peron in 1951 that his country had built a working fusion reactor, the rush by the United States to drop secrecy and publicize its fusion work as a propaganda offensive after the Russian success with Sputnik; the fortune Penthouse magazine publisher Bob Guccione sank into an unconventional fusion device, the skepticism that met an assertion by two University of Utah chemists in 1989 that they had created "cold fusion" in a bottle. Aimed at a general audience, the book describes the scientific basis of controlled fusion--the fusing of atomic nuclei, under conditions hotter than the sun, to release energy. Using personal recollections of scientists involved, it traces the history of this little-known international race that began during the Cold War in secret laboratories in the United States, Great Britain and the Soviet Union, and evolved into an astonishingly open collaboration between East and West.

Fusion positron emission/computed tomography underestimates the presence of hilar nodal metastases in patients with resected non-small cell lung cancer.

PubMed

Carrillo, Sergio A; Daniel, Vincent C; Hall, Nathan; Hitchcock, Charles L; Ross, Patrick; Kassis, Edmund S

2012-05-01

The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X=2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Single n+-i-n+ InP nanowires for highly sensitive terahertz detection.

PubMed

Peng, Kun; Parkinson, Patrick; Gao, Qian; Boland, Jessica L; Li, Ziyuan; Wang, Fan; Mokkapati, Sudha; Fu, Lan; Johnston, Michael B; Tan, Hark Hoe; Jagadish, Chennupati

2017-03-24

Developing single-nanowire terahertz (THz) electronics and employing them as sub-wavelength components for highly-integrated THz time-domain spectroscopy (THz-TDS) applications is a promising approach to achieve future low-cost, highly integrable and high-resolution THz tools, which are desirable in many areas spanning from security, industry, environmental monitoring and medical diagnostics to fundamental science. In this work, we present the design and growth of n + -i-n + InP nanowires. The axial doping profile of the n + -i-n + InP nanowires has been calibrated and characterized using combined optical and electrical approaches to achieve nanowire devices with low contact resistances, on which the highly-sensitive InP single-nanowire photoconductive THz detectors have been demonstrated. While the n + -i-n + InP nanowire detector has a only pA-level response current, it has a 2.5 times improved signal-to-noise ratio compared with the undoped InP nanowire detector and is comparable to traditional bulk THz detectors. This performance indicates a promising path to nanowire-based THz electronics for future commercial applications.

Epithelioid fibrous histiocytoma: molecular characterization of ALK fusion partners in 23 cases.

PubMed

Dickson, Brendan C; Swanson, David; Charames, George S; Fletcher, Christopher Dm; Hornick, Jason L

2018-05-01

Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners. A retrospective archival review was performed to identify cases of epithelioid fibrous histiocytoma (2012-2016). Immunohistochemistry was performed to confirm ALK expression. Targeted next-generation sequencing was applied on RNA extracted from formalin-fixed paraffin-embedded tissue to identify the fusion partners. Twenty-three cases fulfilled inclusion criteria. The mean patient age was 39 years (range, 8-74), there was no sex predilection, and >75% of cases involved the lower extremities. The most common gene fusions were SQSTM1-ALK (N=12; 52%) and VCL-ALK (N=7; 30%); the other four cases harbored novel fusion partners (DCTN1, ETV6, PPFIBP1, and SPECC1L). The pattern of ALK immunoreactivity was usually granular cytoplasmic (N=12; 52%) or granular cytoplasmic and nuclear (N=10; 43%); the case containing an ETV6 fusion partner showed nuclear staining alone. There was no apparent relationship between tumor morphology and the ALK fusion partner. In summary, SQSTM1 and VCL are the most common ALK fusion partners in epithelioid fibrous histiocytoma; DCTN1, ETV6, PPFIBP1, and SPECC1L represent rare fusion partners. The proteins encoded by these genes play diverse roles in scaffolding, cell adhesion, signaling, and transcription (among others) without clear commonalities. These findings expand the oncogenic promiscuity of many of these ALK fusion genes, which drive neoplasia in tumors of diverse lineages with widely varied clinical

Atomic force microscope studies of the fusion of floating lipid bilayers.

PubMed

Abdulreda, Midhat H; Moy, Vincent T

2007-06-15

This study investigated the fusion of apposing floating bilayers of egg L-alpha-phosphatidylcholine (egg PC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Atomic force microscope measurements of fusion forces under different compression rates were acquired to reveal the energy landscape of the fusion process under varied lipid composition and temperature. Between compression rates of approximately 1000 and approximately 100,000 pN/s, applied forces in the range from approximately 100 to approximately 500 pN resulted in fusion of floating bilayers. Our atomic force microscope measurements indicated that one main energy barrier dominated the fusion process. The acquired dynamic force spectra were fit with a simple model based on the transition state theory with the assumption that the fusion activation potential is linear. A significant shift in the energy landscape was observed when bilayer fluidity and composition were modified, respectively, by temperature and different cholesterol concentrations (15% < or = chol < or = 25%). Such modifications resulted in a more than twofold increase in the width of the fusion energy barrier for egg PC and 1,2-dimyristoyl-sn-glycero-3-phosphocholine floating bilayers. The addition of 25% cholesterol to egg PC bilayers increased the activation energy by approximately 1.0 k(B)T compared with that of bilayers with egg PC alone. These results reveal that widening of the energy barrier and consequently reduction in its slope facilitated membrane fusion.

Face-iris multimodal biometric scheme based on feature level fusion

NASA Astrophysics Data System (ADS)

Huo, Guang; Liu, Yuanning; Zhu, Xiaodong; Dong, Hongxing; He, Fei

2015-11-01

Unlike score level fusion, feature level fusion demands all the features extracted from unimodal traits with high distinguishability, as well as homogeneity and compatibility, which is difficult to achieve. Therefore, most multimodal biometric research focuses on score level fusion, whereas few investigate feature level fusion. We propose a face-iris recognition method based on feature level fusion. We build a special two-dimensional-Gabor filter bank to extract local texture features from face and iris images, and then transform them by histogram statistics into an energy-orientation variance histogram feature with lower dimensions and higher distinguishability. Finally, through a fusion-recognition strategy based on principal components analysis and support vector machine (FRSPS), feature level fusion and one-to-n identification are accomplished. The experimental results demonstrate that this method can not only effectively extract face and iris features but also provide higher recognition accuracy. Compared with some state-of-the-art fusion methods, the proposed method has a significant performance advantage.

TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate.

PubMed

Guo, Charles C; Dancer, Jane Y; Wang, Yan; Aparicio, Ana; Navone, Nora M; Troncoso, Patricia; Czerniak, Bogdan A

2011-01-01

Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate (n = 12) in comparison with small cell carcinoma of the urinary bladder (n = 12) and lung (n = 11). Fluorescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic small cell carcinoma (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases, but rearrangement of the ERG gene was not present in any small cell carcinoma of the urinary bladder or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from 2 prostatic small cell carcinomas carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by reverse transcriptase polymerase chain reaction, and DNA sequencing demonstrated that the 2 transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic small cell carcinoma, which may be helpful in distinguishing small cell carcinoma of prostatic origin from nonprostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic small cell carcinoma as well as adenocarcinoma implies that small cell carcinoma may share a common pathogenic pathway with adenocarcinoma in the prostate. Copyright © 2011 Elsevier Inc. All rights reserved.

A metabolic function of FGFR3-TACC3 gene fusions in cancer.

PubMed

Frattini, Véronique; Pagnotta, Stefano M; Tala; Fan, Jerry J; Russo, Marco V; Lee, Sang Bae; Garofano, Luciano; Zhang, Jing; Shi, Peiguo; Lewis, Genevieve; Sanson, Heloise; Frederick, Vanessa; Castano, Angelica M; Cerulo, Luigi; Rolland, Delphine C M; Mall, Raghvendra; Mokhtari, Karima; Elenitoba-Johnson, Kojo S J; Sanson, Marc; Huang, Xi; Ceccarelli, Michele; Lasorella, Anna; Iavarone, Antonio

2018-01-11

Chromosomal translocations that generate in-frame oncogenic gene fusions are notable examples of the success of targeted cancer therapies. We have previously described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases. Subsequent studies have reported similar frequencies of F3-T3 in many other cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR inhibitors, but the downstream oncogenic signalling pathways remain unknown. Here we show that human tumours with F3-T3 fusions cluster within transcriptional subgroups that are characterized by the activation of mitochondrial functions. F3-T3 activates oxidative phosphorylation and mitochondrial biogenesis and induces sensitivity to inhibitors of oxidative metabolism. Phosphorylation of the phosphopeptide PIN4 is an intermediate step in the signalling pathway of the activation of mitochondrial metabolism. The F3-T3-PIN4 axis triggers the biogenesis of peroxisomes and the synthesis of new proteins. The anabolic response converges on the PGC1α coactivator through the production of intracellular reactive oxygen species, which enables mitochondrial respiration and tumour growth. These data illustrate the oncogenic circuit engaged by F3-T3 and show that F3-T3-positive tumours rely on mitochondrial respiration, highlighting this pathway as a therapeutic opportunity for the treatment of tumours with F3-T3 fusions. We also provide insights into the genetic alterations that initiate the chain of metabolic responses that drive mitochondrial metabolism in cancer.

Sensitivity of chemical vapor deposition diamonds to DD and DT neutrons at OMEGA and the National Ignition Facility

NASA Astrophysics Data System (ADS)

Kabadi, N. V.; Sio, H.; Glebov, V.; Gatu Johnson, M.; MacPhee, A.; Frenje, J. A.; Li, C. K.; Seguin, F.; Petrasso, R.; Forrest, C.; Knauer, J.; Rinderknecht, H. G.

2016-11-01

The particle-time-of-flight (pTOF) detector at the National Ignition Facility (NIF) is used routinely to measure nuclear bang-times in inertial confinement fusion implosions. The active detector medium in pTOF is a chemical vapor deposition diamond. Calibration of the detectors sensitivity to neutrons and protons would allow measurement of nuclear bang times and hot spot areal density (ρR) on a single diagnostic. This study utilizes data collected at both NIF and Omega in an attempt to determine pTOF's absolute sensitivity to neutrons. At Omega pTOF's sensitivity to DT-n is found to be stable to within 8% at different bias voltages. At the NIF pTOF's sensitivity to DD-n varies by up to 59%. This variability must be decreased substantially for pTOF to function as a neutron yield detector at the NIF. Some possible causes of this variability are ruled out.

Sensitivity of chemical vapor deposition diamonds to DD and DT neutrons at OMEGA and the National Ignition Facility.

PubMed

Kabadi, N V; Sio, H; Glebov, V; Gatu Johnson, M; MacPhee, A; Frenje, J A; Li, C K; Seguin, F; Petrasso, R; Forrest, C; Knauer, J; Rinderknecht, H G

2016-11-01

The particle-time-of-flight (pTOF) detector at the National Ignition Facility (NIF) is used routinely to measure nuclear bang-times in inertial confinement fusion implosions. The active detector medium in pTOF is a chemical vapor deposition diamond. Calibration of the detectors sensitivity to neutrons and protons would allow measurement of nuclear bang times and hot spot areal density (ρR) on a single diagnostic. This study utilizes data collected at both NIF and Omega in an attempt to determine pTOF's absolute sensitivity to neutrons. At Omega pTOF's sensitivity to DT-n is found to be stable to within 8% at different bias voltages. At the NIF pTOF's sensitivity to DD-n varies by up to 59%. This variability must be decreased substantially for pTOF to function as a neutron yield detector at the NIF. Some possible causes of this variability are ruled out.

Measuring the face-sensitive N170 with a gaming EEG system: A validation study.

PubMed

de Lissa, Peter; Sörensen, Sidsel; Badcock, Nicholas; Thie, Johnson; McArthur, Genevieve

2015-09-30

The N170 is a "face-sensitive" event-related potential (ERP) that occurs at around 170ms over occipito-temporal brain regions. The N170's potential to provide insight into the neural processing of faces in certain populations (e.g., children and adults with cognitive impairments) is limited by its measurement in scientific laboratories that can appear threatening to some people. The advent of cheap, easy-to-use portable gaming EEG systems provides an opportunity to record EEG in new contexts and populations. This study tested the validity of the face-sensitive N170 ERP measured with an adapted commercial EEG system (the Emotiv EPOC) that is used at home by gamers. The N170 recorded through both the gaming EEG system and the research EEG system exhibited face-sensitivity, with larger mean amplitudes in response to the face stimuli than the non-face stimuli, and a delayed N170 peak in response to face inversion. The EPOC system produced very similar N170 ERPs to a research-grade Neuroscan system, and was capable of recording face-sensitivity in the N170, validating its use as research tool in this arena. This opens new possibilities for measuring the face-sensitive N170 ERP in people who cannot travel to a traditional ERP laboratory (e.g., elderly people in care), who cannot tolerate laboratory conditions (e.g., people with autism), or who need to be tested in situ for practical or experimental reasons (e.g., children in schools). Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of fusion gene expression in HCT116 cells.

PubMed

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-12-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2) , EIF3E(e1)-RSPO2(e3) , PTPRK(e1)-RSPO3(e2) , PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E , RSPO2 , PTPRK , RSPO3 , TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma.

Investigation of fusion gene expression in HCT116 cells

PubMed Central

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-01-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma. PMID:29181107

A Multiplexed Amplicon Approach for Detecting Gene Fusions by Next-Generation Sequencing.

PubMed

Beadling, Carol; Wald, Abigail I; Warrick, Andrea; Neff, Tanaya L; Zhong, Shan; Nikiforov, Yuri E; Corless, Christopher L; Nikiforova, Marina N

2016-03-01

Chromosomal rearrangements that result in oncogenic gene fusions are clinically important drivers of many cancer types. Rapid and sensitive methods are therefore needed to detect a broad range of gene fusions in clinical specimens that are often of limited quantity and quality. We describe a next-generation sequencing approach that uses a multiplex PCR-based amplicon panel to interrogate fusion transcripts that involve 19 driver genes and 94 partners implicated in solid tumors. The panel also includes control assays that evaluate the 3'/5' expression ratios of 12 oncogenic kinases, which might be used to infer gene fusion events when the partner is unknown or not included on the panel. There was good concordance between the solid tumor fusion gene panel and other methods, including fluorescence in situ hybridization, real-time PCR, Sanger sequencing, and other next-generation sequencing panels, because 40 specimens known to harbor gene fusions were correctly identified. No specific fusion reads were observed in 59 fusion-negative specimens. The 3'/5' expression ratio was informative for fusions that involved ALK, RET, and NTRK1 but not for BRAF or ROS1 fusions. However, among 37 ALK or RET fusion-negative specimens, four exhibited elevated 3'/5' expression ratios, indicating that fusions predicted solely by 3'/5' read ratios require confirmatory testing. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Electron Beam Irradiation Induced Multiwalled Carbon Nanotubes Fusion inside SEM.

PubMed

Shen, Daming; Chen, Donglei; Yang, Zhan; Liu, Huicong; Chen, Tao; Sun, Lining; Fukuda, Toshio

2017-01-01

This paper reported a method of multiwalled carbon nanotubes (MWCNTs) fusion inside a scanning electron microscope (SEM). A CNT was picked up by nanorobotics manipulator system which was constructed in SEM with 21 DOFs and 1 nm resolution. The CNT was picked up and placed on two manipulators. The tensile force was 140 nN when the CNT was pulled into two parts. Then, two parts of the CNT were connected to each other by two manipulators. The adhered force between two parts was measured to be about 20 nN. When the two parts of CNT were connected again, the contact area was fused by focused electron beam irradiation for 3 minutes. The tensile force of the junction was measured to be about 100 nN. However, after fusion, the tensile force was five times larger than the tensile force connected only by van der Waals force. This force was 70 percent of the tensile force before pulling out of CNTs. The results revealed that the electron beam irradiation was a promising method for CNT fusion. We hope this technology will be applied to nanoelectronics in the near future.

Nuclear fusion driven by Coulomb explosion of homonuclear and heteronuclear deuterium- and tritium-containing clusters

NASA Astrophysics Data System (ADS)

Last, Isidore; Jortner, Joshua

2001-12-01

The ionization and Coulomb explosion of homonuclear Dn and Tn (n=959-8007) and heteronuclear (D2O)n and (T2O)n (n=459-2171) clusters in very intense (I=5×1014-5×1018 W cm-2) laser fields is studied using classical dynamics simulations. The efficiency of the d+d and d+t nuclear fusion driven by the Coulomb explosion (NFDCE) is explored. The d+d NFDCE of (D2O)n heteronuclear clusters is enhanced by energetic and kinematic effects for D+, while for (T2O)n heteronuclear clusters the kinetic energy of T+ is dominated by energetic effects. The cluster size dependence of the fusion reaction yield has been established. The heteronuclear clusters provide considerably higher d+d and d+t fusion reaction yields than the homonuclear clusters of the same size. The clusters consisting of both D and T atoms can provide highly efficient d+t fusion reactions.

Proceedings of the Fifth NASA/NSF/DOD Workshop on Aerospace Computational Control

NASA Technical Reports Server (NTRS)

Wette, M. (Editor); Man, G. K. (Editor)

1993-01-01

The Fifth Annual Workshop on Aerospace Computational Control was one in a series of workshops sponsored by NASA, NSF, and the DOD. The purpose of these workshops is to address computational issues in the analysis, design, and testing of flexible multibody control systems for aerospace applications. The intention in holding these workshops is to bring together users, researchers, and developers of computational tools in aerospace systems (spacecraft, space robotics, aerospace transportation vehicles, etc.) for the purpose of exchanging ideas on the state of the art in computational tools and techniques.

The "grep" command but not FusionMap, FusionFinder or ChimeraScan captures the CIC-DUX4 fusion gene from whole transcriptome sequencing data on a small round cell tumor with t(4;19)(q35;q13).

PubMed

Panagopoulos, Ioannis; Gorunova, Ludmila; Bjerkehagen, Bodil; Heim, Sverre

2014-01-01

Whole transcriptome sequencing was used to study a small round cell tumor in which a t(4;19)(q35;q13) was part of the complex karyotype but where the initial reverse transcriptase PCR (RT-PCR) examination did not detect a CIC-DUX4 fusion transcript previously described as the crucial gene-level outcome of this specific translocation. The RNA sequencing data were analysed using the FusionMap, FusionFinder, and ChimeraScan programs which are specifically designed to identify fusion genes. FusionMap, FusionFinder, and ChimeraScan identified 1017, 102, and 101 fusion transcripts, respectively, but CIC-DUX4 was not among them. Since the RNA sequencing data are in the fastq text-based format, we searched the files using the "grep" command-line utility. The "grep" command searches the text for specific expressions and displays, by default, the lines where matches occur. The "specific expression" was a sequence of 20 nucleotides from the coding part of the last exon 20 of CIC (Reference Sequence: NM_015125.3) chosen since all the so far reported CIC breakpoints have occurred here. Fifteen chimeric CIC-DUX4 cDNA sequences were captured and the fusion between the CIC and DUX4 genes was mapped precisely. New primer combinations were constructed based on these findings and were used together with a polymerase suitable for amplification of GC-rich DNA templates to amplify CIC-DUX4 cDNA fragments which had the same fusion point found with "grep". In conclusion, FusionMap, FusionFinder, and ChimeraScan generated a plethora of fusion transcripts but did not detect the biologically important CIC-DUX4 chimeric transcript; they are generally useful but evidently suffer from imperfect both sensitivity and specificity. The "grep" command is an excellent tool to capture chimeric transcripts from RNA sequencing data when the pathological and/or cytogenetic information strongly indicates the presence of a specific fusion gene.

Biomechanical Characteristics of an Integrated Lumbar Interbody Fusion Device

PubMed Central

Voronov, Leonard I.; Vastardis, Georgios; Zelenakova, Julia; Carandang, Gerard; Havey, Robert M.; Waldorff, Erik I.; Zindrick, Michael R.

2014-01-01

Introduction We hypothesized that an Integrated Lumbar Interbody Fusion Device (PILLAR SA, Orthofix, Lewisville, TX) will function biomechanically similar to a traditional anterior interbody spacer (PILLAR AL, Orthofix, Lewisville, TX) plus posterior instrumentation (FIREBIRD, Orthofix, Lewisville, TX). Purpose of this study was to determine if an Integrated Interbody Fusion Device (PILLAR SA) can stabilize single motion segments as well as an anterior interbody spacer (PILLAR AL) + pedicle screw construct (FIREBIRD). Methods Eight cadaveric lumbar spines (age: 43.9±4.3 years) were used. Each specimen's range of motion was tested in flexion-extension (FE), lateral bending (LB), and axial rotation (AR) under intact condition, after L4-L5 PILLAR SA with intervertebral screws and after L4-L5 360° fusion (PILLAR AL + Pedicle Screws and rods (FIREBIRD). Each specimen was tested in flexion (8Nm) and extension (6Nm) without preload (0 N) and under 400N of preload, in lateral bending (±6 Nm) and axial rotation (±5 Nm) without preload. Results Integrated fusion using the PILLAR SA device demonstrated statistically significant reductions in range of motion of the L4-L5 motion segment as compared to the intact condition for each test direction. PILLAR SA reduced ROM from 8.9±1.9 to 2.9±1.1° in FE with 400N follower preload (67.4%), 8.0±1.7 to 2.5±1.1° in LB, and 2.2±1.2 to 0.7±0.3° in AR. A comparison between the PILLAR SA integrated fusion device versus 360° fusion construct with spacer and bilateral pedicle screws was statistically significant in FE and LB. The 360° fusion yielded motion of 1.0±0.5° in FE, 1.0±0.8° in LB (p0.05). Conclusions The PILLAR SA resulted in motions of less than 3° in all modes of motion and was not as motion restricting as the traditional 360° using bilateral pedicle screws. The residual segmental motions compare very favorably with published biomechanical studies of other interbody integrated fusion devices. PMID:25694931

β-Glucuronidase as a Sensitive and Versatile Reporter in Actinomycetes ▿

PubMed Central

Myronovskyi, Maksym; Welle, Elisabeth; Fedorenko, Viktor; Luzhetskyy, Andriy

2011-01-01

Here we describe a versatile and sensitive reporter system for actinomycetes that is based on gusA, which encodes the β-glucuronidase enzyme. A series of gusA-containing transcriptional and translational fusion vectors were constructed and utilized to study the regulatory cascade of the phenalinolactone biosynthetic gene cluster. Furthermore, these vectors were used to study the efficiency of translation initiation at the ATG, GTG, TTG, and CTG start codons. Surprisingly, constructs using a TTG start codon showed the best activity, whereas those using ATG or GTG were approximately one-half or one-third as active, respectively. The CTG fusion showed only 5% of the activity of the TTG fusion. A suicide vector, pKGLP2, carrying gusA in its backbone was used to visually detect merodiploid formation and resolution, making gene targeting in actinomycetes much faster and easier. Three regulatory genes, plaR1, plaR2, and plaR3, involved in phenalinolactone biosynthesis were efficiently replaced with an apramycin resistance marker using this system. Finally, we expanded the genetic code of actinomycetes by introducing the nonproteinogenic amino acid N-epsilon-cyclopentyloxycarbonyl-l-lysine with the GusA protein as a reporter. PMID:21685164

Role of Mediator and Effects of Temperature on ortho-C-N Bond Fusion Reactions of Aniline Using Ruthenium Templates: Isolation and Characterization of New Ruthenium Complexes of the in-Situ-Generated Ligands.

PubMed

Roy, Suman K; Sengupta, Debabrata; Rath, Santi Prasad; Saha, Tanushri; Samanta, Subhas; Goswami, Sreebrata

2017-05-01

In this work, ortho-C-N bond fusion reactions of aniline are followed by the use of two different ruthenium mediators. Reaction of aniline with [Ru III (terpy)Cl 3 ] (terpy = 2,2':6',2″-terpyridine) resulted in a trans bis-aniline ruthenium(II) complex [1] + which upon oxidation with H 2 O 2 produced compound [2] + of a bidentate ligand, N-phenyl-1,2-benzoquinonediimine, due to an oxidative ortho-C-N bond fusion reaction. Complex [1] + and aniline (neat) at 185 °C produced a bis-chelated ruthenium complex (3). A previously reported complex [Ru II (N-phenyl-1,2-benzoquinonediimine)(aniline) 2 (Cl) 2 ] (5) undergoes similar oxidation by air at 185 °C to produce complex [3]. A separate chemical reaction between aniline and strongly oxidizing tetra-n-propylammonium perruthenate [(n-pr) 4 N] + [RuO 4 ] - in air produced a ruthenium complex [4] of a N 4 -tetraamidophenylmacrocycle ligand via multiple ortho-C-N bond fusion reaction. Notably, the yield of this product is low (5%) at 100 °C but increases to 25% in refluxing aniline. All these complexes are characterized fully by their physicochemical characterizations and X-ray structure determination. From their structural parameters and other spectroscopic studies, complex [2] + is assigned as [Ru II (terpy)(N-phenyl-1,2-benzoquinonediimine)(Cl)] + whereas complex [4] is described as a ruthenium(VI) complex comprised of a reduced deprotonated N-phenyl-1,2-diamidobenzene and N 4 -tetraamidophenylmacrocyclic ligand. Complex [2] + exhibits one reversible oxidation at 1.32 V and one reversible reduction at -0.75 V vs Ag/AgCl reference electrode. EPR of the electrogenerated complexes has revealed that the oxidized complex is a ruthenium(III) complex with an axial EPR spectrum at g av = 2.06. The reduced complex [2], on the other hand, shows a single-line EPR signal at g av = 1.998. In contrast, complex [4] shows two successive one-electron oxidation waves at 0.5 and 0.8 V and an irreversible reduction wave at -0.9 V. EPR

Atomic Force Microscope Studies of the Fusion of Floating Lipid Bilayers

PubMed Central

Abdulreda, Midhat H.; Moy, Vincent T.

2007-01-01

This study investigated the fusion of apposing floating bilayers of egg L-α-phosphatidylcholine (egg PC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Atomic force microscope measurements of fusion forces under different compression rates were acquired to reveal the energy landscape of the fusion process under varied lipid composition and temperature. Between compression rates of ∼1000 and ∼100,000 pN/s, applied forces in the range from ∼100 to ∼500 pN resulted in fusion of floating bilayers. Our atomic force microscope measurements indicated that one main energy barrier dominated the fusion process. The acquired dynamic force spectra were fit with a simple model based on the transition state theory with the assumption that the fusion activation potential is linear. A significant shift in the energy landscape was observed when bilayer fluidity and composition were modified, respectively, by temperature and different cholesterol concentrations (15% ≤ chol ≤ 25%). Such modifications resulted in a more than twofold increase in the width of the fusion energy barrier for egg PC and 1,2-dimyristoyl-sn-glycero-3-phosphocholine floating bilayers. The addition of 25% cholesterol to egg PC bilayers increased the activation energy by ∼1.0 kBT compared with that of bilayers with egg PC alone. These results reveal that widening of the energy barrier and consequently reduction in its slope facilitated membrane fusion. PMID:17400691

A Strategic Vision for NSF Investments in Antarctic and Southern Ocean Research: Recommendations of a New Study from the National Academes of Sciences, Engineering, and Medicine.

NASA Astrophysics Data System (ADS)

Weller, R. A.; Bell, R. E.; Geller, L.

2015-12-01

A Committee convened by the National Academies of Sciences, Engineering, and Medicine carried out a study (at the request of NSF's Division of Polar Programs) to develop a strategic vision for the coming decade of NSF's investments in Antarctic and Southern Ocean research. The study was informed by extensive efforts to gather ideas from researchers across the United States. This presentation will provide an overview of the Committee's recommendations—regarding an overall strategic framework for a robust U.S. Antarctic program, regarding the specific areas of research recommended as highest priority for NSF support, and regarding the types of infrastructure, logistical support, data management, and other critical foundations for enabling and adding lasting value to the proposed research .

Calcium sensitive ring-like oligomers formed by synaptotagmin

PubMed Central

Wang, Jing; Bello, Oscar; Auclair, Sarah M.; Wang, Jing; Coleman, Jeff; Pincet, Frederic; Krishnakumar, Shyam S.; Sindelar, Charles V.; Rothman, James E.

2014-01-01

The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT’s cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18–43 nm, corresponding to 11–26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide–sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded. PMID:25201968

High Level Information Fusion (HLIF) with nested fusion loops

NASA Astrophysics Data System (ADS)

Woodley, Robert; Gosnell, Michael; Fischer, Amber

2013-05-01

Situation modeling and threat prediction require higher levels of data fusion in order to provide actionable information. Beyond the sensor data and sources the analyst has access to, the use of out-sourced and re-sourced data is becoming common. Through the years, some common frameworks have emerged for dealing with information fusion—perhaps the most ubiquitous being the JDL Data Fusion Group and their initial 4-level data fusion model. Since these initial developments, numerous models of information fusion have emerged, hoping to better capture the human-centric process of data analyses within a machine-centric framework. 21st Century Systems, Inc. has developed Fusion with Uncertainty Reasoning using Nested Assessment Characterizer Elements (FURNACE) to address challenges of high level information fusion and handle bias, ambiguity, and uncertainty (BAU) for Situation Modeling, Threat Modeling, and Threat Prediction. It combines JDL fusion levels with nested fusion loops and state-of-the-art data reasoning. Initial research has shown that FURNACE is able to reduce BAU and improve the fusion process by allowing high level information fusion (HLIF) to affect lower levels without the double counting of information or other biasing issues. The initial FURNACE project was focused on the underlying algorithms to produce a fusion system able to handle BAU and repurposed data in a cohesive manner. FURNACE supports analyst's efforts to develop situation models, threat models, and threat predictions to increase situational awareness of the battlespace. FURNACE will not only revolutionize the military intelligence realm, but also benefit the larger homeland defense, law enforcement, and business intelligence markets.

Normal taste acuity and preference in female adolescents with impaired 6-n-propylthiouracil sensitivity.

PubMed

Nagai, Ayako; Kubota, Masaru; Sakai, Midori; Higashiyama, Yukie

2014-01-01

This study was conducted to determine the relationship between 6-n-propylthiouracil sensitivity and taste characteristics in female students at Nara Women's University. Participants (n=135) were screened for 6-npropylthiouracil sensitivity using a taste test with 0.56 mM 6-n-propylthiouracil solution, and the sensitivity was confirmed by an assay for the bitter-taste receptor gene, TAS2R38. Based on the screening results, 33 6-npropylthiouracil tasters and 21 non-tasters were enrolled. The basic characteristics that are thought to influence taste acuity, including body mass index, saliva volume and serum micronutrient concentrations (iron, zinc and copper), were similar between the two groups. In an analysis using a filter-paper disc method, there were no differences in the acuity for four basic tastes (sweet, salty, sour and bitter) between 6-n-propylthiouracil tasters and non-tasters. In addition, the taste preference for the four basic tastes as measured by a visual analogue scale was also comparable between the two groups. This is the first study to demonstrate that 6-n-propylthiouracil nontasters have taste sensitivity for the four basic tastes similar to that in 6-n-propylthiouracil tasters, at least in female adolescents, as measured by the gustatory test using a filter-paper disc method.

Sensitive detection of n-alkanes using a mixed ionization mode proton-transfer-reaction mass spectrometer

NASA Astrophysics Data System (ADS)

Amador-Muñoz, Omar; Misztal, Pawel K.; Weber, Robin; Worton, David R.; Zhang, Haofei; Drozd, Greg; Goldstein, Allen H.

2016-11-01

Proton-transfer-reaction mass spectrometry (PTR-MS) is a technique that is widely used to detect volatile organic compounds (VOCs) with proton affinities higher than water. However, n-alkanes generally have a lower proton affinity than water and therefore proton transfer (PT) by reaction with H3O+ is not an effective mechanism for their detection. In this study, we developed a method using a conventional PTR-MS to detect n-alkanes by optimizing ion source and drift tube conditions to vary the relative amounts of different primary ions (H3O+, O2+, NO+) in the reaction chamber (drift tube). There are very few studies on O2+ detection of alkanes and the mixed mode has never been proposed before. We determined the optimum conditions and the resulting reaction mechanisms, allowing detection of n-alkanes from n-pentane to n-tridecane. These compounds are mostly emitted by evaporative/combustion process from fossil fuel use. The charge transfer (CT) mechanism observed with O2+ was the main reaction channel for n-heptane and longer n-alkanes, while for n-pentane and n-hexane the main reaction channel was hydride abstraction (HA). Maximum sensitivities were obtained at low E / N ratios (83 Td), low water flow (2 sccm) and high O2+ / NO+ ratios (Uso = 180 V). Isotopic 13C contribution was taken into account by subtracting fractions of the preceding 12C ion signal based on the number of carbon atoms and the natural abundance of 13C (i.e., 5.6 % for n-pentane and 14.5 % for n-tridecane). After accounting for isotopic distributions, we found that PT cannot be observed for n-alkanes smaller than n-decane. Instead, protonated water clusters of n-alkanes (M ṡ H3O+) species were observed with higher abundance using lower O2+ and higher water cluster fractions. M ṡ H3O+ species are probably the source for the M + H+ species observed from n-decane to n-tridecane. Normalized sensitivities to O2+ or to the sum of O2++ NO+ were determined to be a good metric with which

Sensitivity of chemical vapor deposition diamonds to DD and DT neutrons at OMEGA and the National Ignition Facility

DOE PAGES

Kabadi, N. V.; Sio, H.; Glebov, V.; ...

2016-08-09

The particle-time-of-flight (pTOF) detector at the National Ignition Facility (NIF) is used routinely to measure nuclear bang-times in inertial confinement fusion implosions. The active detector medium in pTOF is a chemical vapor deposition diamond. Calibration of the detectors sensitivity to neutrons and protons would allow measurement of nuclear bang times and hot spot areal density (ρR) on a single diagnostic. This study utilizes data collected at both NIF and Omega in an attempt to determine pTOF’s absolute sensitivity to neutrons. At Omega pTOF’s sensitivity to DT-n is found to be stable to within 8% at different bias voltages. At themore » NIF pTOF’s sensitivity to DD-n varies by up to 59%. This variability must be decreased substantially for pTOF to function as a neutron yield detector at the NIF. As a result, some possible causes of this variability are ruled out.« less

Sensitivity of chemical vapor deposition diamonds to DD and DT neutrons at OMEGA and the National Ignition Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabadi, N. V.; Sio, H.; Glebov, V.

The particle-time-of-flight (pTOF) detector at the National Ignition Facility (NIF) is used routinely to measure nuclear bang-times in inertial confinement fusion implosions. The active detector medium in pTOF is a chemical vapor deposition diamond. Calibration of the detectors sensitivity to neutrons and protons would allow measurement of nuclear bang times and hot spot areal density (ρR) on a single diagnostic. This study utilizes data collected at both NIF and Omega in an attempt to determine pTOF’s absolute sensitivity to neutrons. At Omega pTOF’s sensitivity to DT-n is found to be stable to within 8% at different bias voltages. At themore » NIF pTOF’s sensitivity to DD-n varies by up to 59%. This variability must be decreased substantially for pTOF to function as a neutron yield detector at the NIF. As a result, some possible causes of this variability are ruled out.« less

A Patron for Pure Science. The National Science Foundation's Formative Years, 1945-57. NSF 82-24.

ERIC Educational Resources Information Center

England, J. Merton

Provided in this book is a legislative and administrative history of the National Science Foundation (NSF) during its formative years (1945-57). The 15 chapter book is organized into three parts. Part 1 ("The Long Debate, 1945-50") narrates the legislative history of the Foundation's creation. Part 2 ("Beginning, 1950-54")…

[DNA-dependent DNA polymerase induced by herpes virus papio (HVP) in producing cells].

PubMed

D'iachenko, A G; Beriia, L Ia; Matsenko, L D; Kakubava, V V; Kokosh, L V

1980-11-01

A new DNA polymerase was found in the cells of suspension lymphoblastoid cultures, which produce lymphotropic baboon herpes virus (HVP). The enzyme was isolated in a partially purified form. In some properties the enzyme differs from other cellular DNA polymerases. The HVP-induced DNA polymerase has the molecular weight of 1,6 x 10(5) and sedimentation coefficient of about 8S. The enzyme is resistant to high salt concentrations and N-ethylmaleimide, but shows a pronounced sensitivity to phosphonoacetate. The enzyme effectively copies "activated" DNA and synthetic deoxyribohomopolymers. The attempts to detect the DNA polymerase activity in HVP virions were unsuccessful.

DNA-polymerase induced by Herpesvirus papio (HVP) in cells of lymphoblastoid cultures derived from lymphomatous baboons. Report V.

PubMed

Djachenko, A G; Lapin, B A

1981-01-01

A new DNA-polymerase was found in the cells of suspension lymphoblastoid cultures which produce lymphotropic baboon herpesvirus (HVP). This enzyme was isolated in a partially purified form. Some of its properties vary from those of other cellular DNA-polymerases. HVP-induced DNA-polymerase has a molecule weight of 160,000 and sedimentation coefficient of about 8 S. The enzyme is resistant to high salt concentration and N-ethylmaleimide, but it is very sensitive to phosphonoacetate. It effectively copies "activated" DNA and synthetic deoxyribohomopolymers. Attempts to reveal the DNA-polymerase activity in HVP virions were unsuccessful.

Multimodal biometric system using rank-level fusion approach.

PubMed

Monwar, Md Maruf; Gavrilova, Marina L

2009-08-01

In many real-world applications, unimodal biometric systems often face significant limitations due to sensitivity to noise, intraclass variability, data quality, nonuniversality, and other factors. Attempting to improve the performance of individual matchers in such situations may not prove to be highly effective. Multibiometric systems seek to alleviate some of these problems by providing multiple pieces of evidence of the same identity. These systems help achieve an increase in performance that may not be possible using a single-biometric indicator. This paper presents an effective fusion scheme that combines information presented by multiple domain experts based on the rank-level fusion integration method. The developed multimodal biometric system possesses a number of unique qualities, starting from utilizing principal component analysis and Fisher's linear discriminant methods for individual matchers (face, ear, and signature) identity authentication and utilizing the novel rank-level fusion method in order to consolidate the results obtained from different biometric matchers. The ranks of individual matchers are combined using the highest rank, Borda count, and logistic regression approaches. The results indicate that fusion of individual modalities can improve the overall performance of the biometric system, even in the presence of low quality data. Insights on multibiometric design using rank-level fusion and its performance on a variety of biometric databases are discussed in the concluding section.

Desensitized Optimal Filtering and Sensor Fusion Toolkit

NASA Technical Reports Server (NTRS)

Karlgaard, Christopher D.

2015-01-01

Analytical Mechanics Associates, Inc., has developed a software toolkit that filters and processes navigational data from multiple sensor sources. A key component of the toolkit is a trajectory optimization technique that reduces the sensitivity of Kalman filters with respect to model parameter uncertainties. The sensor fusion toolkit also integrates recent advances in adaptive Kalman and sigma-point filters for non-Gaussian problems with error statistics. This Phase II effort provides new filtering and sensor fusion techniques in a convenient package that can be used as a stand-alone application for ground support and/or onboard use. Its modular architecture enables ready integration with existing tools. A suite of sensor models and noise distribution as well as Monte Carlo analysis capability are included to enable statistical performance evaluations.

Fusion breeder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moir, R.W.

1982-02-22

The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the US fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the US fusion program and the US nuclear energy program. The purpose of this paper is to suggest this policy change be made and tell why it should be made, and to outlinemore » specific research and development goals so that the fusion breeder will be developed in time to meet fissile fuel needs.« less

Fusion breeder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moir, R.W.

1982-04-20

The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the US fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the US fusion program and the US nuclear energy program. The purpose of this paper is to suggest this policy change be made and tell why it should be made, and to outlinemore » specific research and development goals so that the fusion breeder will be developed in time to meet fissile fuel needs.« less

Viral membrane fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

2015-05-15

Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formedmore » draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.« less

Spatial attention facilitates assembly of the briefest percepts: Electrophysiological evidence from color fusion.

PubMed

Akyürek, Elkan G; van Asselt, E Manon

2015-12-01

When two different color stimuli are presented in rapid succession, the resulting percept is sometimes that of a mixture of both colors, due to a perceptual process called color fusion. Although color fusion might seem to occur very early in the visual pathway, and only happens across the briefest of stimulus presentation intervals (< 50 ms), the present study showed that spatial attention can alter the fusion process. In a series of experiments, spatial cues were presented that either validly indicated the location of a pair of (different) color stimuli in successive stimulus arrays, or did not, pointing toward isoluminant gray distractors in the other visual hemifield. Increased color fusion was observed for valid cues across a range of stimulus durations, at the expense of individual color reports. By contrast, perception of repeated, same-color stimulus pairs did not change, suggesting that the enhancement was specific to fusion, not color discrimination per se. Electrophysiological measures furthermore showed that the amplitude of the N1, N2pc, and P3 components of the ERP were differentially modulated during the perception of individual and fused colors, as a function of cueing and stimulus duration. Fusion itself, collapsed across cueing conditions, was reflected uniquely in N1 amplitude. Overall, the results suggest that spatial attention enhances color fusion and decreases competition between stimuli, constituting an adaptive slowdown in service of temporal integration. © 2015 Society for Psychophysiological Research.

Reconstitution of high affinity. cap alpha. /sub 2/ adrenergic agonist binding by fusion with a pertussis toxin substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M.H.; Neubig, R.R.

1986-03-05

High affinity ..cap alpha../sub 2/ adrenergic agonist binding is thought to occur via a coupling of the ..cap alpha../sub 2/ receptor with N/sub i/, the inhibitory guanyl nucleotide binding protein. Human platelet membranes pretreated at pH 11.5 exhibit a selective inactivation of agonist binding and N/sub i/. To further study the mechanism of agonist binding, alkali treated membranes (ATM) were mixed with membranes pretreated with 10 ..mu..M phenoxybenzamine to block ..cap alpha../sub 2/ receptors (POB-M). The combined membrane pellet was incubated in 50% polyethylene glycol (PEG) to promote membrane-membrane fusion and assayed for binding to the ..cap alpha../sub 2/ agonistmore » (/sup 3/H)UK 14,304 (UK) and the antagonist (/sup 3/H) yohimbine. PEG treatment resulted in a 2-4 fold enhancement of UK binding whereas yohimbine binding was unchanged. No enhancement of UK binding was observed in the absence of PEG treatment. The reconstitution was dependent on the addition of POB-M. They found that a 1:1 ratio of POB-M:ATM was optimal. Reconstituted binding was inhibited by GppNHp. Fusion of rat C6 glioma cell membranes, which do not contain ..cap alpha../sub 2/ receptors, also enhanced agonist binding to ATM. Fusion of C6 membranes from cells treated with pertussis toxin did not enhance (/sup 3/H) UK binding. These data show that a pertussis toxin sensitive membrane component, possibly N/sub i/, can reconstitute high affinity ..cap alpha../sub 2/ agonist binding.« less

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States.

PubMed

Prasad, Manju L; Vyas, Monika; Horne, Matthew J; Virk, Renu K; Morotti, Raffaella; Liu, Zongzhi; Tallini, Giovanni; Nikiforova, Marina N; Christison-Lagay, Emily R; Udelsman, Robert; Dinauer, Catherine A; Nikiforov, Yuri E

2016-04-01

An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAF(V) (600E)) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAF(V) (600E) PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P < .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P = .02); BRAF(V) (600E) PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1). Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAF(V) (600E) PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3

Paramyxovirus fusion: Real-time measurement of parainfluenza virus 5 virus-cell fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connolly, Sarah A.; Lamb, Robert A.

2006-11-25

Although cell-cell fusion assays are useful surrogate methods for studying virus fusion, differences between cell-cell and virus-cell fusion exist. To examine paramyxovirus fusion in real time, we labeled viruses with fluorescent lipid probes and monitored virus-cell fusion by fluorimetry. Two parainfluenza virus 5 (PIV5) isolates (W3A and SER) and PIV5 containing mutations within the fusion protein (F) were studied. Fusion was specific and temperature-dependent. Compared to many low pH-dependent viruses, the kinetics of PIV5 fusion was slow, approaching completion within several minutes. As predicted from cell-cell fusion assays, virus containing an F protein with an extended cytoplasmic tail (rSV5 F551)more » had reduced fusion compared to wild-type virus (W3A). In contrast, virus-cell fusion for SER occurred at near wild-type levels, despite the fact that this isolate exhibits a severely reduced cell-cell fusion phenotype. These results support the notion that virus-cell and cell-cell fusion have significant differences.« less

Quantifying Fusion Born Ion Populations in Magnetically Confined Plasmas using Ion Cyclotron Emission

DOE PAGES

Carbajal, L.; Warwick Univ., Coventry; Dendy, R. O.; ...

2017-03-07

Ion cyclotron emission (ICE) offers unique promise as a diagnostic of the fusion born alpha-particle population in magnetically confined plasmas. Pioneering observations from JET and TFTR found that ICE intensity P ICE scales approximately linearly with the measured neutron flux from fusion reactions, and with the inferred concentration, n /n i , of fusion-born alpha-particles confined within the plasma. We present fully nonlinear self-consistent kinetic simulations that reproduce this scaling for the first time. This resolves a longstanding question in the physics of fusion alpha particle confinement and stability in MCF plasmas. It confirms the MCI as the likely emissionmore » mechanism and greatly strengthens the basis for diagnostic exploitation of ICE in future burning plasmas.« less

A direct fusion drive for rocket propulsion

NASA Astrophysics Data System (ADS)

Razin, Yosef S.; Pajer, Gary; Breton, Mary; Ham, Eric; Mueller, Joseph; Paluszek, Michael; Glasser, Alan H.; Cohen, Samuel A.

2014-12-01

The Direct Fusion Drive (DFD), a compact, anuetronic fusion engine, will enable more challenging exploration missions in the solar system. The engine proposed here uses a deuterium-helium-3 reaction to produce fusion energy by employing a novel field-reversed configuration (FRC) for magnetic confinement. The FRC has a simple linear solenoid coil geometry yet generates higher plasma pressure, hence higher fusion power density, for a given magnetic field strength than other magnetic-confinement plasma devices. Waste heat generated from the plasma's Bremsstrahlung and synchrotron radiation is recycled to maintain the fusion temperature. The charged reaction products, augmented by additional propellant, are exhausted through a magnetic nozzle. A 1 MW DFD is presented in the context of a mission to deploy the James Webb Space Telescope (6200 kg) from GPS orbit to a Sun-Earth L2 halo orbit in 37 days using just 353 kg of propellant and about half a kilogram of 3He. The engine is designed to produce 40 N of thrust with an exhaust velocity of 56.5 km/s and has a specific power of 0.18 kW/kg.

Multimerized CHR-derived peptides as HIV-1 fusion inhibitors.

PubMed

Nomura, Wataru; Hashimoto, Chie; Suzuki, Takaharu; Ohashi, Nami; Fujino, Masayuki; Murakami, Tsutomu; Yamamoto, Naoki; Tamamura, Hirokazu

2013-08-01

To date, several HIV-1 fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of an HIV-1 envelope protein gp41 have been discovered. We have shown that a synthetic peptide mimetic of a trimer form of the CHR-derived peptide C34 has potent inhibitory activity against the HIV-1 fusion mechanism, compared to a monomer C34 peptide. The present study revealed that a dimeric form of C34 is evidently structurally critical for fusion inhibitors, and that the activity of multimerized CHR-derived peptides in fusion inhibition is affected by the properties of the unit peptides C34, SC34EK, and T20. The fluorescence-based study suggested that the N36-interactive sites of the C34 trimer, including hydrophobic residues, are exposed outside the trimer and that trimerization of C34 caused a remarkable increase in fusion inhibitory activity. The present results could be useful in the design of fusion inhibitors against viral infections which proceed via membrane fusion with host cells. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antibody-independent Targeted Quantification of TMPRSS2-ERG Fusion Protein Products in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Jintang; Sun, Xuefei; Shi, Tujin

2014-10-01

Fusions between the transmembrane protease serine 2 (TMPRSS2) and ETS related gene (ERG) represent one of the most specific biomarkers that define a distinct molecular subtype of prostate cancer. The studies on TMPRSS2-ERG gene fusions have seldom been performed at the protein level, primarily due to the lack of high-quality antibodies or an antibody-independent method that is sufficiently sensitive for detecting the truncated ERG protein products resulting from TMPRSS2-ERG gene fusions and alternative splicing. Herein, we applied a recently developed PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) strategy for quantifying ERG protein in prostate cancermore » cell lines and tumors. The highly sensitive PRISM-SRM assays led to confident detection of 6 unique ERG peptides in either the TMPRSS2-ERG positive cell lines or tissues but not in the negative controls, indicating that ERG protein expression is highly correlated with TMPRSS2-ERG gene rearrangements. Significantly, our results demonstrated for the first time that at least two groups of ERG protein isoforms were simultaneously expressed at variable levels in TMPRSS2-ERG positive samples as evidenced by concomitant detection of two mutually exclusive peptides. Three peptides shared across almost all fusion protein products were determined to be the most abundant peptides, and hence can be used as “signature” peptides for detecting ERG overexpression resulting from TMPRSS2-ERG gene fusion. These PRISM-SRM assays provide valuable tools for studying TMPRSS2-ERG gene fusion protein products, thus improving our understanding of the role of TMPRSS2-ERG gene fusion in the biology of prostate cancer.« less

N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based d(10) transition metal complexes and their utilization in co-sensitized solar cells.

PubMed

Wei, Liguo; Yang, Yulin; Fan, Ruiqing; Na, Yong; Wang, Ping; Dong, Yuwei; Yang, Bin; Cao, Wenwu

2014-08-07

N,N'-Bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine based four-coordinated d(10) transition metal complexes (named ML, M = Zn, Cd, Hg) were synthesized and employed as co-sensitizers and co-adsorbents in combination with a ruthenium complex N719 in dye sensitized solar cells. After co-sensitization, not only the incident-photon-to-current conversion efficiency is enhanced but also the dark current is reduced. A short circuit current density of 14.46 mA cm(-2), an open circuit voltage of 0.74 V and a fill factor of 0.62 corresponding to an overall conversion efficiency of 6.65% under AM 1.5 G solar irradiation were achieved when ZnL was used as a co-sensitizer, which are much higher than that for DSSCs only sensitized by N719 (5.22%) under the same conditions. The improvement in efficiency is attributed to the fact that N,N'-bis((6-methoxylpyridin-2-yl)methylene)-p-phenylenediimine coordinated complexes overcome the deficiency of N719 absorption in the low wavelength region of the visible spectrum, prevent its aggregation, offset competitive visible light absorption of I3(-) and reduce charge recombination due to formation of an effective cover layer of the dye molecules on the TiO2 surface. As a result, the synthesized complexes are promising candidates as co-adsorbents and co-sensitizers for highly efficient DSSCs.

Enhancement of electrical and optical performance of N719 by co-sensitization

NASA Astrophysics Data System (ADS)

Shikoh, Ali Sephar; Ahmad, Zubair; Touati, Farid; Al-Muhtaseb, Shaheen A.

2018-04-01

This paper deals with the electrical, optical and electrochemical properties of a metal-free dye C78H74O8 (AS-2), which has been used to improve the photo-detection properties of C58H86N8O8RuS2 (N719) based Dye sensitized photo-sensors (DSPSs). Both dyes were mixed together in various proportions and the most promising ratio N719/AS-2 (1:0.25) was selected for staining photo-anodes for DSPS integration. The fabricated DSPSs were studied in terms of electrical parameters and photodetection properties. The N719/AS-2 (1:0.25) based DSPS were found to have a reduced leakage current, increased breakdown voltage and a closer proximity to an ideal diode, as compared to the N719 based DSPS. Further, the N719/AS-2 (1:0.25) based DSPS was also found to have better linearity at high irradiance levels, thus rendering the co-sensitized device useful as a photosensor in various applications. Electrochemical Impedance Spectroscopy (EIS) analysis was also performed to explain the interfacial charge recombination process.

Sequential Actions of Rab5 and Rab7 Regulate Endocytosis in the Xenopus Oocyte

PubMed Central

Mukhopadhyay, Amitabha; Barbieri, Alejandro M.; Funato, Kouichi; Roberts, Richard; Stahl, Philip D.

1997-01-01

To explore the role of GTPases in endocytosis, we developed an assay using Xenopus oocytes injected with recombinant proteins to follow the uptake of the fluid phase marker HRP. HRP uptake was inhibited in cells injected with GTPγS or incubated with aluminum fluoride, suggesting a general role for GTPases in endocytosis. Injection of Rab5 into oocytes, as well as Rab5:Q79L, a mutant with decreased GTPase activity, increased HRP uptake. Injection of Rab5:S34N, the dominant-negative mutant, inhibited HRP uptake. Injection of N-ethylmaleimide–sensitive factor (NSF) stimulated HRP uptake, and ATPase-defective NSF mutants inhibited HRP uptake when coinjected with Rab5:Q79L, confirming a requirement for NSF in endocytosis. Surprisingly, injection of Rab7:WT stimulated both uptake and degradation/activation of HRP. The latter appears to be due to enhanced transport to a late endosomal/prelysosomal degradative compartment that is monensin sensitive. Enhancement of uptake by Rab7 appears to function via an Rab5-sensitive pathway in oocytes since the stimulatory effect of Rab7 was blocked by coinjection of Rab5:S34N. Stimulation of uptake by Rab5 was blocked by Rab5:S34N but not by Rab7:T22N. Our results suggest that Rab7, while functioning downstream of Rab5, may be rate limiting for endocytosis in oocytes. PMID:9087439

The Arabidopsis R-SNARE VAMP721 Interacts with KAT1 and KC1 K+ Channels to Moderate K+ Current at the Plasma Membrane.

PubMed

Zhang, Ben; Karnik, Rucha; Wang, Yizhou; Wallmeroth, Niklas; Blatt, Michael R; Grefen, Christopher

2015-06-01

SNARE (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) proteins drive vesicle traffic, delivering membrane and cargo to target sites within the cell and at its surface. They contribute to cell homeostasis, morphogenesis, and pathogen defense. A subset of SNAREs, including the Arabidopsis thaliana SNARE SYP121, are known also to coordinate solute uptake via physical interactions with K(+) channels and to moderate their gating at the plasma membrane. Here, we identify a second subset of SNAREs that interact to control these K(+) channels, but with opposing actions on gating. We show that VAMPs (vesicle-associated membrane proteins), which target vesicles to the plasma membrane, also interact with and suppress the activities of the inward-rectifying K(+) channels KAT1 and KC1. Interactions were evident in yeast split-ubiquitin assays, they were recovered in vivo by ratiometric bimolecular fluorescence complementation, and they were sensitive to mutation of a single residue, Tyr-57, within the longin domain of VAMP721. Interaction was also recovered on exchange of the residue at this site in the homolog VAMP723, which normally localizes to the endoplasmic reticulum and otherwise did not interact. Functional analysis showed reduced channel activity and alterations in voltage sensitivity that are best explained by a physical interaction with the channel gates. These actions complement those of SYP121, a cognate SNARE partner of VAMP721, and lead us to propose that the channel interactions reflect a "hand-off" in channel control between the two SNARE proteins that is woven together with vesicle fusion. © 2015 American Society of Plant Biologists. All rights reserved.

HIP1-ALK, a novel ALK fusion variant that responds to crizotinib.

PubMed

Fang, Douglas D; Zhang, Bin; Gu, Qingyang; Lira, Maruja; Xu, Qiang; Sun, Hongye; Qian, Maoxiang; Sheng, Weiqi; Ozeck, Mark; Wang, Zhenxiong; Zhang, Cathy; Chen, Xinsheng; Chen, Kevin X; Li, Jian; Chen, Shu-Hui; Christensen, James; Mao, Mao; Chan, Chi-Chung

2014-03-01

The aim of this study was to identify anaplastic lymphoma kinase (ALK) rearrangements in lung cancer patient-derived xenograft (PDX) models and to explore their responses to crizotinib. Screening of 99 lung cancer PDX models by the NanoString ALK fusion assay identified two ALK-rearranged non-small-cell lung cancer (NSCLC) tumors, including one harboring a previously known echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion and another containing an unknown ALK fusion variant. Expression array, RNA-Seq, reverse transcription polymerase chain reaction, and direct sequencing were then conducted to confirm the rearrangements and to identify the novel fusion partner in the xenograft and/or the primary patient tumor. Finally, pharmacological studies were performed in PDX models to evaluate their responses to ALK inhibitor crizotinib. Two ALK-rearranged NSCLC PDX models were identified: one carried a well-known EML4-ALK variant 3a/b and the other harbored a novel huntingtin interacting protein 1 (HIP1)-ALK fusion gene. Exon 28 of the HIP1 gene located on chromosome 7 was fused to exon 20 of the ALK gene located on chromosome 2. Both cases were clinically diagnosed as squamous cell carcinoma. Compared with the other lung cancer PDX models, both ALK-rearranged models displayed elevated ALK mRNA expression. Furthermore, in vivo efficacy studies demonstrated that, similar to the EML4-ALK-positive model, the HIP1-ALK-containing PDX model was sensitive to treatment with crizotinib. Discovery of HIP1 as a fusion partner of ALK in NSCLC is a novel finding. In addition, the HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib in vivo, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis. Collectively, our results indicate that HIP1-ALK-positive NSCLC may benefit from clinical applications of crizotinib.

Soft X-ray streak camera for laser fusion applications

NASA Astrophysics Data System (ADS)

Stradling, G. L.

1981-04-01

The development and significance of the soft x-ray streak camera (SXRSC) in the context of inertial confinement fusion energy development is reviewed as well as laser fusion and laser fusion diagnostics. The SXRSC design criteria, the requirement for a subkilovolt x-ray transmitting window, and the resulting camera design are explained. Theory and design of reflector-filter pair combinations for three subkilovolt channels centered at 220 eV, 460 eV, and 620 eV are also presented. Calibration experiments are explained and data showing a dynamic range of 1000 and a sweep speed of 134 psec/mm are presented. Sensitivity modifications to the soft x-ray streak camera for a high-power target shot are described. A preliminary investigation, using a stepped cathode, of the thickness dependence of the gold photocathode response is discussed. Data from a typical Argus laser gold-disk target experiment are shown.

Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data

PubMed Central

Kumar, Shailesh; Vo, Angie Duy; Qin, Fujun; Li, Hui

2016-01-01

RNA-Seq made possible the global identification of fusion transcripts, i.e. “chimeric RNAs”. Even though various software packages have been developed to serve this purpose, they behave differently in different datasets provided by different developers. It is important for both users, and developers to have an unbiased assessment of the performance of existing fusion detection tools. Toward this goal, we compared the performance of 12 well-known fusion detection software packages. We evaluated the sensitivity, false discovery rate, computing time, and memory usage of these tools in four different datasets (positive, negative, mixed, and test). We conclude that some tools are better than others in terms of sensitivity, positive prediction value, time consumption and memory usage. We also observed small overlaps of the fusions detected by different tools in the real dataset (test dataset). This could be due to false discoveries by various tools, but could also be due to the reason that none of the tools are inclusive. We have found that the performance of the tools depends on the quality, read length, and number of reads of the RNA-Seq data. We recommend that users choose the proper tools for their purpose based on the properties of their RNA-Seq data. PMID:26862001

Sensitivity of Fermi level position at Ga-polar, N-polar, and nonpolar m-plane GaN surfaces to vacuum and air ambient

NASA Astrophysics Data System (ADS)

Janicki, Łukasz; Ramírez-López, Manolo; Misiewicz, Jan; Cywiński, Grzegorz; Boćkowski, Michał; Muzioł, Grzegorz; Chèze, Caroline; Sawicka, Marta; Skierbiszewski, Czesław; Kudrawiec, Robert

2016-05-01

Ga-polar, N-polar, and nonpolar m-plane GaN UN+ structures have been examined in air and vacuum ambient by contactless electroreflectance (CER). This technique is very sensitive to the surface electric field that varies with the Fermi level position at the surface. For UN+ GaN structures [i.e., GaN (undoped)/GaN (n-type)/substrate], a homogeneous built-in electric field is expected in the undoped GaN layer that is manifested by Franz-Keldysh oscillation (FKO) in CER spectra. A clear change in FKO has been observed in CER spectra for N-polar and nonpolar m-plane structures when changing from air to vacuum ambient. This means that those surfaces are very sensitive to ambient atmosphere. In contrast to that, only a small change in FKO can be seen in the Ga-polar structure. This clearly shows that the ambient sensitivity of the Fermi level position at the GaN surface varies with the crystallographic orientation and is very high for N-polar and nonpolar m-plane surfaces. This feature of the N-polar and nonpolar m-plane surfaces can be very important for GaN-based devices grown on these crystallographic orientations and can be utilized in some of the devices, e.g., sensors.