A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Science.gov (United States)

Garcia-Rodriguez, Consuelo; Razai, Ali; Geren, Isin N; Lou, Jianlong; Conrad, Fraser; Wen, Wei-Hua; Farr-Jones, Shauna; Smith, Theresa J; Brown, Jennifer L; Skerry, Janet C; Smith, Leonard A; Marks, James D

2018-03-01

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (K D ). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had K D values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018.

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

International Nuclear Information System (INIS)

Inui, Ken; Sagane, Yoshimasa; Miyata, Keita; Miyashita, Shin-Ichiro; Suzuki, Tomonori; Shikamori, Yasuyuki; Ohyama, Tohru; Niwa, Koichi; Watanabe, Toshihiro

2012-01-01

Highlights: ► BoNT and NTNHA proteins share a similar protein architecture. ► NTNHA and BoNT were both identified as zinc-binding proteins. ► NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. ► Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X 35 -D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach

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Wanpen Chaicumpa

2011-05-01

Full Text Available Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT derived from heterologous species (immunized animal or mouse hybridoma together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15–20 kDa single domain antibody (VHH that binds specifically to light chain of BoNT serotype A was produced from a humanized-camel VH/VHH phage display library. The VHH has high sequence homology (>80% to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the VHH and the toxin but also an insertion of the VHH CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the VHH to a cell penetrating peptide (CPP, the CPP-VHH fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme.

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

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Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

Epitope-Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent in Cell Inhibitor of Botulinum Neurotoxin**

OpenAIRE

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M.; Das, Samir; Nag, Arundhati; Agnew, Heather D.; Heath, James R.

2015-01-01

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ ...

Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

Energy Technology Data Exchange (ETDEWEB)

Inui, Ken [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Sagane, Yoshimasa [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Miyata, Keita [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Miyashita, Shin-Ichiro [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Suzuki, Tomonori [Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikamori, Yasuyuki [Agilent Technologies International Japan, Ltd. Takaura-cho 9-1, Hachioji-shi, Tokyo 192-0033 (Japan); Ohyama, Tohru; Niwa, Koichi [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan); Watanabe, Toshihiro, E-mail: t-watana@bioindustry.nodai.ac.jp [Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493 (Japan)

2012-03-16

Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structure classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.

Mass Spectrometric Detection of Botulinum Neurotoxin by Measuring its Activity in Serum and Milk

Science.gov (United States)

Kalb, Suzanne R.; Pirkle, James L.; Barr, John R.

Botulinum neurotoxins (BoNTs) are bacterial protein toxins which are considered likely agents for bioterrorism due to their extreme toxicity and high availability. A new mass spectrometry based assay called Endopep MS detects and defines the toxin serotype in clinical and food matrices via toxin activity upon a peptide substrate which mimics the toxin's natural target. Furthermore, the subtype of the toxin is differentiated by employing mass spectrometry based proteomic techniques on the same sample. The Endopep-MS assay selectively detects active BoNT and defines the serotype faster and with sensitivity greater than the mouse bioassay. One 96-well plate can be analyzed in under 7 h. On higher level or "hot" samples, the subtype can then be differentiated in less than 2 h with no need for DNA.

Generation and Characterization of Six Recombinant Botulinum Neurotoxins as Reference Material to Serve in an International Proficiency Test

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Jasmin Weisemann

2015-11-01

Full Text Available The detection and identification of botulinum neurotoxins (BoNT is complex due to the existence of seven serotypes, derived mosaic toxins and more than 40 subtypes. Expert laboratories currently use different technical approaches to detect, identify and quantify BoNT, but due to the lack of (certified reference materials, analytical results can hardly be compared. In this study, the six BoNT/A1–F1 prototypes were successfully produced by recombinant techniques, facilitating handling, as well as improving purity, yield, reproducibility and biosafety. All six BoNTs were quantitatively nicked into active di-chain toxins linked by a disulfide bridge. The materials were thoroughly characterized with respect to purity, identity, protein concentration, catalytic and biological activities. For BoNT/A1, B1 and E1, serotypes pathogenic to humans, the catalytic activity and the precise protein concentration were determined by Endopep-mass spectrometry and validated amino acid analysis, respectively. In addition, BoNT/A1, B1, E1 and F1 were successfully detected by immunological assays, unambiguously identified by mass spectrometric-based methods, and their specific activities were assigned by the mouse LD50 bioassay. The potencies of all six BoNT/A1–F1 were quantified by the ex vivo mouse phrenic nerve hemidiaphragm assay, allowing a direct comparison. In conclusion, highly pure recombinant BoNT reference materials were produced, thoroughly characterized and employed as spiking material in a worldwide BoNT proficiency test organized by the EQuATox consortium.

Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

Science.gov (United States)

Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

2014-05-01

Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

Genetic Diversity Among Botulinum Neurotoxin Producing Clostridial Strains

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Hill, K K; Smith, T J; Helma, C H; Ticknor, L O; Foley, B T; Svennson, R T; Brown, J L; Johnson, E A; Smith, L A; Okinaka, R T; Jackson, P J; Marks, J D

2006-07-06

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and even death in humans and various other animal species. A collection of 174 C. botulinum strains were examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the16S rRNA sequences confirmed earlier reports of at least four distinct genomic backgrounds (Groups I-IV) each of which has independently acquired one or more BoNT serotypes through horizontal gene transfer. AFLP analysis provided higher resolution, and can be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from serotypes A, B and E in multiple strains confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes, and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven serotypes of BoNT were compared and show varying degrees of interrelatedness and recombination as has been previously noted for the NTNH gene which is linked to BoNT. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism.

Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain.

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Sharad P Adekar

2008-08-01

Full Text Available Botulinum neurotoxins (BoNT are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC, a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A. The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro.An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

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Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam

2015-11-15

The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins. Because of their extreme toxicity and history of weaponization, the BoNTs are regarded as potential biowarfare/bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than intensive care; therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was evaluated in a FRET assay for its ability to inhibit BoNT/A light chain (Balc). CPI was found to be highly potent, exhibiting a Ki of 12.3 nM with full-length Balc448 and 39.2 nM using a truncated crystallizable form of the light chain (Balc424). Cocrystallization studies revealed that in the Balc424-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn(2+) binding region involved in catalysis. This differs from linear peptide inhibitors described to date which block only the latter. Published by Elsevier Ltd.

Botulinum Neurotoxins: Qualitative and Quantitative Analysis Using the Mouse Phrenic Nerve Hemidiaphragm Assay (MPN

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Hans Bigalke

2015-11-01

Full Text Available The historical method for the detection of botulinum neurotoxin (BoNT is represented by the mouse bioassay (MBA measuring the animal survival rate. Since the endpoint of the MBA is the death of the mice due to paralysis of the respiratory muscle, an ex vivo animal replacement method, called mouse phrenic nerve (MPN assay, employs the isolated N. phrenicus-hemidiaphragm tissue. Here, BoNT causes a dose-dependent characteristic decrease of the contraction amplitude of the indirectly stimulated muscle. Within the EQuATox BoNT proficiency 13 test samples were analysed using the MPN assay by serial dilution to a bath concentration resulting in a paralysis time within the range of calibration curves generated with BoNT/A, B and E standards, respectively. For serotype identification the diluted samples were pre-incubated with polyclonal anti-BoNT/A, B or E antitoxin or a combination of each. All 13 samples were qualitatively correctly identified thereby delivering superior results compared to single in vitro methods like LFA, ELISA and LC-MS/MS. Having characterized the BoNT serotype, the final bath concentrations were calculated using the calibration curves and then multiplied by the respective dilution factor to obtain the sample concentration. Depending on the source of the BoNT standards used, the quantitation of ten BoNT/A containing samples delivered a mean z-score of 7 and of three BoNT/B or BoNT/E containing samples z-scores <2, respectively.

Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays.

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Erkan Kiris

Full Text Available There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC. Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs. Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.

A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

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Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng; Lou, Jianlong; Conrad, Fraser; Ho, Mengfei; Pires-Alves, Melissa; Wilson, Brenda A.; Stevens, Raymond C.; Marks, James D. (UIUC); (Scripps); (UCSF)

2010-08-13

Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody) antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.

Challenges in searching for therapeutics against Botulinum Neurotoxins.

Science.gov (United States)

Pirazzini, Marco; Rossetto, Ornella

2017-05-01

Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

What Clinical Strategies Are Applied for Botulinum Toxin Injection in the Oromandibular Region?

DEFF Research Database (Denmark)

Bakke, Merete; Dalager, Torben; Møller, Eigild

2016-01-01

Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from cholinergic nerve terminals in muscles or salivary glands. With reduced activation, the muscle activity or secretion decreases. Indications for medical, non‐cosmetic use of BoNT in the orofacial area include among others...

Botulinum toxin: yesterday, today, tomorrow

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A. R. Artemenko

2013-01-01

Full Text Available Botulinum toxin (BoNT is a bacterial neurotoxin presented with seven serotypes that inhibit neurotransmitter release from nerve endings. The serotypes of BoNT are antigenically dissimilar, act via different, but interconnected mechanisms, and are not interchangeable. The activity of BoNT is associated with impaired neuroexocytosis occurring in several steps: from the binding of BoNT to its specific receptor on the axon terminal membrane to the proteolytic enzymatic cleavage of SNARE substrate. The effect of BoNT is considered to be restricted to the peripheral nervous system, but when given in particularly high doses, it has been recently shown to affect individual brain structures. In addition, by modulating peripheral afferentation, BoNT may influence the excitability of central neuronal structures at both spinal and cortical levels. Only BoNT serotypes A and B are used in clinical practice and aesthetic medicine. The type A has gained the widest acceptance as a therapeutic agent for more than 100 abnormalities manifesting themselves as muscular hyperactivity, hyperfunction of endocrine gland, and chronic pain. The effect of BoNT preparations shows itself 2-5 days after injection, lasts 3 months or more, and gradually decreases with as a result of pharmacokinetic and intracellular reparative processes. Biotechnology advances and potentialities allow purposefully modification of the protein molecular structure of BoNT, which expands the use and efficiency of performed therapy with neurotoxins. Recombinant technologies provide a combination of major therapeutic properties of each used BoNT serotype and expand indications for recombinant chimeric toxins.

Selection of RNA Aptamers Against Botulinum Neurotoxin Type A Light Chain Through a Non-Radioactive Approach.

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Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Cai, Shuowei

2016-09-01

Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive-based systematic evolution of ligands by exponential enrichment (SELEX) process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nanomolar range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting that they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that the 2'-fluorine-pyrimidine-modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for SELEX, by using regular nucleotide during SELEX, and 2'-fluorine-pyrimidine-modified nucleotide for final application to enhance their RNase-resistance.

The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

Science.gov (United States)

Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

2016-02-01

Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Detecting Anthrax, Botulinum Toxin, and Ricin – Immunoassay Test Strips

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This assay is listed as Tier I for presumptive analysis of BoNTs in drinking water samples and Tier II for presumptive analysis of BoNTs in other environmental sample types. The lateral flow immunochromatographic assay uses two antibodies in combination to

Mass Spectrometric Identification and Differentiation of Botulinum Neurotoxins through Toxin Proteomics.

Science.gov (United States)

Kalb, Suzanne R; Barr, John R

2013-08-01

Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A-G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence and immunogenic properties, and some subtypes are further differentiated into toxin variants. Toxin characterization is important as different types of BoNT can respond differently to medical countermeasures for botulism, and characterization of the toxin can aid in epidemiologic and forensic investigations. Proteomic techniques have been established to determine the serotype, subtype, or toxin variant of BoNT. These techniques involve digestion of the toxin into peptides, tandem mass spectrometric (MS/MS) analysis of the peptides, and database searching to identify the BoNT protein. These techniques demonstrate the capability to detect BoNT and its neurotoxin-associated proteins, and differentiate the toxin from other toxins which are up to 99.9% identical in some cases. This differentiation can be accomplished from toxins present in a complex matrix such as stool, food, or bacterial cultures and no DNA is required.

Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E.

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Mascher, Gerald; Mertaoja, Anna; Korkeala, Hannu; Lindström, Miia

2017-10-01

Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA-binding domain of Spo0A directly bound to a putative Spo0A-binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C. botulinum type E. Unlike other C. botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C. botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Comparison of Toxicological Properties of Botulinum Neurotoxin Serotypes A and B in Mice

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Botulinum neurotoxins (BoNTs) are among the most toxic biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the human foodborne intoxications. In this study, we compared the toxicological properties of BoNT serotype A and B holotoxins and compl...

Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 - 2014).

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Kane, Christopher D; Nuss, Jonathan E; Bavari, Sina

2015-06-01

Botulinum neurotoxins (BoNTs) are among the most toxic of known biological molecules and function as acetylcholine release inhibitors and neuromuscular blocking agents. Paradoxically, these properties also make them valuable therapeutic agents for the treatment of movement disorders, urological conditions and hypersecretory disorders. Greater understanding of their molecular mechanism of action and advances in protein engineering has led to significant efforts to improve and expand their function with a view towards broadening their therapeutic potential. Searches of Espacenet and Google Patent have revealed a number of patents related to BoNTs. This review will focus on novel therapeutic uses and formulations disclosed during 2012 - 2014. The seven patents discussed will include nanoformulations of FDA-approved BoNTs, additional BoNT subtypes and novel BoNT variants and chimeras created through protein engineering. Supporting patents and related publications are also briefly discussed. The clinical and commercial success of BoNTs has prompted investigation into novel BoNTs or BoNT-mediated chimeras with promising in vitro results. Distinct strategies including the use of nanoformulations and targeted delivery have been implemented to identify new indication and improved functionality. Greater understanding of their systemic exposure, efficacy and safety profiles will be required for further development.

Inhibiting oral intoxication of botulinum neurotoxin A by carbohydrate receptor mimics

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Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes of BoNT intoxication, where BoNT assembles with several auxiliary proteins to surviv...

Recent advances in botulinum neurotoxin inhibitor development.

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Kiris, Erkan; Burnett, James C; Kane, Christopher D; Bavari, Sina

2014-01-01

Botulinum neurotoxins (BoNTs) are endopeptidases that target motor neurons and block acetylcholine neurotransmitter release. This action results in the muscle paralysis that defines the disease botulism. To date, there are no FDA-approved therapeutics to treat BoNT-mediated paralysis after intoxication of the motor neuron. Importantly, the rationale for pursuing treatments to counter these toxins is driven by their potential misuse. Current drug discovery efforts have mainly focused on small molecules, peptides, and peptidomimetics that can directly and competitively inhibit BoNT light chain proteolytic activity. Although this is a rational approach, direct inhibition of the Zn(2+) metalloprotease activity has been elusive as demonstrated by the dearth of candidates undergoing clinical evaluation. Therefore, broadening the scope of viable targets beyond that of active site protease inhibitors represents an additional strategy that could move the field closer to the clinic. Here we review the rationale, and discuss the outcomes of earlier approaches and highlight potential new targets for BoNT inhibition. These include BoNT uptake and processing inhibitors, enzymatic inhibitors, and modulators of neuronal processes associated with toxin clearance, neurotransmitter potentiation, and other pathways geared towards neuronal recovery and repair.

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

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Kull, Skadi; Schulz, K Melanie; Weisemann, Jasmin; Kirchner, Sebastian; Schreiber, Tanja; Bollenbach, Alexander; Dabrowski, P Wojtek; Nitsche, Andreas; Kalb, Suzanne R; Dorner, Martin B; Barr, John R; Rummel, Andreas; Dorner, Brigitte G

2015-01-01

Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might

Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

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Sharad P Adekar

2011-03-01

Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

Diffusion, spread, and migration of botulinum toxin.

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Ramirez-Castaneda, Juan; Jankovic, Joseph; Comella, Cynthia; Dashtipour, Khashayar; Fernandez, Hubert H; Mari, Zoltan

2013-11-01

Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular blocking agent used for the treatment of a variety of neurologic and medical conditions. The efficacy and safety of BoNT depends on accurate selection and identification of intended targets but also may be determined by other factors, including physical spread of the molecule from the injection site, passive diffusion, and migration to distal sites via axonal or hematogenous transport. The passive kinetic dispersion of the toxin away from the injection site in a gradient-dependent manner may also play a role in toxin spread. In addition to unique properties of the various BoNT products, volume and dilution may also influence local and systemic distribution of BoNT. Most of the local and remote complications of BoNT injections are thought to be due to unwanted spread or diffusion of the toxin's biologic activity into adjacent and distal muscles. Despite widespread therapeutic and cosmetic use of BoNT over more than three decades, there is a remarkable paucity of published data on the mechanisms of distribution and its effects on clinical outcomes. The primary aim of this article is to critically review the available experimental and clinical literature and place it in the practical context. © 2013 International Parkinson and Movement Disorder Society.

Botulinum neurotoxin: a marvel of protein design.

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Montal, Mauricio

2010-01-01

Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

Botulinum toxin injections for low-back pain and sciatica.

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Waseem, Zeeshan; Boulias, Chris; Gordon, Allan; Ismail, Farooq; Sheean, Geoffrey; Furlan, Andrea D

2011-01-19

Adequate relief from low-back pain (LBP) is not always possible. Emerging evidence suggests a role for botulinum neurotoxin (BoNT) injections in treating pain disorders. Proponents of BoNT suggest its properties can decrease muscle spasms, ischemia and inflammatory markers, thereby reducing pain. To determine the effects of botulinum toxin injections in adults with LBP. We searched CENTRAL (The Cochrane Library 2009, issue 3) and MEDLINE, EMBASE, and CINAHL to August 2009; screened references from included studies; consulted with content experts and Allergan. We included published and unpublished randomised controlled trials without language restrictions We included randomised trials that evaluated BoNT serotypes versus other treatments in patients with non-specific LBP of any duration. Two review authors selected the studies, assessed the risk of bias using the Cochrane Back Review Group criteria, and extracted the data using standardized forms. We performed a qualitative analysis due to lack of data. We excluded evidence from nineteen studies due to non-randomisation, incomplete or unpublished data. We included three randomised trials (N =123 patients). Only one study included patients with chronic non-specific LBP; the other two examined unique subpopulations. Only one of the three trials had a low risk of bias and demonstrated that BoNT injections reduced pain at three and eight weeks and improved function at eight weeks better than saline injections. The second trial showed that BoNT injections were better than injections of corticosteroid plus lidocaine or placebo in patients with sciatica attributed to piriformis syndrome. The third trial concluded that BoNT injections were better than traditional acupuncture in patients with third lumbar transverse process syndrome. Both studies with high risk of bias had several key limitations. Heterogeneity of the studies prevented meta-analysis. There is low quality evidence that BoNT injections improved pain, function

Clostridium botulinum neurotoxin type B is heat-stable in milk and not inactivated by pasteurization.

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Rasooly, Reuven; Do, Paula M

2010-12-08

Foodborne botulism is caused by the ingestion of foods containing botulinum neurotoxins (BoNTs). To study the heat stability of Clostridium botulinum neurotoxins, we needed to measure and compare the activity of botulinum neurotoxins, serotypes A and B, under various pasteurization conditions. Currently, the only accepted assay to detect active C. botulinum neurotoxin is an in vivo mouse bioassay, which raises ethical concerns with regard to the use of experimental animals. In this study, noninvasive methods were used to simultaneously detect and distinguish between active BoNT serotypes A and B in one reaction and sample. We developed an enzymatic activity assay employing internally quenched fluorogenic peptides corresponding to SNAP-25, for BoNT-A, and VAMP2, for BoNT-B, as an alternative method to the mouse bioassay. Because each peptide is labeled with different fluorophores, we were able to distinguish between these two toxins. We used this method to analyze the heat stability of BoNT-A and BoNT-B. This study reports that conventional milk pasteurization (63 °C, 30 min) inactivated BoNT serotype A; however, serotype B is heat-stable in milk and not inactivated by pasteurization. Using this activity assay, we also showed that the commonly used food processes such as acidity and pasteurization, which are known to inhibit C. botulinum growth and toxin production, are more effective in inactivating BoNT serotype A than serotype B when conventional pasteurization (63 °C, 30 min) is used.

Bontá a vista d'occhio

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Lunadei, Loredana

2008-01-01

I consumatori moderni sono informati ed esigenti e nelle loro scelte alimentari prediligono indubbiamente prodotti di qualità elevata, sia sotto il profi lo nutrizionale che sensoriale e igienico-sanitario. Nel caso dei prodotti ortofrutticoli, l�attributo in grado di condizionare maggiormente l�acquisto è sicuramente l�aspetto, inteso come colore, forma, presenza di difetti esterni, ecc. Per questo motivo, dal momento della raccolta fi no alla distribuzione, risulta di fondamen...

Botulinum Neurotoxin Detection Methods for Public Health Response and Surveillance

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Nagarajan Thirunavukkarasu

2018-06-01

Full Text Available Botulism outbreak due to consumption of food contaminated with botulinum neurotoxins (BoNTs is a public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns due to the potential for high mortality and morbidity. Rapid and reliable detection methods are necessary to support clinical diagnosis and surveillance for identifying the source of contamination, performing epidemiological analysis of the outbreak, preventing and responding to botulism outbreaks. This review considers the applicability of various BoNT detection methods and examines their fitness-for-purpose in safeguarding the public health and security goals.

The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond.

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Grando, S A; Zachary, C B

2018-05-01

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. This review aims to provide an update on the non-neuronal and nonmuscular effects of botulinum toxin. We critically analysed recent reports on the structure and function of cellular signalling systems subserving biological effects of BoNTs. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in how BoNT binds to, and acts on, neuronal vs. non-neuronal cells. The non-neuronal cells that express one or more BoNT/A-binding proteins, and/or cleavage target synaptosomal-associated protein 25, include: epidermal keratinocytes; mesenchymal stem cells from subcutaneous adipose; nasal mucosal cells; urothelial cells; intestinal, prostate and alveolar epithelial cells; breast cell lines; neutrophils; and macrophages. Serotype BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. Nontraditional applications of BoNT have been reported for the treatment of the following dermatological conditions: hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland naevi, congenital eccrine naevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies have demonstrated the ability of BoNT/A to protect skin flaps, facilitate wound healing, decrease thickness of hypertrophic scars, produce an anti-ageing effect, improve a mouse model of psoriasiform dermatitis, and have also revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anticancer properties. BoNTs have a much wider range of applications than originally understood, and the individual cellular responses

Structural Analysis of Botulinum Neurotoxin Type G Receptor Binding

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Schmitt, John; Karalewitz, Andrew; Benefield, Desire A.; Mushrush, Darren J.; Pruitt, Rory N.; Spiller, Benjamin W.; Barbieri, Joseph T.; Lacy, D. Borden (Vanderbilt); (MCW)

2010-10-19

Botulinum neurotoxin (BoNT) binds peripheral neurons at the neuromuscular junction through a dual-receptor mechanism that includes interactions with ganglioside and protein receptors. The receptor identities vary depending on BoNT serotype (A-G). BoNT/B and BoNT/G bind the luminal domains of synaptotagmin I and II, homologous synaptic vesicle proteins. We observe conditions under which BoNT/B binds both Syt isoforms, but BoNT/G binds only SytI. Both serotypes bind ganglioside G{sub T1b}. The BoNT/G receptor-binding domain crystal structure provides a context for examining these binding interactions and a platform for understanding the physiological relevance of different Syt receptor isoforms in vivo.

Gut content analysis of Lake Michigan waterbirds in years with avian botulism type E mortality, 2010–2012

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Essian, David A.; Chipault, Jennifer G.; Lafrancois, Brenda M.; Leonard, Jill B.K.

2016-01-01

Waterbird die-offs caused by Clostridium botulinum neurotoxin type E (BoNT/E) have occurred sporadically in the Great Lakes since the late 1960s, with a recent pulse starting in the late 1990s. In recent die-offs, round gobies (Neogobius melanostomus) have been implicated as vectors for the transfer of BoNT/E to fish-eating birds due to the round goby invasion history and their importance as prey. Dreissenid mussels (Dreissena spp.) are also potentially involved in BoNT/E transmission to birds and round gobies. We examined gut contents of waterbirds collected in Lake Michigan during die-offs in 2010–2012, and the gut contents of culled, presumably BoNT/E-free double-crested cormorants (Phalacrocorax auritus). Round gobies were found in 86% of the BoNT/E-positive individuals, 84% of the BoNT/E-negative birds, and 94% of the BoNT/E-free cormorants examined. Double-crested cormorants, ring-billed gulls (Larus delewarensis), and common loons (Gavia immer) consumed larger-sized round gobies than horned and red-necked grebes (Podiceps auritus and Podiceps grisegena), white-winged scoters (Melanitta deglandi), and long-tailed ducks (Clangula hymealis). Other common prey included dreissenid mussels, terrestrial insects, and alewives (Alosa pseudoharengus). Our data emphasize the importance of round gobies and mussels in diets of Lake Michigan waterbirds and suggest they may play a role in the transfer of BoNT/E to waterbirds; however, round gobies and mussels were found in BoNT/E-positive, -negative, and -free individuals, suggesting that other factors, such as alternative trophic pathways for toxin transfer, bird migratory timing and feeding locations, prey behavior, and individual physiological differences across birds may affect the likelihood that a bird will succumb to BoNT/E intoxication.

The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles.

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Pirazzini, Marco; Azarnia Tehran, Domenico; Zanetti, Giulia; Lista, Florigio; Binz, Thomas; Shone, Clifford C; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new treatment for focal dystonias: incobotulinumtoxinA (Xeomin®, a botulinum neurotoxin type A free from complexing proteins

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Jimenez-Shahed J

2011-12-01

Full Text Available Joohi Jimenez-ShahedDepartment of Neurology, Baylor College of Medicine, Houston, TX, USAAbstract: Dystonia is a movement disorder of uncertain pathogenesis that is characterized by involuntary and inappropriate muscle contractions which cause sustained abnormal postures and movements of multiple or single (focal body regions. The most common focal dystonias are cervical dystonia (CD and blepharospasm (BSP. The first-line recommended treatment for CD and BSP is injection with botulinum toxin (BoNT, of which two serotypes are available: BoNT type A (BoNT/A and BoNT type B (BoNT/B. Conventional BoNT formulations include inactive complexing proteins, which may increase the risk for antigenicity, possibly leading to treatment failure. IncobotulinumtoxinA (Xeomin®; Merz Pharmaceuticals GmbH, Frankfurt, Germany is a BoNT/A agent that has been recently Food and Drug Administration-approved for the treatment of adults with CD and adults with BSP previously treated with onabotulinumtoxinA (Botox®; Allergen, Inc, Irvine, CA – a conventional BoNT/A. IncobotulinumtoxinA is the only BoNT product that is free of complexing proteins. The necessity of complexing proteins for the effectiveness of botulinum toxin treatment has been challenged by preclinical and clinical studies with incobotulinumtoxinA. These studies have also suggested that incobotulinumtoxinA is associated with a lower risk for stimulating antibody formation than onabotulinumtoxinA. In phase 3 noninferiority trials, incobotulinumtoxinA demonstrated significant improvements in CD and BSP symptoms in both primary and secondary measures, compared with baseline, and met criteria for noninferiority versus onabotulinumtoxinA. In placebo-controlled trials, incobotulinumtoxinA also significantly improved the symptoms of CD and BSP, with robust outcomes in both primary and secondary measures. The use of incobotulinumtoxinA has been well tolerated in all trials, with an adverse event profile similar

Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1 and A5.

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Wang, Dongxia; Krilich, Joan; Pellett, Sabine; Baudys, Jakub; Tepp, William H; Barr, John R; Johnson, Eric A; Kalb, Suzanne R

2013-12-01

Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening disease botulism through the inhibition of neurotransmitter release by cleaving essential SNARE proteins. There are seven serologically distinctive types of BoNTs and many subtypes within a serotype have been identified. BoNT/A5 is a recently discovered subtype of type A botulinum neurotoxin which possesses a very high degree of sequence similarity and identity to the well-studied A1 subtype. In the present study, we examined the endopeptidase activity of these two BoNT/A subtypes and our results revealed significant differences in substrate binding and cleavage efficiency between subtype A5 and A1. Distinctive hydrolysis efficiency was observed between the two toxins during cleavage of the native substrate SNAP-25 versus a shortened peptide mimic. N-terminal truncation studies demonstrated that a key region of the SNAP-25, including the amino acid residues at 151 through 154 located in the remote binding region of the substrate, contributed to the differential catalytic properties between A1 and A5. Elevated binding affinity of the peptide substrate resulted from including these important residues and enhanced BoNT/A5's hydrolysis efficiency. In addition, mutations of these amino acid residues affect the proteolytic performance of the two toxins in different ways. This study provides a better understanding of the biological activity of these toxins, their performance characteristics in the Endopep-MS assay to detect BoNT in clinical samples and foods, and is useful for the development of peptide substrates. © 2013. Published by Elsevier B.V. All rights reserved.

Isolation and functional characterization of the novel Clostridium botulinum neurotoxin A8 subtype.

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Skadi Kull

Full Text Available Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT. Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed

Comparing two botulinum toxin type A formulations using manufacturers' product summaries.

Science.gov (United States)

Wenzel, R; Jones, D; Borrego, J A

2007-08-01

Because of the unique pharmacology and clinical versatility of botulinum toxin (BoNT), particularly BoNT serotype A (BoNTA), a need exists for discussion of the current data on similarities and differences between two BoNTA products, BOTOX and Dysport. We compared the physiochemical and pharmacological properties of BOTOX and Dysport using information from the Summary of Product Characteristics (SmPC) documents from a number of countries around the world. Our analysis based on the SmPC documents demonstrated distinct differences in physical characteristics, breadth of approved indications, dosing and administration, and the incidence and severity of adverse events. BOTOX and Dysport are not bioequivalent. Many of the differences between BOTOX and Dysport discussed within are probably related to the differences in their physical characteristics.

A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus.

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Ramachandran, Roshni; Marino, Marc J; Paul, Snighdha; Wang, Zhenping; Mascarenhas, Nicholas L; Pellett, Sabine; Johnson, Eric A; DiNardo, Anna; Yaksh, Tony L

2018-03-23

Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation.

Assembly and function of the botulinum neurotoxin progenitor complex.

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Gu, Shenyan; Jin, Rongsheng

2013-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous substances known to man, but paradoxically, BoNT-containing medicines and cosmetics have been used with great success in the clinic. Accidental BoNT poisoning mainly occurs through oral ingestion of food contaminated with Clostridium botulinum. BoNTs are naturally produced in the form of progenitor toxin complexes (PTCs), which are high molecular weight (up to ~900 kDa) multiprotein complexes composed of BoNT and several non-toxic neurotoxin-associated proteins (NAPs). NAPs protect the inherently fragile BoNTs against the hostile environment of the gastrointestinal (GI) tract and help BoNTs pass through the intestinal epithelial barrier before they are released into the general circulation. These events are essential for ingested BoNTs to gain access to motoneurons, where they inhibit neurotransmitter release and cause muscle paralysis. In this review, we discuss the structural basis for assembly of NAPs and BoNT into the PTC that protects BoNT and facilitate its delivery into the bloodstream.

Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.

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Minamoto, Viviane B; Suzuki, Kentaro P; Bremner, Shannon N; Lieber, Richard L; Ward, Samuel R

2015-10-01

Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. © 2015 Wiley Periodicals, Inc.

Therapeutic Approaches of Botulinum Toxin in Gynecology.

Science.gov (United States)

Moga, Marius Alexandru; Dimienescu, Oana Gabriela; Bălan, Andreea; Scârneciu, Ioan; Barabaș, Barna; Pleș, Liana

2018-04-21

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

Probiotic microorganisms inhibit epithelial cell internalization of botulinum neurotoxin serotype A

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Botulinum neurotoxins (BoNTs) are some of the most poisonous natural toxins known to man and are threats to public health and safety. Previous work from our laboratory showed that BoNT serotype A (BoNT/A) complex (holotoxin with neurotoxin-associated proteins) bind and transit through the intestinal...

DEVELOPMENT OF ENZYME-LINKAGE IMMUNOSORBENT ASSAY AGAINST TYPE B OF CLOSTRIDIUM BOTULINUM: A PRELIMINARY STUDY

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S. N. Depamede

2011-12-01

Full Text Available Clostridium botulinum neurotoxin (BoNTs is one of the causes of economic loss in the livestock industry. This economic loss would be as a direct result when animals poisoned by BoNTs or indirectly when the livestock products are contaminated by BoNTs, which end up with the products are banned by authority. Therefore a routine surveillance of BoNTs in the farm and in livestock product processing industry is urgently needed. One of the most relatively quick and accurate methods to perform a routine detection of the presence of BoNTs is enzyme-linkage immunosorbant assay (ELISA. In this article we describe the results of the development of ELISA, using polyclonal antibodies against BoNTs-B produced locally. Antibodies were generated from six Balb/c mice with standard immunological methods. Mice were immunized three times for a period of 8 weeks with a commercial type B Clostridium botulinum toxoid at a dose of 100 ng per mouse per injection. The resulting antibody was purified by a combination of ammonium sulfate precipitation 50% (w/v technique and a protein A column method. The results of this preliminary study indicated that the developed ELISA method capable of detecting type B Clostridium botulinum toxin up to 1.0 ng/ml.

SiMa Cells for a Serotype Specific and Sensitive Cell-Based Neutralization Test for Botulinum Toxin A and E.

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Bak, Nicola; Rajagopal, Shalini; Stickings, Paul; Sesardic, Dorothea

2017-07-20

Botulinum toxins (BoNTs), of which there are seven serotypes, are among the most potent neurotoxins, with serotypes A, B and E causing human botulism. Antitoxins form the first line of treatment for botulism, and functional, highly sensitive in vitro methods for toxin neutralization are needed to replace the current in vivo methods used for determination of antitoxin potency. In this preliminary proof of concept study, we report the development of a neutralization test using the neuroblastoma SiMa cell line. The assay is serotype specific for either BoNT/A or BoNT/E, which both cleave unique sequences on SNAP-25 within SiMa cells. The end point is simple immunodetection of cleaved SNAP-25 from cell lysates with antibodies detecting only the newly exposed sequence on SNAP-25. Neutralizing antibodies prevent the toxin-induced cleavage of SNAP-25. The toxin neutralization assay, with an EC50 of ~2 mIU/mL determined with a standardized reference antiserum, is more sensitive than the mouse bioassays. Relevance was demonstrated with commercial and experimental antitoxins targeting different functional domains, and of known in vivo neutralizing activities. This is the first report describing a simple, specific, in vitro cell-based assay for the detection of neutralizing antibodies against BoNT/A and BoNT/E with a sensitivity exceeding that of the mouse bioassay.

Using llama derived single domain antibodies to target botulinum neurotoxins

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Swain, Marla D.; Anderson, George P.; Bernstein, Rachael D.; Liu, Jinny L.; Goldman, Ellen R.

2010-04-01

Llama serum contains both conventional IgG as well as unique forms of antibody that contain only heavy chains where antigen binding is mediated through a single variable domain. These variable domains can be expressed recombinantly and are referred to as single domain antibodies (sdAb). SdAb are among the smallest known naturally derived antigen binding fragments, possess good solubility, thermal stability, and can refold after heat and chemical denaturation. Llamas were immunized with either BoNT A or B toxoid and phage display libraries prepared. Single domain antibodies (sdAb) that were able to detect botulinum neurotoxin (BoNT) serotypes A and B were selected from their respective libraries. Here, the binders obtained by panning the BoNT B library on either BoNT B toxoid or BoNT B complex toxoid coated plates or BoNT B toxin coupled microspheres are described. Using these panning methods, we selected for binders that showed specificity for BoNT B. Phage displayed binders were screened, moved to a protein expression vector and soluble sdAb was produced. Using a Luminex flow cytometer binders were evaluated in direct binding assays. We have exploited the unique properties of sdAb and used them as biological recognition elements in immuno-based sensors that can detect BoNT B.

Is activation analysis still active?

International Nuclear Information System (INIS)

Chai Zhifang

2001-01-01

This paper reviews some aspects of neutron activation analysis (NAA), covering instrumental neutron activation analysis (INAA), k 0 method, prompt gamma-ray neutron activation analysis (PGNAA), radiochemical neutron activation analysis (RNAA) and molecular activation analysis (MAA). The comparison of neutron activation analysis with other analytical techniques are also made. (author)

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

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Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

2017-04-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.

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Yoneyama, Tohru; Miyata, Keita; Chikai, Tomoyuki; Mikami, Akifumi; Suzuki, Tomonori; Hasegawa, Kimiko; Ikeda, Toshihiko; Watanabe, Toshihiro; Ohyama, Tohru; Niwa, Koichi

2008-12-01

Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures

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Katharine E. Alter

2017-12-01

Full Text Available Injections of botulinum neurotoxins (BoNTs are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

Temporomandibular Myofacial Pain Treated with Botulinum Toxin Injection

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Niv Mor

2015-07-01

Full Text Available This article reviews the diagnoses and treatment of temporomandibular disorders (TMD and outlines of the role of botulinum toxin (BoNT in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD.

Therapeutic Approaches of Botulinum Toxin in Gynecology

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Marius Alexandru Moga

2018-04-01

Full Text Available Botulinum toxins (BoNTs are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G. Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration.

Qualitative and Quantitative Detection of Botulinum Neurotoxins from Complex Matrices: Results of the First International Proficiency Test

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Sylvia Worbs

2015-11-01

Full Text Available In the framework of the EU project EQuATox, a first international proficiency test (PT on the detection and quantification of botulinum neurotoxins (BoNT was conducted. Sample materials included BoNT serotypes A, B and E spiked into buffer, milk, meat extract and serum. Different methods were applied by the participants combining different principles of detection, identification and quantification. Based on qualitative assays, 95% of all results reported were correct. Successful strategies for BoNT detection were based on a combination of complementary immunological, MS-based and functional methods or on suitable functional in vivo/in vitro approaches (mouse bioassay, hemidiaphragm assay and Endopep-MS assay. Quantification of BoNT/A, BoNT/B and BoNT/E was performed by 48% of participating laboratories. It turned out that precise quantification of BoNT was difficult, resulting in a substantial scatter of quantitative data. This was especially true for results obtained by the mouse bioassay which is currently considered as “gold standard” for BoNT detection. The results clearly demonstrate the urgent need for certified BoNT reference materials and the development of methods replacing animal testing. In this context, the BoNT PT provided the valuable information that both the Endopep-MS assay and the hemidiaphragm assay delivered quantitative results superior to the mouse bioassay.

Rapid microfluidic assay for the detection of botulinum neurotoxin in animal sera

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The potent botulinum neurotoxins (BoNTs) represent a threat to public health and safety. Botulism is a disease caused by BoNT intoxication that results in muscle paralysis that can be fatal. Sensitive assays capable of detecting BoNTs from different substrates and settings are essential to limit f...

A Review of the Disruptive Potential of Botulinum Neurotoxins as Chemical Warfare Agents

Science.gov (United States)

2011-10-01

canned; fermented , uncooked; or improperly cooked dishes); 2 • Ingestion of spores, which in turn colonize the small intestine (occurs in...should also be noted that some food products may be more amenable to contamination with active BoNT than milk-based dairy products, although for

Comparison of oral toxicological properties of botulinum neurotoxin

Science.gov (United States)

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated ...

Therapeutic Approaches of Botulinum Toxin in Gynecology

OpenAIRE

Marius Alexandru Moga; Oana Gabriela Dimienescu; Andreea Bălan; Ioan Scârneciu; Barna Barabaș; Liana Pleș

2018-01-01

Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT...

Association of toxin-producing Clostridium botulinum with the macroalga Cladophora in the Great Lakes.

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Chun, Chan Lan; Ochsner, Urs; Byappanahalli, Muruleedhara N; Whitman, Richard L; Tepp, William H; Lin, Guangyun; Johnson, Eric A; Peller, Julie; Sadowsky, Michael J

2013-03-19

Avian botulism, a paralytic disease of birds, often occurs on a yearly cycle and is increasingly becoming more common in the Great Lakes. Outbreaks are caused by bird ingestion of neurotoxins produced by Clostridium botulinum, a spore-forming, gram-positive, anaerobe. The nuisance, macrophytic, green alga Cladophora (Chlorophyta; mostly Cladophora glomerata L.) is a potential habitat for the growth of C. botulinum. A high incidence of botulism in shoreline birds at Sleeping Bear Dunes National Lakeshore (SLBE) in Lake Michigan coincides with increasingly massive accumulations of Cladophora in nearshore waters. In this study, free-floating algal mats were collected from SLBE and other shorelines of the Great Lakes between June and October 2011. The abundance of C. botulinum in algal mats was quantified and the type of botulism neurotoxin (bont) genes associated with this organism were determined by using most-probable-number PCR (MPN-PCR) and five distinct bont gene-specific primers (A, B, C, E, and F). The MPN-PCR results showed that 16 of 22 (73%) algal mats from the SLBE and 23 of 31(74%) algal mats from other shorelines of the Great Lakes contained the bont type E (bont/E) gene. C. botulinum was present up to 15000 MPN per gram dried algae based on gene copies of bont/E. In addition, genes for bont/A and bont/B, which are commonly associated with human diseases, were detected in a few algal samples. Moreover, C. botulinum was present as vegetative cells rather than as dormant spores in Cladophora mats. Mouse toxin assays done using supernatants from enrichment of Cladophora containing high densities of C. botulinum (>1000 MPN/g dried algae) showed that Cladophora-borne C. botulinum were toxin-producing species (BoNT/E). Our results indicate that Cladophora provides a habitat for C. botulinum, warranting additional studies to better understand the relationship between this bacterium and the alga, and how this interaction potentially contributes to botulism

Botulinum neurotoxin G binds synaptotagmin-II in a mode similar to that of serotype B: tyrosine 1186 and lysine 1191 cause its lower affinity.

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Willjes, Gesche; Mahrhold, Stefan; Strotmeier, Jasmin; Eichner, Timo; Rummel, Andreas; Binz, Thomas

2013-06-04

Botulinum neurotoxins (BoNTs) block neurotransmitter release by proteolyzing SNARE proteins in peripheral nerve terminals. Entry into neurons occurs subsequent to interaction with gangliosides and a synaptic vesicle protein. Isoforms I and II of synaptotagmin were shown to act as protein receptors for two of the seven BoNT serotypes, BoNT/B and BoNT/G, and for mosaic-type BoNT/DC. BoNT/B and BoNT/G exhibit a homologous binding site for synaptotagmin whose interacting part adopts helical structure upon binding to BoNT/B. Whereas the BoNT/B-synaptotagmin-II interaction has been elucidated in molecular detail, corresponding information about BoNT/G is lacking. Here we systematically mutated the synaptotagmin binding site in BoNT/G and performed a comparative binding analysis with mutants of the cell binding subunit of BoNT/B. The results suggest that synaptotagmin takes the same overall orientation in BoNT/B and BoNT/G governed by the strictly conserved central parts of the toxins' binding site. The surrounding nonconserved areas differently contribute to receptor binding. Reciprocal mutations Y1186W and L1191Y increased the level of binding of BoNT/G approximately to the level of BoNT/B affinity, suggesting a similar synaptotagmin-bound state. The effects of the mutations were confirmed by studying the activity of correspondingly mutated full-length BoNTs. On the basis of these data, molecular modeling experiments were employed to reveal an atomistic model of BoNT/G-synaptotagmin recognition. These data suggest a reduced length and/or a bend in the C-terminal part of the synaptotagmin helix that forms upon contact with BoNT/G as compared with BoNT/B and are in agreement with the data of the mutational analyses.

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

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Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons.

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Laura Restani

2012-12-01

Full Text Available The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neurotransmitters in the spinal cord, causing a spastic paralysis. In contrast, botulinum neurotoxins (BoNTs block acetylcholine release at the neuromuscular junction, therefore inducing a flaccid paralysis. Whilst overt experimental evidence supports the sorting of TeNT to the axonal retrograde transport pathway, recent findings challenge the established view that BoNT trafficking is restricted to the neuromuscular junction by highlighting central effects caused by these neurotoxins. These results suggest a more complex scenario whereby BoNTs also engage long-range trafficking mechanisms. However, the intracellular pathways underlying this process remain unclear. We sought to fill this gap by using primary motor neurons either in mass culture or differentiated in microfluidic devices to directly monitor the endocytosis and axonal transport of full length BoNT/A and BoNT/E and their recombinant binding fragments. We show that BoNT/A and BoNT/E are internalised by spinal cord motor neurons and undergo fast axonal retrograde transport. BoNT/A and BoNT/E are internalised in non-acidic axonal carriers that partially overlap with those containing TeNT, following a process that is largely independent of stimulated synaptic vesicle endo-exocytosis. Following intramuscular injection in vivo, BoNT/A and TeNT displayed central effects with a similar time course. Central actions paralleled the peripheral spastic paralysis for TeNT, but lagged behind the onset of flaccid paralysis for BoNT/A. These results suggest that the fast axonal retrograde transport compartment is composed of multifunctional trafficking organelles orchestrating the simultaneous transfer

Botulinum toxin type a for chronic migraine.

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Ashkenazi, Avi

2010-03-01

Chronic migraine (CM) is the leading cause of chronic daily headache, a common and debilitating headache syndrome. The management of CM patients is challenging, with only limited benefit from available oral preventive medications. Botulinum neurotoxin (BoNT) has been used extensively to treat disorders associated with increased muscle tone. More recent scientific data support an analgesic effect of the toxin. The pharmacokinetic and pharmacodynamic profiles of BoNT make it an appealing candidate for migraine prevention. Results from older clinical trials on the efficacy of the toxin in CM were inconclusive. However, recent trials using more stringent inclusion criteria have shown positive results, supporting the use of the toxin in some patients with this disorder. This review summarizes the scientific data on the analgesic properties of BoNT, as well as the clinical data on the efficacy of the toxin in treating CM.

Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments

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Sheng Chen

2012-10-01

Full Text Available Botulinum neurotoxins (BoNTs cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs.

An update on neurotoxin products and administration methods.

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Lanoue, Julien; Dong, Joanna; Do, Timothy; Goldenberg, Gary

2016-09-01

Since onabotulinumtoxinA for nonsurgical aesthetic enhancement of glabellar lines was initially reported, the popularity of botulinum neurotoxin (BoNT) products among both clinicians and consumers has rapidly grown, and we have seen several additional BoNT formulations enter the market. As the demand for minimally invasive cosmetic procedures continues to increase, we will see the introduction of additional formulations of BoNT products as well as new delivery devices and administration techniques. In this article, we provide a brief update on current and upcoming BoNT products and also review the literature on novel administration methods based on recently published studies.

Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

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Nuemket, Nipawan [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Yoshikazu [Creative Research Institution ' Sousei,' Hokkaido University, Sapporo 001-0021 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tsukamoto, Kentaro; Tsuji, Takao [Department of Microbiology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192 (Japan); Nakamura, Keiji; Kozaki, Shunji [Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka 598-8531 (Japan); Yao, Min [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Tanaka, Isao, E-mail: tanaka@castor.sci.hokudai.ac.jp [Graduate School of Life Sciences, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan)

2011-07-29

Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinum neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.

Rational design of botulinum neurotoxin A1 mutants with improved oxidative stability.

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López de la Paz, Manuela; Scheps, Daniel; Jurk, Marcel; Hofmann, Fred; Frevert, Jürgen

2018-06-01

Botulinum neurotoxins (BoNTs) are the most potent toxic proteins to mankind known but applied in low doses trigger a localized muscle paralysis that is beneficial for the therapy of several neurological disorders and aesthetic treatment. The paralytic effect is generated by the enzymatic activity of the light chain (LC) that cleaves specifically one of the SNARE proteins responsible for neurotransmitter exocytosis. The activity of the LC in a BoNT-containing therapeutic can be compromised by denaturing agents present during manufacturing and/or in the cell. Stabilization of the LC by reducing vulnerability towards denaturants would thus be advantageous for the development of BoNT-based therapeutics. In this work, we focused on increasing the stability of LC of BoNT/A1 (LC/A1) towards oxidative stress. We tackled this task by rational design of mutations at cysteine and methionine LC/A1 sites. Designed mutants showed improved oxidative stability in vitro and equipotency to wildtype toxin in vivo. Our results suggest that suitable modification of the catalytic domain can lead to more stable BoNTs without impairing their therapeutic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implementing the Bruker MALDI Biotyper in the Public Health Laboratory for C. botulinum Neurotoxin Detection

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Michael J. Perry

2017-03-01

Full Text Available Currently, the gold standard method for active botulinum neurotoxin (BoNT detection is the mouse bioassay (MBA. A Centers for Disease Control and Prevention-developed mass spectrometry (MS-based assay that detects active BoNT was successfully validated and implemented in a public health laboratory in clinical matrices using the Bruker MALDI-TOF MS (Matrix-assisted laser desorption ionization–time of flight mass spectrometry Biotyper. For the first time, a direct comparison with the MBA was performed to determine MS-based assay sensitivity using the Bruker MALDI Biotyper. Mice were injected with BoNT/A, /B, /E, and /F at concentrations surrounding the established MS assay limit of detection (LOD and analyzed simultaneously. For BoNT/B, /E, and /F, MS assay sensitivity was equivalent or better than the MBA at 25, 0.3, and 8.8 mLD50, respectively. BoNT/A was detected by the MBA between 1.8 and 18 mLD50, somewhat more sensitive than the MS method of 18 mLD50. Studies were performed to compare assay performance in clinical specimens. For all tested specimens, the MS method rapidly detected BoNT activity and serotype in agreement with, or in the absence of, results from the MBA. We demonstrate that the MS assay can generate reliable, rapid results while eliminating the need for animal testing.

Standardizing Activation Analysis: New Software for Photon Activation Analysis

Science.gov (United States)

Sun, Z. J.; Wells, D.; Segebade, C.; Green, J.

2011-06-01

Photon Activation Analysis (PAA) of environmental, archaeological and industrial samples requires extensive data analysis that is susceptible to error. For the purpose of saving time, manpower and minimizing error, a computer program was designed, built and implemented using SQL, Access 2007 and asp.net technology to automate this process. Based on the peak information of the spectrum and assisted by its PAA library, the program automatically identifies elements in the samples and calculates their concentrations and respective uncertainties. The software also could be operated in browser/server mode, which gives the possibility to use it anywhere the internet is accessible. By switching the nuclide library and the related formula behind, the new software can be easily expanded to neutron activation analysis (NAA), charged particle activation analysis (CPAA) or proton-induced X-ray emission (PIXE). Implementation of this would standardize the analysis of nuclear activation data. Results from this software were compared to standard PAA analysis with excellent agreement. With minimum input from the user, the software has proven to be fast, user-friendly and reliable.

Standardizing Activation Analysis: New Software for Photon Activation Analysis

International Nuclear Information System (INIS)

Sun, Z. J.; Wells, D.; Green, J.; Segebade, C.

2011-01-01

Photon Activation Analysis (PAA) of environmental, archaeological and industrial samples requires extensive data analysis that is susceptible to error. For the purpose of saving time, manpower and minimizing error, a computer program was designed, built and implemented using SQL, Access 2007 and asp.net technology to automate this process. Based on the peak information of the spectrum and assisted by its PAA library, the program automatically identifies elements in the samples and calculates their concentrations and respective uncertainties. The software also could be operated in browser/server mode, which gives the possibility to use it anywhere the internet is accessible. By switching the nuclide library and the related formula behind, the new software can be easily expanded to neutron activation analysis (NAA), charged particle activation analysis (CPAA) or proton-induced X-ray emission (PIXE). Implementation of this would standardize the analysis of nuclear activation data. Results from this software were compared to standard PAA analysis with excellent agreement. With minimum input from the user, the software has proven to be fast, user-friendly and reliable.

Botulinum neurotoxin: unique folding of enzyme domain of the most-poisonous poison.

Science.gov (United States)

Kumar, Raj; Kukreja, Roshan V; Li, Li; Zhmurov, Artem; Kononova, Olga; Cai, Shuowei; Ahmed, Syed A; Barsegov, Valeri; Singh, Bal Ram

2014-01-01

Botulinum neurotoxin (BoNT), the most toxic substance known to mankind, is the first example of the fully active molten globule state. To understand its folding mechanism, we performed urea denaturation experiments and theoretical modeling using BoNT serotype A (BoNT/A). We found that the extent of BoNT/A denaturation from the native state (N) shows a nonmonotonic dependence on urea concentration indicating a unique multistep denaturation process, N → I1 [Formula: see text] I2 [Formula: see text] U, with two intermediate states I1 and I2. BoNT/A loses almost all its secondary structure in 3.75 M urea (I1), yet it displays a native-like secondary structure in 5 M urea (I2). This agrees with the results of theoretical modeling, which helped to determine the molecular basis of unique behavior of BoNT/A in solution. Except for I2, all the states revert back to full enzymatic activity for SNAP-25 including the unfolded state U stable in 7 M urea. Our results stress the importance of structural flexibility in the toxin's mechanism of survival and action, an unmatched evolutionary trait from billion-year-old bacteria, which also correlates with the long-lasting enzymatic activity of BoNT inside neuronal cells. BoNT/A provides a rich model to explore protein folding in relation to functional activity.

The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

Science.gov (United States)

Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

2016-07-22

The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo.

A protein chip membrane-capture assay for botulinum neurotoxin activity

International Nuclear Information System (INIS)

Marconi, Severine; Ferracci, Geraldine; Berthomieu, Maelys; Kozaki, Shunji; Miquelis, Raymond; Boucraut, Jose; Seagar, Michael

2008-01-01

Botulinum neurotoxins A and B (BoNT/A and B) are neuromuscular blocking agents which inhibit neurotransmission by cleaving the intra-cellular presynaptic SNARE proteins SNAP-25 and VAMP2, localized respectively in plasma membrane and synaptic vesicles. These neurotoxins are both dangerous pathogens and powerful therapeutic agents with numerous clinical and cosmetic applications. Consequently there is a need for in vitro assays of their biological activity to screen for potential inhibitors and to replace the widely used in vivo mouse assay. Surface plasmon resonance (SPR) was used to measure membrane vesicle capture by antibodies against SNAP-25 and VAMP2. Substrate cleavage by BoNTs modified capture providing a method to assay toxin activity. Firstly using synaptic vesicles as a substrate, a comparison of the EC 50 s for BoNT/B obtained by SPR, ELISA or flow cytometry indicated similar sensitivity although SPR assays were more rapid. Sonication of brain or neuronal cultures generated plasma membrane fragments with accessible intra-cellular epitopes adapted to measurement of BoNT/A activity. SPR responses were proportional to antigen concentration permitting detection of as little as 4 pM SNAP-25 in crude lysates. BoNT/A activity was assayed using monoclonal antibodies that specifically recognize a SNAP-25 epitope generated by the proteolytic action of the toxin. Incubation of intact primary cultured neurons with BoNT/A yielded an EC 50 of 0.5 pM. The SPR biosensor method was sensitive enough to monitor BoNT/A and B activity in cells cultured in a 96-well format providing an alternative to experimental animals for toxicological assays

Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

Science.gov (United States)

Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

2008-07-01

A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip.

Science.gov (United States)

Tehran, Domenico Azarnia; Pirazzini, Marco

2018-05-10

Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip

Directory of Open Access Journals (Sweden)

Domenico Azarnia Tehran

2018-05-01

Full Text Available Botulinum neurotoxins (BoNTs, the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.

Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex

OpenAIRE

Matsui, Tsutomu; Gu, Shenyan; Lam, Kwok-ho; Carter, Lester G.; Rummel, Andreas; Mathews, Irimpan I.; Jin, Rongsheng

2014-01-01

Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and release it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent co...

Clostridium botulinum group I strain genotyping by 15-locus multilocus variable-number tandem-repeat analysis

NARCIS (Netherlands)

Fillo, S.; Giordani, F.; Anniballi, F.; Gorgé, O.; Ramisse, V.; Vergnaud, G.; Riehm, J.M.; Scholz, H.C.; Splettstoesser, W.D.; Kieboom, J.; Olsen, J.-S.; Fenicia, L.; Lista, F.

2011-01-01

Clostridium botulinum is a taxonomic designation that encompasses a broad variety of spore-forming, Gram-positive bacteria producing the botulinum neurotoxin (BoNT). C. botulinum is the etiologic agent of botulism, a rare but severe neuroparalytic disease. Fine-resolution genetic characterization of

Effects of intraplantar botulinum toxin-B on carrageenan-induced changes in nociception and spinal phosphorylation of GluA1 and Akt.

Science.gov (United States)

Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni

2016-07-01

Increasing evidence suggests that botulinum neurotoxins (BoNTs) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N-methylaleimide-sensitive attachment protein receptor by BoNTs can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity-evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin- B (BoNT-B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57BL/6 mice (male) received unilateral intraplantar BoNT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N-methyl-D-aspartate (NMDA), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit (pGluA1ser845) and a serine/threonine-specific protein kinase (pAktser473) in spinal dorsal horn along with an increased incidence of spinal c-Fos positive cells. Pre-treatment with intraplantar BoNT-B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pGluA1 and pAkt and (iii) c-Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pGluA1 and pAkt. Intraplantar BoNT-B inhibited NMDA, but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes

OpenAIRE

Sharma, Shashi K.; Basavanna, Uma; Shukla, Hem D.

2009-01-01

Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among differe...

In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.

Science.gov (United States)

Ravichandran, Easwaran; Janardhanan, Pavithra; Patel, Kruti; Riding, Stephen; Cai, Shuowei; Singh, Bal Ram

2016-03-01

A double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT. We determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model. drBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin. Based on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.

Investigating CRISPR-Cas systems in Clostridium botulinum via bioinformatics tools.

Science.gov (United States)

Negahdaripour, Manica; Nezafat, Navid; Hajighahramani, Nasim; Rahmatabadi, Seyyed Soheil; Ghasemi, Younes

2017-10-01

The Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a type of innate immunity found in some prokaryotes, which protect them against alien genetic elements by targeting foreign nucleic acids. Some other functions are also attributed to these systems. Clostridium botulinum bacteria produce botulinum neurotoxins (BoNT), one of the deadliest known toxins for humans and some animals. Food poisoning due to these bacteria is still a challenge in food industries. On the other hand, BoNT has been widely investigated for therapeutic applications including different muscle disorders. Bont genes may be located on bacterial chromosomes, plasmids, or even prophages. Generally, the genomes of Cl. botulinum show a high level of plasticity. In order to investigate the presence and characteristics of CRISPRs in these anaerobe bacteria, an in silico study on 113 CRISPR arrays identified in 38 Cl. botulinum strains was performed. A high occurrence of CRISPR arrays (80%) were found, with a remarkable frequency on plasmids. Several (CRISPR-associated) Cas proteins from different types were recognized in the studied strains, which were mostly Cas6. The CRISPR-Cas systems were identified as type I or III, but no type II. The spacers showed more homology with bacterial plasmids than phages. Active CRISPR-Cas systems can prevent the transfer of foreign genes, which may also include bont genes. This study provides the first insight into the probable roles of CRISPR-Cas systems in Cl. botulinum strains such as toxigenicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemodenervation of the Larynx

Directory of Open Access Journals (Sweden)

Rachel Kaye

2017-11-01

Full Text Available Botulinum neurotoxin (BoNT has existed for thousands of years; however, it was not medically utilized until investigations into its therapeutic use began in sincerity during the late 1970s and 1980s. This, coupled with the reclassification of spasmodic dysphonia as a focal dystonia, led to the use of chemodenervation for this disorder, which has since become a refined technique. Indeed, due to its safety and efficacy, BoNT has been investigated in multiple neurolaryngology disorders, including spasmodic dysphonia, vocal tremor, and muscle tension dysphonia. BoNT has been shown to be a useful and safe adjunct in the treatment for these disorders and may reduce or eliminate oral pharmacotherapy and/or prevent the need for a surgical intervention. We present the historical background, development, proposed mechanisms of action, uses, and techniques for administering BoNT for laryngeal disorders, with a particular focus on spasmodic dysphonia.

Chemodenervation of the Larynx

Science.gov (United States)

Kaye, Rachel; Blitzer, Andrew

2017-01-01

Botulinum neurotoxin (BoNT) has existed for thousands of years; however, it was not medically utilized until investigations into its therapeutic use began in sincerity during the late 1970s and 1980s. This, coupled with the reclassification of spasmodic dysphonia as a focal dystonia, led to the use of chemodenervation for this disorder, which has since become a refined technique. Indeed, due to its safety and efficacy, BoNT has been investigated in multiple neurolaryngology disorders, including spasmodic dysphonia, vocal tremor, and muscle tension dysphonia. BoNT has been shown to be a useful and safe adjunct in the treatment for these disorders and may reduce or eliminate oral pharmacotherapy and/or prevent the need for a surgical intervention. We present the historical background, development, proposed mechanisms of action, uses, and techniques for administering BoNT for laryngeal disorders, with a particular focus on spasmodic dysphonia. PMID:29099066

Activation analysis. Chapter 4

International Nuclear Information System (INIS)

1976-01-01

The principle, sample and calibration standard preparation, activation by neutrons, charged particles and gamma radiation, sample transport after activation, activity measurement, and chemical sample processing are described for activation analysis. Possible applications are shown of nondestructive activation analysis. (J.P.)

Researchers unmask secret to long-lasting effects of botulinum neurotoxin A in motor neurons | Center for Cancer Research

Science.gov (United States)

A team of scientists led by the Center for Cancer Research's Allan M. Weissman, M.D., and Yien Che Tsai, Ph.D., has discovered a molecular mechanism that explains the extreme toxicity of botulinum neurotoxin A (BoNT/A), the most potent BoNT strain. The discovery, published June 5 in PNAS, also identifies a molecular target that the researchers hope will eventually lead to improved therapies to treat exposure and severely undermine the potential use of BoNTs as bioweapons.  Read more...  

A new facility for rapid neutron activation analysis

International Nuclear Information System (INIS)

Zeisler, R.; Makarewicz, M.; Grass, F.; Casta, J.

1996-01-01

Many research groups have undertaken efforts on the utilization of short-lived nuclides in a broad spectrum of neutron activation analysis (NAA) applications. The advantages of these approaches are obvious because the information on the sample can be extracted more rapidly. In addition to its other advantages, NAA can become extremely competitive in price and analysis time. Nevertheless, NAA with short-lived nuclides has not gained broad popularity, perhaps because of some difficulties in accuracy and the availability of suitable irradiation facilities. This report discusses the ASTRA reactor for neutron activation analysis capabilities

Botulinum toxin effect on salivary flow rate in children with cerebral palsy.

NARCIS (Netherlands)

Jongerius, P.H.; Rotteveel, J.J.; Limbeek, J. van; Gabreëls, F.J.M.; Hulst, K. van; Hoogen, F.J.A. van den

2004-01-01

OBJECTIVE: To investigate the effectiveness of botulinum neurotoxin (BoNT) type A in reducing salivary flow rate in children with cerebral palsy (CP) with severe drooling. METHODS: During a controlled clinical trial, single-dose BoNT injections into the submandibular salivary glands were compared

Activation analysis of coal with the help of a microtron

International Nuclear Information System (INIS)

Sodnom, N.; Gehrbish, Sh.

1989-01-01

Activation analysis techniques using microtron bremsstrahlung and photoneutrons have been developed for the multielemental analysis of coal. Analysis data for coals from 17 mines of Mongolia are presented. The chlorine content of coal and the distribution of elements in coal burning products are determined. Control experiments were performed at the reactors IBR-2 and ARGUS. The results of the gamma activation analysis are compared with neutron activation and X-ray fluorescence analyses data. It is shown that the microtron irradiation techniques employed provide a satisfactory multielemental basis for the analysis of coal. (author)

Safety and administration of treatment with botulinum neurotoxin for sialorrhoea in ALS patients: Review of the litterature and a proposal for tailored treatment

DEFF Research Database (Denmark)

Stokholm, Morten; Bisgård, Carsten; Vilholm, Ole Jakob

2013-01-01

Botulinum neurotoxin (BoNT) is a second-line treatment of sialorrhoea in ALS (amyotrophic lateral sclerosis) patients. This article is a review of the published literature concerning safety and administration of this treatment to ALS patients. A PubMed search was performed. All original publicati......Botulinum neurotoxin (BoNT) is a second-line treatment of sialorrhoea in ALS (amyotrophic lateral sclerosis) patients. This article is a review of the published literature concerning safety and administration of this treatment to ALS patients. A PubMed search was performed. All original...

Instrumental neutron activation analysis as a routine method for rock analysis

International Nuclear Information System (INIS)

Rosenberg, R.J.

1977-06-01

Instrumental neutron activation methods for the analysis of geological samples have been developed. Special emphasis has been laid on the improvement of sensitivity and accuracy in order to maximize tha quality of the analyses. Furthermore, the procedures have been automated as far as possible in order to minimize the cost of the analysis. A short review of the basic literature is given followed by a description of the principles of the method. All aspects concerning the sensitivity are discussed thoroughly in view of the analyst's possibility of influencing them. Experimentally determined detection limits for Na, Al, K, Ca, Sc, Cr, Ti, V, Mn, Fe, Ni, Co, Rb, Zr, Sb, Cs, Ba, La, Ce, Nd, Sm, Eu, Gd, Tb, Dy, Yb, Lu, Hf, Ta, Th and U are given. The errors of the method are discussed followed by actions taken to avoid them. The most significant error was caused by flux deviation, but this was avoided by building a rotating sample holder for rotating the samples during irradiation. A scheme for the INAA of 32 elements is proposed. The method has been automated as far as possible and an automatic γ-spectrometer and a computer program for the automatic calculation of the results are described. Furthermore, a completely automated uranium analyzer based on delayed neutron counting is described. The methods are discussed in view of their applicability to rock analysis. It is stated that the sensitivity varies considerably from element to element and instrumental activation analysis is an excellent method for the analysis of some specific elements like lanthanides, thorium and uranium but less so for many other elements. The accuracy is good varying from 2% to 10% for most elements. Instrumental activation analysis for most elements is rather an expensive method there being, however, a few exceptions. The most important of these is uranium. The analysis of uranium by delayed neutron counting is an inexpensive means for the analysis of large numbers of samples needed for

Activation analysis in water chemistry

International Nuclear Information System (INIS)

Szabo, A.; Toth, A.

1978-01-01

The potential applications of activation analysis in water chemistry are discussed. The principle, unit operations, the radiation sources and measuring instruments of activation analysis are described. The sensitivity of activation analysis is given in tabulated form for some elements of major importance in water chemistry and the elements readily accessible to determination by measurement of the spontaneous gamma radiation are listed. A few papers selected from the recent international professional literature are finally reviewed, in which the authors report on the results obtained by activation analysis applied to water chemistry. (author)

Instrumental neutron activation analysis - a routine method

International Nuclear Information System (INIS)

Bruin, M. de.

1983-01-01

This thesis describes the way in which at IRI instrumental neutron activation analysis (INAA) has been developed into an automated system for routine analysis. The basis of this work are 20 publications describing the development of INAA since 1968. (Auth.)

Activation analysis. Detection limits

International Nuclear Information System (INIS)

Revel, G.

1999-01-01

Numerical data and limits of detection related to the four irradiation modes, often used in activation analysis (reactor neutrons, 14 MeV neutrons, photon gamma and charged particles) are presented here. The technical presentation of the activation analysis is detailed in the paper P 2565 of Techniques de l'Ingenieur. (A.L.B.)

A computer program for activation analysis

International Nuclear Information System (INIS)

Rantanen, J.; Rosenberg, R.J.

1983-01-01

A computer program for calculating the results of activation analysis is described. The program comprises two gamma spectrum analysis programs, STOAV and SAMPO and one program for calculating elemental concentrations, KVANT. STOAV is based on a simple summation of channels and SAMPO is based on fitting of mathematical functions. The programs are tested by analyzing the IAEA G-1 test spectra. In the determination of peak location SAMPO is somewhat better than STOAV and in the determination of peak area SAMPO is more than twice as accurate as STOAV. On the other hand, SAMPO is three times as expensive as STOAV with the use of a Cyber 170 computer. (author)

Neutron activation analysis in Romania

International Nuclear Information System (INIS)

Apostolescu, St.

1985-01-01

The following basic nuclear facilities are used for neutron activation analysis: a 2000 KW VVR-S Nuclear Reactor, a U-200 Cyclotron, a 30 MeV Betatron, several 14 MeV neutron generators and a king size High Voltage tandem Van de'Graaff accelerator. The main domains of application of the thermal neutron activation analysis are: geology and mining, processing of materials, environment and biology, achaeology. Epithermal neutron activation analysis has been used for determination of uranium and thorium in ores with high Th/U ratios or high rare earth contents. One low energy accelerator, used as 14.1 Mev neutron source, is provided with special equipmen for oxigen and low mass elements determination. An useful alternating way to support fast neutron activation analysis is an accurate theoretical description of the fast neutron induced reactions based on the statistical model (Hauser-Feubach STAPRE code) and the preequilibrium decay geometry dependent model. A gravitational sample changer has been installed at the end of a beam line of the Cyclotron, which enables to perform charged particles activation analysis for protein determination in grains

Activation analysis in national economy

International Nuclear Information System (INIS)

1974-01-01

The collected papers are based on the materials of the III All-Union Activation Analysis Meeting. The papers selected deal with the theoretical questions of the activation analysis, its hardware, latest developments in the field of automatic analysis and computer methods employment in the treatment of analytical information. Described are the new techniques for determination of a large number of elements in samples of biological and geological origin. Some results of the use of the activation analysis in various fields of science and technology are provided. The volume reflects the present status of activation analysis techniques in the USSR and might be of interest both for specialists, and for those involved in obtaining and using information on the composition of substances. (auth.)

A study of environmental analysis of urban river sediments using activation analysis

International Nuclear Information System (INIS)

Tanaka, Y.; Kuno, A.; Matsuo, M.

2003-01-01

Sediments of the Kitajukkengawa River (Sumida-ku, Tokyo, Japan) were analyzed by activation analyses. Concentrations of 36 elements for each sample were determined by instrumental neutron activation analysis (INAA) and neutron induced prompt gamma-ray analysis (PGA). Based on the correlation matrix between the elements in vertical distribution, principal component analysis (PCA) was performed. The degree of chemical weathering of silicate minerals was highest in the middle layer of the Kitajukkengawa River sediment and that adsorbed amount of trace metals such as Cd and Cr was increased along with chemical weathering. (author)

Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin.

Science.gov (United States)

Kumar, Raj; Kukreja, Roshan V; Cai, Shuowei; Singh, Bal R

2014-06-01

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37°C. LCE, on the other hand, was although optimally active at 37°C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe?

Directory of Open Access Journals (Sweden)

Fraint A

2016-02-01

Full Text Available Avram Fraint,1 Padmaja Vittal,2 Cynthia Comella2 1Department of Neurological Sciences, 2Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA Introduction: Botulinum toxin (BoNT is the treatment of choice for many neurologic movement disorders, including blepharospasm, hemifacial spasm, and cervical dystonia. There are two serotypes approved for use by the US Food and Drug Administration: three brands of serotype A and one of serotype B. Many attempts have been made at establishing dose conversion ratios between brands and serotypes. This review focuses on the existing data comparing different formulations of the same BoNT serotypes as well as that comparing different serotypes with one another. We focus on existing data regarding switching from one formulation or serotype to another and will also discuss the issue of immunogenicity of BoNT. With this information as a foundation, recommendations on safety of switching agents are addressed. Method: Literature review searching PubMed and Google Scholar using the search terms “switching botox”, “dosing equivalency in botox”, and “comparing botox”. Results/conclusion: Overall, there are many studies that demonstrate the efficacy and safety of each of the brands of BoNTs used in clinical practice. However, determination of dosing equivalencies among these brands and serotypes is complex with inconsistencies among the studies. When switching from one brand to another, the clinician should be aware of these issues, and not make the assumption that such ratios exist. Tailoring the dosage of each brand of BoNT to the clinical situation is the most prudent treatment strategy rather than focusing closely on conversion factors and concerns for immunogenicity. Keywords: botulinum toxin, BoNT, abobotulinumtoxin A, onabotulinumtoxin A, incobotulinumtoxin A, rimabotulinumtoxin B

Activation analysis in Greece

International Nuclear Information System (INIS)

Grimanis, A.P.

1985-01-01

A review of research and development on NAA as well as examples of applications of this method are presented, taken from work carried out over the last 21 years at the Radioanalytical Laboratory of the Department of Chemistry in the Greek Nuclear Research Center ''Demokritos''. Improved and faster radiochemical NAA methods have been developed for the determination of Au, Ni, Cl, As, Cu, U, Cr, Eu, Hg and Mo in several materials, for the simultaneous determination of Br and I; Mg, Sr and Ni; As and Cu; As, Sb and Hg; Mn, Sr and Ba; Cd and Zn; Se and As; Mo and Cr in biological materials. Instrumental NAA methods have also been developed for the determination of Ag, Cl and Na in lake waters, Al, Ca, Mg and V in wines, 7 trace elements in biological materials, 17 trace elements in sediments and 20 minor and trace elements in ceramics. A comprehensive computer program for routine activation analysis using Ge(Li) detectors have been worked out. A rather extended charged-particle activation analysis program is carried out for the last 10 years, including particle induced X-ray emission (PIXE) analysis, particle induced prompt gamma-ray emission analysis (PIGE), other nuclear reactions and proton activation analysis. A special neutron activation method, the delayed fission neutron counting method is used for the analysis of fissionable elements, as U, Th, Pu, in samples of the whole nuclear fuel cycle including geological, enriched and nuclear safeguards samples

Automation of activation analysis

International Nuclear Information System (INIS)

Ivanov, I.N.; Ivanets, V.N.; Filippov, V.V.

1985-01-01

The basic data on the methods and equipment of activation analysis are presented. Recommendations on the selection of activation analysis techniques, and especially the technique envisaging the use of short-lived isotopes, are given. The equipment possibilities to increase dataway carrying capacity, using modern computers for the automation of the analysis and data processing procedure, are shown

A program for activation analysis data processing

International Nuclear Information System (INIS)

Janczyszyn, J.; Loska, L.; Taczanowski, S.

1978-01-01

An ALGOL program for activation analysis data handling is presented. The program may be used either for single channel spectrometry data or for multichannel spectrometry. The calculation of instrumental error and of analysis standard deviation is carried out. The outliers are tested, and the regression line diagram with the related observations are plotted by the program. (author)

Charged-particle activation analysis

International Nuclear Information System (INIS)

Schweikert, E.A.

1978-01-01

The paper discusses the methodology and application of nuclear activation with ion beams (1 9 via 16 O( 3 He,p) 18 F, 12 C( 3 He,α) 11 C and 14 N(p,α) 11 C respectively. Recently, triton activation has been shown to be inherently still superior to 3 He activation for the determination of oxygen [ 16 O( 3 H,n) 18 F]. Lithium, boron, carbon and sulphur can be detected rapidly, nondestructively and with high sensitivity (approximately 0.25ppm for Li and B) via ''quasi-prompt'' activation based on the detection of short-lived, high-energy beta emitters (10ms 1 H( 7 Li,n) 7 Be for example. Nondestructive multielement analysis: Proton activation has the inherent potential for meeting requirements of broad elemental coverage, sensitivity (ppm and sub-ppm range) and selectivity. Up to 30 elements have been determined in Al, Co, Ag, Nb, Rh, Ta and biological samples, using 12-MeV proton activation followed by gamma-ray spectrometry. These capabilities are further enhanced with the counting of X-ray emitters, 28 elements (26 9 ) and accuracy using proton activation. 204 Pb/ 206 Pb ratios can also be determined with a relative precision of a few per cent. Although charged-particle activation analysis is a well-established trace analysis technique, broad potential capabilities remain to be explored, e.g. those arising from ultrashort-lived nuclides, heavy ion interactions and the combination of delayed and prompt methods. (author)

Activation analysis in food analysis. Pt. 9

International Nuclear Information System (INIS)

Szabo, S.A.

1992-01-01

An overview is presented on the application of activation analysis (AA) techniques for food analysis, as reflected at a recent international conference titled Activation Analysis and its Applications. The most popular analytical techniques include instrumental neutron AA, (INAA or NAA), radiochemical NAA (RNAA), X-ray fluorescence analysis and mass spectrometry. Data are presented for the multielemental NAA of instant soups, for elemental composition of drinking water in Iraq, for Na, K, Mn contents of various Indian rices, for As, Hg, Sb and Se determination in various seafoods, for daily microelement takeup in China, for the elemental composition of Chinese teas. Expected development trends in AA are outlined. (R.P.) 24 refs.; 8 tabs

Fast neutron activation analysis

International Nuclear Information System (INIS)

Pepelnik, R.

1986-01-01

Since 1981 numerous 14 MeV neutron activation analyses were performed at Korona. On the basis of that work the advantages of this analysis technique and therewith obtained results are compared with other analytical methods. The procedure of activation analysis, the characteristics of Korona, some analytical investigations in environmental research and material physics, as well as sources of systematic errors in trace analysis are described. (orig.) [de

Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.

Directory of Open Access Journals (Sweden)

Luciana A F Gil

Full Text Available Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB, a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH3 developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH3 developed a protective immune response against both BoNT/C (5 IU/mL and BoNT/D (10 IU/mL, as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle.

Clostridium botulinum type E occurs and grows in the alga Cladophora glomerata

Science.gov (United States)

Byappanahalli, M.N.; Whitman, R.L.

2009-01-01

In recent years, massive avian die-offs from Clostridium botulinum type E infection have occurred in the Sleeping Bear Dunes National Lakeshore (SLBE) area of Lake Michigan. These outbreaks have been coincidental with massive blooms of the green algae Cladophora, mostly Cladophora glomerata. We tested the hypothesis that Clostridium botulinum type E can grow under suitable conditions in these algal mats. In a lab mesocosm study, Cladophora from four outbreak-impacted beaches from SLBE were compared with four unimpacted beaches in the Milwaukee–Racine area for bontE gene of Clostridium botulinum. Frequency of the bontE gene was higher after incubation (25 °C for up to 6 weeks) of Cladophora from impacted vs. the unimpacted area. Since no type E gene was detected initially in Cladophora from any of the eight locations, we infer that the increased occurrence of type E gene arose from spore germination or vegetative Clostridium growth within the existing algal mats of SLBE. Moreover, we found that the congener Clostridium perfringens readily grows in mesocosms containing Cladophora.

Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson's disease.

Science.gov (United States)

Triadafilopoulos, George; Gandhy, Rita; Barlow, Carrolee

2017-11-01

Gastrointestinal symptoms, such as dysphagia, postprandial bloating, and defecatory straining are common in Parkinson's Disease (PD) and they impact quality of life. Endoscopic botulinum neurotoxin (BoNT) injection has been used in the treatment of dysphagia, gastroparesis and chronic anismus. To examine the feasibility, safety and efficacy of endoscopically delivered BoNT injection to distal esophagus, pylorus or anal canal aiming at relieving regional gastrointestinal symptoms in patients with PD. This is a retrospective open cohort pilot study to assess the clinical response to endoscopic BoNT injection on selected PD patients with symptoms and identifiable abnormalities on high-resolution manometry and wireless motility capsule, to generate early uncontrolled data on feasibility, tolerability, safety and efficacy. Baseline symptoms and response to therapy were assessed by questionnaires. Fourteen PD patients (10 M:4 F), mean age 73 (range: 62-93) were treated. Three patients had esophageal Botox for ineffective esophageal motility (IEM) (n = 1), esophago-gastric junction outlet obstruction (EGJOO) & IEM (n = 1), and diffuse esophageal spasm (DES) (n = 1). Nine patients were treated with pyloric BoNT injection for gastroparesis with mean gastric transit time of 21.2 h; range 5.2-44.2 h. Two patients received anal Botox for defecatory dyssynergia ((Type I) (n = 1) and overlap (slow-transit and dyssynergic) constipation (n = 1). Endoscopic BoNT injection (100-200 units) was well tolerated and there were no significant adverse events. Endoscopic BoNT injection to esophagus, pylorus or anal canal is safe, well-tolerated and leads to symptomatic improvement that lasts up to several months. The procedure can be repeated as needed and combined with other therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neutron activation analysis of biological substances

International Nuclear Information System (INIS)

Ordogh, M.

1978-08-01

A Bowen cabbage sample was used as a reference material for the neutron activation studies, and the method was checked by the analysis of other biological substances (blood or serum etc.). For nondestructive measurements also some non-trace elements were determined in order to decide whether the activation analysis is a useful means for such measurements. The new activation analysis procedure was used for biomedical studies as, e.g., for trace element determination in body fluids, and for the analysis of inorganic components in air samples. (R.P.)

Content Analysis of a Computer-Based Faculty Activity Repository

Science.gov (United States)

Baker-Eveleth, Lori; Stone, Robert W.

2013-01-01

The research presents an analysis of faculty opinions regarding the introduction of a new computer-based faculty activity repository (FAR) in a university setting. The qualitative study employs content analysis to better understand the phenomenon underlying these faculty opinions and to augment the findings from a quantitative study. A web-based…

Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents

Science.gov (United States)

Collazo, M. Thelma; Garza, John A.; Hayhurst, Andrew

2010-01-01

Background There are currently 7 known serotypes of botulinum neurotoxin (BoNT) classified upon non-cross reactivity of neutralizing immunoglobulins. Non-neutralizing immunoglobulins, however, can exhibit cross-reactivities between 2 or more serotypes, particularly mosaic forms, which can hamper the development of highly specific immunoassays, especially if based on polyclonal antisera. Here we employ facile recombinant antibody technology to subtractively select ligands to each of the 7 BoNT serotypes, resulting in populations with very high specificity for their intended serotype. Methods and Findings A single llama was immunized with a cocktail of 7 BoNT toxoids to generate a phage display library of single domain antibodies (sdAb, VHH or nanobodies) which were selected on live toxins. Resulting sdAb were capable of detecting both toxin and toxin complex with the best combinations able to detect 100s-10s of pg per 50 µL sample in a liquid bead array. The most sensitive sdAb were combined in a heptaplex assay to identify each of the BoNT serotypes in buffer and milk and to a lesser extent in carrot juice, orange juice and cola. Several anti-A(1) sdAb recognized A2 complex, showing that subtype cross-reactivity within a serotype was evident. Many of our sdAb could act as both captor and tracer for several toxin and toxin complexes suggesting sdAb can be used as architectural probes to indicate BoNT oligomerisation. Six of 14 anti-A clones exhibited inhibition of SNAP-25 cleavage in the neuro-2A assay indicating some sdAb had toxin neutralizing capabilities. Many sdAb were also shown to be refoldable after exposure to high temperatures in contrast to polyclonal antisera, as monitored by circular dichroism. Conclusions Our panel of molecularly flexible antibodies should not only serve as a good starting point for ruggedizing assays and inhibitors, but enable the intricate architectures of BoNT toxins and complexes to be probed more extensively. PMID:20098614

Evaluation of nuclear reactor based activation analysis techniques

International Nuclear Information System (INIS)

Obrusnik, I.; Kucera, J.

1977-09-01

A survey is presented of the basic types of activation analysis applied in environmental control. Reactor neutron activation analysis is described (including the reactor as a neutron source, sample activation in the reactor, methodology of neutron activation analysis, sample transport into the reactor and sample packaging after irradiation, instrumental activation analysis with radiochemical separation, data measurement and evaluation, sampling and sample preparation). Sources of environmental contamination with trace elements, sampling and sample analysis by neutron activation are described. The analysis is described of soils, waters and biological materials. Methods are shown of evaluating neutron activation analysis results and of their interpretation for purposes of environmental control. (J.B.)

Neutron activation analysis of geochemical samples

International Nuclear Information System (INIS)

Rosenberg, R.; Zilliacus, R.; Kaistila, M.

1983-06-01

The present paper will describe the work done at the Technical Research Centre of Finland in developing methods for the large-scale activation analysis of samples for the geochemical prospecting of metals. The geochemical prospecting for uranium started in Finland in 1974 and consequently a manually operated device for the delayed neutron activation analysis of uranium was taken into use. During 1974 9000 samples were analyzed. The small capacity of the analyzer made it necessary to develop a completely automated analyzer which was taken into use in August 1975. Since then 20000-30000 samples have been analyzed annually the annual capacity being about 60000 samples when running seven hours per day. Multielemental instrumental neutron activation analysis is used for the analysis of more than 40 elements. Using instrumental epithermal neutron activation analysis 25-27 elements can be analyzed using one irradiation and 20 min measurement. During 1982 12000 samples were analyzed for mining companies and Geological Survey of Finland. The capacity is 600 samples per week. Besides these two analytical methods the analysis of lanthanoids is an important part of the work. 11 lanthanoids have been analyzed using instrumental neutron activation analysis. Radiochemical separation methods have been developed for several elements to improve the sensitivity of the analysis

An analysis of a board game as a treatment activity.

Science.gov (United States)

Neistadt, M E; McAuley, D; Zecha, D; Shannon, R

1993-02-01

Occupational therapists often use tabletop board games in treatment to help adult clients with physical disabilities improve the perceptual, cognitive, sensory, and fine motor skill components of occupational behavior. Detailed activity analyses of these types of activities, including performance norms, are not available in the occupational therapy literature. Such analyses would help therapists consider the multiple skill demands of tabletop games and allow more systematic grading of these treatment activities. This paper presents a model for analyzing therapeutic activities in relation to relevant motor learning and cognitive-perceptual literature. Included in this analysis are a description of the activity, examination of its component skills and of the qualitative features of activity performance, suggestions for grading and for treatment goals, and some preliminary performance standards derived from a pilot study of 18 adults without physical disabilities. The issue of transfer of skills between games and functional activities is also discussed.

Critical reflection activation analysis - a new near-surface probe

International Nuclear Information System (INIS)

Gunn, J.M.F.; Trohidou, K.N.

1988-09-01

We propose a new surface analytic technique, Critical Reflection Activation Analysis (CRAA). This technique allows accurate depth profiling of impurities ≤ 100A beneath a surface. The depth profile of the impurity is simply related to the induced activity as a function of the angle of reflection. We argue that the technique is practical and estimate its accuracy. (author)

Physical Activity and Cognitive Development: A Meta-Analysis.

Science.gov (United States)

Jackson, William M; Davis, Nicholas; Sands, Stephen A; Whittington, Robert A; Sun, Lena S

2016-10-01

Is there an association between regular exercise, defined as a structured program of increased physical activity at least 1 month in duration, and improvements in measures of executive functions compared with children who engage in their normal daily activities? The association between increased physical activity and changes in performance on tasks of executive functions have not been well elucidated in children. Executive functioning is important to intellectual development and academic success in children, and inexpensive, nonpharmacological methods for the treatment of executive dysfunction represent an attractive interventional target. To estimate the effect of a structured regular exercise program on neuropsychological domains of executive function in children ages 7 to 12. We performed a systematic review of English and non-English articles using Cochrane Library, EBSCO CINAHL, Ovid MEDLINE, PSYCInfo, Pubmed, and Web of Science, including all years allowed by each individual search engine. The search string used was "(exercise OR phys*) AND (cognit* OR executive) AND (child* OR preadolesc*)." The authors of the studies selected for review were contacted for any unpublished data. Randomized controlled trials, which enrolled children between the ages of 7 and 12, with randomization to either normal activity or a structured physical activity intervention consisting of scheduled aerobic exercise, at least once per week, for a period of at least 1 month. Eligible studies must have included a neuropsychological battery of tests that measured at least 1 executive function both before and after the intervention was completed. Two independent reviewers examined the screened studies in detail for potential inclusion. The results of the individual examinations were compared; if any discrepancies were present, a third party analyzed the study to determine if it should be included in the meta-analysis. A total of 18 studies were identified by abstract as candidates for

Increasing physical activity with mobile devices: a meta-analysis.

Science.gov (United States)

Fanning, Jason; Mullen, Sean P; McAuley, Edward

2012-11-21

Regular physical activity has established physical and mental health benefits; however, merely one quarter of the U.S. adult population meets national physical activity recommendations. In an effort to engage individuals who do not meet these guidelines, researchers have utilized popular emerging technologies, including mobile devices (ie, personal digital assistants [PDAs], mobile phones). This study is the first to synthesize current research focused on the use of mobile devices for increasing physical activity. To conduct a meta-analysis of research utilizing mobile devices to influence physical activity behavior. The aims of this review were to: (1) examine the efficacy of mobile devices in the physical activity setting, (2) explore and discuss implementation of device features across studies, and (3) make recommendations for future intervention development. We searched electronic databases (PubMed, PsychINFO, SCOPUS) and identified publications through reference lists and requests to experts in the field of mobile health. Studies were included that provided original data and aimed to influence physical activity through dissemination or collection of intervention materials with a mobile device. Data were extracted to calculate effect sizes for individual studies, as were study descriptives. A random effects meta-analysis was conducted using the Comprehensive Meta-Analysis software suite. Study quality was assessed using the quality of execution portion of the Guide to Community Preventative Services data extraction form. Four studies were of "good" quality and seven of "fair" quality. In total, 1351 individuals participated in 11 unique studies from which 18 effects were extracted and synthesized, yielding an overall weight mean effect size of g = 0.54 (95% CI = 0.17 to 0.91, P = .01). Research utilizing mobile devices is gaining in popularity, and this study suggests that this platform is an effective means for influencing physical activity behavior. Our focus

Comparison of instrumental neutron activation analysis and instrumental charged-particle activation analysis for determining of Zn-68 abundance

International Nuclear Information System (INIS)

Rafii, H.; Mirzaei, M.; Aslani, G.R.; Kamali-Dehghan, M.; Rajamand, A-A.; Rahiminejad, A.; Mirzajani, N.; Sardari, D.; Shahabi, I.; Majidi, F.

2004-01-01

Gallium-67 has found important applications in nuclear medicine since last decades. The bombardment of enriched zinc-68 by proton beams in cyclotron is the most suitable method for the carrier-free production of this radionuclide. Any traces and isotopic impurities of the target cause serious radiological hazards because of their associated induced radioactivities. Trace analysis and Zn-68 content determination of the target material before any bombardment and chemical separation provide a valuable assessment of desired product. The elemental abundance evaluation of enriched isotopes is generally carried out by inductively coupled plasma-mass spectrometry method, ICP-Ms Instrumental neutron activation analysis and instrumental charged particle activation analysis. International neutron activation analysis and instrumental charged- particle activation analysis, looks be an alternative nuclear method for determining the abundance evaluation of enriched Zn-68 enrichment in two different samples has been studied by mean of international neutron activation analysis and instrumental charged- particle activation analysis . One sample was purchased from a French company, cortecnet, and the other was separated by an electromagnetic system in the Ions source department of our center, NRCAM. The neutron or proton irradiation was took place respectively in miniature neutron source reactor of Esfahan by flux of (1 to 5) 10 11 n/cm 2 .sec for 30 min and in Cyclon30 by 19 MeV proton beams of 100μA current for 12 min. The produced radioactivity was measured by HpGe detector for determination of trace impurities and evaluation of Zn-68 content in the samples. The result shows a good agreement with the reported ones by their producers and their low derivation of about ± indicates that the international neutron activation analysis and instrumental charged- particle activation analysis are relatively precise and rapid and each one can be used as a supplemental method for analyzing

Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay.

Science.gov (United States)

Williamson, Charles H D; Vazquez, Adam J; Hill, Karen; Smith, Theresa J; Nottingham, Roxanne; Stone, Nathan E; Sobek, Colin J; Cocking, Jill H; Fernández, Rafael A; Caballero, Patricia A; Leiser, Owen P; Keim, Paul; Sahl, Jason W

2017-09-15

Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Coding region sequences unique to each of the four species/subgroups were identified by in silico analyses of thousands of genome assemblies, and PCR primers were designed to amplify each marker. The resulting multiplex PCR assay correctly assigned 41 tested isolates to the appropriate species or subgroup. A separate PCR assay to determine the presence of the ntnh gene (a gene associated with the botulinum neurotoxin gene cluster) was developed and validated. The ntnh gene PCR assay provides information about the presence or absence of the botulinum neurotoxin gene cluster and the type of gene cluster present ( ha positive [ ha + ] or orfX + ). The increased availability of whole-genome sequence data and comparative genomic tools enabled the design of these assays, which provide valuable information for characterizing BoNT-producing clostridia. The PCR assays are rapid, inexpensive tests that can be applied to a variety of sample types to assign isolates to species/subgroups and to detect clostridia with botulinum neurotoxin gene ( bont ) clusters. IMPORTANCE Diverse clostridia produce the botulinum neurotoxin, one of the most potent known neurotoxins. In this study, a multiplex PCR assay was developed to differentiate clostridia that are most commonly isolated in connection with human botulism cases: C. botulinum group I, C. sporogenes , and two major subgroups within C. botulinum group II. Since Bo

A description of the BNL active surface analysis facility

International Nuclear Information System (INIS)

Tyler, J.W.

1989-11-01

Berkeley Nuclear Laboratories has a responsibility for the assessment of radioactive specimens arising both from post irradiation examination of power reactor components and structures and experimental programmes concerned with fission and activation product transport. Existing analytical facilities have been extended with the commissioning of an active surface analysis instrument (XSAM 800pci, Kratos Analytical). Surface analysis involves the characterisation of the outer few atomic layers of a solid surface/interface whose chemical composition and electronic structure will probably be different from the bulk. The new instrument consists three interconnected chambers positioned in series; comprising of a high vacuum sample introduction chamber, an ultra-high vacuum sample treatment/fracture chamber and an ultra-high vacuum sample analysis chamber. The sample analysis chamber contains the electron, X-ray and ion-guns and the electron and ion detectors necessary for performing X-ray photoelectron spectroscopy, scanning Auger microscopy and secondary-ion mass spectroscopy. The chamber also contains a high stability manipulator to enable sub-micron imaging of specimens to be achieved and provide sample heating and cooling between - 180 and 600 0 C. (author)

Analysis of Precision of Activation Analysis Method

DEFF Research Database (Denmark)

Heydorn, Kaj; Nørgaard, K.

1973-01-01

The precision of an activation-analysis method prescribes the estimation of the precision of a single analytical result. The adequacy of these estimates to account for the observed variation between duplicate results from the analysis of different samples and materials, is tested by the statistic T...

Non-traditional neutron activation analysis by use of a nuclear reactor

International Nuclear Information System (INIS)

Mukhammedov, S.

2003-01-01

Full text: Traditional reactor neutron activation analysis (NAA) based on (n, γ) - thermal neutron capture nuclear reaction has been developed into a reliable and powerful analytical method, for trace element analysis, allowing the determination of over 60 chemical elements, with good accuracy and low detection limits. Considering all possibilities of activation and a radiochemical separation of the indicator radionuclide, the majority of the elements of this group can be determined at the ppm concentration level and below. However, for solving a number of analytical problems NAA technique is not well suited or it cannot be used at all. An important limitation is that all light elements, some medium and heavy elements cannot be determined even at ppm concentration level by this method, for example, H, Be, Li, B, C, N, O, Ti, Nb, Pb, etc. Accurate determination of lithium, oxygen and other light elements in sub-microgram level is of importance in geochemical and material studies. Such examples are great many. On such instances, several non-traditional reactor activation analysis can be used which have increasingly been developed and applied to several fields of semiconductor industry, biology, geology in recent years. The purpose of this presentation is to review the modern status of non-traditional nuclear reactor activation analysis based on use of nuclear reactions excited by the flow of secondary charged particles which are produced by two methods. In first method the triton flow is produced by thermal neutrons flux which excites the nuclear reaction 6 Li(n, α)T on lithium. The neutron activation analysis associated with two consecutive reactions 6 Li(n, α)T + 16 O(T, n) 18 F is established to determine trace amounts either of lithium or of oxygen in different geological, ecological and technological samples. Besides, the triton flow can be used for the determination of other light elements, for instance, B, N, S, Mg. This nuclear reactor triton activation

Utilization of chemical derivatives in activation analysis

International Nuclear Information System (INIS)

Ehmann, W.D.

1990-01-01

Derivative activation analysis (DAA) is a method to enhance the sensitivity of nuclear activation analysis for the more elusive elements. It may also allow a degree of chemical speciation for the element of interest. DAA uses a preirradiation chemical reaction on the sample to initiate the formation of, or an exchange with, a chemical complex which contains a surrogate element, M. As a result, the amount of the element or the chemical species to be determined, X, is now represented by measurement of the amount of the surrogate element, M, that is made part of, or released by the complex species. The surrogate element is selected for its superior properties for nuclear activation analysis and the absence of interference reaction in its final determination by instrumental neutron activation analysis (INAA) after some preconcentration or separation chemistry. Published DAA studies have been limited to neutron activation analysis. DAA can offer the analyst some important advantages. It can determine elements, functional groups, or chemical species which cannot be determined directly by INAA, fast neutron activation analysis (FNAA), prompt gamma neutron activation analysis (PGNAA), or charged particle activation analysis (CPAA) procedures. When compared with conventional RNAA, there are fewer precautions with respect to handling of intensely radioactive samples, since the chemistry is done before the irradiation. The preirradiation chemistry may also eliminate many interferences that might occur in INAA and, through use of an appropriate surrogate element, can place the analytical gamma-ray line in an interference-free region of the gamma-ray spectrum

Religious Activities and Suicide Prevention: A Gender Specific Analysis

Directory of Open Access Journals (Sweden)

Steven Stack

2018-04-01

Full Text Available The present analysis contributes to the existing literature on religion and suicide in three interrelated ways: (1 providing an analysis of suicide completions whereas most research is based on non-lethal levels of suicidality; (2 assessing the relationship with concrete individual level data on completed suicides instead of aggregated data marked by the ecological fallacy issue; and (3 providing gender specific analyses to determine if the relationship is gendered. METHODS. Data come from the U.S. Public Health Service, National Mortality Followback Survey. They refer to 16,795 deaths including 1385 suicides. Significant others of the deceased were interviewed to measure all variables. The dependent variable is a binary variable where 1 = death by suicide and 0 = all other causes. The central independent variable is an index of religious activities. Controls are included for five categories of confounders (1 psychiatric morbidity; (2 help-seeking behavior; (3 Opportunity factors such as firearms; (4 social integration; and (5 demographics. RESULTS. Multivariate logistic regression analysis determined that controlling for 16 predictors of suicide, a one unit increase in religious activities reduced the odds of a suicide death by 17% for males and by 15% for females. The difference in coefficients is not significant (Z = 0.51. Other significant predictors of suicide deaths included suicide ideation (OR = 8.87, males, OR = 11.48, females and firearm availability (OR = 4.21, males, OR = 2.83, females. DISCUSSION. Religious activities were found to lower suicide risk equally for both men and women. Further work is needed to assess pathways, including suicide ideation, between religious activities and lowered suicide risk. This is the first U.S. based study to test for a gendered association between religion and suicide at the individual level of analysis.

Proceedings of national seminar neutron activation analysis

International Nuclear Information System (INIS)

Agus Taftazani; Muhayatun Santoso; Budi Haryanto; Khatarina Oginawati

2010-11-01

Proceedings of national seminar neutron activation analysis in 2010 with the theme of the Role of Nuclear Analytical Techniques in the Field of Environment, Health and Industry. The seminar was organized by Indonesians Neutron Activation Analysis and BATAN Forum. These proceedings contain the result of environmental research in BATAN, universities and institutions associated with the application on neutron activation analysis technique. The purpose of these proceedings was as a useful source of information to spur research and development of activation analysis applications in various fields for the Indonesian welfare. There are 40 articles. (PPIKSN).

Neutron activation analysis-comparative (NAAC)

International Nuclear Information System (INIS)

Zimmer, W.H.

1979-01-01

A software system for the reduction of comparative neutron activation analysis data is presented. Libraries are constructed to contain the elemental composition and isotopic nuclear data of an unlimited number of standards. Ratios to unknown sample data are performed by standard calibrations. Interfering peak corrections, second-order activation-product corrections, and deconvolution of multiplets are applied automatically. Passive gamma-energy analysis can be performed with the same software. 3 figures

Neutron activation analysis

International Nuclear Information System (INIS)

Taure, I.; Riekstina, D.; Veveris, O.

2004-01-01

Neutron activation analysis (NAA) in Latvia began to develop after 1961 when nuclear reactor in Salaspils started to work. It provided a powerful neuron source, which is necessary for this analytical method. In 1963 at Institute of Physics of the Latvian Academy of Sciences the Laboratory of Neutron Activation Analysis was formed. At the first stage of development the main tasks were of theoretical and technical aspects of NAA. Later the NAA was used to solve problems in technology, biology, and medicine. In the beginning of the 80-ties more attention was focussed to the use of NAA in the environmental research. Environmental problems stayed the main task till the closing the nuclear reactor in Salaspils in 1998 that ceased the main the existence of the laboratory and of NAA, this significant and powerful analytical method in Latvia and Baltic in general. (authors)

Forensic neutron activation analysis

International Nuclear Information System (INIS)

Kishi, T.

1987-01-01

The progress of forensic neutron activation analysis (FNAA) in Japan is described. FNAA began in 1965 and during the past 20 years many cases have been handled; these include determination of toxic materials, comparison examination of physical evidences (e.g., paints, metal fragments, plastics and inks) and drug sample differentiation. Neutron activation analysis is applied routinely to the scientific criminal investigation as one of multielement analytical techniques. This paper also discusses these routine works. (author) 14 refs

A Spatial Analysis of Tourism Activity in Romania

Directory of Open Access Journals (Sweden)

Daniela Luminita Constantin

2018-02-01

Full Text Available Location is a key concept in tourism sector analysis, given the dependence of this activity on the natural, built, cultural and social characteristics of a certain territory. As a result, the tourist zoning is an important instrument for delimiting tourist areas in accordance with multiple criteria, so as to lay the foundations for finding the most suitable solutions of turning to good account the resources in this field. The modern approaches proposed in this paper use a series of analytical tools that combine GIS and spatial agglomeration analysis based techniques. They can be also employed in order to examine and explain the differences between tourist zones (and sub-zones in terms of economic and social results and thus to suggest realistic ways to improve the efficiency and effectiveness of tourist activities in various geographical areas. In the described context this paper proposes an interdisciplinary perspective (spatial statistics and Geographical Information Systems for analysing the tourism activity in Romania, mainly aiming to identify the agglomerations of companies acting in this industry and assess their performance and contribution to the economic development of the corresponding regions. It also intends to contribute to a better understanding of the way in which tourism related business activities develop, in order to enhance appropriate support networks. Territorial and spatial statistics, as well as GIS based analyses are applied, using data about all companies acting in tourism industry in Romania provided by the National Authority for Tourism as well as data from the Environmental Systems Research Institute (ESRI.

Analysis by nuclear reactions and activations. A current bibliography

International Nuclear Information System (INIS)

Bujdoso, E.

2001-01-01

A current bibliography based on INIS Atomindex with 78 references on Analysis by nuclear reactions and activations has been prepared for year 1998. References are arranged by first authors' name. (N.T.)

Peptide inhibitors of botulinum neurotoxin by mRNA display

International Nuclear Information System (INIS)

Yiadom, Kwabena P.A.B.; Muhie, Seid; Yang, David C.H.

2005-01-01

Botulinum neurotoxins (BoNTs) are extremely toxic. The metalloproteases associated with the toxins cleave proteins essential for neurotransmitter secretion. Inhibitors of the metalloprotease are currently sought to control the toxicity of BoNTs. Toward that goal, we produced a synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein, and constructed a combinatorial peptide library to screen for BoNT/A light chain inhibitors using mRNA display. A protease assay was developed using immobilized intact SNAP-25 as the substrate. The new peptide inhibitors showed a 10-fold increase in affinity to BoNT/A light chain than the parent peptide. Interestingly, the sequences of the new peptide inhibitors showed abundant hydrophobic residues but few hydrophilic residues. The results suggest that mRNA display may provide a general approach in developing peptide inhibitors of BoNTs

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H

OpenAIRE

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-01-01

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed Bo...

Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

Science.gov (United States)

Mor, Niv; Tang, Christopher; Blitzer, Andrew

2016-09-01

Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Prompt gamma neutron activation analysis

International Nuclear Information System (INIS)

Goswami, A.

2003-01-01

Prompt gamma neutron activation analysis (PGNAA) is a technique for the analysis of elements present in solid, liquid and gaseous samples by measuring the capture gamma rays emitted from the sample during neutron irradiation. The technique is complementary to conventional neutron activation analysis (NAA) as it can be used in number of cases where NAA fails. Though the technique was first used in sixties, the advantage of the technique was first highlighted by Lindstrom and Anderson. PGNAA is increasingly being used as a rapid, instrumental, nondestructive and multielement analysis technique. A monograph and several excellent reviews on this topic have appeared recently. In this review, an attempt has been made to bring out the essential aspects of the technique, experimental arrangement and instrumentation involved, and areas of application. Some of the results will also be presented

Activation analysis with small mobile reactors

International Nuclear Information System (INIS)

Chung, C.

1990-01-01

A small nuclear reactor (a low-power reactor without heat removal devices) usually has thermal power output under 100 W and an average in-core thermal neutron flux below 10 9 n/cm 2 s. Conventional activation analysis is restricted to determination of specific elements with large neutron capture cross sections in sizable samples. In-vivo prompt gamma activation analysis (IVPGAA) can be used for diagnosis of elemental composition of the human body, particularly the essential elements Ca, Cl, N, and P in the whole body, and toxic Cd and Hg in contaminated organs. In this chapter, activation analysis using an external neutron beam from the Tsing Hua Mobile Educational Reactor (THMER) for in vivo activation is described. Characteristics of the mobile reactor, in-vivo medical diagnosis, and radiation safety are emphasized. 17 refs, 12 figs, 3 tabs

Activation analysis in Europe: present and future perspectives

International Nuclear Information System (INIS)

De Corte, F.; Hoste, J.

1984-01-01

A survey is given of the present-day European contribution to activation analysis, covering neutron activation analysis (NAA), charged particle activation analysis (CPAA) and photon activation analysis (PAA). Attention is paid to the available irradiation facilities, in particular nuclear reactors, cyclotrons and Van de Graaff accelerators, and linear electron accelerators. Mention is made of progress in fundamental fields, but the attention is especially focussed on practical applications: environmental, geochemical/cosmochemical, biological/medical, and high-purity materials. Eventually, the role of activation analysis in research projects of the Commission of the European Communities (CEC) and in the Reference Materials program of the Community Bureau of Reference (BCR) is emphasized

A concept analysis of voluntary active euthanasia.

Science.gov (United States)

Guo, Fenglin

2006-01-01

Euthanasia has a wide range of classifications. Confusion exists in the application of specific concepts to various studies. To analyze the concept of voluntary active euthanasia using Walker and Avant's concept analysis method. A comprehensive literature review from various published literature and bibliographies. Clinical, ethical, and policy differences and similarities of euthanasia need to be debated openly, both within the medical profession and publicly. Awareness of the classifications about euthanasia may help nurses dealing with "end of life issues" properly.

Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

Directory of Open Access Journals (Sweden)

Suzanne R. Kalb

2017-06-01

Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

Large sample neutron activation analysis of a reference inhomogeneous sample

International Nuclear Information System (INIS)

Vasilopoulou, T.; Athens National Technical University, Athens; Tzika, F.; Stamatelatos, I.E.; Koster-Ammerlaan, M.J.J.

2011-01-01

A benchmark experiment was performed for Neutron Activation Analysis (NAA) of a large inhomogeneous sample. The reference sample was developed in-house and consisted of SiO 2 matrix and an Al-Zn alloy 'inhomogeneity' body. Monte Carlo simulations were employed to derive appropriate correction factors for neutron self-shielding during irradiation as well as self-attenuation of gamma rays and sample geometry during counting. The large sample neutron activation analysis (LSNAA) results were compared against reference values and the trueness of the technique was evaluated. An agreement within ±10% was observed between LSNAA and reference elemental mass values, for all matrix and inhomogeneity elements except Samarium, provided that the inhomogeneity body was fully simulated. However, in cases that the inhomogeneity was treated as not known, the results showed a reasonable agreement for most matrix elements, while large discrepancies were observed for the inhomogeneity elements. This study provided a quantification of the uncertainties associated with inhomogeneity in large sample analysis and contributed to the identification of the needs for future development of LSNAA facilities for analysis of inhomogeneous samples. (author)

Analysis of coal by neutron activation

International Nuclear Information System (INIS)

Burtner, D.R.

1983-01-01

The development of a thermal-neutron activation analysis procedure for determining elemental concentrations in whole coal samples, and the goal of combining this technique with other nuclear methods for determining a total mass balance in these and similar complex materials, is described. Problems of applying a fast-neutron activation analysis method for nitrogen are discussed, as well as an efficient procedure for drying and packaging coal samples. A thermal-neutron activation analysis (TNAA) procedure was developed for determining up to 27 elements in coal samples from the US, China, Nigeria, and Brazil. The comparator form of TNAA was applied, using a unique multielement standard, which contained 48 elements. The difference in net photopeak counts between sample and standard, due to γ-ray attenuation, was reduced by preparing this standard in an organic matrix, which simulates the composition and physical structure of the coal material. The simultaneous irradiation of several aliquots of this standard enabled high precision and accuracy to be attained. An accurate value for oxygen, determined by fast-neutron activation analysis, is used to correct for this effect in the nitrogen determination method

A survey of social media data analysis for physical activity surveillance.

Science.gov (United States)

Liu, Sam; Young, Sean D

2018-07-01

Social media data can provide valuable information regarding people's behaviors and health outcomes. Previous studies have shown that social media data can be extracted to monitor and predict infectious disease outbreaks. These same approaches can be applied to other fields including physical activity research and forensic science. Social media data have the potential to provide real-time monitoring and prediction of physical activity level in a given region. This tool can be valuable to public health organizations as it can overcome the time lag in the reporting of physical activity epidemiology data faced by traditional research methods (e.g. surveys, observational studies). As a result, this tool could help public health organizations better mobilize and target physical activity interventions. The first part of this paper aims to describe current approaches (e.g. topic modeling, sentiment analysis and social network analysis) that could be used to analyze social media data to provide real-time monitoring of physical activity level. The second aim of this paper was to discuss ways to apply social media analysis to other fields such as forensic sciences and provide recommendations to further social media research. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Neutron activation spectrometry and neutron activation analysis in analytical geochemistry

International Nuclear Information System (INIS)

Dulski, P.; Moeller, P.

1975-07-01

The present report is to show the geochemists who are interested in neutron activation spectrometry (NAS) and neutron activation analysis (NAA) which analytical possibilities these methods offer him. As a review of these analytical possibilities, a lieterature compolation is given which is subdivided into two groups: 1) rock (basic, intermediary, acid, sediments, soils and nuds, diverse minerals, tectites, meteorites and lunar material). 2) ore (Al, Au, Be, Cr, Cu, Mn, Mo, Fe, Pb, Pt, Sn, Ti, W, Zn, Zr, U and phosphate ore, polymetallic ores, fluorite, monazite and diverse ores). The applied methods as well as the determinable elements in the given materials can be got from the tables. On the whole, the literature evaluation carried out makes it clear that neutron activation spectrometry is a very useful multi-element method for the analysis of rocks. The analysis of ores, however, is subjected to great limitations. As rock analysis is very frequently of importance in prospecting for ore deposits, the NAS proves to be extremely useful for this very field of application. (orig./LH) [de

Data reduction for a high-throughput neutron activation analysis system

International Nuclear Information System (INIS)

Bowman, W.W.

1979-01-01

To analyze samples collected as part of a geochemical survey for the National Uranium Resource Evaluation program, Savannah River Laboratory has installed a high-throughput neutron activation analysis system. As part of that system, computer programs have been developed to reduce raw data to elemental concentrations in two steps. Program RAGS reduces gamma-ray spectra to lists of photopeak energies, peak areas, and statistical errors. Program RICHES determines the elemental concentrations from photopeak and delayed-neutron data, detector efficiencies, analysis parameters (neutron flux and activation, decay, and counting times), and spectrometric and cross-section data from libraries. Both programs have been streamlined for on-line operation with a minicomputer, each requiring approx. 64 kbytes of core. 3 tables

Current Status and Future Directions of Botulinum Neurotoxins for Targeting Pain Processing

Directory of Open Access Journals (Sweden)

Sabine Pellett

2015-11-01

Full Text Available Current evidence suggests that botulinum neurotoxins (BoNTs A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics.

'ACTIV' - a package of codes for charged particle and neutron activation analysis

International Nuclear Information System (INIS)

Cincu, Em.; Alexandreanu, B.; Manu, V.; Moisa, V.

1997-01-01

The 'ACTIV' Program is an advanced software package dedicated to applications of the thermal neutron and charged particle activation (NAA and CPA) induced reactions. The program is designed to run on personal computers compatible IBM PC-Models XT/AT, 286 or more advanced, operating under DOS version 5.0 or later, on systems with minimum 5 MB of hard disk memory. The package consists of 6 software modules and a Nuclear Data Base comprising physical, nuclear reaction and decay data for: thermal neutron, proton, deuteron and α-particle induced reactions on 15 selected metallic elements; the nuclear reaction data corresponds to the energy range (5-100) MeV. In the first version - ACTIV 1.0 - the set of input data concerns: the sample type, irradiation and measurement conditions, the γ-ray spectrum identification code, selected detection efficiency calibration curve, selected radionuclides, selected standardization method for elemental analysis, version of results. At present, the 'ACTIV' package comprises 6 soft modules for processing the experimental data, which ensure computation of the quantities: radionuclide activities, activation yield data (case of CPA) and elemental concentration by relative and absolute standardization methods. Recently, the software designed to processing complex γ-ray spectra was acquired and installed on our PC 486 (8 MB RAM, 100 MHz). The next step in developing the 'ACTIV' program envisages improving the existing computing codes, completing the data libraries, incorporating a new soft for the direct use of the 'Quantum TM MCA' data, developing modules dedicated to uncertainty computation and optimization of the activation experiments

A Markovian Entropy Measure for the Analysis of Calcium Activity Time Series.

Science.gov (United States)

Marken, John P; Halleran, Andrew D; Rahman, Atiqur; Odorizzi, Laura; LeFew, Michael C; Golino, Caroline A; Kemper, Peter; Saha, Margaret S

2016-01-01

Methods to analyze the dynamics of calcium activity often rely on visually distinguishable features in time series data such as spikes, waves, or oscillations. However, systems such as the developing nervous system display a complex, irregular type of calcium activity which makes the use of such methods less appropriate. Instead, for such systems there exists a class of methods (including information theoretic, power spectral, and fractal analysis approaches) which use more fundamental properties of the time series to analyze the observed calcium dynamics. We present a new analysis method in this class, the Markovian Entropy measure, which is an easily implementable calcium time series analysis method which represents the observed calcium activity as a realization of a Markov Process and describes its dynamics in terms of the level of predictability underlying the transitions between the states of the process. We applied our and other commonly used calcium analysis methods on a dataset from Xenopus laevis neural progenitors which displays irregular calcium activity and a dataset from murine synaptic neurons which displays activity time series that are well-described by visually-distinguishable features. We find that the Markovian Entropy measure is able to distinguish between biologically distinct populations in both datasets, and that it can separate biologically distinct populations to a greater extent than other methods in the dataset exhibiting irregular calcium activity. These results support the benefit of using the Markovian Entropy measure to analyze calcium dynamics, particularly for studies using time series data which do not exhibit easily distinguishable features.

A Markovian Entropy Measure for the Analysis of Calcium Activity Time Series.

Directory of Open Access Journals (Sweden)

John P Marken

Full Text Available Methods to analyze the dynamics of calcium activity often rely on visually distinguishable features in time series data such as spikes, waves, or oscillations. However, systems such as the developing nervous system display a complex, irregular type of calcium activity which makes the use of such methods less appropriate. Instead, for such systems there exists a class of methods (including information theoretic, power spectral, and fractal analysis approaches which use more fundamental properties of the time series to analyze the observed calcium dynamics. We present a new analysis method in this class, the Markovian Entropy measure, which is an easily implementable calcium time series analysis method which represents the observed calcium activity as a realization of a Markov Process and describes its dynamics in terms of the level of predictability underlying the transitions between the states of the process. We applied our and other commonly used calcium analysis methods on a dataset from Xenopus laevis neural progenitors which displays irregular calcium activity and a dataset from murine synaptic neurons which displays activity time series that are well-described by visually-distinguishable features. We find that the Markovian Entropy measure is able to distinguish between biologically distinct populations in both datasets, and that it can separate biologically distinct populations to a greater extent than other methods in the dataset exhibiting irregular calcium activity. These results support the benefit of using the Markovian Entropy measure to analyze calcium dynamics, particularly for studies using time series data which do not exhibit easily distinguishable features.

Preliminary X-ray crystallographic study of the receptor-binding domain of the D/C mosaic neurotoxin from Clostridium botulinum

International Nuclear Information System (INIS)

Nuemket, Nipawan; Tanaka, Yoshikazu; Tsukamoto, Kentaro; Tsuji, Takao; Nakamura, Keiji; Kozaki, Shunji; Yao, Min; Tanaka, Isao

2010-01-01

To determine the binding mechanism of BoNT/OFD05 and its ganglioside receptors on neuronal cells, recombinant BoNT/OFD05 receptor-binding domain has been expressed, purified and crystallized. Botulinum toxin (BoNT) from Clostridium botulinum OFD05, isolated from bovine botulism, is a D/C mosaic-type BoNT. BoNTs possess binding, translocation and catalytic domains. The BoNT/OFD05 binding domain exhibits significant sequence identity to BoNT/C, which requires a single ganglioside as a binding receptor on neuronal cells, while BoNT/A and BoNT/B require two receptors for specific binding. To determine the binding mechanism of BoNT/OFD05 and its ganglioside receptors on neuronal cells, recombinant BoNT/OFD05 receptor-binding domain has been expressed, purified and crystallized. Native and SeMet-derivative crystals showed X-ray diffraction to 2.8 and 3.1 Å resolution, respectively. The crystals belonged to space group P2 1 2 1 2 1

Practical aspects of operating a neutron activation analysis laboratory

International Nuclear Information System (INIS)

1990-07-01

This book is intended to advise in everyday practical problems related to operating a neutron activation analysis (NAA) laboratory. It gives answers to questions like ''what to use NAA for'', ''how to find relevant research problems'', ''how to find users for the technique'', ''how to estimate the cost of the analysis and how to finance the work'', ''how to organize the work in a rational way'' and ''how to perform the quality control''. It gives advice in choosing staff, equipment, and consumables and how to design facilities and procedures according to need and available resources. Potential applications of economic or environmental importance, reactor facilities, counting and measuring equipment of the lab, cooperation with other analytical groups and competitiveness of NAA are discussed by experienced analysts. The compiled 8 tables of data useful for neutron activation analysts are a valuable asset for research labs as well as industrial quality control units. Refs, figs and tabs

Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin

National Research Council Canada - National Science Library

Montal, Mauricio

2006-01-01

.... The major focus thus far has been the implementation of a reliable and robust high-throughput screen for blockers specific for BoNT using Neuro 2A cells in which BoNTA forms channels with similar properties to those previously characterized in lipid bilayers. The immediate task during the present reporting period involved the detailed characterization of the channel and chaperone activity of BoNTA on Neuro2A cells.

Small-molecule quinolinol inhibitor identified provides protection against BoNT/A in mice.

Directory of Open Access Journals (Sweden)

Padma Singh

Full Text Available Botulinum neurotoxins (BoNTs, etiological agents of the life threatening neuroparalytic disease botulism, are the most toxic substances currently known. The potential for the use as bioweapon makes the development of small-molecule inhibitor against these deadly toxins is a top priority. Currently, there are no approved pharmacological treatments for BoNT intoxication. Although an effective vaccine/immunotherapy is available for immuno-prophylaxis but this cannot reverse the effects of toxin inside neurons. A small-molecule pharmacological intervention, especially one that would be effective against the light chain protease, would be highly desirable. Similarity search was carried out from ChemBridge and NSC libraries to the hit (7-(phenyl(8-quinolinylaminomethyl-8-quinolinol; NSC 84096 to mine its analogs. Several hits obtained were screened for in silico inhibition using AutoDock 4.1 and 19 new molecules selected based on binding energy and Ki. Among these, eleven quinolinol derivatives potently inhibited in vitro endopeptidase activity of botulinum neurotoxin type A light chain (rBoNT/A-LC on synaptosomes isolated from rat brain which simulate the in vivo system. Five of these inhibitor molecules exhibited IC(50 values ranging from 3.0 nM to 10.0 µM. NSC 84087 is the most potent inhibitor reported so far, found to be a promising lead for therapeutic development, as it exhibits no toxicity, and is able to protect animals from pre and post challenge of botulinum neurotoxin type A (BoNT/A.

Photon activation analysis on building materials

International Nuclear Information System (INIS)

Schulze, D.; Heller, W.; Kupsch, H.

1988-01-01

With regard to the planned construction of a new microtron, first investigations on raw materials for the aerated concrete production have been done to clear up the possibilities of photon activation analysis (PAA). Irradiations have been partly carried out on linear accelerators with a self-developed moveable activation equipment. PAA results of qualitative and quantitative elemental analysis are described. The detection of chlorine is important for studying the oversalting processes in buildings. (author)

Leisure-time physical activity and sciatica: A systematic review and meta-analysis.

Science.gov (United States)

Shiri, R; Falah-Hassani, K; Viikari-Juntura, E; Coggon, D

2016-11-01

The role of leisure-time physical activity in sciatica is uncertain. This study aimed to assess the association of leisure-time physical activity with lumbar radicular pain and sciatica. Literature searches were conducted in PubMed, Embase, Web of Science, Scopus, Google Scholar and ResearchGate databases from 1964 through August 2015. A random-effects meta-analysis was performed, and heterogeneity and small-study bias were assessed. Ten cohort (N = 82,024 participants), four case-control (N = 9350) and four cross-sectional (N = 10,046) studies qualified for meta-analysis. In comparison with no regular physical activity, high level of physical activity (≥4 times/week) was inversely associated with new onset of lumbar radicular pain or sciatica in a meta-analysis of prospective cohort studies [risk ratio (RR) = 0.88, 95% CI 0.78-0.99, I 2  = 0%, 7 studies, N = 78,065]. The association for moderate level of physical activity (1-3 times/week) was weaker (RR = 0.93, CI 0.82-1.05, I 2  = 0%, 6 studies, N = 69,049), and there was no association with physical activity for at least once/week (RR = 0.99, CI 0.86-1.13, 9 studies, N = 73,008). In contrast, a meta-analysis of cross-sectional studies showed a higher prevalence of lumbar radicular pain or sciatica in participants who exercised at least once/week [prevalence ratio (PR) = 1.29, CI 1.09-1.53, I 2  = 0%, 4 studies, N = 10,046], or 1-3 times/week (PR = 1.34, CI 1.02-1.77, I 2  = 0%, N = 7631) than among inactive participants. There was no evidence of small-study bias. This meta-analysis suggests that moderate to high level of leisure physical activity may have a moderate protective effect against development of lumbar radicular pain. However, a large reduction in risk (>30%) seems unlikely. Leisure-time physical activity may reduce the risk of developing lumbar radicular pain. © 2016 European Pain Federation - EFIC®.

Large Sample Neutron Activation Analysis: A Challenge in Cultural Heritage Studies

International Nuclear Information System (INIS)

Stamatelatos, I.E.; Tzika, F.

2007-01-01

Large sample neutron activation analysis compliments and significantly extends the analytical tools available for cultural heritage and authentication studies providing unique applications of non-destructive, multi-element analysis of materials that are too precious to damage for sampling purposes, representative sampling of heterogeneous materials or even analysis of whole objects. In this work, correction factors for neutron self-shielding, gamma-ray attenuation and volume distribution of the activity in large volume samples composed of iron and ceramic material were derived. Moreover, the effect of inhomogeneity on the accuracy of the technique was examined

High-capacity neutron activation analysis facility

International Nuclear Information System (INIS)

Hochel, R.C.

1979-01-01

A high-capacity neutron activation analysis facility, the Reactor Activation Facility, was designed and built and has been in operation for about a year at one of the Savannah River Plant's production reactors. The facility determines uranium and about 19 other trace elements in hydrogeochemical samples collected in the National Uranium Resource Evaluation program. The facility has a demonstrated average analysis rate of over 10,000 samples per month, and a peak rate of over 16,000 samples per month. Uranium is determined by cyclic activation and delayed neutron counting of the U-235 fission products; other elements are determined from gamma-ray spectra recorded in subsequent irradiation, decay, and counting steps. The method relies on the absolute activation technique and is highly automated for round-the-clock unattended operation

Gamma activation analysis with microtron

International Nuclear Information System (INIS)

Fiderkiewicz, A.; Kierzek, J.; Parus, J.; Swiderska-Kowalczyk, M.; Wolski, W.; Zoltowski, T.

1989-01-01

The physical principles of gamma activation analysis, its capabilities as well as its application to analyse polymetallic ores with use of mean power microtron are presented. Limits of detection and determination for above twenty elements occurring in those ores with use of short- and longlived radioisotopes are specified. The work contains conception of construction of race-track microtron with electrons energy adjusted in 10-30 MeV range and with current not less than 20 μA. Besides the development of microtrons, the reason for choosing the race-track construction for gamma activation analysis is given. 69 refs., 35 figs., 5 tabs. (author)

Biofac, a microbiological multimedia tool to perform the analysis of activated sludge

International Nuclear Information System (INIS)

Ferrer Torregrosa, C.; Llopis Nicolau, A.; Claramonte Santarrufina, J.; Alonso Hernandez, S.

2009-01-01

The composition and structure of the macrobiotic that is part of the active sludge, its temporal evolution, and the analysis of the macroscopic and microscopic characteristics of it are a source of information of great help in making decisions for plant operators. Lack of training and access to specific information linked to the missing standardization of analysis processes hinder the implementation and interpretation of them. Using a multimedia tool in DVD, Facsa has developed the Biofac, an application in which it is documented and illustrated the most relevant aspects that allow the user to perform the analysis of activated sludge. (Author)

Software for a measuring facility for activation analysis

International Nuclear Information System (INIS)

De Keyser, A.; De Roost, E.

1985-01-01

A software package has been developed for an APPLE P.C. The programs are intended to control an automated measuring station for photon activation analysis at GELINA, the linear accelerator of C.B.N.M. at Geel (Belgium). They allow to set-up a measuring scheme, to execute it under computer control, to accumulate and store 2 K-spectra using a built-in ADC and to output the results as listings, plots or evaluated reports

Automated activation-analysis system

International Nuclear Information System (INIS)

Minor, M.M.; Garcia, S.R.; Denton, M.M.

1982-01-01

An automated delayed neutron counting and instrumental neutron activation analysis system has been developed at Los Alamos National Laboratory's Omega West Reactor (OWR) to analyze samples for uranium and 31 additional elements with a maximum throughput of 400 samples per day

Heavy ion activation analysis

International Nuclear Information System (INIS)

Lass, B.D.; Roche, N.G.; Sanni, A.O.; Schweikert, E.A.; Ojo, J.F.

1982-01-01

A report on radioactivation with ion beams of 3 6 Li and 14 N is presented with some analytical applications: the determination of C via 12 C( 6 Li,αn) 13 N; the determination of Li and Be, using 14 N activation. Next, examples, with limitations in selectivity. The detection limits using a 1 μA h of activation irradiation are 5 ppm for C and 1 ppm for Li or Be. With 9 Be suitable for analytical applications are: sup(10,11)B( 9 Be,xn) 18 F and 14 N( 9 Be,αn) 18 F. Assuming a 1 μA h irradiation the detection limits for N and B are 1.5 ng and 0.5 ng, respectively, using a 7.8 MeV 9 Be beam. For activation with 12 C, experimental results with 12 MeV 12 C beam demonstrate that the beam is best suited for 7 Li analysis by the reaction 7 Li( 12 C,n) 18 F. The detection limit for a 1 μA h irradiation is 1 ng and the only other low Z elements activated are B and C. Finally, 12 C radioactivation was further combined with autoradiography for positional analysis. The spatial resolution of the technique was estimated to be 40 μm for an exposure corresponding to 6x10 5 disintegrations. As low as 10 -12 g of Li was readily detected by autoradiography. (author)

Practical considerations in instrumental neutron activation analysis

International Nuclear Information System (INIS)

Ahmad, N.

2001-01-01

Activation analysis is a technique of elemental analysis based on the measurement of characteristics radiation from radionuclides formed directly or indirectly by activation. The activation can be induced by bombarding the material with neutrons or charged particles or gamma rays. This is a well-accepted analytical technique for the determination of composition of complex materials. This technique is also sensitive at trace levels and is almost free from analytical interferences of matrix. It is used for multi-elemental determination in rocks, minerals, alloys, biological materials, geological samples, non-destructive analysis of materials and environmental samples such as water, air particulate matter, plants, soil, sediments and diets. This method is also used for production and measurements of radioisotopes in materials of known composition, for example, when radioactivation is used for nuclear reaction studies, for flux and beam intensity measurements for trace experiments and process quality control. In this article the parameters affecting the sensitivity of instrumental neutron activation analysis are briefly discussed. (author)

Botulinum Neurotoxin Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation with and without Neurogenic Muscular Hyperactivity

Directory of Open Access Journals (Sweden)

Kazuya Yoshida

2018-04-01

Full Text Available The aim of this study was to compare treatment outcomes following intramuscular injection of botulinum neurotoxin (BoNT in patients with recurrent temporomandibular joint dislocation, with and without muscle hyperactivity due to neurological diseases. Thirty-two patients (19 women and 13 men, mean age: 62.3 years with recurrent temporomandibular joint dislocation were divided into two groups: neurogenic (8 women and 12 men and habitual (11 women and 1 man. The neurogenic group included patients having neurological disorders, such as Parkinson’s disease or oromandibular dystonia, that are accompanied by muscle hyperactivity. BoNT was administered via intraoral injection to the inferior head of the lateral pterygoid muscle. In total, BoNT injection was administered 102 times (mean 3.2 times/patient. The mean follow-up duration was 29.5 months. The neurogenic group was significantly (p < 0.001 younger (47.3 years than the habitual group (84.8 years and required significantly (p < 0.01 more injections (4.1 versus 1.7 times to achieve a positive outcome. No significant immediate or delayed complications occurred. Thus, intramuscular injection of BoNT into the lateral pterygoid muscle is an effective and safe treatment for habitual temporomandibular joint dislocation. More injections are required in cases of neurogenic temporomandibular joint dislocation than in those of habitual dislocation without muscle hyperactivity.

Quality assurance techniques for activation analysis

International Nuclear Information System (INIS)

Becker, D.A.

1984-01-01

The principles and techniques of quality assurance are applied to the measurement method of activation analysis. Quality assurance is defined to include quality control and quality assessment. Plans for quality assurance include consideration of: personnel; facilities; analytical design; sampling and sample preparation; the measurement process; standards; and documentation. Activation analysis concerns include: irradiation; chemical separation; counting/detection; data collection, and analysis; and calibration. Types of standards discussed include calibration materials and quality assessment materials

Clinical process analysis and activity-based costing at a heart center.

Science.gov (United States)

Ridderstolpe, Lisa; Johansson, Andreas; Skau, Tommy; Rutberg, Hans; Ahlfeldt, Hans

2002-08-01

Cost studies, productivity, efficiency, and quality of care measures, the links between resources and patient outcomes, are fundamental issues for hospital management today. This paper describes the implementation of a model for process analysis and activity-based costing (ABC)/management at a Heart Center in Sweden as a tool for administrative cost information, strategic decision-making, quality improvement, and cost reduction. A commercial software package (QPR) containing two interrelated parts, "ProcessGuide and CostControl," was used. All processes at the Heart Center were mapped and graphically outlined. Processes and activities such as health care procedures, research, and education were identified together with their causal relationship to costs and products/services. The construction of the ABC model in CostControl was time-consuming. However, after the ABC/management system was created, it opened the way for new possibilities including process and activity analysis, simulation, and price calculations. Cost analysis showed large variations in the cost obtained for individual patients undergoing coronary artery bypass grafting (CABG) surgery. We conclude that a process-based costing system is applicable and has the potential to be useful in hospital management.

Neutron activation analysis of high-purity iron in comparison with chemical analysis

International Nuclear Information System (INIS)

Kinomura, Atsushi; Horino, Yuji; Takaki, Seiichi; Abiko, Kenji

2000-01-01

Neutron activation analysis of iron samples of three different purity levels has been performed and compared with chemical analysis for 30 metallic and metalloid impurity elements. The concentration of As, Cl, Cu, Sb and V detected by neutron activation analysis was mostly in agreement with that obtained by chemical analysis. The sensitivity limits of neutron activation analysis of three kinds of iron samples were calculated and found to be reasonable compared with measured values or detection limits of chemical analysis; however, most of them were above the detection limits of chemical analysis. Graphite-shielded irradiation to suppress fast neutron reactions was effective for Mn analysis without decreasing sensitivity to the other impurity elements. (author)

Short-time activation analysis with and without a 6LiD converter

International Nuclear Information System (INIS)

Grass, F.; Holzner, H.; Ritschel, A.; Ismail, S.S.; Dorner, J.

1994-01-01

Neutron activation analysis (NAA) at various irradiation and measurement systems of the Institute's TRIGA mark II reactor provides a choice of sample oriented analyzing systems. This is demonstrated on the analysis of waste products, on an analysis of the phase content of a high-T c superconductor and on a fluorine analysis in a standard reference material. (author) 17 refs.; 4 figs.; 5 tabs

Development of Distinction Method of Production Area of Ginsengs by Using a Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Jin; Chung, Yong Sam; Sun, Gwang Min; Lee, Yu Na; Yoo, Sang Ho [KAERI, Daejeon (Korea, Republic of)

2010-05-15

Distinction of production area of Korean ginsengs has been tried by using neutron activation techniques such as an instrumental neutron activation analysis (INAA) and a prompt gamma activation analysis (PGAA). A distribution of elements has varied according to the part of plant clue to the difference of enrichment effect and influence from a soil where the plants have been grown. So correlation study between plants and soil has been an Issue. In this study, the distribution of trace elements within a Korean ginseng was investigated by using an instrumental neutron activation analysis

Methods of charged-particle activation analysis

International Nuclear Information System (INIS)

Chaudhri, M. Anwar; Chaudhri, M. Nasir; Jabbar, Q.; Nadeem, Q.

2006-01-01

The accuracy of Chaudhri's method for charged-particle activation analysis published in J. Radioanal. Chem. (1977) v. 37 p. 243 has been further demonstrated by extensive calculations. The nuclear reactions 12 C(d,n) 13 N, 63 Cu( 3 He,p) 65 Zn, 107 Ag(α,n) 110 In and 208 Pb(d,p) 209 Pb, the cross sections of which were easily available, have been examined for the detection of 12 C, 63 Cu, 107 Ag and 208 Pb, respectively, in matrices of Cu, Zr and Pb, at the bombarding energies of 4 - 22 MeV. The 'standard' is assumed to be in a carbon matrix. It has been clearly demonstrated that Chaudhri's method, which makes the charged particle activation analysis as simple as neutron activation analysis, provides results which are almost identical to, or only about 1-2 % different, from the results obtained using the full 'Activity Equation' involving solving complex integrals. It is valid even when the difference in the average atomic weights of matrices of the standard and the sample is large. (author)

Multilevel predictors of adolescent physical activity: a longitudinal analysis

Directory of Open Access Journals (Sweden)

Hearst Mary O

2012-02-01

Full Text Available Abstract Background To examine how factors from a social ecologic model predict physical activity (PA among adolescents using a longitudinal analysis. Methods Participants in this longitudinal study were adolescents (ages 10-16 at baseline and one parent enrolled in the Transdisciplinary Research on Energetics and Cancer-Identifying Determinants of Eating and Activity (TREC-IDEA and the Etiology of Childhood Obesity (ECHO. Both studies were designed to assess a socio-ecologic model of adolescent obesity risk. PA was collected using ActiGraph activity monitors at two time points 24 months apart. Other measures included objective height and weight, adolescent and parent questionnaires on multilevel psychological, behavioral and social determinants of PA, and a home PA equipment inventory. Analysis was conducted using SAS, including descriptive characteristics, bivariate and stepped multivariate mixed models, using baseline adjustment. Models were stratified by gender. Results There were 578 adolescents with complete data. Results suggest few statistically significant longitudinal associations with physical activity measured as minutes of MVPA or total counts from accelerometers. For boys, greater self-efficacy (B = 0.75, p = 0.01 and baseline MVPA (B = 0.55, p p = 0.01 and barriers (B = -0.32, p = 0.05 significantly predicted MVPA at follow-up in the full model. The full multilevel model explained 30% of the variance in PA among boys and 24% among girls. Conclusions PA change in adolescents is a complex issue that is not easily understood. Our findings suggest early PA habits are the most important predictor of PA levels in adolescence. Intervention may be necessary prior to middle school to maintain PA through adolescence.

Impact of insurance sector activity on economic growth – A meta-analysis

Directory of Open Access Journals (Sweden)

Zuzana Richterková

2013-01-01

Full Text Available The aim of this study is to compute the overall effect size concerning the impact of insurance sector activity on economic growth. The connection of insurance activity and economic growth has been a widely investigated topic due to numerous papers and research attempts performed so far. The results, however, often differ among individual studies. Therefore a comprehensive analysis of the significance of causality from insurance activity, measured by insurance premium, to business cycle fluctuation, is well-required. Using 10 published and unpublished studies, we conduct a meta-analysis of the literature on the impact of insurance activity on economic growth. Insurance premium is taken as the measure of insurance activity. The combined significance test of individual t-statistics is employed. The calculation of the effect size allows understand the true effect relying on synthesis of so far published research with significantly higher amount of observations and better precision. Our results confirm positive effect of insurance activity on economic growth and are particularly important for policy makers who set the policy towards subjects in the insurance market.

Analysis of some Egyptian cosmetic samples by fast neutron activation analysis

International Nuclear Information System (INIS)

Medhat, M.E.; Ali, M.A.; Hassan, M.F.

2001-01-01

A description of D-T neutron generator (NG) is presented. This generator can be used for fast neutron activation analysis applied to determine some selected elements, especially light elements, in different materials. The concentrations of the elements Na, Mg, Al, Si, K, Cl, Ca and Fe were determined in two domestic brands of face powder by using 14 MeV neutron activation analysis

High-capacity neutron activation analysis facility

International Nuclear Information System (INIS)

Hochel, R.C.; Bowman, W.W.; Zeh, C.W.

1980-01-01

A high-capacity neutron activation analysis facility, the Reactor Activation Facility, was designed and built and has been in operation for about a year at one of the Savannah River Plant's production reactors. The facility determines uranium and about 19 other elements in hydrogeochemical samples collected in the National Uranium Resource Evaluation program, which is sponsored and funded by the United States Department of Energy, Grand Junction Office. The facility has a demonstrated average analysis rate of over 10,000 samples per month, and a peak rate of over 16,000 samples per month. Uranium is determined by cyclic activation and delayed neutron counting of the U-235 fission products; other elements are determined from gamma-ray spectra recorded in subsequent irradiation, decay, and counting steps. The method relies on the absolute activation technique and is highly automated for round-the-clock unattended operation

Radioactivity analysis in niobium activation foils

Energy Technology Data Exchange (ETDEWEB)

Mueller, G.E.

1995-06-01

The motivation for this study was to measure and analyze the activity of six (6) niobium (Nb) foils (the x-rays from an internal transition in Nb-93m) and apply this information with previously obtained activation foil data. The niobium data was used to determine the epithermal to MeV range for the neutron spectrum and fluence. The foil activation data was re-evaluated in a spectrum analysis code (STAY`SL) to provide new estimates of the exposure at the Los Alamos Spallation Radiation Effect Facility (LASREF). The activity of the niobium foils was measured and analyzed at the University of Missouri-Columbia (UMC) under the direction of Professor William Miller. The spectrum analysis was performed at the University of Missouri-Rolla (UMR) by Professor Gary Mueller.

Analysis of active piezoelectric energy harvester

Directory of Open Access Journals (Sweden)

Yiliang CUI

2018-02-01

Full Text Available Most of the existing piezoelectric traps are designed for a narrow frequency range of vibration, but the surrounding environment has a very wide frequency range, and the frequency may also be subject to change, causing the problem of difficult to achieve energy capture or capture inefficiency. In order to solve problem, a new T-type piezoelectric cantilever is proposed as a capture energy structure in the paper. To begin with the aspects of structural design and circuit design, the static analysis, modal analysis and resonance analysis of the structure are carried out and the natural frequency and excitation frequency of the device are analyzed. The design and calculation of the power consumption and the loss of the components of the circuit are analyzed by the simulation and verification of the active capture energy circuit, and the active and passive techniques are compared and analyzed, the simulation of the active capture circuit is verified by analyzing the power consumption of the circuit and the maximum power obtained by the active technology is 5 times of that of the passive technology. And then the voltage-controlled active boundary control method can be used for interface circuit design, taking the initiative to use each piezoelectric transduction cycle triggered by the electrical boundary conditions to effectively increase the input piezoelectric pump energy, and then increase output power. The way of utilizing the active trapping of piezoelectric materials is innovated, which has a positive effect on the development of piezoelectric traps.

Analysis of Some Egyptian Cosmetic Samples by Fast Neutron Activation Analysis

CERN Document Server

Medhat, M E; Fayez-Hassan, M

2001-01-01

A description of D-T neutron generator (NG) is presented. This generator can be used for fast neutron activation analysis applied to determine some selected elements, especially light elements, in different materials. In our work, the concentration of the elements Na, Mg, Al, Si, K, Cl, Ca and Fe, were determined in two domestic brands of face powder by using 14 MeV neutron activation analysis.

Specific classification of financial analysis of enterprise activity

Directory of Open Access Journals (Sweden)

Synkevych Nadiia I.

2014-01-01

Full Text Available Despite the fact that one can find a big variety of classifications of types of financial analysis of enterprise activity, which differ with their approach to classification and a number of classification features and their content, in modern scientific literature, their complex comparison and analysis of existing classification have not been done. This explains urgency of this study. The article studies classification of types of financial analysis of scientists and presents own approach to this problem. By the results of analysis the article improves and builds up a specific classification of financial analysis of enterprise activity and offers classification by the following features: objects, subjects, goals of study, automation level, time period of the analytical base, scope of study, organisation system, classification features of the subject, spatial belonging, sufficiency, information sources, periodicity, criterial base, method of data selection for analysis and time direction. All types of financial analysis significantly differ with their inherent properties and parameters depending on the goals of financial analysis. The developed specific classification provides subjects of financial analysis of enterprise activity with a possibility to identify a specific type of financial analysis, which would correctly meet the set goals.

Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E in Pichia pastoris.

Science.gov (United States)

Baghban, Roghayyeh; Gargari, Seyed Latif Mousavi; Rajabibazl, Masoumeh; Nazarian, Shahram; Bakherad, Hamid

2016-01-01

Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Investigation of Clostridium botulinum group III's mobilome content.

Science.gov (United States)

Woudstra, Cédric; Le Maréchal, Caroline; Souillard, Rozenn; Anniballi, Fabrizio; Auricchio, Bruna; Bano, Luca; Bayon-Auboyer, Marie-Hélène; Koene, Miriam; Mermoud, Isabelle; Brito, Roseane B; Lobato, Francisco C F; Silva, Rodrigo O S; Dorner, Martin B; Fach, Patrick

2018-02-01

Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C. botulinum group III were developed with the objective to better characterize C. botulinum group III strains. The investigation of 110 C. botulinum group III strains and 519 naturally contaminated samples collected during botulism outbreaks in Europe showed alpha-toxin and C2-I/C2-II markers to be systematically associated with type C/D bont-positive samples, which may indicate an important role of these elements in the pathogenicity mechanisms. On the contrary, bont type D/C strains and the related positive samples appeared to contain almost none of the markers tested. Interestingly, 31 bont-negative samples collected on farms after a botulism outbreak revealed to be positive for some of the genetic mobile elements tested. This suggests loss of the bont phage, either in farm environment after the outbreak or during laboratory handling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphorus Determination by Derivative Activation Analysis: A Multifaceted Radiochemical Application.

Science.gov (United States)

Kleppinger, E. W.; And Others

1984-01-01

Although determination of phosphorus is important in biology, physiology, and environmental science, traditional gravimetric and colorimetric methods are cumbersome and lack the requisite sensitivity. Therefore, a derivative activation analysis method is suggested. Background information, procedures, and results are provided. (JN)

Neutron activation analysis of Etruscan pottery

International Nuclear Information System (INIS)

Whitehead, J.; Silverman, A.; Ouellet, C.G.; Clark, D.D.; Hossain, T.Z.

1992-01-01

Neutron activation analysis (NAA) has been widely used in archaeology for compositional analysis of pottery samples taken from sites of archaeological importance. Elemental profiles can determine the place of manufacture. At Cornell, samples from an Etruscan site near Siena, Italy, are being studied. The goal of this study is to compile a trace element concentration profile for a large number of samples. These profiles will be matched with an existing data bank in an attempt to understand the place of origin for these samples. The 500 kW TRIGA reactor at the Ward Laboratory is used to collect NAA data for these samples. Experiments were done to set a procedure for the neutron activation analysis with respect to sample preparation, selection of irradiation container, definition of activation and counting parameters and data reduction. Currently, we are able to analyze some 27 elements in samples of mass 500 mg with a single irradiation of 4 hours and two sequences of counting. Our sensitivity for many of the trace elements is better than 1 ppm by weight under the conditions chosen. In this talk, details of our procedure, including quality assurance as measured by NIST standard reference materials, will be discussed. In addition, preliminary results from data treatment using cluster analysis will be presented. (author)

Building an applied activation analysis centre

International Nuclear Information System (INIS)

Bartosek, J.; Kasparec, I.; Masek, J.

1972-01-01

Requirements are defined and all available background material is reported and discussed for the building up of a centre of applied activation analysis in Czechoslovakia. A detailed analysis of potential users and the centre's envisaged availability is also presented as part of the submitted study. A brief economic analysis is annexed. The study covers the situation up to the end of 1972. (J.K.)

Application of neutron activation analysis

International Nuclear Information System (INIS)

Dybczynski, R.

2001-01-01

The physical basis and analytical possibilities of neutron activation analysis have been performed. The number of applications in material engineering, geology, cosmology, oncology, criminology, biology, agriculture, environment protection, archaeology, history of art and especially in chemical analysis have been presented. The place of the method among other methods of inorganic quantitative chemical analysis for trace elements determination has been discussed

Conference on instrumental activation analysis IAA 92

International Nuclear Information System (INIS)

Frana, J.; Obrusnik, I.

1992-05-01

The publication contains 26 abstracts primarily concerned with neutron activation analysis, although other analytical techniques based on X-ray fluorescence analysis, PIXE, PIGE, RBS are also included. Some contributions deal with aspects of quality practice and assurance in radioanalytical laboratories, with marketing of instrumental neutron activation analysis services, with hard- and software aspects of radiation detection, etc. (Z.S.)

Automated activation-analysis system

International Nuclear Information System (INIS)

Minor, M.M.; Hensley, W.K.; Denton, M.M.; Garcia, S.R.

1981-01-01

An automated delayed neutron counting and instrumental neutron activation analysis system has been developed at Los Alamos National Laboratory's Omega West Reactor (OWR) to analyze samples for uranium and 31 additional elements with a maximum throughput of 400 samples per day. The system and its mode of operation for a large reconnaissance survey are described

Physical activity and stroke: a meta-analysis of observational data

NARCIS (Netherlands)

Wendel-Vos, G.C.W.; Schuit, A.J.; Feskens, E.J.M.; Boshuizen, H.C.; Verschuren, W.M.M.; Saris, W.H.M.; Kromhout, D.

2004-01-01

Background Based on studies published so far, the protective effect of physical activity on stroke remains controversial. Specifically, there is a lack of insight into the sources of heterogeneity between studies. Methods Meta-analysis of observational studies was used to quantify the relationship

Activation analysis of air particulate matter

International Nuclear Information System (INIS)

Alian, A.; Sansoni, B.

1988-11-01

This review on activation analysis of air particulate matter is an extended and updated version of a review given by the same authors in 1985. The main part is aimed at the analytical scheme and refers to rules and techniques for sampling, sample and standard preparation, irradiation and counting procedures, as well as data processing, - evaluation, and - presentation. Additional chapters deal with relative and monostandard methods, the use of activation analysis for atmosphere samples in various localities, and level of toxic and other elements in the atmosphere. The review contains 190 references. (RB)

Particulate matter and neutron activation analysis

International Nuclear Information System (INIS)

Otoshi, Tsunehiko

2003-01-01

In these years, economy of East Asian region is rapidly growing, and countries in this region are facing serious environmental problems. Neutron activation analysis is known as one of high-sensitive analytical method for multi elements. And it is a useful tool for environmental research, particularly for the study on atmospheric particulate matter that consists of various constituents. Elemental concentration represents status of air, such as emission of heavy metals from industries and municipal incinerators, transportation of soil derived elements more than thousands of kilometers, and so on. These monitoring data obtained by neutron activation analysis can be a cue to evaluate environment problems. Japanese government launched National Air Surveillance Network (NASN) employing neutron activation analysis in 1974, and the data has been accumulated at about twenty sampling sites. As a result of mitigation measure of air pollution sources, concentrations of elements that have anthropogenic sources decreased particularly at the beginning of the monitoring period. However, even now, concentrations of these anthropogenic elements reflect the characteristics of each sampling site, e.g. industrial/urban, rural, and remote. Soil derived elements have a seasonal variation because of the contribution of continental dust transported by strong westerly winds prevailing in winter and spring season. The health effects associated with trace elements in particulate matter have not been well characterized. However, there is increasing evidence that particulate air pollution, especially fine portion of particles in many different cities is associated with acute mortality. Neutron activation analysis is also expected to provide useful information to this new study field related to human exposures and health risk. (author)

Activation product analysis in a mixed sample containing both fission and neutron activation products

Energy Technology Data Exchange (ETDEWEB)

Morrison, Samuel S.; Clark, Sue B.; Eggemeyer, Tere A.; Finn, Erin C.; Hines, C. Corey; King, Mathew D.; Metz, Lori A.; Morley, Shannon M.; Snow, Mathew S.; Wall, Donald E.; Seiner, Brienne N.

2017-11-02

Activation analysis of gold (Au) is used to estimate neutron fluence resulting from a criticality event; however, such analyses are complicated by simultaneous production of other gamma-emitting fission products. Confidence in neutron fluence estimates can be increased by quantifying additional activation products such as platinum (Pt), tantalum (Ta), and tungsten (W). This work describes a radiochemical separation procedure for the determination of these activation products. Anion exchange chromatography is used to separate anionic forms of these metals in a nitric acid matrix; thiourea is used to isolate the Au and Pt fraction, followed by removal of the Ta fraction using hydrogen peroxide. W, which is not retained on the first anion exchange column, is transposed to an HCl/HF matrix to enhance retention on a second anion exchange column and finally eluted using HNO3/HF. Chemical separations result in a reduction in the minimum detectable activity by a factor of 287, 207, 141, and 471 for 182Ta, 187W, 197Pt, and 198Au respectively, with greater than 90% recovery for all elements. These results represent the highest recoveries and lowest minimum detectable activities for 182Ta, 187W, 197Pt, and 198Au from mixed fission-activation product samples to date, enabling considerable refinement in the measurement uncertainties for neutron fluences in highly complex sample matrices.

Longitudinal Physical Activity Patterns Among Older Adults: A Latent Transition Analysis.

Science.gov (United States)

Mooney, Stephen J; Joshi, Spruha; Cerdá, Magdalena; Kennedy, Gary J; Beard, John R; Rundle, Andrew G

2018-05-14

Most epidemiologic studies of physical activity measure either total energy expenditure or engagement in a single activity type, such as walking. These approaches may gloss over important nuances in activity patterns. We performed a latent transition analysis to identify patterns of activity types as well as neighborhood and individual determinants of changes in those activity patterns over two years in a cohort of 2,023 older adult residents of New York City, NY, surveyed between 2011 and 2013. We identified seven latent classes: 1) Mostly Inactive, 2) Walking, 3) Exercise, 4) Household Activities and Walking, 5) Household Activities and Exercise, 6) Gardening and Household Activities, and 7) Gardening, Household Activities, and Exercise. The majority of subjects retained the same activity patterns between waves (54% unchanged between waves 1 and 2, 66% unchanged between waves 2 and 3).Most latent class transitions were between classes distinguished only by one form of activity, and only neighborhood unemployment was consistently associated with changing between activity latent classes. Future latent transition analyses of physical activity would benefit from larger cohorts and longer follow-up periods to assess predictors of and long-term impacts of changes in activity patterns.

Activation analysis of biological materials at the Activation Analysis Centre

International Nuclear Information System (INIS)

Kukula, F.; Obrusnik, I.; Simkova, M.; Kucera, J.; Krivanek, M.

1976-01-01

A review is presented of the work of the Activation Analysis Centre of the Nuclear Research Institute for different fields of the Czechoslovak economy, aimed primarily at analyzing biological materials with the purpose of determining the contents of the so-called vital trace elements and of elements which already have a toxic effect on the organism in trace concentrations. Another important field of research is the path of trace elements from the environment to the human organism. A destructive method for the simultaneous determination of 12 trace elements in 11 kinds of human tissue has been studied. (Z.M.)

Manganese contents of soils as determined by activation analysis

International Nuclear Information System (INIS)

El-Kholi, A.F.; Hamdy, A.A.; Al Metwally, A.I.; El-Damaty, A.H.

1976-01-01

The object of this investigation is to determine total manganese by means of neutron activation analysis and evaluate this technique in comparison with the corresponding data obtained by conventional chemical analysis. Data obtained revealed that the values of total manganese in calcareous soils obtained by both chemical analysis and that by neutron activation analysis were similar. Therefore, activation analysis could be recommended as a quick laboratory, less tedious, and time consuming method for the determination of Mn content in both soils and plants than the conventional chemical techniques due to its great specificity, sensitivity and simplicity. Statistical analysis showed that there is a significant correlation at 5% probability level between manganese content in Soybean plant and total manganese determined by activation and chemical analysis giving the evidence that in the case of those highly calcareous soils of low total manganese content this fraction has to be considered as far as available soil manganese is concerned

7th international conference ''Modern trends in activation analysis''

International Nuclear Information System (INIS)

Obrusnik, I.

1987-01-01

The conference was held on 23-27 June, 1986 in Copenhagen (DK) with the participation of specialists from 42 countries. 175 papers were submitted covering the wide field of applications of neutron activation analysis, from novel techniques to sample preparation, information processes and control, activation techniques, light element and rare earth element determination, ultratracer analysis, quality assurance, comparator methods, and reference materials. The poster session was mainly oriented to industrial applications of activation analysis, biological applications, in vivo use of neutron activation analysis, the applications of neutron activation analysis in environmental control, criminology, etc. (E.S.)

A monoclonal antibody based capture ELISA for botulinum neurotoxin serotype B: toxin detection in food

Science.gov (United States)

Botulism is a serious foodborne neuroparalyic disease caused by botulinum neurotoxin (BoNT) produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We repo...

Nuclear power company activity based costing management analysis

International Nuclear Information System (INIS)

Xu Dan

2012-01-01

With Nuclear Energy Industry development, Nuclear Power Company has the continual promoting stress of inner management to the sustainable marketing operation development. In view of this, it is very imminence that Nuclear Power Company should promote the cost management levels and built the nuclear safety based lower cost competitive advantage. Activity based costing management (ABCM) transfer the cost management emphases from the 'product' to the 'activity' using the value chain analysis methods, cost driver analysis methods and so on. According to the analysis of the detail activities and the value chains, cancel the unnecessary activity, low down the resource consuming of the necessary activity, and manage the cost from the source, achieve the purpose of reducing cost, boosting efficiency and realizing the management value. It gets the conclusion from the detail analysis with the nuclear power company procedure and activity, and also with the selection to 'pieces analysis' of the important cost related project in the nuclear power company. The conclusion is that the activities of the nuclear power company has the obviously performance. It can use the management of ABC method. And with the management of the procedure and activity, it is helpful to realize the nuclear safety based low cost competitive advantage in the nuclear power company. (author)

Epithermal neutron activation analysis using a boron carbide irradiation filter

International Nuclear Information System (INIS)

Ehmann, W.D.; Brueckner, J.

1980-01-01

The use of boron carbide as a thermal neutron filter in epithermal neutron activation (ENAA) analysis has been investigated. As compared to the use of a cadmium filter, boron provides a greater reduction of activities from elements relatively abundant in terrestrial rocks and fossil fuels, such as Na, La, Sc and Fe. These elements have excitation functions which follow the 1/v law in the 1 to 10 eV lower epithermal region. This enhances the sensitivity of ENAA for elements such as U, Th, Ba and etc. which have strong resonances in the higher epithermal region above 10 eV. In addition, a boron carbide filter has the advantages over cadmium of acquiring a relatively low level of induced activity which poses minimal radiation safety problems, when used for ENAA. (author)

Neutron Activation Analysis with k0-standardisation

International Nuclear Information System (INIS)

Pomme, S.

2001-01-01

SCK-CEN's programme on Neutron Activation Analysis with k 0 -standardisation concentrates on the improvement of the standardisation method and the characterisation of the neutron field as well as on the improvement of the statistical control on neutron activation analysis. Main achievements in 2000 are reported

A new microcomputer program for processing data in neutron activation analysis

International Nuclear Information System (INIS)

Beeley, P.A.; Page, J.A.; Heimlich, M.S.; Queen's Univ., Kingston, ON; Edward, J.B.; Bennett, L.G.I.

1993-01-01

A new utility program for processing data in neutron activation analysis (NAA) has been developed for use on MS-DOS microcomputers. Peak areas are read from ASCII data files of gamma-ray spectra which have been processed by a Gaussian peak fitting program, GAMANAL-PC. Elemental concentrations are then calculated by this new program, QUACANAL, via a semi-absolute algorithm that uses pre-determined activation constants. User-defined ASCII library files are employed to specify the elements of interest required for analysis, and (n, p) and (n, α) interferences are taken into account. The program has been written in turbo PASCAL, is menu driven and contains options for processing data from cyclic NAA. An interactive philosophy has been used in designing the program. (author) 12 refs.; 2 figs.; 1 tab

Multi trace element analysis of dry biological materials by neutron activation analysis including a chemical group separation

International Nuclear Information System (INIS)

Weers, C.A.

1980-07-01

Multi-element analysis of dry biological material by neutron activation analysis has to include radiochemical separation. The evaporation process is described in terms of the half-volume. The pretreatment of the samples and the development of the destruction-evaporation apparatus are described. The successive adsorption steps with active charcoal, Al 2 O 3 and coprecipitation with Fe(OH) 3 are described. Results obtained for standard reference materials are summarized. (G.T.H.)

Spectral analysis of coolant activity from a commercial nuclear generating station

International Nuclear Information System (INIS)

Swann, J.D.; Lewis, B.J.; Ip, M.

2008-01-01

In support of the development of a real-time on-line fuel failure monitoring system for the CANDU reactor, actual gamma spectroscopy data files from the gaseous fission product (GFP) monitoring system were acquired from almost four years of operation at a commercial Nuclear Generating Station (NGS). Several spectral analysis techniques were used to process the data files. Radioisotopic activity from the plant information (PI) system was compared to an in-house C++ code that was used to determine the photopeak area and to a separate analysis with commercial software from Canberra-Aptec. These various techniques provided for a calculation of the coolant activity concentration of the noble gas and iodine species in the primary heat transport system. These data were then used to benchmark the Visual DETECT code, a user friendly software tool which can be used to characterize the defective fuel state based on a coolant activity analysis. Acceptable agreement was found with the spectral techniques when compared to the known defective bundle history at the commercial reactor. A more generalized method of assessing the fission product release data was also considered with the development of a pre-processor to evaluate the radioisotopic release rate from mass balance considerations. The release rate provided a more efficient means to characterize the occurrence of a defect and was consistent with the actual defect situation at the power plant as determined from in-bay examination of discharged fuel bundles. (author)

Neutron activation analysis in minerals prospecting

International Nuclear Information System (INIS)

Gomez, H.; Duque O, J.

1988-01-01

One method multielemental analysis in geological samples has been developed by neutron activation analysis without using standards and by eliminating many of the error sources of the absolute method. It uses the ratio of the activities induced by mass unit, between the element in the sample and one cobalt monitor. The detection limits are good for more than thirty elements in many prospecting programs, with a standard deviation less than 7%. The neutron flux used is 2x10 11 nxcm -2 .S -1 and the HPGE detector has a relative efficiency of 20% and an energy resolution of 1.9 KeV in 1332 KeV photopeak

Neutron activation analysis in archaeological chemistry

Energy Technology Data Exchange (ETDEWEB)

Harbottle, G [Brookhaven National Lab., Upton, NY (United States)

1990-01-01

There is a long history of the application of chemical analysis to archaeological problems, extending to the last years of the 18th century. The nuclear-age technique of neutron activation analysis, permitting the simultaneous, sensitive, non-destructive estimation of many elements in an archaeological specimen, has found wide application. Important advances have been made, using this technique, in locating the origins of archaeological artifacts such as ceramics, metals, obsidian and semiprecious stones, among other articles of ancient ritual and commerce. In addition, the technique of neutron activation analysis has proved to be almost ideal in studies tracing the development of ancient technologies such as glass-making and smelting. In the future, the development of data banks of analyses of archaeological materials should provide an excellent new tool in studies of prehistory.

Neutron activation analysis in archaeological chemistry

International Nuclear Information System (INIS)

Harbottle, G.

1990-01-01

There is a long history of the application of chemical analysis to archaeological problems, extending to the last years of the 18th century. The nuclear-age technique of neutron activation analysis, permitting the simultaneous, sensitive, non-destructive estimation of many elements in an archaeological specimen, has found wide application. Important advantages have been made, using this technique, in locating the origins of archaeological artifacts such as ceramics, metals, obsidian and semiprecious stones, among other articles of ancient ritual and commerce. In addition, the technique of neutron activation analysis has proved to be almost ideal in studies tracing the development of ancient technologies such as glass-making and smelting. In the future, the development of data banks of analyses of archaeological materials should provide an excellent new tool in studies of prehistory. (orig.)

Patterns of health behaviour associated with active travel: a compositional data analysis.

Science.gov (United States)

Foley, Louise; Dumuid, Dorothea; Atkin, Andrew J; Olds, Timothy; Ogilvie, David

2018-03-21

Active travel (walking or cycling for transport) is associated with favourable health outcomes in adults. However, little is known about the concurrent patterns of health behaviour associated with active travel. We used compositional data analysis to explore differences in how people doing some active travel used their time compared to those doing no active travel, incorporating physical activity, sedentary behaviour and sleep. We analysed cross-sectional data from the 2014/15 United Kingdom Harmonised European Time Use Survey. Participants recorded two diary days of activity, and we randomly selected one day from participants aged 16 years or over. Activities were categorised into six mutually exclusive sets, accounting for the entire 24 h: (1) sleep; (2) leisure moderate to vigorous physical activity (MVPA); (3) leisure sedentary screen time; (4) non-discretionary time (work, study, chores and caring duties); (5) travel and (6) other. This mixture of activities was defined as a time-use composition. A binary variable was created indicating whether participants reported any active travel on their selected diary day. We used compositional multivariate analysis of variance (MANOVA) to test whether mean time-use composition differed between individuals reporting some active travel and those reporting no active travel, adjusted for covariates. We then used adjusted linear regression models and bootstrap confidence intervals to identify which of the six activity sets differed between groups. 6143 participants (mean age 48 years; 53% female) provided a valid diary day. There was a statistically significant difference in time-use composition between those reporting some active travel and those reporting no active travel. Those undertaking active travel reported a relatively greater amount of time in leisure MVPA and travel, and a relatively lower amount of time in leisure sedentary screen time and sleep. Compared to those not undertaking active travel, those who did

Modeling activity patterns of wildlife using time-series analysis.

Science.gov (United States)

Zhang, Jindong; Hull, Vanessa; Ouyang, Zhiyun; He, Liang; Connor, Thomas; Yang, Hongbo; Huang, Jinyan; Zhou, Shiqiang; Zhang, Zejun; Zhou, Caiquan; Zhang, Hemin; Liu, Jianguo

2017-04-01

The study of wildlife activity patterns is an effective approach to understanding fundamental ecological and evolutionary processes. However, traditional statistical approaches used to conduct quantitative analysis have thus far had limited success in revealing underlying mechanisms driving activity patterns. Here, we combine wavelet analysis, a type of frequency-based time-series analysis, with high-resolution activity data from accelerometers embedded in GPS collars to explore the effects of internal states (e.g., pregnancy) and external factors (e.g., seasonal dynamics of resources and weather) on activity patterns of the endangered giant panda ( Ailuropoda melanoleuca ). Giant pandas exhibited higher frequency cycles during the winter when resources (e.g., water and forage) were relatively poor, as well as during spring, which includes the giant panda's mating season. During the summer and autumn when resources were abundant, pandas exhibited a regular activity pattern with activity peaks every 24 hr. A pregnant individual showed distinct differences in her activity pattern from other giant pandas for several months following parturition. These results indicate that animals adjust activity cycles to adapt to seasonal variation of the resources and unique physiological periods. Wavelet coherency analysis also verified the synchronization of giant panda activity level with air temperature and solar radiation at the 24-hr band. Our study also shows that wavelet analysis is an effective tool for analyzing high-resolution activity pattern data and its relationship to internal and external states, an approach that has the potential to inform wildlife conservation and management across species.

Insurer’s activity as object of economic analysis

Directory of Open Access Journals (Sweden)

O.O. Poplavskiy

2015-12-01

Full Text Available The article is devoted to the substantiation of theoretical fundamentals of insurer’s analysis and peculiarities of its implementation. The attention has been focused on the important role of economic analysis in economic science which is confirmed by its active use in research and practical orientation. The author summarizes the classification and principles of insurer’s activity analysis, supplements it with specific principles for insurer’s environment, publicity and risk-orientation which enable increasingly to take into account the peculiarities of insurance relations. The paper pays attention to the specification of elements of analysis and its key directions including the analysis of insurer’s financing, the analysis of insurance operations and the analysis of investment activity which will allow the effective functioning of risk management system.

Active tourism as a tourist mode in expansion. Analysis of the supply of active tourism in Spain

Directory of Open Access Journals (Sweden)

Noelia Araújo Vila

2012-06-01

Full Text Available Parallel to the social and economic situation, where the experience economy is a reality, new tourist typologies are emerging in line with this demand experiential. Tourists are looking for sensations and emotions, so tourism sector has diversified its offer adapting to this desire. Active tourism appears, mode belonging to a larger field, nature tourism, a booming tourist type today by the increase of tourists interested in its activities. Therefore, this paper takes from this concept to below detail the types that are part of it, and finally it does an analysis of the active tourism offer of the Spanish territory, territory that is appropriate for this type of activity.

Physical activity and body image among men and boys: A meta-analysis.

Science.gov (United States)

Bassett-Gunter, Rebecca; McEwan, Desmond; Kamarhie, Aria

2017-09-01

Three meta-analytic reviews have concluded that physical activity is positively related to body image. Historically, research regarding physical activity and body image has been disproportionately focused on female samples. For example, the most recent meta-analysis (2009) extracted 56 effect sizes for women and only 12 for men. The current paper provides an update to the literature regarding the relationship between physical activity and body image among men and boys across 84 individual effect sizes. The analysis also provides insight regarding moderator variables including participant age, and physical activity type and intensity. Overall, physical activity was positively related to body image among men and boys with various moderator variables warranting further investigation. Pragmatic implications are discussed as well as the limitations within existing research and need for additional research to further understand moderator and mediator variables. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation analysis in the environment: Science and technology

International Nuclear Information System (INIS)

Lenihan, J.

1989-01-01

Science is disciplined curiosity. Activation analysis was created more than 50 yr ago by Hevesy's curiosity and Levi's experimental skill. Technology is the exploitation of machines and materials for the fulfillment of human needs or wants. The early history of neutron activation analysis (NAA) was greatly influenced by military requirements. Since then the technique has found applications in many disciplines, including materials science, medicine, archaeology, geochemistry, agriculture, and forensic science. More recently, neutron activation analysts, responding to increasing public interest and concern, have made distinctive contributions to the study of environmental problems. Activation analysis, though it uses some procedures derived from physics, is essentially a chemical technique. The chemical study of the environment may be reviewed under many headings; three are discussed here: 1. occupational medicine 2. health of the general public 3. environmental pollution

Methodological developments and applications of neutron activation analysis

International Nuclear Information System (INIS)

Kucera, J.

2007-01-01

The paper reviews the author's experience acquired and achievements made in methodological developments of neutron activation analysis (NAA) of mostly biological materials. These involve epithermal neutron activation analysis, radiochemical neutron activation analysis using both single- and multi-element separation procedures, use of various counting modes, and the development and use of the self-verification principle. The role of NAA in the detection of analytical errors is discussed and examples of applications of the procedures developed are given. (author)

Examination of a Social-Networking Site Activities Scale (SNSAS) Using Rasch Analysis

Science.gov (United States)

Alhaythami, Hassan; Karpinski, Aryn; Kirschner, Paul; Bolden, Edward

2017-01-01

This study examined the psychometric properties of a social-networking site (SNS) activities scale (SNSAS) using Rasch Analysis. Items were also examined with Rasch Principal Components Analysis (PCA) and Differential Item Functioning (DIF) across groups of university students (i.e., males and females from the United States [US] and Europe; N =…

Profiling physical activity motivation based on self-determination theory: a cluster analysis approach.

Science.gov (United States)

Friederichs, Stijn Ah; Bolman, Catherine; Oenema, Anke; Lechner, Lilian

2015-01-01

In order to promote physical activity uptake and maintenance in individuals who do not comply with physical activity guidelines, it is important to increase our understanding of physical activity motivation among this group. The present study aimed to examine motivational profiles in a large sample of adults who do not comply with physical activity guidelines. The sample for this study consisted of 2473 individuals (31.4% male; age 44.6 ± 12.9). In order to generate motivational profiles based on motivational regulation, a cluster analysis was conducted. One-way analyses of variance were then used to compare the clusters in terms of demographics, physical activity level, motivation to be active and subjective experience while being active. Three motivational clusters were derived based on motivational regulation scores: a low motivation cluster, a controlled motivation cluster and an autonomous motivation cluster. These clusters differed significantly from each other with respect to physical activity behavior, motivation to be active and subjective experience while being active. Overall, the autonomous motivation cluster displayed more favorable characteristics compared to the other two clusters. The results of this study provide additional support for the importance of autonomous motivation in the context of physical activity behavior. The three derived clusters may be relevant in the context of physical activity interventions as individuals within the different clusters might benefit most from different intervention approaches. In addition, this study shows that cluster analysis is a useful method for differentiating between motivational profiles in large groups of individuals who do not comply with physical activity guidelines.

Assembling the puzzle for promoting physical activity in Brazil: a social network analysis.

Science.gov (United States)

Brownson, Ross C; Parra, Diana C; Dauti, Marsela; Harris, Jenine K; Hallal, Pedro C; Hoehner, Christine; Malta, Deborah Carvalho; Reis, Rodrigo S; Ramos, Luiz Roberto; Ribeiro, Isabela C; Soares, Jesus; Pratt, Michael

2010-07-01

Physical inactivity is a significant public health problem in Brazil that may be addressed by partnerships and networks. In conjunction with Project GUIA (Guide for Useful Interventions for Physical Activity in Brazil and Latin America), the aim of this study was to conduct a social network analysis of physical activity in Brazil. An online survey was completed by 28 of 35 organizations contacted from December 2008 through March 2009. Network analytic methods examined measures of collaboration, importance, leadership, and attributes of the respondent and organization. Leadership nominations for organizations studied ranged from 0 to 23. Positive predictors of collaboration included: south region, GUIA membership, years working in physical activity, and research, education, and promotion/practice areas of physical activity. The most frequently reported barrier to collaboration was bureaucracy. Social network analysis identified factors that are likely to improve collaboration among organizations in Brazil.

Neutron activation analysis of geological material

International Nuclear Information System (INIS)

Greef, G.J.

1977-05-01

In neutron activation analysis the precision and accuracy of results are often misleading, since only the statistical errors which accompany the measuring of radioactivity are taken into consideration. Several other factors can, however, also influence precision and accuracy. It was found that a geological sample was contaminated with the construction material of the mill in which it had been pulverised. Several geometrical differences which could possibly play a role were also investigated. Impurities in the irradiation containers affect the determination of some elements in the samples; the contamination materials in quarts irradiation tubes were determined. The flux gradients which may effect the relative activities of the samples and standards were measured. Suitable standards are necessary to ensure accurate analyses of geological material. Available natural standards were critically evaluated and several methods were investigated by which synthetic standards may be prepared. In order to accurately determine gallium, lanthanum and samarium by means of neutron activation analysis, sodium first had to be removed. After irradiation the sample was dissolved in a mixture of acids and the soidium absorbed from the solution on a hydrated antimony pentoxide column. Gallium, lanthanum and samarium activities were measured by means of precision gamma-spectrometry

Prompt gamma activation analysis (PGAA) and short-lived neutron activation analysis (NAA) applied to the characterization of legacy materials

International Nuclear Information System (INIS)

English, G.A.; Firestone, R.B.; Perry, D.L.; Reijonen, J.P.; Ka-Ngo Leung; Garabedian, G.F.; Molnar, G.L.; Revay, Zs.

2008-01-01

Without quality historical records that provide the composition of legacy materials, the elemental and/or chemical characterization of such materials requires a manual analytical strategy that may expose the analyst to unknown toxicological hazards. In addition, much of the existing legacy inventory also incorporates radioactivity, and, although radiological composition may be determined by various nuclear-analytical methods, most importantly, gamma-spectroscopy, current methods of chemical characterization still require direct sample manipulation, thereby presenting special problems with broad implications for both the analyst and the environment. Alternately, prompt gamma activation analysis (PGAA) provides a 'single-shot' in-situ, non-destructive method that provides a complete assay of all major entrained elemental constituents. Additionally, neutron activation analysis (NAA) using short-lived activation products complements PGAA and is especially useful when NAA activation surpasses the PGAA in elemental sensitivity. (author)

Prompt gamma activation analysis (PGAA) and short-lived neutron activation analysis (NAA) applied to the characterization of legacy materials

International Nuclear Information System (INIS)

Firestone, Richard B; English, G.A.; Firestone, R.B.; Perry, D.L.; Reijonen, J.P.; Leung, Ka-Ngo; Garabedian, G.F.; Molnar, G.L.; Revay, Zs.

2008-01-01

Without quality historical records that provide the composition of legacy materials, the elemental and/or chemical characterization of such materials requires a manual analytical strategy that may expose the analyst to unknown toxicological hazards. In addition, much of the existing legacy inventory also incorporates radioactivity, and, although radiological composition may be determined by various nuclear-analytical methods, most importantly, gamma-spectroscopy, current methods of chemical characterization still require direct sample manipulation, thereby presenting special problems with broad implications for both the analyst and the environment. Alternately, prompt gamma activation analysis (PGAA) provides a 'single-shot' in-situ, non-destructive method that provides a complete assay of all major entrained elemental constituents.1-3. Additionally, neutron activation analysis (NAA) using short-lived activation products complements PGAA and is especially useful when NAA activation surpasses the PGAA in elemental sensitivity

Structural basis of the pH-dependent assembly of a botulinum neurotoxin complex.

Science.gov (United States)

Matsui, Tsutomu; Gu, Shenyan; Lam, Kwok-Ho; Carter, Lester G; Rummel, Andreas; Mathews, Irimpan I; Jin, Rongsheng

2014-11-11

Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and releases it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent conformation with limited domain flexibility. Intriguingly, the free form NTNHA-A adopts pH-dependent conformational changes due to a torsional motion of its C-terminal domain. Once forming a complex at acidic pH, they each adopt a stable conformation that is similar to that observed in the crystal structure of the M-PTC. Our results suggest that assembly of the M-PTC depends on the environmental pH and that the complex form of BoNT/A is induced by interacting with NTNHA-A at acidic pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of educational program for neutron activation analysis

International Nuclear Information System (INIS)

Chung, Yong Sam; Moon, Jong Hwa; Kim, Sun Ha; Ryel, Sung; Kang, Young Hwan; Lee, Kil Yong; Yeon, Yeon Yel; Cho, Seung Yeon

2000-08-01

This technical report is developed to apply an educational and training program for graduate student and analyst utilizing neutron activation analysis. The contents of guide book consists of five parts as follows; introduction, gamma-ray spectrometry and measurement statistics, its applications, to understand of comprehensive methodology and to utilize a relevant knowledge and information on neutron activation analysis

Development of educational program for neutron activation analysis

Energy Technology Data Exchange (ETDEWEB)

Chung, Yong Sam; Moon, Jong Hwa; Kim, Sun Ha; Ryel, Sung; Kang, Young Hwan; Lee, Kil Yong; Yeon, Yeon Yel; Cho, Seung Yeon

2000-08-01

This technical report is developed to apply an educational and training program for graduate student and analyst utilizing neutron activation analysis. The contents of guide book consists of five parts as follows; introduction, gamma-ray spectrometry and measurement statistics, its applications, to understand of comprehensive methodology and to utilize a relevant knowledge and information on neutron activation analysis.

Analytic Provenance Datasets: A Data Repository of Human Analysis Activity and Interaction Logs

OpenAIRE

Mohseni, Sina; Pachuilo, Andrew; Nirjhar, Ehsanul Haque; Linder, Rhema; Pena, Alyssa; Ragan, Eric D.

2018-01-01

We present an analytic provenance data repository that can be used to study human analysis activity, thought processes, and software interaction with visual analysis tools during exploratory data analysis. We conducted a series of user studies involving exploratory data analysis scenario with textual and cyber security data. Interactions logs, think-alouds, videos and all coded data in this study are available online for research purposes. Analysis sessions are segmented in multiple sub-task ...

Nuclear data for proton activation analysis

Energy Technology Data Exchange (ETDEWEB)

Mukhammedov, S; Vasidov, A [Institute of Nuclear Physics of Academy of Sciences of Uzbekistan, 702132 Ulugbek, Tashkent (Uzbekistan); Comsan, M N.H. [Nuclear Research Centre, Inshas Cyclotron Facility, AEA 13759 Cairo (Egypt)

2000-11-15

The activation analysis with charged particles (ChPAA), as well as proton activation analysis (PAA), mainly requires separately irradiation of thick (thicker than the range of particles) samples and standard. Therefore for simplicity of determination of traces of chemical elements by instrumental PAA the absolute activity of the radionuclides must be known. Consequently we compilated data for nuclear decays (half life, radiation energy and intensity, type of decay, saturation factor), for nuclear reactions (excitation function, threshold energy, Q-value, yields of radionuclides), for the element under study (natural isotopic abundance of the nuclide, which yields the nuclear reaction considered, molar mass), stopping power of the irradiated material and the range of the particle that are used in the calculation of the absolute activity of the radionuclides and for the resolution of a nuclear interference problems of PAA. These data are tabulated. The tables of the radionuclides are presented in dependence on increasing atomic number and radiation energy as well as on methods of the radionuclide formation. The thick target yields of analytical radionuclides are presented versus particle energy.

Nuclear data for proton activation analysis

International Nuclear Information System (INIS)

Mukhammedov, S.; Vasidov, A.; Comsan, M.N.H.

2000-01-01

The activation analysis with charged particles (ChPAA), as well as proton activation analysis (PAA), mainly requires separately irradiation of thick (thicker than the range of particles) samples and standard. Therefore for simplicity of determination of traces of chemical elements by instrumental PAA the absolute activity of the radionuclides must be known. Consequently we compilated data for nuclear decays (half life, radiation energy and intensity, type of decay, saturation factor), for nuclear reactions (excitation function, threshold energy, Q-value, yields of radionuclides), for the element under study (natural isotopic abundance of the nuclide, which yields the nuclear reaction considered, molar mass), stopping power of the irradiated material and the range of the particle that are used in the calculation of the absolute activity of the radionuclides and for the resolution of a nuclear interference problems of PAA. These data are tabulated. The tables of the radionuclides are presented in dependence on increasing atomic number and radiation energy as well as on methods of the radionuclide formation. The thick target yields of analytical radionuclides are presented versus particle energy

Modulation of urinary bladder innervation: TRPV1 and botulinum toxin A.

Science.gov (United States)

Charrua, Ana; Avelino, António; Cruz, Francisco

2011-01-01

The persisting interest around neurotoxins such as vanilloids and botulinum toxin (BoNT) derives from their marked effect on detrusor overactivity refractory to conventional antimuscarinic treatments. In addition, both are administered by intravesical route. This offers three potential advantages. First, intravesical therapy is an easy way to provide high concentrations of pharmacological agents in the bladder tissue without causing unsuitable levels in other organs. Second, drugs effective on the bladder, but inappropriate for systemic administration, can be safely used as it is the case of vanilloids and BoNT. Third, the effects of one single treatment might be extremely longlasting, contributing to render these therapies highly attractive to patients despite the fact that the reasons to the prolonged effect are still incompletely understood. Attractive as it may be, intravesical pharmacological therapy should still be considered as a second-line treatment in patients refractory to conventional oral antimuscarinic therapy or who do not tolerate its systemic side effects. However, the increasing off-label use of these neurotoxins justifies a reappraisal of their pharmacological properties.

Neutron activation analysis for antimetabolites. [in food samples

Science.gov (United States)

1973-01-01

Determination of metal ion contaminants in food samples is studied. A weighed quantity of each sample was digested in a concentrated mixture of nitric, hydrochloric and perchloric acids to affect complete solution of the food products. The samples were diluted with water and the pH adjusted according to the specific analysis performed. The samples were analyzed by neutron activation analysis, polarography, and atomic absorption spectrophotometry. The solid food samples were also analyzed by neutron activation analysis for increased sensitivity and lower levels of detectability. The results are presented in tabular form.

Mobile health: a synopsis and comment on "Increasing physical activity with mobile devices: a meta-analysis".

Science.gov (United States)

Johnston, Winter; Hoffman, Sara; Thornton, Louise

2014-03-01

We offer a synopsis and commentary on J. Fanning and colleagues' article "Increasing Physical Activity with Mobile Devices: A Meta-Analysis" published in the Journal of Medical Internet Research. Although regular physical activity has a range of benefits, very few adults in the USA meet recommended guidelines for daily physical activity. The meta-analysis of Fanning et al. (2012) aimed to synthesize the results of research using mobile devices to increase physical activity. Their review identified 11 studies that used mobile technologies, including short message service (SMS), apps, or personal digital assistant (PDA) to improve physical activity behaviors among participants. Fanning et al. conclude that while literature in this area is limited to date, there is initial support for the efficacy of mobile-based interventions for improving physical activity. Included studies varied greatly, and the majority used only SMS to influence physical behaviors, meaning generalization of results to other forms of mobile technologies may be premature. This review does, however, provide a foundation for understanding how mobile-based interventions may be used efficaciously for the development of future interventions to improve health behaviors.

Studies in heavy ion activation analysis Pt. 4

International Nuclear Information System (INIS)

Lass, B.D.; Ojo, J.F.; Schweikert, E.A.

1980-01-01

The use of 7 MeV 6 Li + for heavy ion activation analysis was investigated. A survey of reactions, involving targets of lithium through oxygen inclusive, were studied for production of β + radioactivation products with half-lives of 10 1 -10 5 seconds. Specific activities for all reactions under the experimental conditions are reported and their use for analysis is assessed. (author)

Nuclear activation analysis work at Analytical Chemistry Division: an overview

International Nuclear Information System (INIS)

Verma, R.; Swain, K.K.; Remya Devi, P.S.; Dalvi, Aditi A.; Ajith, Nicy; Ghosh, M.; Chowdhury, D.P.; Datta, J.; Dasgupta, S.

2016-04-01

Nuclear activation analysis using neutron and charged particles is used routinely for analysis and research at Analytical Chemistry Division (ACD), Bhabha Atomic Research Centre (BARC). Neutron activation analysis at ACD, BARC, Mumbai, India has been pursued since late fifties using Apsara, CIRUS, Dhruva and Critical facility Research reactors, 239 Pu-Be neutron source and neutron generator. Instrumental, Radiochemical, Chemical and Derivative neutron activation analysis approaches are adopted depending on the analyte and the matrix. Large sample neutron activation analysis as well as k 0 -based internal monostandard neutron activation analysis is also used. Charged particle activation analysis at ACD, Variable Energy Cyclotron Centre (VECC), Kolkata started in late eighties and is being used for industrial applications and research. Proton, alpha, deuteron and heavy ion beams from 224 cm room temperature Variable Energy Cyclotron are used for determination of trace elements, measurement of excitation function, thin layer activation and preparation of endohedral fullerenes encapsulated with radioactive isotopes. Analytical Chemistry Division regularly participates in Inter and Intra laboratory comparison exercises conducted by various organizations including International Atomic Energy Agency (IAEA) and the results invariably include values obtained by neutron activation analysis. (author)

Neutron activation analysis: principle and methods

International Nuclear Information System (INIS)

Reddy, A.V.R.; Acharya, R.

2006-01-01

Neutron activation analysis (NAA) is a powerful isotope specific nuclear analytical technique for simultaneous determination of elemental composition of major, minor and trace elements in diverse matrices. The technique is capable of yielding high analytical sensitivity and low detection limits (ppm to ppb). Due to high penetration power of neutrons and gamma rays, NAA experiences negligible matrix effects in the samples of different origins. Depending on the sample matrix and element of interest NAA technique is used non-destructively, known as instrumental neutron activation analysis (INAA), or through chemical NAA methods. The present article describes principle of NAA, different methods and gives a overview some applications in the fields like environment, biology, geology, material sciences, nuclear technology and forensic sciences. (author)

Nondestructive neutron activation analysis of mineral materials. III

International Nuclear Information System (INIS)

Randa, Z.; Benada, J.; Kuncir, J.; Vobecky, M.

1979-01-01

A description is presented of sampling, calibration standards, the method of activation and measurement, activation product identification, the respective nuclear reactions, interfering admixtures, and pre-activation operations. The analysis is described of sulphides, halogenides, oxides, sulphates, carbonates, phosphates, silicates, aluminosilicates, composite minerals containing lanthanides, rocks, tektites, meteors, and plant materials. The method allows determining mainly F, Mg, Al, Ti, V, Nb, Rh, and I which cannot be determined by long-term activation (LTA). It is more sensitive than LTA in determining Ca, Cu, In, and Dy. The analysis takes less time, irradiation and measurement are less costly. The main mineral components are quickly found. (M.K.)

A thermal spike analysis of low energy ion activated surface processes

International Nuclear Information System (INIS)

Gilmore, G.M.; Haeri, A.; Sprague, J.A.

1989-01-01

This paper reports a thermal spike analysis utilized to predict the time evolution of energy propagation through a solid resulting from energetic particle impact. An analytical solution was developed that can predict the number of surface excitations such as desorption, diffusion or chemical reaction activated by an energetic particle. The analytical solution is limited to substrates at zero Kelvin and to materials with constant thermal diffusivities. These limitations were removed by developing a computer numerical integration of the propagation of the thermal spike through the solid and the subsequent activation of surface processes

Analysis of the effectiveness of moderate levels of physical activity to reduce the risk of cardiovascular disease, A Meta-analysis

Directory of Open Access Journals (Sweden)

Christian Martin Garcia

2014-12-01

Full Text Available Objectives: a. The determination of the efficacy of physical activity in reducing the risk of cardiovascular disease; b. The Analysis of the relative changes in the levels of cardiovascular disease risk according to different intensities of physical activity (low-moderate. Methodology: The search was performed for studies with PUBMED data base. Then, the mean effect size of the studies included in the meta-analysis was calculated and Egger's test was applied to rule out any possible publication bias. Upon detection of heterogeneity, we proceeded to an analysis of the moderating variables. Results: A mean effect size of 0.762 (95% confidence interval 0678-0857 was obtained. Then The Egger test was applied which yielded a p-value of 0.67 (CI 0.95, such that the absence of publication bias was confirmed. The analysis of the moderating variables determined that the ensuing years (p = 0.000, 95% CI and the countries of study (p = 0.0096; 95% CI in part explain the heterogeneity detected. Conclusion: It can be concluded that the practice of physical activity at moderate intensities provides a protective effect on the individuals who make physical activity by reducing the risk these individuals to cardiovascular diseases.

Trace element analysis of common salt using neutron activation analysis

International Nuclear Information System (INIS)

Usman, K.

1993-01-01

Instrumental Fast Neutron Activation Analysis (IFNAA) technique has been used in the qualitative and quantitative determination of the impurity elements in common salt. Samples of the different types of common salt processed in Nigeria and some of those imported into the country were used. The type A711 KAMAN neutron generator and a high-purity Germanium (HpGe) gamma spectrometer available at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria has been used. The ORTEC ADCAM 100 Emulation Software (Maestro) was used in the qualitative measurement of the detected elements. The G.R.G Activation Analysis System by G. R. Gilmore, 1987, was used in the quantitative determination of the elements detected by relative method. Aluminium and arsenic were detected and measured

A file of reference data for multiple-element neutron activation analysis

International Nuclear Information System (INIS)

Kabina, L.P.; Kondurov, I.A.; Shesterneva, I.M.

1983-12-01

Data needed for planning neutron activation analysis experiments and processing their results are given. The decay schemes of radioactive nuclei formed in irradiation with thermal neutrons during the (n,γ) reaction taken from the international ENSDF file are used for calculating the activities of nuclei and for drawing up an optimum table for identifying gamma lines in the spectra measured. (author)

Neutron activation analysis of atmospheric aerosol

International Nuclear Information System (INIS)

Obrusnik, I.

1986-01-01

Neutron activation analysis (NAA) is a modern analytical method well suited for the analysis of atmospheric aerosols. Particular steps of the NAA procedure and especially different types of aerosol sampling and sample preparation for analysis are discussed in detail. Several possible NAA techniques are described and the advantages of a purely instrumental technique with short and long irradiation are pointed out. Important performance characteristics of the NAA method such as precision, accuracy, sensitivity and detection limits are also discussed. Different applications of NAA in environmental studies are reviewed. (author)

Proton activation analysis at the Harvard Cyclotron Laboratory

International Nuclear Information System (INIS)

Sisterson, J.M.; Koehler, A.M.

1984-01-01

High-energy proton activation analysis (PAA), a simple non-destructive technique, has been developed for use as an adjunct to neutron activation analysis. Potential advantages of protons include the ability to achieve very precise localization of the activation volume over a pre-determined depth in the target. To demonstrate the versatility of PAA, results are reported on the measurement of the whole body calcium content in animals and on the determination of the Ca/P molar ratio in small quantities (<50 mg) of chemical and biological samples. The animal experiments demonstrate the ability to achieve a uniform irradiation over a large volume and utilizes large NaI crystals with a special chamber for uniform combined detection efficiency, where the Ca/P molar ratio determination requires a Ge/Li detector and analysis of the resulting gamma ray spectrum. The feasibility is being assessed of using proton beam activation of the eye to measure blood flow in the rabbit choroid, based on earlier work where it was used to measure blood in mouse skeletal tissue. 6 references, 7 figures, 4 tables

Cultural differences in human brain activity: a quantitative meta-analysis.

Science.gov (United States)

Han, Shihui; Ma, Yina

2014-10-01

Psychologists have been trying to understand differences in cognition and behavior between East Asian and Western cultures within a single cognitive framework such as holistic versus analytic or interdependent versus independent processes. However, it remains unclear whether cultural differences in multiple psychological processes correspond to the same or different neural networks. We conducted a quantitative meta-analysis of 35 functional MRI studies to examine cultural differences in brain activity engaged in social and non-social processes. We showed that social cognitive processes are characterized by stronger activity in the dorsal medial prefrontal cortex, lateral frontal cortex and temporoparietal junction in East Asians but stronger activity in the anterior cingulate, ventral medial prefrontal cortex and bilateral insula in Westerners. Social affective processes are associated with stronger activity in the right dorsal lateral frontal cortex in East Asians but greater activity in the left insula and right temporal pole in Westerners. Non-social processes induce stronger activity in the left inferior parietal cortex, left middle occipital and left superior parietal cortex in East Asians but greater activations in the right lingual gyrus, right inferior parietal cortex and precuneus in Westerners. The results suggest that cultural differences in social and non-social processes are mediated by distinct neural networks. Moreover, East Asian cultures are associated with increased neural activity in the brain regions related to inference of others' mind and emotion regulation whereas Western cultures are associated with enhanced neural activity in the brain areas related to self-relevance encoding and emotional responses during social cognitive/affective processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Kinetic and Thermodynamic Analysis of Acetyl-CoA Activation of Staphylococcus aureus Pyruvate Carboxylase.

Science.gov (United States)

Westerhold, Lauren E; Bridges, Lance C; Shaikh, Saame Raza; Zeczycki, Tonya N

2017-07-11

Allosteric regulation of pyruvate carboxylase (PC) activity is pivotal to maintaining metabolic homeostasis. In contrast, dysregulated PC activity contributes to the pathogenesis of numerous diseases, rendering PC a possible target for allosteric therapeutic development. Recent research efforts have focused on demarcating the role of acetyl-CoA, one of the most potent activators of PC, in coordinating catalytic events within the multifunctional enzyme. Herein, we report a kinetic and thermodynamic analysis of acetyl-CoA activation of the Staphylococcus aureus PC (SaPC)-catalyzed carboxylation of pyruvate to identify novel means by which acetyl-CoA synchronizes catalytic events within the PC tetramer. Kinetic and linked-function analysis, or thermodynamic linkage analysis, indicates that the substrates of the biotin carboxylase and carboxyl transferase domain are energetically coupled in the presence of acetyl-CoA. In contrast, both kinetic and energetic coupling between the two domains is lost in the absence of acetyl-CoA, suggesting a functional role for acetyl-CoA in facilitating the long-range transmission of substrate-induced conformational changes within the PC tetramer. Interestingly, thermodynamic activation parameters for the SaPC-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA. Our results also reveal the possibility that global conformational changes give rise to observed species-specific thermodynamic activation parameters. Taken together, our kinetic and thermodynamic results provide a possible allosteric mechanism by which acetyl-CoA coordinates catalysis within the PC tetramer.

Study on neutron activation analysis

International Nuclear Information System (INIS)

Chung, Yong Sam; Cho, Seung Yeon

1993-01-01

Environmental samples were analyzed quantitatively by neutron activation analysis using high resolution γ-ray spectrometry. The accuracy and precision of the method were checked by the analysis of reference materials, Urban Particulate Matter (NBS SRM 1648) and Coalfly ash (NBS SRM 1633a). Airborne particulates collected for 6 months with low volume air sampler at the outer area of Seoul were analyzed as the start of full scale airborne particulates research. We analyzed 19 trace elements from the samples and the NAA method was confirmed to be utilized for environmental pollution research. (Author)

Elemental analysis using instrumental neutron activation analysis and inductively coupled plasma atomic emission spectrometry: a comparative study

International Nuclear Information System (INIS)

Chung, Yong Sam; Choi, Kwang Soon; Moon, Jong Hwa; Kim, Sun Ha; Lim, Jong Myoung; Kim, Young Jin; Quraishi, Shamshad Begum

2003-05-01

Elemental analyses for certified reference materials were carried out using instrumental neutron activation analysis and inductively coupled plasma-atomic emission spectrometry. Five Certified Reference Materials (CRM) were selected for the study on comparative analysis of environmental samples. The CRM are Soil (NIST SRM 2709), Coal fly ash (NIST SRM 1633a), urban dust (NIST SRM 1649a) and air particulate on filter media (NIST SRM 2783 and human hair (GBW 09101)

High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Valachis, Antonis [Dept. of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala,, (Sweden)], e-mail: Valachis@hotmail.com, Antonis.Valachis@akademiska.uu.se; Nearchou, Andreas [Dept, of Oncology, Maelarsjukhuset., Eskilstuna (Sweden); Univ. of Uppsala., Uppsala (Sweden)

2013-08-15

Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity.

High versus low radioiodine activity in patients with differentiated thyroid cancer - A meta-analysis

International Nuclear Information System (INIS)

Valachis, Antonis; Nearchou, Andreas

2013-01-01

Background: The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design: A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results: Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85 - 1.04, p-value 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72 - 1.06, p-value 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93 - 1.07, p-value 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion: Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity

Neutron activation analysis for environmental sample in Thailand

International Nuclear Information System (INIS)

Busamongkol, Arporn; Nouchpramool, Sunun; Bunprapob, Supamatthree; Sumitra, Tatchai

2003-01-01

Neutron Activation Analysis has been applied for the trace elements analysis in environmental samples. Thirty three samples of airborne particulate were collected every week at Ongkharak Nuclear Research Center (ONRC) during the period of June 1998 to March 1999. The Ti, I, Mg, Na, V, K, Cl, Al, Mn, Ca, As, Sm, Sb, Br, La, Ce, Th, Cr, Cs, Sc, Rb, Fe, Zn and Co were analyzed by Neutron Activation Analysis utilizing 2 MW TRIGA MARK III research reactor. The certified reference materials 1632a and 1633a from National Bureau of Standard were select as standard. (author)

Activation analysis by filtered neutrons. Preliminary investigation

International Nuclear Information System (INIS)

Skarnemark, G.; Rodinson, T.; Skaalberg, M.; Tokay, R.K.

1986-01-01

In order to investigate if measuring sensibility and precision by epithermal neutron activation analysis may be improved, different types of geological and biologic test samples were radiated. The test samples were enclosed in an extra filter of tungsten or sodium in order to reduce the flux of those neutrons that otherwise would induce interfering activity in the sample. The geological test samples consist of granites containing lanthanides which had been crushed in tung- sten carbide grinder. Normally such test samples show a interferins 1 87W-activity. By use of a tungsten filter the activity was reduced by up to 60%, which resulted in a considerable improvement of sensibility and precision of the measurement. The biologic test samples consisted of evaporated urine from patients treated with the cell poison cis-platinol. A reliable method to measure the platinum content has not existed so far. This method, however, enables platinum contents as low as about 0.1 ppm to be determined which is quite adequate. To sum up this preliminary study has demonstrated that activation analysis using filtered neutrons, correctly applied, is a satisfactory method of reducing interferences without complicated and time-consuming chemical separation procedures. (O.S.)

Activated sludge characterization through microscopy: A review on quantitative image analysis and chemometric techniques

Energy Technology Data Exchange (ETDEWEB)

Mesquita, Daniela P. [IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Amaral, A. Luís [IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Instituto Politécnico de Coimbra, ISEC, DEQB, Rua Pedro Nunes, Quinta da Nora, 3030-199 Coimbra (Portugal); Ferreira, Eugénio C., E-mail: ecferreira@deb.uminho.pt [IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal)

2013-11-13

Graphical abstract: -- Highlights: •Quantitative image analysis shows potential to monitor activated sludge systems. •Staining techniques increase the potential for detection of operational problems. •Chemometrics combined with quantitative image analysis is valuable for process monitoring. -- Abstract: In wastewater treatment processes, and particularly in activated sludge systems, efficiency is quite dependent on the operating conditions, and a number of problems may arise due to sludge structure and proliferation of specific microorganisms. In fact, bacterial communities and protozoa identification by microscopy inspection is already routinely employed in a considerable number of cases. Furthermore, quantitative image analysis techniques have been increasingly used throughout the years for the assessment of aggregates and filamentous bacteria properties. These procedures are able to provide an ever growing amount of data for wastewater treatment processes in which chemometric techniques can be a valuable tool. However, the determination of microbial communities’ properties remains a current challenge in spite of the great diversity of microscopy techniques applied. In this review, activated sludge characterization is discussed highlighting the aggregates structure and filamentous bacteria determination by image analysis on bright-field, phase-contrast, and fluorescence microscopy. An in-depth analysis is performed to summarize the many new findings that have been obtained, and future developments for these biological processes are further discussed.

The value of psychosocial group activity in nursing education: A qualitative analysis.

Science.gov (United States)

Choi, Yun-Jung

2018-05-01

Nursing faculty often struggle to find effective teaching strategies for nursing students that integrate group work into nursing students' learning activities. This study was conducted to evaluate students' experiences in a psychiatric and mental health nursing course using psychosocial group activities to develop therapeutic communication and interpersonal relationship skills, as well as to introduce psychosocial nursing interventions. A qualitative research design was used. The study explored nursing students' experiences of the course in accordance with the inductive, interpretative, and constructive approaches via focus group interviews. Participants were 17 undergraduate nursing students who registered for a psychiatric and mental health nursing course. The collected data were analyzed by qualitative content analysis. The analysis resulted in 28 codes, 14 interpretive codes, 4 themes (developing interpersonal relationships, learning problem-solving skills, practicing cooperation and altruism, and getting insight and healing), and a core theme (interdependent growth in self-confidence). The psychosocial group activity provided constructive opportunities for the students to work independently and interdependently as healthcare team members through reflective learning experiences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physical activity and risk of pancreatic cancer: a systematic review and meta-analysis.

Science.gov (United States)

Behrens, Gundula; Jochem, Carmen; Schmid, Daniela; Keimling, Marlen; Ricci, Cristian; Leitzmann, Michael F

2015-04-01

Physical activity may prevent pancreatic cancer by regulating body weight and decreasing insulin resistance, DNA damage, and chronic inflammation. Previous meta-analyses found inconsistent evidence for a protective effect of physical activity on pancreatic cancer but those studies did not investigate whether the association between physical activity and pancreatic cancer varies by smoking status, body mass index (BMI), or level of consistency of physical activity over time. To address these issues, we conducted an updated meta-analysis following the PRISMA guidelines among 30 distinct studies with a total of 10,501 pancreatic cancer cases. Random effects meta-analysis of cohort studies revealed a weak, statistically significant reduction in pancreatic cancer risk for high versus low levels of physical activity (relative risk (RR) 0.93, 95 % confidence interval (CI) 0.88-0.98). By comparison, case-control studies yielded a stronger, statistically significant risk reduction (RR 0.78, 95 % CI 0.66-0.94; p-difference by study design = 0.07). When focusing on cohort studies, physical activity summary risk estimates appeared to be more pronounced for consistent physical activity over time (RR 0.86, 95 % CI 0.76-0.97) than for recent past physical activity (RR 0.95, 95 % CI 0.90-1.01) or distant past physical activity (RR 0.95, 95 % CI 0.79-1.15, p-difference by timing in life of physical activity = 0.36). Physical activity summary risk estimates did not differ by smoking status or BMI. In conclusion, physical activity is not strongly associated with pancreatic cancer risk, and the relation is not modified by smoking status or BMI level. While overall findings were weak, we did find some suggestion of potential pancreatic cancer risk reduction with consistent physical activity over time.

Recent applications of neutron activation analysis at Lucas Heights

International Nuclear Information System (INIS)

Fardy, J.J.

1978-01-01

The use of neutron activation analysis to determine key elemental distribution patterns in samples from both the energy industry and health science field is summarised. Instrumental neutron activation analysis has successfully measured simultaneously more than twenty elements in a sample of brown coal from Victoria, black coal from New South Wales and samples from the product stream of ACIRL's batch autoclave, solvent-refined, coal hydrogenation process. Four gallstones removed from the same gallbladder have been examined instrumentally by neutron activation analysis. A total of sixteen trace elements were detected with concentrations in the range 0.8 ng g -1 for gold to 7,800 μg g -1 for calcium

Activation Analysis of Aluminium

Energy Technology Data Exchange (ETDEWEB)

Brune, Dag

1961-01-15

An analysis of pure aluminium alloyed with magnesium was per- formed by means of gamma spectrometry , Chemical separations were not employed. The isotopes to be determined were obtained in conditions of optimum activity by suitably choosing the time of irradiation and decay. The following elements were detected and measured quantitatively: Iron, zinc, copper, gallium, manganese, chromium, scandium and hafnium.

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

Science.gov (United States)

Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

2015-08-01

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

Development of neutron activation analysis software

International Nuclear Information System (INIS)

Wang Liyu

1987-10-01

The software for quantitative neutron activation analysis was developed to run under the MS/DOS operating system. The programmes of the IBM/SPAN include: spectra file transfer from and to a Canberra Series 35 multichannel analyzer, spectrum evaluation routines, calibration subprogrammes, and quantitative analysis. The programmes for spectrum analysis include fitting routine for separation of multiple lines by reproducing the peak shape with a combination of Gaussian and exponential terms. The programmes were tested on an IBM/AT-compatible computer. The programmes and the sources are available costfree for the IAEA projects of Technical Cooperation. 7 refs, 3 figs

A Comprehensive Analysis on Wearable Acceleration Sensors in Human Activity Recognition.

Science.gov (United States)

Janidarmian, Majid; Roshan Fekr, Atena; Radecka, Katarzyna; Zilic, Zeljko

2017-03-07

Sensor-based motion recognition integrates the emerging area of wearable sensors with novel machine learning techniques to make sense of low-level sensor data and provide rich contextual information in a real-life application. Although Human Activity Recognition (HAR) problem has been drawing the attention of researchers, it is still a subject of much debate due to the diverse nature of human activities and their tracking methods. Finding the best predictive model in this problem while considering different sources of heterogeneities can be very difficult to analyze theoretically, which stresses the need of an experimental study. Therefore, in this paper, we first create the most complete dataset, focusing on accelerometer sensors, with various sources of heterogeneities. We then conduct an extensive analysis on feature representations and classification techniques (the most comprehensive comparison yet with 293 classifiers) for activity recognition. Principal component analysis is applied to reduce the feature vector dimension while keeping essential information. The average classification accuracy of eight sensor positions is reported to be 96.44% ± 1.62% with 10-fold evaluation, whereas accuracy of 79.92% ± 9.68% is reached in the subject-independent evaluation. This study presents significant evidence that we can build predictive models for HAR problem under more realistic conditions, and still achieve highly accurate results.

a Three-Step Spatial-Temporal Clustering Method for Human Activity Pattern Analysis

Science.gov (United States)

Huang, W.; Li, S.; Xu, S.

2016-06-01

How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time) to four dimensions (space, time and semantics). More specifically, not only a location and time that people stay and spend are collected, but also what people "say" for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The results show that the

Forensic neutron activation analysis - the Japanese scene

International Nuclear Information System (INIS)

Kishi, Tohru.

1986-01-01

The progress of forensic neutron activation analysis/FNAA/ in Japan is described. FNAA began in 1965 and during the past 20 years many cases have been handled; these include determination of toxic materials, comparison examination of physical evidences /e.g.,paints, metal fragments, plastics and inks/ and drug sample differenciation. Neutron activation analysis is applied routinely to the scientific criminal investigation as one of multielement analytical techniques. This paper also discusses these routine works. (author)

Eco-efficiency analysis for intensified production of an active pharmaceutical ingredient : a case study

NARCIS (Netherlands)

Dencic, I.; Ott-Reinhardt, D.; Kralisch, D.; Noel, T.; Meuldijk, J.; Croon, de M.H.J.M.; Hessel, V.; Laribi, Y.; Perrichon, P.

2014-01-01

This article presents results on cost and performance benefit analysis of optimization and intensification activities of a pharmaceutical process. A batch process for the production of a low-volume, high value active pharmaceutical ingredient, developed at Sanofi (France), has been used as a case

Media Portrayals of Hashtag Activism: A Framing Analysis of Canada’s #Idlenomore Movement

OpenAIRE

Derek Moscato

2016-01-01

The confluence of activism and social media - legitimized by efforts such as the Arab Spring and Occupy Movements - represents a growing area of mainstream media focus. Using Canada’s #IdleNoMore movement as a case, this study uses framing theory to better understand how traditional media are representing activism borne of social media such as Twitter, and how such activism can ultimately have an impact in political and public policy debates. A qualitative framing analysis is used to ident...

An activity theory perspective of how scenario-based simulations support learning: a descriptive analysis.

Science.gov (United States)

Battista, Alexis

2017-01-01

The dominant frameworks for describing how simulations support learning emphasize increasing access to structured practice and the provision of feedback which are commonly associated with skills-based simulations. By contrast, studies examining student participants' experiences during scenario-based simulations suggest that learning may also occur through participation. However, studies directly examining student participation during scenario-based simulations are limited. This study examined the types of activities student participants engaged in during scenario-based simulations and then analyzed their patterns of activity to consider how participation may support learning. Drawing from Engeström's first-, second-, and third-generation activity systems analysis, an in-depth descriptive analysis was conducted. The study drew from multiple qualitative methods, namely narrative, video, and activity systems analysis, to examine student participants' activities and interaction patterns across four video-recorded simulations depicting common motivations for using scenario-based simulations (e.g., communication, critical patient management). The activity systems analysis revealed that student participants' activities encompassed three clinically relevant categories, including (a) use of physical clinical tools and artifacts, (b) social interactions, and (c) performance of structured interventions. Role assignment influenced participants' activities and the complexity of their engagement. Importantly, participants made sense of the clinical situation presented in the scenario by reflexively linking these three activities together. Specifically, student participants performed structured interventions, relying upon the use of physical tools, clinical artifacts, and social interactions together with interactions between students, standardized patients, and other simulated participants to achieve their goals. When multiple student participants were present, such as in a

Storage and pre-neutron-activation-analysis treatment for trace-element analysis in urine

International Nuclear Information System (INIS)

Blotcky, A.J.; Rack, E.P.

1985-01-01

The problems regarding storage and pre-neutron-activation-analysis treatment for the elements aluminum, calcium, vanadium, selenium, copper, iodine, zinc, manganese, and magnesium in a urine matrix are reviewed. The type of collection and storage procedure and pre-neutron activation analysis treatment of urine depend on the specific trace element; that is, its inherent physical and chemical properties. Specifically polyethylene in teflon containers are the most suitable for general determinations. Whether any preservative is added would depend upon the stability of the trace element and its tendency for surface adsorption. Preferably, preservatives should contain no radioactivatable elements for maximum efficacy. Freeze drying or packing urine shipments under dry ice needs to be explored on an individual basis. Each pre- or post-neutron activation analysis treatment is specific and optimized for the trace element analyzed

Multi trace element analysis of dry biological materials by neutron activation analysis including a chemical group separation

International Nuclear Information System (INIS)

Weers, C.A.

1980-01-01

The principles of activation analysis and the practical aspects of neutron activation analysis are outlined. The limits which are set to accuracy and precision are defined. The description of the evaporation process is summarised in terms of the half-volume. This quantity is then used to define the resolving power. The formulation is checked by radiotracer experiments. Dried animal blood is used as the testing material. The pretreatment of the samples and (the development of) the destruction-evaporation apparatus is described. Four successive devices were built and tested. The development of the successive adsorption steps with active charcoal, Al 2 O 3 and coprecipitation with Fe(OH) 3 is presented. Seven groups of about 25 elements in total can be determined this way. The results obtained for standard reference materials are summarized and compared with literature data. (Auth.)

INDUSTRIAL/MILITARY ACTIVITY-INITIATED ACCIDENT SCREENING ANALYSIS

Energy Technology Data Exchange (ETDEWEB)

D.A. Kalinich

1999-09-27

Impacts due to nearby installations and operations were determined in the Preliminary MGDS Hazards Analysis (CRWMS M&O 1996) to be potentially applicable to the proposed repository at Yucca Mountain. This determination was conservatively based on limited knowledge of the potential activities ongoing on or off the Nevada Test Site (NTS). It is intended that the Industrial/Military Activity-Initiated Accident Screening Analysis provided herein will meet the requirements of the ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987) in establishing whether this external event can be screened from further consideration or must be included as a design basis event (DBE) in the development of accident scenarios for the Monitored Geologic Repository (MGR). This analysis only considers issues related to preclosure radiological safety. Issues important to waste isolation as related to impact from nearby installations will be covered in the MGR performance assessment.

Activation analysis. A basis for chemical similarity and classification

Energy Technology Data Exchange (ETDEWEB)

Beeck, J OP de [Ghent Rijksuniversiteit (Belgium). Instituut voor Kernwetenschappen

1977-01-01

It is shown that activation analysis is especially suited to serve as a basis for determining the chemical similarity between samples defined by their trace-element concentration patterns. The general problem of classification and identification is discussed. The nature of possible classification structures and their appropriate clustering strategies is considered. A practical computer method is suggested and its application as well as the graphical representation of classification results are given. The possibility for classification using information theory is mentioned. Classification of chemical elements is discussed and practically realized after Hadamard transformation of the concentration variation patterns in a series of samples.

Activation analysis for the IFF system in RAON facility

International Nuclear Information System (INIS)

LEE, Cheol Woo; LEE, Young-Ouk; KIM, Jong Won; KIM, Mijung

2014-01-01

A heavy-ion accelerator facility is under a development in Korea to use in the basic science research and various application areas. In this facility, the In-Flight Fragment (IFF) target and isotope separator has been designed to produce various isotopes and transport the interesting isotopes into the experimental rooms. In this work, activation analysis for the pre-separator was performed in the IFF target room. In this work, activation analysis for the pre-separator was performed for the IFF target system in RAON heavy-ion accelerator facility. At first, radiation source terms were evaluated with the primary beams and target conditions. Using the evaluated source terms, induced activities in all component of pre-separator were calculated. The decay gamma-rays produced after a shutdown was estimated based on the activation analysis and gamma-ray dose rate according to the cooling time was evaluated

Prompt gamma-ray activation analysis (PGAA)

International Nuclear Information System (INIS)

Kern, J.

1996-01-01

The paper deals with a brief description of the principles of prompt gamma-ray activation analysis (PGAA), with the detection of gamma-rays, the PGAA project at SINQ and with the expected performances. 8 figs., 3 tabs., 10 refs

Prompt gamma-ray activation analysis (PGAA)

Energy Technology Data Exchange (ETDEWEB)

Kern, J [Fribourg Univ. (Switzerland). Inst. de Physique

1996-11-01

The paper deals with a brief description of the principles of prompt gamma-ray activation analysis (PGAA), with the detection of gamma-rays, the PGAA project at SINQ and with the expected performances. 8 figs., 3 tabs., 10 refs.

Antipruritic effects of botulinum neurotoxins

DEFF Research Database (Denmark)

Gazerani, Parisa

2018-01-01

This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted. Potent....... Potential mechanisms underlying antipruritic effects will also be discussed and ongoing challenges and unmet needs will be addressed.......This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted...

Speciation analysis of cobalt in foods by high-performance liquid chromatography and neutron activation analysis

International Nuclear Information System (INIS)

Muto, Toshio; Koyama, Motoko

1994-01-01

A combined method by coupling high-performance liquid chromatography (HPLC, as a separation method) with neutron activation analysis (as a detection method) have been applied to the speciation analysis of cobalt in daily foods (e.g. egg, fish and milk). Cobalt species including free cobalt, vitamin B 12 and protein-bound cobalt were separated with a preparative HPLC and a centrifuge. Subsequently, the determination of cobalt in the separated species was made by neutron activation analysis. The results showed that the content of the total cobalt in the foods was found to lie in the range 0.4-11ng/g(0.4-11ppb) based on wet weight. The compositions of free cobalt, vitamin B 12 and protein-bound cobalt were ranged 16-43%, 55-73%, 2.3-17%, respectively. These experimental evidences suggest that the combination of HPLC and neutron activation analysis is expected to be a useful tool for speciation analysis of trace elements in biological as well as environmental materials. (author)

Neutron activation analysis of artefacts

International Nuclear Information System (INIS)

Mohd Suhaimi Hamzah; Shamsiah Abd Rahman

2004-01-01

The paper discussed the utilization of neutron activation analysis in this field. NAA, an analytical technique which analyzing the elements in the sample without any chemical treatment. It is sensitive and accurate. Archaeological objects i.e. ceramics, historical building materials, metals, etc can be analyze with this technique. The analysis results were presented in form of characterization of the artefacts in chemical profiles, which can present the information of the origin of the artefacts as well as it originality. (Author)

Antioxidant activity of Costa Rican propolis: a multivariate analysis approach

International Nuclear Information System (INIS)

Umana Rojas, Eduardo; Solado, Godofredo; Tamayo-Castillo, Giselle

2013-01-01

Propolis is produced by Apis mellifera bees from resins of plants that are found around the apiary. The chemical composition is highly variable and Costa Rica has reported without studies of characterization to define the types of propolis in the country. 119 samples were collected from beekeeping areas of the country. The spectrum of 1 H-NMR and its antioxidant activity against DPPH radical were measured. The spectra have been divided into 243 blocks of 0,04 ppm and processed with the Minitab software for multivariate analysis. 99 of the samples collected were used for construction of models for the valuation of the predictive ability of the model have been used coefficients of determination (R 2 ) of prediction by the software and the remaining 20 samples. The existence of three types of propolis with chemically different metabolomes were determined by principal component analysis (PCA). A prediction model was constructed by analysis of partial least squares (PLS). The prediction model has allowed to classify a propolis according to the level of antioxidant activity (AAO), high (type I and II) or low (type III) from the spectrum of 1 H-NMR. The R 2 has been 0.88 and R 2 prediction of 0, 718 for new samples. The nconiferyl benzoate of group I and nemorosone of the group II as two discriminated antioxidants among the groups I and II were isolated and high concentration levels of these compounds have been differentiated with respect to type III. This has allowed the construction of a linear discriminant model with a success rate of 100% for the samples used for formulation and 92,9 for the prediction of different samples. The classification systems could be applied to the standardization of the quality of propolis from Costa Rica for future medicinal or cosmetic applications that take advantage of its antioxidant properties. Also, the methylated derivative has isolated and identified of the nconiferyl benzoate thereof propolis than was obtained his counterpart

A Comprehensive Analysis on Wearable Acceleration Sensors in Human Activity Recognition

Directory of Open Access Journals (Sweden)

Majid Janidarmian

2017-03-01

Full Text Available Sensor-based motion recognition integrates the emerging area of wearable sensors with novel machine learning techniques to make sense of low-level sensor data and provide rich contextual information in a real-life application. Although Human Activity Recognition (HAR problem has been drawing the attention of researchers, it is still a subject of much debate due to the diverse nature of human activities and their tracking methods. Finding the best predictive model in this problem while considering different sources of heterogeneities can be very difficult to analyze theoretically, which stresses the need of an experimental study. Therefore, in this paper, we first create the most complete dataset, focusing on accelerometer sensors, with various sources of heterogeneities. We then conduct an extensive analysis on feature representations and classification techniques (the most comprehensive comparison yet with 293 classifiers for activity recognition. Principal component analysis is applied to reduce the feature vector dimension while keeping essential information. The average classification accuracy of eight sensor positions is reported to be 96.44% ± 1.62% with 10-fold evaluation, whereas accuracy of 79.92% ± 9.68% is reached in the subject-independent evaluation. This study presents significant evidence that we can build predictive models for HAR problem under more realistic conditions, and still achieve highly accurate results.

Computer-automated neutron activation analysis system

International Nuclear Information System (INIS)

Minor, M.M.; Garcia, S.R.

1983-01-01

An automated delayed neutron counting and instrumental neutron activation analysis system has been developed at Los Alamos National Laboratory's Omega West Reactor (OWR) to analyze samples for uranium and 31 additional elements with a maximum throughput of 400 samples per day. 5 references

Application of activation techniques to biological analysis

International Nuclear Information System (INIS)

Bowen, H.J.M.

1981-01-01

Applications of activation analysis in the biological sciences are reviewed for the period of 1970 to 1979. The stages and characteristics of activation analysis are described, and its advantages and disadvantages enumerated. Most applications involve activation by thermal neutrons followed by either radiochemical or instrumental determination. Relatively little use has been made of activation by fast neutrons, photons, or charged particles. In vivo analyses are included, but those based on prompt gamma or x-ray emission are not. Major applications include studies of reference materials, and the elemental analysis of plants, marine biota, animal and human tissues, diets, and excreta. Relatively little use of it has been made in biochemistry, microbiology, and entomology, but it has become important in toxicology and environmental science. The elements most often determined are Ag, As, Au, Br, Ca, Cd, Cl, Co, Cr, Cs, Cu, Fe, Hg, I, K, Mn, Mo, Na, Rb, Sb, Sc, Se, and Zn, while few or no determinations of B, Be, Bi, Ga, Gd, Ge, H, In, Ir, Li, Nd, Os, Pd, Pr, Pt, Re, Rh, Ru, Te, Tl, or Y have been made in biological materials

Proceedings of the specialist research meeting on 'the latest study on analysis of trace amount of elements using activation analysis and the results and future prospects of activation analysis using KUR'

International Nuclear Information System (INIS)

Ebihara, Mitsuru; Shibata, Seiichi; Sekimoto, Shun

2014-01-01

This Specialist Research Meeting report is the summary of the lectures that were delivered at the Specialist Research Meeting of Kyoto University Reactor Research Institute on January 25, 2013 and October 30, 2013. These meetings were held under the subtitles of 'Current state of trace element analysis using activation analysis' and 'Achievements and future prospects of activation analysis using Kyoto University research reactor (KUR)', respectively. At the former meeting, 14 speeches were delivered including the following: (1) introduction of Australia Nuclear Science and Technology Organisation (ANSTO), (2) determination of element concentration in the hairs in frequent ALS (amyotrophic lateral sclerosis) occurrence zones, (3) effects of vegetation on the acid neutralizing capacity of soil, (4) activation analysis of geological samples, and (5) current situation of KUR. At the latter meeting, 15 speeches were delivered including the following: (1) neutron activation analysis of iron meteorites and Chinese herbal medicines / herbs, (2) neutron activation analysis at KUR using IAEA-k0 method, (3) current state of KUR, (4) development and applications of automatic prompt gamma-ray analysis equipment. (A.O.)

Optimizing human activity patterns using global sensitivity analysis.

Science.gov (United States)

Fairchild, Geoffrey; Hickmann, Kyle S; Mniszewski, Susan M; Del Valle, Sara Y; Hyman, James M

2014-12-01

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies

Directory of Open Access Journals (Sweden)

Christine Rasetti-Escargueil

2017-10-01

Full Text Available The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies. For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs. The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans.

Conference on instrumental activation analysis - IAA 89

International Nuclear Information System (INIS)

Vobecky, M.; Obrusnik, I.

1989-05-01

The proceedings contain 40 abstracts of papers all of which have been incorporated in INIS. The papers were centred on the applications of radioanalytical methods, especialy on neutron activation analysis, X-ray fluorescence analysis, PIXE analysis and tracer techniques in biology, medicine and metallurgy, measuring instruments including microcomputers, and data processing methods. (J.P.)

Epithermal neutron activation analysis for studying the environment

International Nuclear Information System (INIS)

Frontas'eva, M.V.; Steinnes, E.

1997-01-01

Epithermal neutron activation analysis (ENAA) has certain advantages over the conventional instrumental analysis (INAA) in terms of improvement in precision and lowering of detection limits, reduction of high matrix activity and fission interferences if any. The current status and the applications of ENAA to environmental samples are reviewed. Experience in the use of ENAA in the monitoring of atmospheric depositions by means of moss-biomonitors at pulsed fast reactor IBR-2 in Dubna is summarized. INAA has shown to be useful for a number of sample types of interest in environmental studies, and should find more extensive use in this area. Analysis of airborne particulate matter is a case where ENAA should be particularly useful. A similar case where ENAA has shown strong performance is in the analysis of mosses used as biomonitors of atmospheric deposition, where 45 elements were determined. In this and other cases, however, induction-coupled plasma mass spectrometry is a very strong competitor, offering data for even more elements. A comparison of ENAA and ICP-MS for moss analysis is presented, and cases where ENAA is unique are discussed

Recurrence analysis of ant activity patterns.

Directory of Open Access Journals (Sweden)

Felipe Marcel Neves

Full Text Available In this study, we used recurrence quantification analysis (RQA and recurrence plots (RPs to compare the movement activity of individual workers of three ant species, as well as a gregarious beetle species. RQA and RPs quantify the number and duration of recurrences of a dynamical system, including a detailed quantification of signals that could be stochastic, deterministic, or both. First, we found substantial differences between the activity dynamics of beetles and ants, with the results suggesting that the beetles have quasi-periodic dynamics and the ants do not. Second, workers from different ant species varied with respect to their dynamics, presenting degrees of predictability as well as stochastic signals. Finally, differences were found among minor and major caste of the same (dimorphic ant species. Our results underscore the potential of RQA and RPs in the analysis of complex behavioral patterns, as well as in general inferences on animal behavior and other biological phenomena.

Betatron activation analysis of cupriferous flotation pulp

International Nuclear Information System (INIS)

Kaminski, R.; Matenko, J.; Mencel, J.; Janiczek, J.; Kielsznia, J.

1974-01-01

A method of copper determination in cupriferous flotation pulp by photo-activation analysis using betatron and another equipments of existent ''analytical line'' intended for copper determination in dry samples has been described. An activation has been achieved with 14.9 MeV γ-photons. The excitation activity was investigated by using two scintillation detectors and a fast coincidence circuit with resolution time 80 ns. The precision of method was determined as +- 4.25% in 0.95 confidence level for pulp with concentration 5% Cu and +- 24% for 0.06% Cu. (author)

Neutron Activation analysis of waste water

International Nuclear Information System (INIS)

Hernandez H, V.

1997-01-01

An instrumental neutron activation analysis for the simultaneous determination of chlorine, bromine, sodium, manganese, cobalt, copper, chromium, zinc, nickel, antimony and iron in waste water is described. They were determined in waste water samples under normal conditions by non-destructive neutron activation simultaneously using a suitable monostandard method. Standardized water samples were used and irradiated in polyethylene ampoules at a neutron flux of 10 13 cm -2 s -1 for periods of 1 minute, 1 and 10 hours. A Ge hyperpure detector was used for your activity determination, with count times of 60, 180, 300 and 600 seconds. The obtained results show than the method can be utilized for the determination of this elements without realize anything previous treatment of the samples. (Author)

Analysis by neutronic activation of the active principles of MIBI

International Nuclear Information System (INIS)

Capote Rodriguez, G.; Hernandez Rivero, A.T.; Moreno Bermudez, J.; Ribeiro Guevara, S.; Molina Insfran, J.; Perez Zayas, G.

1997-01-01

In the present job the obtained results are shown through the application of an analysis by neutronic activation, in their instrumental variant, for the determination of the elementary composition of three Cuban radiopharmaceuticals. (author) [es

Teenage girls' experience of the determinants of physical activity promotion: A theory-based qualitative content analysis.

Science.gov (United States)

Borhani, Mahboobe; Sadeghi, Roya; Shojaeizadeh, Davoud; Harandi, Tayebeh Fasihi; Vakili, Mohammad Ali

2017-08-01

The progress of technology in developed countries has changed lifestyles to sedentary and has increased non-communicable diseases. Identifying factors affecting patterns of physical activity among adolescents is valuable and it is important to change these pattern. This study aimed to explore teenage girls' experiences regarding the determinants of physical activity promotion based on Pender's Health Promotion Model. This qualitative study is a content analysis research on the girls of three high schools in Minoodasht city for six months from September 2015 until the end of February 2016. The data were obtained by focused group discussions and semi-structured in-depth interviews from 48 girls ranging from 15 to 18 years old and six teachers. Data analysis was done using theory-driven qualitative content analysis. Data analysis resulted in a total number of 53 primary codes which were classified in the six predetermined classifications of Pender's Health Promotion Model (Perceived benefits, perceived barriers, perceived self-efficacy of physical activity behavior, feelings related to physical activity behavior, interpersonal and situational influencers). The results showed that two classifications (perceived barriers, and situational influencers) were considered more important than other classifications in reducing levels of physical activity in adolescent girls and also high self-efficacy for promoting physical activity in adolescents. The results obtained from this study specified the determinants affecting the promotion of physical activity among adolescent girls and can help the planners to choose the most appropriate methods and strategies in order to promote physical activity among adolescent girls and to prevent chronic non-communicable diseases in this age group and gender.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples.

Science.gov (United States)

Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B

2015-11-26

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A-G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as "category A" bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Activation analysis in the Americas: recent and future perspectives

International Nuclear Information System (INIS)

Guinn, V.P.

1984-01-01

A total of 243 publications in the field of nuclear activation analysis and its applications during the period of 1977 through mid-1983, from laboratories in North, Central, and South America were reviewed. Various aspects of these populations are treated statistically, for indication of trends, and 146 of these are cited as publications that illustrate the extent of usage of various special forms of the nuclear activation analysis method (e.g., cyclic INAA, prompt-gamma INAA, epithermal NAA, the delayed-neutron method, the use of pre-irradiation chemical separations, etc.) - or that illustrate applications in such fields as archaeology, geochemistry, environmental chemistry, medicine, industry, and forensic chemistry. The overall conclusion is that the method of nuclear activation analysis continues to flourish in this region

Natural gold composition studied by proton activation analysis (PAA)

International Nuclear Information System (INIS)

Cojocaru, V.; Badica, T.; Popescu, I.V.

2003-01-01

The minor and trace element concentration of natural gold is essential for provenance studies of gold archaeological artifacts. In this work proton activation analysis is used in order to find what elements can be put into evidence in natural gold. For that purpose some gold nuggets from Romania were used. It was found that PAA is a good supplemental method to neutron activation analysis. (authors)

Fast neutron activation analysis of Kalewa (Myanmar) coal

Energy Technology Data Exchange (ETDEWEB)

Myint, U; Naing, W [Yangon Univ. (Myanmar). Dept. of Chemistry

1994-06-01

Aluminium, silicon, copper, iron, magnesium and sulfur in Kalewa (Myanmar) coal were determined by fast neutron activation analysis. For activation a KAMAN A-710 Neutron Generator was used. Kalewa coal was found to be low in sulfur and relatively rich in iron. (author) 2 refs.; 1 fig.; 1 tab.

Fast neutron activation analysis of Kalewa (Myanmar) coal

International Nuclear Information System (INIS)

Myint, U.; Naing, W.

1994-01-01

Aluminium, silicon, copper, iron, magnesium and sulfur in Kalewa (Myanmar) coal were determined by fast neutron activation analysis. For activation a KAMAN A-710 Neutron Generator was used. Kalewa coal was found to be low in sulfur and relatively rich in iron. (author) 2 refs.; 1 fig.; 1 tab

Cold neutron prompt gamma activation analysis at NIST; A progress report

Energy Technology Data Exchange (ETDEWEB)

Paul, R L; Lindstrom, R M [National Inst. of Standards and Technology, Gaithersburg, MD (United States). Div. of Inorganic Analytical Research; Vincent, D H [Michigan Univ., Ann Arbor, MI (United States). Dept. of Nuclear Engineering

1994-05-01

An instrument for prompt gamma-ray activation analysis is now in operation at the NIST Cold Neutron Research Facility (CNRF). The cold neutron beam is relatively free of contamination by fast neutrons and reactor gamma rays, and the neutron fluence rate is 1.5 x 10 [sup 8] cm [sup -2] x s [sup -1] (thermal equivalent). As a result of a compact target-detector geometry the sensitivity is better by a factor of as much as seven than that obtained with an existing thermal instrument, and hydrogen background is a factor of 50 lower. This instrument was applied to multielement analysis of the Allende meteorite and other materials. (author) 14 refs.; 2 figs.; 1 tab.

Physical basis for prompt-neutron activation analysis

International Nuclear Information System (INIS)

Chrien, R.E.

1982-01-01

The technique called prompt ν-ray neutron activation analysis has been applied to rapid materials analysis. The radiation following the neutron radiation capture is prompt in the sense that the nuclear decay time is on the order of 10 - 15 second, and thus the technique is not strictly activation, but should be called radiation neutron capture spectroscopy or neutron capture ν-ray spectroscopy. This paper reviews the following: sources and detectors, theory of radiative capture, nonstatistical capture, giant dipole resonance, fast neutron capture, and thermal neutron capture ν-ray spectra. 14 figures

Applications of neutron activation analysis in environmental science, biology and geoscience

International Nuclear Information System (INIS)

1992-01-01

The applications of neutron activation analysis technique with high sensitivity, good accuracy, multielemental analysis and non-destruction of samples in hydrosphere, soil and lithosphere, atmosphere, cosmosphere and biosphere were introduced in this book. A large amount of research activities in this field during the 20 years and more carried out by Neutron Activation Analysis Laboratory, Institute of High Energy Physics, Academia Sinica, was summarized. A number of the data and information with important scientific significance was provided

Activation Analysis and Public Health. Survey Paper

Energy Technology Data Exchange (ETDEWEB)

Lenihan, I. M.A. [Western Regional Hospital Board, Glasgow (United Kingdom); Smith, H. [University of Glasgow, Glasgow (United Kingdom)

1967-10-15

The technique of activation analysis has useful and distinctive applications, not yet fully recognized or exploited, in public health. Three areas of usefulness may be recognized. 1. Industrial hygiene. Activation analysis offers a simple and efficient method for assessing and controlling occupational hazards associated with the handling of toxic materials, such as compounds of arsenic and of mercury. Examination of hair and nail samples, taken at six-monthly intervals, will yield a surprising amount of information regarding the influence on occupational exposure of individual variation in working habits, and inadequacy or non-observance of hygienic rules and other prescribed safety measures. 2. Epidemiology. The advantage conferred by activation analysis lies in the possibility of rapid and accurate estimation of trace element concentrations in small samples of tissue or other materials, such as can readily be obtained from population groups large enough to be statistically significant. Surveys of this kind have interesting potentialities in relation to dental caries, cancer, cirrhosis of the liver and heart disease. 3. Recognition of essential trace elements. Surveys of trace element concentrations suggest that the variability of tissue levels among members of a population is smaller for essential trace elements than for non-essential elements. It is possible also that tissue levels show a normal distribution for essential elements and a log-normal distribution for non-essential elements. (author)

Structural analysis and biological activity of a highly regular glycosaminoglycan from Achatina fulica.

Science.gov (United States)

Liu, Jie; Zhou, Lutan; He, Zhicheng; Gao, Na; Shang, Feineng; Xu, Jianping; Li, Zi; Yang, Zengming; Wu, Mingyi; Zhao, Jinhua

2018-02-01

Edible snails have been widely used as a health food and medicine in many countries. A unique glycosaminoglycan (AF-GAG) was purified from Achatina fulica. Its structure was analyzed and characterized by chemical and instrumental methods, such as Fourier transform infrared spectroscopy, analysis of monosaccharide composition, and 1D/2D nuclear magnetic resonance spectroscopy. Chemical composition analysis indicated that AF-GAG is composed of iduronic acid (IdoA) and N-acetyl-glucosamine (GlcNAc) and its average molecular weight is 118kDa. Structural analysis clarified that the uronic acid unit in glycosaminoglycan (GAG) is the fully epimerized and the sequence of AF-GAG is →4)-α-GlcNAc (1→4)-α-IdoA2S (1→. Although its structure with a uniform repeating disaccharide is similar to those of heparin and heparan sulfate, this GAG is structurally highly regular and homogeneous. Anticoagulant activity assays indicated that AF-GAG exhibits no anticoagulant activities, but considering its structural characteristic, other bioactivities such as heparanase inhibition may be worthy of further study. Copyright © 2017 Elsevier Ltd. All rights reserved.

The verification of neutron activation analysis support system (cooperative research)

Energy Technology Data Exchange (ETDEWEB)

Sasajima, Fumio; Ichimura, Shigeju; Ohtomo, Akitoshi; Takayanagi, Masaji [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Sawahata, Hiroyuki; Ito, Yasuo [Tokyo Univ. (Japan). Research Center for Nuclear Science and Technology; Onizawa, Kouji [Radiation Application Development Association, Tokai, Ibaraki (Japan)

2000-12-01

Neutron activation analysis support system is the system in which even the user who has not much experience in the neutron activation analysis can conveniently and accurately carry out the multi-element analysis of the sample. In this verification test, subjects such functions, usability, precision and accuracy of the analysis and etc. of the neutron activation analysis support system were confirmed. As a method of the verification test, it was carried out using irradiation device, measuring device, automatic sample changer and analyzer equipped in the JRR-3M PN-3 facility, and analysis software KAYZERO/SOLCOI based on the k{sub 0} method. With these equipments, calibration of the germanium detector, measurement of the parameter of the irradiation field and analysis of three kinds of environmental standard sample were carried out. The k{sub 0} method adopted in this system is primarily utilized in Europe recently, and it is the analysis method, which can conveniently and accurately carried out the multi-element analysis of the sample without requiring individual comparison standard sample. By this system, total 28 elements were determined quantitatively, and 16 elements with the value guaranteed as analytical data of the NIST (National Institute of Standards and Technology) environment standard sample were analyzed in the accuracy within 15%. This report describes content and verification result of neutron activation support system. (author)

A provenance study of coffee by photon activation analysis

International Nuclear Information System (INIS)

Sun, Z.J.; Wells, D.P.; Maschner, H.; Idaho State University, Pocatello, ID; Idaho State University, Pocatello, ID; Benson, B.

2013-01-01

Photon activation analysis (PAA) is a multi-elemental radioanalytical technique in trace elements analysis with high accuracy and precision. Researchers at the Idaho accelerator center performed PAA analysis on coffee samples from several locations around the world as an initial step in assessing the relationship between trace elements in illicit drugs and the soils in which they were grown. The preliminary results show coffees from different locations have different concentrations of trace elements. In the three cases where we have soil samples, the matrices of elements in the coffee samples are closely related to the matrices of the elements of the local soil samples. The majority of trace elemental content is similar to that of the local soil sample in which the coffee is planted. It may be that coffee assimilates numerous elements from the soil where it is grown in similar ratios as is found in the soil. Thus, it is conceivable that the elemental content could serve as 'fingerprint' to trace the origins of the coffee. To verify our analytical results we applied X-ray fluorescence (XRF) methods as well. Our PAA results are consistent with XRF experimental data. The future of tracing the origin of illicit drugs with the PAA technique is promising. (author)

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Directory of Open Access Journals (Sweden)

Stéphanie Simon

2015-11-01

Full Text Available Botulinum neurotoxins (BoNTs cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G, of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Applications of neutrons for laboratory and industrial activation analysis problems

International Nuclear Information System (INIS)

Szabo, Elek; Bakos, Laszlo

1986-01-01

This chapter presents some particular applications and case studies of neutrons in activation analysis for research and industrial development purposes. The reactor neutrons have been applied in Hungarian laboratories for semiconductor research, for analysis of geological (lunar) samples, and for a special comparator measurement of samples. Some industrial applications of neutron generator and sealed sources for analytical problems are presented. Finally, prompt neutron activation analysis is outlined briefly. (R.P.)

Application of nuclear activation analysis

International Nuclear Information System (INIS)

Mamonov, E.I.; Khlystova, A.F.

1979-01-01

Consideration is given to the applications of nuclear-activation analysis (NAA) as discussed at the International Conference of 1977. One of the new results in the present-day NAA practices is the growing number of elements detected in samples without using a destructive radiochemical separation. An essential feature in this context is the development of the system automation of control and information NAA operations through the use computers. In biological medicine a multicomponent NAA is employed to determine the concentration of elements in various human organs and objects, in metabolic studies and for diagnostic purposes. In agriculture NAA finds applications in the evaluation of grain protein, analysis of element feed composition, soil and fertilizers. The application of this method to the environmental monitoring is considered with particular reference to the element analysis of water (especially drinking water), air, plant residues. Data are presented for the use of NAA in metallurgy, geology, archaeology and criminal law. Tables are provided to illustrate the uses of NAA in various fields

Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis

International Nuclear Information System (INIS)

Black, J.D.; Dolly, J.O.

1986-01-01

Using pharmacological and autoradiographic techniques it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In the present study, the nature of this uptake process was investigated using electron microscopic autoradiography. It was found that internalization is acceptor-mediated and that binding to specific cell surface acceptors involves the heavier chain of the toxin. In addition, uptake was shown to be energy and temperature-dependent and to be accelerated by nerve stimulation, a treatment which also shortens the time course of the toxin-induced neuroparalysis. These results, together with the observation that silver grains were often associated with endocytic structures within the nerve terminal, suggested that acceptor-mediated endocytosis is responsible for toxin uptake. Possible recycling of BoNT acceptors (an important aspect of acceptor-mediated endocytosis of toxins) at motor nerve terminals was indicated by comparing the extent of labeling in the presence and absence of metabolic inhibitors. On the basis of these collective results, it is concluded that BoNT is internalized by acceptor-mediated endocytosis and, hence, the data support the proposal that this toxin inhibits release of acetylcholine by interaction with an intracellular target

A Functional Analysis of Moderate-to-Vigorous Physical Activity in Young Children

Science.gov (United States)

Larson, Tracy A.; Normand, Matthew P.; Morley, Allison J.; Miller, Bryon G.

2013-01-01

Inadequate physical activity increases the risks related to a number of health problems in children, most notably obesity and the corresponding range of associated health problems. The purpose of the current study was to conduct a functional analysis to investigate the effects of several consequent variables on moderate-to-vigorous physical…

ENTREPRENEURIAL ACTIVITY IN ROMANIA – A TIME SERIES CLUSTERING ANALYSIS AT THE NUTS3 LEVEL

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Sipos-Gug Sebastian

2013-07-01

Full Text Available Entrepreneurship is an active field of research, having known a major increase in interest and publication levels in the last years (Landström et al., 2012. Within this field recently there has been an increasing interest in understanding why some regions seem to have a significantly higher entrepreneurship activity compared to others. In line with this research field, we would like to investigate the differences in entrepreneurial activity among the Romanian counties (NUTS 3 regions. While the classical research paradigm in this field is to conduct a temporally stationary analysis, we choose to use a time series clustering analysis to better understanding the dynamics of entrepreneurial activity between counties. Our analysis showed that if we use the total number of new privately owned companies that are founded each year in the last decade (2002-2012 we can distinguish between 5 clusters, one with high total entrepreneurial activity (18 counties, one with above average activity (8 counties, two clusters with average and slightly below average activity (total of 18 counties and one cluster with low and declining activity (2 counties. If we are interested in the entrepreneurial activity rate, that is the number of new privately owned companies founded each year adjusted by the population of the respective county, we obtain 4 clusters, one with a very high entrepreneurial rate (1 county, one with average rate (10 counties, and two clusters with below average entrepreneurial rate (total of 31 counties. In conclusion, our research shows that Romania is far from being a homogeneous geographical area in respect to entrepreneurial activity. Depending on what we are interested in, it can be divided in 5 or 4 clusters of counties, which behave differently as a function of time. Further research should be focused on explaining these regional differences, on studying the high performance clusters and trying to improve the low performing ones.

Nondestructive neutron activation analysis of silicon carbide

Energy Technology Data Exchange (ETDEWEB)

Vandergraaf, T. T.; Wikjord, A. G.

1973-10-15

Instrumentel neutron activation analysis was used to determine trace constituents in silicon carbide. Four commercial powders of different origin, an NBS reference material, and a single crystal were characterized. A total of 36 activation species were identified nondestructively by high resolution gamma spectrometry; quantitative results are given for 12 of the more predominant elements. The limitations of the method for certain elements are discussed. Consideration is given to the depression of the neutron flux by impurities with large neutron absorption cross sections. Radiation fields from the various specimens were estimated assuming all radionuclides have reached their saturation activities. (auth)

A THREE-STEP SPATIAL-TEMPORAL-SEMANTIC CLUSTERING METHOD FOR HUMAN ACTIVITY PATTERN ANALYSIS

Directory of Open Access Journals (Sweden)

W. Huang

2016-06-01

Full Text Available How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time to four dimensions (space, time and semantics. More specifically, not only a location and time that people stay and spend are collected, but also what people “say” for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The

Neutron activation analysis of certified samples by the absolute method

Science.gov (United States)

Kadem, F.; Belouadah, N.; Idiri, Z.

2015-07-01

The nuclear reactions analysis technique is mainly based on the relative method or the use of activation cross sections. In order to validate nuclear data for the calculated cross section evaluated from systematic studies, we used the neutron activation analysis technique (NAA) to determine the various constituent concentrations of certified samples for animal blood, milk and hay. In this analysis, the absolute method is used. The neutron activation technique involves irradiating the sample and subsequently performing a measurement of the activity of the sample. The fundamental equation of the activation connects several physical parameters including the cross section that is essential for the quantitative determination of the different elements composing the sample without resorting to the use of standard sample. Called the absolute method, it allows a measurement as accurate as the relative method. The results obtained by the absolute method showed that the values are as precise as the relative method requiring the use of standard sample for each element to be quantified.

[Preparation of a kind of SERS-active substrates for spot fast analysis].

Science.gov (United States)

Ji, Nan; Li, Zhi-Shi; Zhao, Bing; Zou, Bo

2013-02-01

A kind of SERS-active substrates was prepared using chemical self-assembly method, aiming at spot fast analysis using portable Raman spectrometer. PDDA was first absorbed on the inner wall of vials, and then Ag colloids were assembled on the inner wall. UV-Vis spectra and Raman spectra of two kinds of blank vials were investigated and the transparent vials were thought to be better for SERS-vials. UV-Vis spectra were used to monitor the assembly process of Ag colloids. SERS activity of our substrates was characterized using p-ATP as probing molecules.

Simulation for sodium-24 production using cyclic neutron activation analysis

International Nuclear Information System (INIS)

Ahamed, O. M. H.

2012-04-01

The cyclic neutron activation analysis is a method for elemental analysis which is preferred to use short-lived radio-nuclides. In recent years this method became a new application for radioisotope production especially in low power research reactors. In this study instrumental cyclic neutron activation analysis was used for 2 4N a production using 2 3N a (n, γ) 2 4N a reaction. The simplified westcott convention method is used neutron activation analysis in a research reactor. The method takes into account all corrections that can affect that yield created. In this work a model was devolving for calculations through this simplified Westcott convention method by using C++ program and selecting good parameters that can produce the expected activity. The simulation is used for the theoretical yield calculated has been validated by data from the 1 77L u production used for theoretical yield which it gives the approached result had been obtained by FORTRAN 90 from literature (8). The results were achieved for expected activity at full power (1 x 10 1 2n cm -2 s - 1 ) and half power (5 x 10 11 cm -2 s -1 ) for research reactor MNSR. The activity at full power was equal to about twice the activity at half power ( 49±7, 24.9 ± MBq/g), respectively. The irradiation parameters selected were irradiation time 4 min and decay time 12 min. Sample weight was 50 mg at 12 numbers of cycles, when the K-factor was equal to 1.74. This work is considered as first step for production of 2 4N a which can use such parameters experimentally. It is then possible to compare the expected activity with measured activity. (Author)

Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies.

Science.gov (United States)

Tang, D W; Fellows, L K; Small, D M; Dagher, A

2012-06-06

In healthy individuals, food cues can trigger hunger and feeding behavior. Likewise, smoking cues can trigger craving and relapse in smokers. Brain imaging studies report that structures involved in appetitive behaviors and reward, notably the insula, striatum, amygdala and orbital frontal cortex, tend to be activated by both visual food and smoking cues. Here, by carrying out a meta-analysis of human neuro-imaging studies, we investigate the neural network activated by: 1) food versus neutral cues (14 studies, 142 foci) 2) smoking versus neutral cues (15 studies, 176 foci) 3) smoking versus neutral cues when correlated with craving scores (7 studies, 108 foci). PubMed was used to identify cue-reactivity imaging studies that compared brain response to visual food or smoking cues to neutral cues. Fourteen articles were identified for the food meta-analysis and fifteen articles were identified for the smoking meta-analysis. Six articles were identified for the smoking cue correlated with craving analysis. Meta-analyses were carried out using activation likelihood estimation. Food cues were associated with increased blood oxygen level dependent (BOLD) response in the left amygdala, bilateral insula, bilateral orbital frontal cortex, and striatum. Smoking cues were associated with increased BOLD signal in the same areas, with the exception of the insula. However, the smoking meta-analysis of brain maps correlating cue-reactivity with subjective craving did identify the insula, suggesting that insula activation is only found when craving levels are high. The brain areas identified here are involved in learning, memory and motivation, and their cue-induced activity is an index of the incentive salience of the cues. Using meta-analytic techniques to combine a series of studies, we found that food and smoking cues activate comparable brain networks. There is significant overlap in brain regions responding to conditioned cues associated with natural and drug rewards

A bibliometric analysis of the development of next generation active nanotechnologies

International Nuclear Information System (INIS)

Suominen, Arho; Li, Yin; Youtie, Jan; Shapira, Philip

2016-01-01

Delineating the emergence of nanotechnologies that offer new functionalities is an important element in an anticipatory approach to the governance of nanotechnology and its potential impacts. This paper examines the transition to next generation active nanotechnologies which incorporate functions that respond to the environment or systems concepts that combine devices and structures that are dynamic and which may change their states in use. We develop an approach to identifying these active nanotechnologies and then use bibliometric analysis to examine the extent of research papers and patents involving these concepts. We also examine references to environmental, health, and safety concepts in these papers, given that these next generation nanotechnologies are likely to have risk profiles that are different from those of first-generation passive nanomaterials. Our results show a steady growth overall in focus on active nanotechnologies in the research literature and in patents over the study period of 1990–2010. We also find an increase in consideration given to environmental, health, and safety topics. While gaps are highlighted in our understanding of research and innovation in active nanotechnologies, the results suggest that there is beginning to be a shift to active nanotechnologies, with the implication that governance processes need to be conscious of this shift and to prepare for it.

A bibliometric analysis of the development of next generation active nanotechnologies

Energy Technology Data Exchange (ETDEWEB)

Suominen, Arho [VTT Technical Research Centre of Finland (Finland); Li, Yin; Youtie, Jan, E-mail: jan.youtie@innovate.gatech.edu; Shapira, Philip [Georgia Institute of Technology (United States)

2016-09-15

Delineating the emergence of nanotechnologies that offer new functionalities is an important element in an anticipatory approach to the governance of nanotechnology and its potential impacts. This paper examines the transition to next generation active nanotechnologies which incorporate functions that respond to the environment or systems concepts that combine devices and structures that are dynamic and which may change their states in use. We develop an approach to identifying these active nanotechnologies and then use bibliometric analysis to examine the extent of research papers and patents involving these concepts. We also examine references to environmental, health, and safety concepts in these papers, given that these next generation nanotechnologies are likely to have risk profiles that are different from those of first-generation passive nanomaterials. Our results show a steady growth overall in focus on active nanotechnologies in the research literature and in patents over the study period of 1990–2010. We also find an increase in consideration given to environmental, health, and safety topics. While gaps are highlighted in our understanding of research and innovation in active nanotechnologies, the results suggest that there is beginning to be a shift to active nanotechnologies, with the implication that governance processes need to be conscious of this shift and to prepare for it.

Molecular activation analysis for chemical species studies

International Nuclear Information System (INIS)

Chai Zhifang; Mao Xueying; Wang Yuqi; Sun Jingxin; Qian Qingfang; Hou Xiaolin; Zhang Peiqun; Chen Chunying; Feng Weiyu; Ding Wenjun; Li Xiaolin; Li Chunsheng; Dai Xiongxin

2001-01-01

The Molecular Activation Analysis (MAA) mainly refers to an activation analysis method that is able to provide information about the chemical species of elements in systems of interest, though its exact definition has remained to be assigned. Its development is strongly stimulated by the urgent need to know the chemical species of elements, because the bulk contents or concentrations are often insignificant for judging biological, environmental or geochemical effects of elements. In this paper, the features, methodology and limitation of MAA were outlined. Further, the up-to-date MAA progress made in our laboratory was introduced as well. (author)

Molecular activation analysis for chemical speciation studies

International Nuclear Information System (INIS)

Chai-Chifang

1998-01-01

The term of Molecular Activation Analysis (MAA) refers to an activation analysis method that is able to provide information about the chemical species of elements in system of interests, though its definition has remained to be assigned. Its development is strongly stimulated by the urgent need to know the chemical species of elements, because the total concentrations are often without any meaning when assessing health or environmental risks of trace elements.In practice, the MAA is a combination of conventional instrumental or radiochemical activation analysis and physical, chemical or biochemical separation techniques. The MAA is able to play a particular role in speciation studies. However, the critical point in the MAA is that it is not permitted to change the primitive chemical species of elements in systems, or the change has to be under control; in the meantime it is not allowed to form the 'new artifact' originally not present in systems. Some practical examples of MAA for chemical species research performed recently in our laboratory will be presented as follows: Chemical species of platinum group elements in sediment; Chemical species of iodine in marine algae; Chemical species of mercury in human tissues; Chemical species of selenium in corn; Chemical species of rare earth elements in natural plant, etc. The merits and limitations of MAA will be described as well. (author)

Large Sample Neutron Activation Analysis of Heterogeneous Samples

International Nuclear Information System (INIS)

Stamatelatos, I.E.; Vasilopoulou, T.; Tzika, F.

2018-01-01

A Large Sample Neutron Activation Analysis (LSNAA) technique was developed for non-destructive analysis of heterogeneous bulk samples. The technique incorporated collimated scanning and combining experimental measurements and Monte Carlo simulations for the identification of inhomogeneities in large volume samples and the correction of their effect on the interpretation of gamma-spectrometry data. Corrections were applied for the effect of neutron self-shielding, gamma-ray attenuation, geometrical factor and heterogeneous activity distribution within the sample. A benchmark experiment was performed to investigate the effect of heterogeneity on the accuracy of LSNAA. Moreover, a ceramic vase was analyzed as a whole demonstrating the feasibility of the technique. The LSNAA results were compared against results obtained by INAA and a satisfactory agreement between the two methods was observed. This study showed that LSNAA is a technique capable to perform accurate non-destructive, multi-elemental compositional analysis of heterogeneous objects. It also revealed the great potential of the technique for the analysis of precious objects and artefacts that need to be preserved intact and cannot be damaged for sampling purposes. (author)

Neutron activation analysis: an emerging technique for conservation/preservation

International Nuclear Information System (INIS)

Sayre, E.V.

1976-01-01

The diverse applications of neutron activation in analysis, preservation, and documentation of art works and artifacts are described with illustrations for each application. The uses of this technique to solve problems of attribution and authentication, to reveal the inner structure and composition of art objects, and, in some instances to recreate details of the objects are described. A brief discussion of the theory and techniques of neutron activation analysis is also included

Neutron activation analysis using TRIGA

International Nuclear Information System (INIS)

Byrne, A.R.

1972-01-01

Activation analysis with TRIGA MARK II is the main part of the work of the nuclear Chemistry Section at the Institute. A major part of the effort in this field is concerned with the determination of trace elements at the micro and nanogram level in a wide variety of materials, and with the development of new methods, (or the adaptation of known methods,) applicable to these determinations. In particular, specific and group radiochemical separations are studied

Anatomical recommendations for safe botulinum toxin injection into temporalis muscle: a simplified reproducible approach.

Science.gov (United States)

Lee, Won-Kang; Bae, Jung-Hee; Hu, Kyung-Seok; Kato, Takafumi; Kim, Seong-Taek

2017-03-01

The objective of this study was to simplify the anatomically safe and reproducible approach for BoNT injection and to generate a detailed topographic map of the important anatomical structures of the temporal region by dividing the temporalis into nine equally sized compartments. Nineteen sides of temporalis muscle were used. The topographies of the superficial temporal artery, middle temporal vein, temporalis tendon, and the temporalis muscle were evaluated. Also evaluated was the postural relations among the foregoing anatomical structures in the temporalis muscle, pivoted upon a total of nine compartments. The temporalis above the zygomatic arch exhibited an oblique quadrangular shape with rounded upper right and left corners. The distance between the anterior and posterior margins of the temporalis muscle was equal to the width of the temporalis rectangle, and the distance between the reference line and the superior temporalis margin was equal to its height. The mean ratio of width to height was 5:4. We recommend compartments Am, Mu, and Pm (coordinates of the rectangular outline) as areas in the temporal region for BoNT injection, because using these sites will avoid large blood vessels and tendons, thus improving the safety and reproducibility of the injection.

Fast neutron activation analysis in metallurgy

International Nuclear Information System (INIS)

Sterlinski, S.

1981-01-01

Article discusses the usage of a 14 MeV neutron generator for producing fast neutrons of different energies and intensities. A complete instrumental set-up for the neutron activation analysis (NAA) is given. In metallurgy the device is mainly used in the determination of oxygen and silicon in steel and non-ferrous metal, including different alloys

Multielement analysis of biological standards by neutron activation analysis

International Nuclear Information System (INIS)

Nadkarni, R.A.

1977-01-01

Up to 28 elements were determined in two IAEA standards: Animal Muscle H4 and Fish Soluble A 6/74, and three NBS standards: Spinach: SRM-1570, Tomato Leaves: SRM-1573 and Pine Needles: SRM-1575 by instrumental neutron-activation analysis. Seven noble metals were determined in two NBS standards: Coal: SRM-1632 and Coal Fly Ash: SRM-1633 by radiochemical procedure while 11 rare earth elements were determined in NBS standard Orchard Leaves: SRM-1571 by instrumental neutron-activation analysis. The results are in good agreement with the certified and/or literature data where available. The irradiations were performed at the Cornell TRIGA Mark II nuclear reactor at a thermal neutron flux of 1-3x10 12 ncm -2 sec -1 . The short-lived species were determined after a 2-minute irradiation in the pneumatic rabbit tube, and the longer-lived species after an 8-hour irradiation in the central thimble facility. The standards and samples were counted on coaxial 56-cm 3 Ge(Li) detector. The system resolution was 1.96 keV (FWHM) with a peak to Compton ratio of 37:1 and counting efficiency of 13%, all compared to the 1.332 MeV photopeak of Co-60. (T.I.)

Pneumatic transport devices based on the ARS equipment set for activation analysis

International Nuclear Information System (INIS)

Ivanov, I.V.; Ivanets, V.N.; Rogachev, V.M.; Zakharov, E.A.

1978-01-01

The AGIDEL and ARS-28G facilities manufactured on the basis of a set of standardized and aggregated products for activation analysis are described. The AGIDEL is designed for automatic activation analysis of relatively homogeneous samples from oil boreholes. The ARS-28G is designed for transporting the test samples during activation analysis, using a fast-neutron generator. Structurally, the ARS-28 is based on a pneumatic transportation system with two independenhat transport cnnels and a two-channel rotating irradiation unit. The analyzed samples are transported in polyethylene containers, which are moved by compressed air. The facility has been successfully tested and is used in an automated system for multielement activation analysis

Fast neutron activation analysis at Texas A and M University

International Nuclear Information System (INIS)

James, W.D.

1997-01-01

Fast neutron generators are used at Texas A and M University to provide a supply of high energy neutrons for nuclear analytical measurements. A series of neutron activation analysis procedures have been developed for determining various major, minor and trace constituents in a variety of materials. These procedures are primarily developed to compliment our reactor based NAA program, thereby expanding the list of determinable elements to include those difficult or impossible to measure using thermal neutrons. A few typical methods are discussed. The unique implementation of the methodologies at Texas A and M are explained. (author)

Limits of detection in instrumental neutron activation analysis

International Nuclear Information System (INIS)

Guinn, V.P.

1990-01-01

Lower limits of detection (LLODs), frequently referred to simply as limits of detection and abbreviated as LODs, often appear in the literature of analytical chemistry - for numerous different methods of elemental and/or molecular analysis. In this chapter, one particular method of quantitative elemental analysis, that of instrumental neutron activation analysis (INAA), is the subject discussed, with reference to LODs. Particularly in the literature of neutron activation analysis (NAA), many tables of 'interference-free' NAA LODs are available. Not all of these are of much use, because (1) for many the definition used for LOD is not clear, or reasonable, (2) for many, the analysis conditions used are not clearly specified, and (3) for many, the analysis conditions used are specified, but not very practicable for most laboratories. For NAA work, such tables of interference-free LODs are, in any case, only applicable to samples in which, at the time of counting, only one radionuclide is present to any significant extent in the activated sample. It is important to note that tables of INAA LODs, per se, do not exist - since the LOD for a given element, under stated analysis conditions, can vary by orders of magnitude, depending on the elemental composition of the matrix in which it is present. For any given element, its INAA LOD will always be as large as, and usually much larger than, its tabulated 'interference-free' NAA LOD - how much larger depending upon the elemental composition of the matrix in which it is present. As discussed in this chapter, however, an INAA computer program exists that can calculate realistic INAA LODs for any elements of interest, in any kind of specified sample matrix, under any given set of analysis conditions

A computer language for reducing activation analysis data

International Nuclear Information System (INIS)

Friedman, M.H.; Tanner, J.T.

1978-01-01

A program, written in FORTRAN, which defines a language for reducing activation analysis data is described. An attempt was made to optimize the choice of commands and their definitions so as to concisely express what should be done, make the language natural to use and easy to learn, arranqe a system of checks to guard against communication errors and have the language be inclusive. Communications are effected through commands, and these can be given in almost any order. Consistency checks are done and diagnostic messages are printed automatically to guard against the incorrect use of commands. Default options on the commands allow instructions to be expressed concisely while providing a capability to specify details for the data reduction process. The program has been implemented on a UNIVAC 1108 computer. A complete description of the commands, the algorithms used, and the internal consistency checks used are given elsewhere. The applications of the program and the methods for obtaining data automatically have already been described. (T.G.)

US--ITER activation analysis

International Nuclear Information System (INIS)

Attaya, H.; Gohar, Y.; Smith, D.

1990-09-01

Activation analysis has been made for the US ITER design. The radioactivity and the decay heat have been calculated, during operation and after shutdown for the two ITER phases, the Physics Phase and the Technology Phase. The Physics Phase operates about 24 full power days (FPDs) at fusion power level of 1100 MW and the Technology Phase has 860 MW fusion power and operates for about 1360 FPDs. The point-wise gamma sources have been calculated everywhere in the reactor at several times after shutdown of the two phases and are then used to calculate the biological dose everywhere in the reactor. Activation calculations have been made also for ITER divertor. The results are presented for different continuous operation times and for only one pulse. The effect of the pulsed operation on the radioactivity is analyzed. 6 refs., 12 figs., 1 tab

Initial testing of a neutron activation analysis system by analysing standard reference materials

International Nuclear Information System (INIS)

Suhaimi Hamzah; Roslan Idris; Abdul Khalik Haji Wood; Che Seman Mahmood; Abdul Rahim Mohamad Noor.

1983-01-01

This paper describes the data acquisition and processing system in our laboratories (ND6600), the methods of activation analysis and the results obtained from our analysis of IAEA standard reference material (SL-l lake sediments and NBS coal ash 1632a). These standards were analysed in order to check the capability of the system, which was designed in such a way as to enable the user to independently collect and process data from multiple radiation detectors. (author)

Minimal Essential Domains Specifying Toxicity of the Light Chains of Tetanus Toxin and Botulinum Neurotoxin Type A

NARCIS (Netherlands)

Kurazono, Hisao; Mochida, Sumiko; Binz, Thomas; Eisel, Ulrich; Quanz, Martin; Grebenstein, Oliver; Wernars, Karel; Poulain, Bernard; Tauc, Ladislav; Niemann, Heiner

1992-01-01

To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/Cl, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical

Multi-level Discourse Analysis in a Physics Teaching Methods Course from the Psychological Perspective of Activity Theory

Science.gov (United States)

Vieira, Rodrigo Drumond; Kelly, Gregory J.

2014-11-01

In this paper, we present and apply a multi-level method for discourse analysis in science classrooms. This method is based on the structure of human activity (activity, actions, and operations) and it was applied to study a pre-service physics teacher methods course. We argue that such an approach, based on a cultural psychological perspective, affords opportunities for analysts to perform a theoretically based detailed analysis of discourse events. Along with the presentation of analysis, we show and discuss how the articulation of different levels offers interpretative criteria for analyzing instructional conversations. We synthesize the results into a model for a teacher's practice and discuss the implications and possibilities of this approach for the field of discourse analysis in science classrooms. Finally, we reflect on how the development of teachers' understanding of their activity structures can contribute to forms of progressive discourse of science education.

Applications of neutron activation analysis in industry

International Nuclear Information System (INIS)

Zaini Hamzah.

1985-01-01

Neutron activation analysis technique is discussed in brief. This technique is used for quality control of raw materials, process materials and finished products, as well as activities in research and development for the improvement of the products and new products. The uses of this technique in several experienced industries are mentioned (author)

Multiplex Biosensing Based on Highly Sensitive Magnetic Nanolabel Quantification: Rapid Detection of Botulinum Neurotoxins A, B, and E in Liquids.

Science.gov (United States)

Orlov, Alexey V; Znoyko, Sergey L; Cherkasov, Vladimir R; Nikitin, Maxim P; Nikitin, Petr I

2016-11-01

We present a multiplex quantitative lateral flow (LF) assay for simultaneous on-site detection of botulinum neurotoxin (BoNT) types A, B, and E in complex matrixes, which is innovative by virtually no sacrifice in performance while transition from the single-plex assays and by characteristics on the level of laboratory quantitative methods. The novel approach to easy multiplexing is realized via joining an on-demand set of single-plex LF strips, which employ magnetic nanolabels, into a miniature cylinder cartridge that mimics LF strip during all assay stages. The cartridge is read out by an original portable multichannel reader based on the magnetic particle quantification technique. The developed reader offers the unmatched 60 zmol detection limit and 7-order linear dynamic range for volumetric registration of magnetic labels inside a cartridge of several millimeters in diameter regardless of its optical transparency. Each of the test strips, developed here as building blocks for the multiplex assay, can be used "as is" for autonomous quantitative single-plex detection with the same measuring setup, exhibiting the limits of detection (LOD) of 0.22, 0.11, and 0.32 ng/mL for BoNT-A, -B, and -E, respectively. The proposed multiplex assay has demonstrated the remarkably similar LOD values of 0.20, 0.12, 0.35 ng/mL under the same conditions. The multiplex assay performance was successfully validated by BoNT detection in milk and apple and orange juices. The developed methods can be extended to other proteins and used for rapid multianalyte tests for point-of-care in vitro diagnostics, food analysis, biosafety and environmental monitoring, forensics, and security, etc.

Neutron activation analysis

International Nuclear Information System (INIS)

Okada, Yukiko

2005-01-01

Trends and progress in neutron activation analysis (NAA) for the period starting in 1999 to 2003 are presented. Numbers of published reports on NAA are decreasing year by year as investigated from the database JST and NUCLEN. Summary reports on the international conferences held on NAA are followed by classifying according to the fields: various measurement techniques and application fields. Specially focused topics are newly developed techniques for measuring trace elements with high sensitivity and high accuracy such as (1) by diminishing the Compton-background gamma-rays using anti-coincidence technique, (2) by using prompt-gamma rays measurement method (PGAA) and (3) by using a gamma-ray detector array (GEMINI), which has succeeded in a simultaneous quantification of 27 elements from a standard rock sample having a weight of only 10 milligrams, and others. These techniques will be applied in the space and earth sciences and medical fields. (S. Ohno)

Cost-effectiveness analysis of a statewide media campaign to promote adolescent physical activity.

Science.gov (United States)

Peterson, Michael; Chandlee, Margaret; Abraham, Avron

2008-10-01

A cost-effectiveness analysis of a statewide social marketing campaign was performed using a statewide surveillance survey distributed to 6th through 12th graders, media production and placement costs, and 2000 census data. Exposure to all three advertisements had the highest impact on both intent and behavior with 65.6% of the respondents considering becoming more active and 58.3% reporting becoming more active. Average cost of the entire campaign was $4.01 per person to see an ad, $7.35 per person to consider being more active, and $8.87 per person to actually become more active, with billboards yielding the most positive cost-effectiveness. Findings highlight market research as an essential part of social marketing campaigns and the importance of using multiple marketing modalities to enhance cost-effectiveness and impact.

A study on cigarette tobacco by instrumental neutron activation analysis

International Nuclear Information System (INIS)

Md Soot Haji Ahmad; Tey Nsan Yen

1987-01-01

The concentration of 25 elements in cigarette tobacco of popular brands locally marketed were determined using instrumental neutron activation analysis. These elements are: Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Eu, Fe, Hf, Hg, K, La, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, Th, and Zn. Comparison of the element contents to the reported cigarette tobacco of Egypt, Iran and Turkey was also done. (author)

Does birth weight influence physical activity in youth? A combined analysis of four studies using objectively measured physical activity

DEFF Research Database (Denmark)

Ridgway, Charlotte L; Brage, Søren; Sharp, Stephen J

2011-01-01

Animal models suggest growth restriction in utero leads to lower levels of motor activity. Furthermore, individuals with very low birth weight report lower levels of physical activity as adults. The aim of this study was to examine whether birth weight acts as a biological determinant of physical...... activity and sedentary time. This study uses combined analysis of three European cohorts and one from South America (n = 4,170). Birth weight was measured or parentally reported. Height and weight were measured and used to calculate Body Mass Index (BMI). PA was objectively measured using accelerometry...... for ≥3 days, ≥10 hours day. Data was standardized to allow comparisons between different monitors. Total physical activity was assessed as counts per minute (cpm), with time spent above moderate activity (MVPA) >2,000 counts and time spent sedentary (...

14 MeV proton activation analysis

International Nuclear Information System (INIS)

Constantinescu, B.; Ivanov, E.; Plostinaru, D.; Popa-Nemoiu, A.; Pascovichi, G.

1985-01-01

A fast nuclear nondestructive method for protein analysis using the 14 MeV proton activation has been developed. The total nitrogen content was measured through the reaction: 14 N (p,n) 14 O, (Tsub(1/2)=71 s). The 14 O activity was detected by means of its characteristic 2.312 MeV gamma-ray line with a NaI(Tl) detector. For a fast determination of a large number of samples a mechanized sistem reacting a rate of one sample per minute has been developed. The laboratory electronics comprises a multichannel analyser, a PDP computer and an electronic module comtroller. Comparison of the results obtained by the method described and the classical Kjeldal technique for samples of various cereal grains (soya bean seads, wheat, barley and corn) showed good correlation. A problem of the analysis of the whole protein region on corn and soya-bean seads, where this region is thicker (0,2 - 2 mm), is mentioned. In this case flour was proposed to be used to obtain a protein homogeneous sample and the irradiaton dose for a sample was about 33,000 Gy, mainly (99%) from protons (27 s x 100 nA x 14 MeV)

Phosphorus analysis in milk samples by neutron activation analysis method

International Nuclear Information System (INIS)

Oliveira, R.M. de; Cunha, I.I.L.

1991-01-01

The determination of phosphorus in milk samples by instrumental thermal neutron activation analysis is described. The procedure involves a short irradiation in a nuclear reactor and measurement of the beta radiation emitted by phosphorus - 32 after a suitable decay period. The sources of error were studied and the established method was applied to standard reference materials of known phosphorus content. (author)

Systems Studies Department FY 78 activity report. Volume 2. Systems analysis

International Nuclear Information System (INIS)

Gold, T.S.

1979-02-01

The Systems Studies Department at Sandia Laboratories Livermore (SLL) has two primary responsibilities: to provide computational and mathematical services and to perform systems analysis studies. This document (Volume 2) describes the FY Systems Analysis highlights. The description is an unclassified overview of activities and is not complete or exhaustive. The objective of the systems analysis activities is to evaluate the relative value of alternative concepts and systems. SLL systems analysis activities reflect Sandia Laboratory programs and in 1978 consisted of study efforts in three areas: national security: evaluations of strategic, theater, and navy nuclear weapons issues; energy technology: particularly in support of Sandia's solar thermal programs; and nuclear fuel cycle physical security: a special project conducted for the Nuclear Regulatory Commission. Highlights of these activities are described in the following sections. 7 figures

Studies in heavy ion activation analysis Pt. 5

International Nuclear Information System (INIS)

Ojo, J.F.; Lass, B.D.; Schweikert, E.A.

1980-01-01

Nondestructive heavy ion activation analysis has been used to determine the carbon content in various NBS SRM steel samples with a 7.0 MeV 6 Li + beam. The reaction 12 C( 6 Li,αn) 13 N allows for carbon analysis with the only possible interference being beryllium, 9 Be( 6 Li,2n) 13 N. Under interference-free conditions, and employing a post-irradiation etch, the detection limit for carbon analysis in steel was 5 ppm. (author)

Development of HANARO Activation Analysis System and Utilization Technology

Energy Technology Data Exchange (ETDEWEB)

Chung, Y. S.; Moon, J. H.; Cho, H. J. (and others)

2007-06-15

1. Establishment of evaluation system using a data for a neutron activation analysis : Improvement of NAA measurement system and its identification, Development of combined data evaluation code of NAA/PGAA, International technical cooperation project 2. Development of technique for a industrial application of high precision gamma nuclide spectroscopic analysis : Analytical quality control, Development of industrial application techniques and its identification 3. Industrial application research for a prompt gamma-ray activation analysis : Improvement of Compton suppression counting system (PGAA), Development of applied technology using a PGAA system 4. Establishment of NAA user supporting system and KOLAS management : Development and validation of KOLAS/ISO accreditation testing and identification method, Cooperation researches for a industrial application, Establishment of integrated user analytical supporting system, Accomplishment of sample irradiation facility.