691 research outputs found
Botting (Gary), Fundamental Freedoms and Jehovah's Witnesses
No full textDericquebourg Régis. Botting (Gary), Fundamental Freedoms and Jehovah's Witnesses. In: Archives de sciences sociales des religions, n°94, 1996. pp. 58-59
Season 10 Episode 9: Ethics of Hostage Negotiation
No full textAn angry criminal takes a hostage and demands to speak with authorities. Who’s most qualified to take the phone? What strategy might have worked with David Koresh? Jim Botting, author of Bullets, Bombs and Fast Talk: 25 Years of FBI War Stories, describes the adventures and dilemmas of his seventeen years as hostage negotiator for the FBI. Shirley Hoogstra hosts. Episode #1009
Botting, D. — Humboldt and the Cosmos, Londres, Sphere Books Ltd. 1973
No full textBourlière François. Botting, D. — Humboldt and the Cosmos, Londres, Sphere Books Ltd. 1973. In: La Terre et La Vie, Revue d'Histoire naturelle, tome 28, n°3, 1974. p. 476
Semantic fluency in deaf children who use spoken and signed language, in comparison to hearing peers
No full textBackground
Deafness has an adverse impact on children’s ability to acquire spoken languages. Signed languages offer a more accessible input for deaf children, but because the vast majority are born to hearing parents who do not sign, their early exposure to sign language is limited. Deaf children as a whole are therefore at high risk of language delays.
Aims
We compared deaf and hearing children’s performance on a semantic fluency task. Optimal performance on this task requires a systematic search of the mental lexicon, the retrieval of words within a subcategory, and, when that subcategory is exhausted, switching to a new subcategory. We compared retrieval patterns between groups, and also compared the responses of deaf children who used British Sign Language (BSL) to those who used spoken English. We investigated how semantic fluency performance related to children’s expressive vocabulary and executive function skills, and also re-tested semantic fluency in the majority of the children nearly two years later, in order to investigate how much progress they had made in that time.
Methods and procedures
Participants were deaf children aged 6-11 years (N=106, comprising 69 users of spoken English, 29 users of BSL and 8 users of Sign Supported English) compared to hearing children (N=120) of the same age who used spoken English. Semantic fluency was tested for the category “animals”. We coded for errors, clusters (e.g., “pets”, “farm animals”) and switches. Participants also completed the Expressive One-Word Picture Vocabulary Test and a battery of six non-verbal executive function tasks. In addition, we collected follow-up semantic fluency data for 70 deaf and 74 hearing children, nearly 2 years after they were first tested.
Outcomes and results
Deaf children, whether using spoken or signed language, produced fewer items in the semantic fluency task than hearing children, but they showed similar patterns of responses for items most commonly produced, clustering of items into subcategories and switching between subcategories. Both vocabulary and executive function scores predicted the number of correct items produced. Follow-up data from deaf participants showed continuing delays relative to hearing children two years later.
Conclusions and implications
We conclude that semantic fluency can be used experimentally to investigate lexical organisation in deaf children, and that it potentially has clinical utility across the heterogeneous deaf population. We present normative data to aid clinicians who wish to use this task with deaf children
N-hydroxyguanidines and related compounds as nitric oxide donors
No full textThe design of new, improved NO-donor drugs is an important pharmacological objective
due to the biological importance of nitric oxide. N-Hydroxyguanidines represent a useful class of
NO donors where the mechanism of action is based on the biosynthetic pathway for NO.
Thirty new N-arylalkyl-N’-hydroxyguanidines were synthesized and their vasodilatation
activity examined by myography in rat aortic rings. The observed relaxations were reversed by
ODQ, which is an inhibitor of the guanylate cyclase, implying that this was an NO dependent
vasodilatation. The most active compounds were also tested in the isolated perfused kidney
(IPK) giving the vasodilatation properties. Preliminary results indicated that N-phenyl-N’-
hydroxyguanidine showed the best pharmacological profile with EC₅₀= 19.9 μM and ca. 100%
reversibility with ODQ. A series of N-phenylalkyl-N’-hydroxyguanidines were synthesised. NO
donor activity was found to be fairly constant up to three methylene groups, and then decreased.
Substitutions in the benzene ring of N-phenylethyl-N’-hydroxyguanidine demonstrated that
various electron-withdrawing and electron-donating groups in the para position did not
significantly affect the NO donor activity of this series of analogues. The nitro and
trifluoromethyl substituted compounds gave the best biological profiles. Additionally, a novel
heterocyclic, N–furfuryl-N’–hydroxyguanidine possessed very promising vasodilatation
properties. In general, almost all the N-arylalkyl-N’-hydroxyguanidines behaved as potent NO
donors in the rat aorta assay.
In order to establish the influence of the free NH₂ group in the hydroxyguanidine
functionality on the vasodilatation properties, N,N-dimethyl and N-methyl-N’-
hydroxyguanidines were successfully synthesised. Unfortunately, they have not been tested yet in
the biological assay. However, their NMR spectra showed some unusual features and their
detailed analysis and X-ray data are presented herein.
In addition a series of hydroxamic acids was synthesised and the NO donor activity
investigated using the same biological methodology. It was found that the
3-phenylpropionohydroxamic acid was the most potent compound with EC₅₀ = 6 μM and ODQ = 96%. However, behavior in the IPK indicated that hydroxamic acids did not undergo
the same biological pathway as in the rat aorta.
Two different types of enzyme-activated pro-drugs were designed using
N-hydroxyguanidines as the NO donating molecule. Synthetic studies towards these targets were
carried out using various synthetic approaches. The desired molecules have not yet been
synthesised but the chemistry explored so far has indicated potentially more successful
approaches that could be attempted
The strategies that peanut and nut-allergic consumers employ to remain safe when travelling abroad
No full textCopyright @ 2012 Barnett et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The article has been made available through the Brunel Open Access Publishing Fund.Background: An understanding of the management strategies used by food allergic individuals is needed as a prerequisite to improving avoidance and enhancing quality of life. Travel abroad is a high risk time for severe and fatal food allergic reactions, but there is paucity of research concerning foreign travel. This study is the first to investigate the experiences of, and strategies used by peanut and tree nut allergic individuals when travelling abroad. Methods: Thirty-two adults with a clinical history of reaction to peanuts or tree nuts consistent with IgE-mediated allergy participated in a qualitative interview study. Results: Travel abroad was considered difficult with inherent risks for allergic individuals. Many participants recounted difficulties with airlines or restaurants. Inconsistency in managing allergen avoidance by airlines was a particular risk and a cause of frustration to participants. Individuals used a variety of strategies to remain safe including visiting familiar environments, limiting their activities, carrying allergy information cards in the host language, preparing their own food and staying close to medical facilities. Conclusions: Participants used a variety of allergen avoidance strategies, which were mostly extensions or modifications of the strategies that they use when eating at home or eating-out in the UK. The extended strategies reflected their recognition of enhanced risk during travel abroad. Their risk assessments and actions were generally well informed and appropriate. A need for airline policy regarding allergy to be declared and adhered to is needed, as is more research to quantify the true risks of airborne allergens in the cabin. Recommendations arising from our study are presented.This study is funded by the UK Food Standards Agency under project code T07058
QPRTase: quinolinic acid analogue synthesis and non-enzymic decarboxylation of N-alkylquinolinic acids
No full textQuinolinate phosphoribosyltransferase (QPRTase, E.C. 2.4.2.19) is considered to be a unique enzyme in that it is thought to catalyse two distinct chemical reactions. Both the transfer of a phosphoribosyl group from 5-phosphoribosyl-1- pyrophosphate onto the nitrogen of quinolinic acid and the subsequent decarboxylation of the intermediate to form nicotinic acid mononucleotide are thought to be catalysed by the QPRTase system. Analogues of quinolinic acid were designed as potential inhibitors of QPRTase. These contain acidic groups at the 2- and 3- positions but are unable to decarboxylate. However, such compounds may be able to undergo the phosphoribosyl transfer reaction, potentially increasing their inhibitory potency. These compounds may be useful as "biological tools" allowing the neurological effects of an increase in quinolinic acid levels to be investigated. The compounds may show anti-fungal activity blocking the kynurenine pathway for NAD production. 2-Sulfonicotinic acid was synthesised by the oxidation of 2-mercaptonicotinic acid by either basic potassium permanganate, or iodine, with the structure was confirmed by X-ray crystallography. In biological testing the acid was shown to be neither an agonist nor antagonist of the NMDA receptor, or to be neurotoxic. A number of synthetic routes towards 2-phosphononicotinic acid, an alternative quinolinic acid analogue, were attempted though none were successful. These included orthometallation strategies and palladium coupling reactions to incorporate the phosphonic acid group at the 2- position. Nucleophilic addition routes, methods of building up the pyridine ring and including non-selective phosphonic acid addition were also examined. However, a related derivative, 2-(phosphonomethyl)nicotinic acid, was successfully synthesised. The non-enzymic decarboxylation of N-alkyl quinolinic acids was investigated, for comparison with the decarboxylation reaction catalysed by QPRTase. Both N- methyl and N-ethylquinolinic acid were synthesised, and the pH versus rate profiles measured. The rate maximum for both compounds was at pH 1.5, with the rate decreasing both above and below the maximum. N-Methylquinolinic acid was 10 times faster than quinolinic acid itself, demonstrating the effect of the nitrogen substituent. The N-ethyl derivative decarboxylated a further 1.5 times faster, showing the effect of increasing the size of the substituent. An Arrhenius plot was also carried out, giving an activation energy for the reaction of 153 kJ mol-1. Attempts to prepare the N-propyl derivative were unsuccessful, as decarboxylation occurred very readily to give N- propylnicotinic acid
Enzyme immobilisation and catalysis in ordered mesoporous silica
No full textA range of mesoporous materials based on SBA-15 have been prepared and characterised. The materials were templated by neutral block copolymer P123, and typically have a hexagonal (p6mm) pore structure, with high surface areas and narrow pore size distributions. The removal of the surfactant template by calcination and solvent extraction has been investigated. The aqueous stability of this material, and the hydrolysis of the surface was studied.
Organic functional groups were incorporated into the silica surface by co-condensation, or by post synthesis grafting. A range of functional groups were incorporated, including amine, carboxy, allyl and thiol groups. The pore size of the materials was controlled by the addition of trimethoxybenzene during synthesis, which significantly increased the pore size and uptake capacity of the materials.
The adsorption of CALB by SBA-15 was investigated, with support materials extracted by calcination or solvent extraction. Rapid uptake at high loading was observed, with a maximum loading of 450 mg g-1 measured. The leaching of the enzyme from the support was investigated, and found to be high with unfunctionalised supports. The leaching from functionalised supports incorporating sulfur groups was significantly reduced.
The activity of the immobilised CALB was measured by tributyrin hydrolysis in aqueous media, and by enantioselective transesterification of (R)-1-phenylethanol in organic media. The effect of surface functionalisation for reusability and thermal stability in aqueous systems was investigated.
Preliminary studies of supported CALB for dynamic kinetic resolution were carried out, with an investigation of acidic zeolites and a mesoporous supported catalyst for 1-phenylethanol racemisation. The encapsulation of immobilised CALB was investigated, and the activity and reusability of these systems studied
Language in autism and specific language impairment: Where are the links?
No full textIt has been suggested that language impairment in autism is behaviourally, neurobiologically, and etiologically related to specific language impairment (SLI). In this paper, we review evidence at each level and argue that the vast majority of data does not support the view that language impairment in autism can be explained in terms of co-morbid SLI. We make recommendations for how this debate might be resolved and we suggest a shift in research focus. We recommend that researchers concentrate on those aspects of language impairment that predominate in each disorder rather than on those comparatively small areas of potential overlap
Differentiating normal variability from inconsistency in children's speech: normative data
No full textBackground: In young, typically developing children, some word production variability is expected, but highly inconsistent speech is considered a clinical marker for disorder. Speech-language pathologists need to identify variability versus inconsistency, yet these terms are not clearly differentiated. Not only is it important to identify inconsistency, but also it needs to be defined and measured so that clinical decisions are evidence based. In order to understand inconsistent speech production, typical variability must be described. Aims: This paper differentiates between variability and inconsistent productions. Variability is defined as productions that differ, but can be attributed to factors described in normal acquisition and use of speech. Inconsistency is speech characterized by a high proportion of differing repeated productions with multiple error types, both segmental (phoneme) and structural errors (consonant-vowel sequence within a syllable). The study describes and quantifies the consistency of word production in typically developing children aged between 3;0 and 6;11 years. Methods and Procedures: This paper reports a large cross-sectional study (n = 409) of the consistency of children's production of words within the same linguistic context. Outcomes and Results: The study found that the speech of typically developing children is highly consistent. Children in the youngest age group demonstrated the highest levels of variability, but it remained below 13% with 10% reflecting maturational influences. Conclusions: Inconsistent production cannot be considered a typical feature of speech development. The results inform differential diagnosis of speech disorder
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