667 research outputs found
Estimated Contribution of Four Biotechnologies to New Zealand Agriculture
No full textThe impact of biotechnology is an important consideration for New Zealand. The country depends significantly on agricultural production and exports (Ministry of Agriculture and Forestry, 2004), and has relied in part on modern biotechnology for productivity increases over the last 20 years (Evenson & Gollin, 2003; Jacobsen & Scobie, 1999; Ovenden, Anderson, Armstrong, & Mitchel, 1985). A recent survey of individuals in agriculture and biotechnology generated a comprehensive list of products and processes that are derived from four specific biotechnologies and are commercially significant in agriculture (Kaye-Blake, Saunders, Emanuelsson, Dalziel, & Wreford, 2005). This innovative research generated primary data on the actual impacts that biotechnology is currently having on agricultural production and produced a unique dataset of biotechnology products and processes and their value to New Zealand agriculture. Analysis found that these four biotechnologies are contributing approximately 206 million per year to agriculture. This analysis, however, assumed perfectly elastic international prices, and thus that New Zealand agricultural producers would capture the benefits of increased productivity. Literature on the impacts of productivity increases suggests that the distribution of benefits from increased productivity depends on how widely a technology is adopted. For example, genetic improvements in the crops of one country can allow domestic producers to increase producer surplus at the expense of producers in the rest of the world (Frisvold, Sullivan, & Raneses, 2003). By contrast, domestic farmers may be worse off if innovations are adopted in both the home country and the rest of the world (Moschini, Lapan, & Sobolevsky, 2000). The literature also suggests that specific impact of a novel technology is important to its impacts on agricultural producers. For example, technology that increases yields may be less beneficial for farmers than technology that reduces costs (Moschini et al., 2000). In addition, innovations that increase productivity of commodity products with low price elasticities of demand may not benefit farmers as much as innovations that increase consumer demand for agricultural products (Saunders & Cagatay, 2003). These findings are relevant because some features of New Zealand's primary sector suggest that international price impacts may be important. New Zealand is an open economy (Ministry of Agriculture and Forestry (MAF), 2004) and a significant exporter on world markets, particularly in pastoral products (Ministry of Agriculture and Forestry (MAF), 2004; Saunders & Cagatay, 2003). Modelling the movement of international prices may be done in several ways. The general equilibrium GTAP model (Hertel, 1997), for example, has been used to examine the potential impacts of biotechnology on producer and consumer welfare assuming different levels of adoption and consumer acceptance (e.g., Anderson & Jackson, 2005; Stone, Matysek, & Dolling, 2002). These impacts have also been analysed with partial equilibrium models, in particular models derived originally from the Uruguay Round of trade negotiations (Roningen, 1997), such as SWOPSIM (Frisvold et al., 2003; Roningen, Dixit, Sullivan, & Hart, 1991) and LTEM (Saunders & Cagatay, 2003). Partial equilibrium models are particularly appropriate for analysing impacts on a single sector of the economy: they allow substantial disaggregation by commodity and examination of the linkages that lead to model results (Gaisford & Kerr, 2001). In order to investigate the possible impact of biotechnological innovations on commodity prices and agricultural producers, the results of the original findings based on elastic prices were incorporated into a partial equilibrium model of world agricultural commodity trade (Cagatay & Saunders, 2003; Saunders & Cagatay, 2003). The model contained 19 commodities, including the major trade commodities for New Zealand (dairy products and meat). World trade was divided into 17 countries and the rest of the world, including New Zealand as a separate entity as well as the US, EU, Australia, Japan and others. As a partial equilibrium model, it examined the agricultural sector in isolation from other sectors of the economy. The base year was 2000, and impacts were modelled to 2005. The base solution modelled current production, which included biotechnological innovations. Alternative scenarios modelled the impact of the absence or loss of biotechnological innovations. The first scenario modelled the absence of innovations in all countries, while the second scenario examined the impact of innovations specific to New Zealand. The contribution of biotechnology to productivity was assessed separately for each commodity, using the original dataset (Kaye-Blake et al., 2005). For each commodity in the model, the analysis calculated the change in producer prices and total producer returns (price x quantity). The modelling results conformed to expectations. In the first scenario, a worldwide reduction in productivity in the primary sector led market prices to adjust upward in response to the lower production. For the second scenario, the price impacts were smaller for sectors with innovations specific to New Zealand. These changes were then combined with the original, constant-price estimate to calculate price-adjusted figures. The constant price analysis found that the contribution of the biotechnologies was 206 million. The first modelling scenario found that the economic benefit of the biotechnologies was only 191 million, suggesting that adopting New Zealandspecific innovations might not have a large impact on aggregate trade and might have allowed domestic producers to capture much of the increased welfare from innovations. Economic impacts, however, were spread unevenly across the commodities. In both trade scenarios, dairy producers increased producer returns through biotechnology, regardless of how widely the innovations were adopted. Meat producers, on the other hand, improved their returns when the innovations were specific to New Zealand, but were somewhat worse off when the innovations were available worldwide. This research contributes to understanding of the impacts of biotechnology in several ways. First, the productivity impacts were based on empirical findings regarding estimated impacts of actual commercially released biotechnologies; these were estimates of impacts that have actually occurred. Secondly, the productivity effects varied by commodity in the model, so that the impacts on different commodities could be estimated. Finally, by using a disaggregated, multi-commodity model, the cross-effects from resources shifting into other agricultural uses could be captured.Research and Development/Tech Change/Emerging Technologies,
The model theory of generic cuts
No full textWe survey some properties of the recently discovered notion of generic cuts [6, 8], and discuss the model-theoretic context of these results for theo-ries of pairs (M, I) where I is a generic cut of a model M of Peano arithmetic. The main new results are that such pairs possess certain model completeness properties (Section 4), and they are existentially closed in a suitable category (Section 5). Part of this work is from the second author’s doctoral dissertation [14], written under the supervision of the first author. While this paper was being written, the second author was supported financially by the Department of Mathematics at the National University of Singapore. He would like to thank Professor Chitat Chong for this. We also wish to thank the anonymous referee, whose comments helped improve the quality of this paper. 1 Preliminaries For background in model theory, see Hodges [4]. Unless otherwise stated, we follow the notation in the books by Kaye [5] and by Kossak–Schmerl [12]. We fix some notation and repeat a few more relevant definitions here. The usual language for arithmetic {0, 1,+,×, <} is denoted by LA. Let LSk denote the Skolemised language for arithmetic, i.e., LSk contains, in addition to the symbols in LA, a function symbol fθ(x̄) for each formula θ(x̄, y) ∈ LA, intending to mean the least y satisfying θ(x̄, y). By ‘definable’, we always mean ‘definable with parameters’. All our types can only contain finitely many pa-rameters. We write Qx... for ‘there are cofinally many x such that... ’. Peano arithmetic is abbreviated as PA. A cut of a model of arithmetic is a nonempty proper initial segment I that has no maximum element. We write I ⊆e M for ‘I is a cut of M ’. If I is, in addition, an elementary substructure of the model, then we say that I is an elementary cut. Let c ̄ ∈ M | = PA. We denote by Aut(M) the automorphism group of M, and by Aut(M, c̄) the pointwise stabiliser of c ̄ in Aut(M). If X ⊆ M and f is a function with domain M, then Xf denotes the image of X under f, i.e., Xf = {f(x) : x ∈ X}. 1 Similarly, we sometimes write xf for f(x). Two cuts I, J ⊆e M are conjugate over c ̄ if there is g ∈ Aut(M, c̄) such that Ig = J. 2 Generi
Roles of TRIM24 in macrophage activation and experimental visceral leishmaniasis
No full textVisceral leishmaniasis (VL) causes immune and haematological dysfunction and is fatal in >95% of cases if left untreated. While macrophages are vital for efficient Leishmania parasite clearance, parasite-macrophage interactions are critical for VL progression. The transcription factor tripartite motif protein 24 (TRIM24) was recently predicted to be downregulated in an experimental VL mouse model. However, roles of TRIM24 in macrophage activation remain poorly understood, and have not been explored in VL. Here, we use TRIM24 knockout (KO) C57BL/6 mice to investigate roles of TRIM24 in bone marrow-derived macrophage (BMDM) activation in vitro, and the effects of TRIM24 deletion in an experimental model of VL in vivo using a combination of microscopy, flow cytometry, and single cell RNA sequencing (scRNA-seq).Firstly, we show that TNF and IL-6 production in KO BMDMs is unaffected after TLR4 stimulation. However, more nitric oxide was released by KO BMDMs, attributed to higher iNOS expression. Accompanying increases in IFNβ release and interferon response-related transcriptional signatures indicated an increased propensity for KO BMDMs to produce and respond to interferons. Uptake of L. donovani amastigotes was unaffected in KO BMDMs. ScRNA-seq of L. donovani-infected BMDMs revealed a metabolic shift in KO BMDMs towards parasite-permissive oxidative phosphorylation, while also potentiating interferon responses.Flow cytometric analysis of total KO lymphoid organs revealed the dispensability of TRIM24 during homeostatic leukocyte development. However, assessment of relative fitness during 50:50 mixed bone marrow (BM) chimeric reconstitution revealed an advantage of KO leukocytes in lymphoid organs, with 80% of BM CD45+ cells deficient in TRIM24 at 10 weeks post-reconstitution. L. donovani infection reduced this skew in spleen and liver but not in BM, identifying a potential role for TRIM24 in BM retention that persists during infection independently of the CXCR4-CXCL12 axis. Immune responses characteristic of VL were unaffected by TRIM24 deletion (IFNγ, TNF, IL-10, IL-6 production, granuloma size and number, Kupffer cell iNOS expression), and hepatic parasite burden was slightly increased. Elevated mRNA abundance of interferon-stimulated genes was observed in KO spleen 24 hours post-infection.Finally, we used scRNA-seq to report a transcriptional landscape of L. donovani-infected WT murine BM, providing evidence for an emergency myelopoiesis-promoting environment. Haematopoietic stem and progenitor cells were directly responding to CD4+ T cell-derived IFNγ, and we identify CD4+ T cells as a major source of Csf1 during infection. Ccl5 was expressed by several cell types, and parasite-permissive metabolic shifts were also observed, all contributing factors to myelopoiesis. These metabolic shifts were exacerbated by TRIM24 deletion, probably through modulation of mTOR signalling. This data therefore provides an interesting avenue for future investigation of TRIM24 in immunometabolism
Process versus product: which determines consumer demand for genetically modified apples?
No full textOne debate in the literature regarding consumers’ reactions to genetically modified food (GMF) centres on whether consumers react to the process of gene technology or to the specific GMF products. Results from a choice experiment survey in New Zealand indicate that consumers are heterogeneous with regard to GMF and that some modifications are viewed more positively than others. These findings suggest that for some consumers the process of gene technology is the decisive factor in evaluatingGMF, while for others the different potential GMF products are valued according to their enhanced attributes.choice modelling, consumer surveys, food, genetic modification, preferences, Consumer/Household Economics, Demand and Price Analysis,
Roles of TRIM24 in macrophage activation and experimental visceral leishmaniasis
No full textVisceral leishmaniasis (VL) causes immune and haematological dysfunction and is fatal in >95% of cases if left untreated. While macrophages are vital for efficient Leishmania parasite clearance, parasite-macrophage interactions are critical for VL progression. The transcription factor tripartite motif protein 24 (TRIM24) was recently predicted to be downregulated in an experimental VL mouse model. However, roles of TRIM24 in macrophage activation remain poorly understood, and have not been explored in VL. Here, we use TRIM24 knockout (KO) C57BL/6 mice to investigate roles of TRIM24 in bone marrow-derived macrophage (BMDM) activation in vitro, and the effects of TRIM24 deletion in an experimental model of VL in vivo using a combination of microscopy, flow cytometry, and single cell RNA sequencing (scRNA-seq).Firstly, we show that TNF and IL-6 production in KO BMDMs is unaffected after TLR4 stimulation. However, more nitric oxide was released by KO BMDMs, attributed to higher iNOS expression. Accompanying increases in IFNβ release and interferon response-related transcriptional signatures indicated an increased propensity for KO BMDMs to produce and respond to interferons. Uptake of L. donovani amastigotes was unaffected in KO BMDMs. ScRNA-seq of L. donovani-infected BMDMs revealed a metabolic shift in KO BMDMs towards parasite-permissive oxidative phosphorylation, while also potentiating interferon responses.Flow cytometric analysis of total KO lymphoid organs revealed the dispensability of TRIM24 during homeostatic leukocyte development. However, assessment of relative fitness during 50:50 mixed bone marrow (BM) chimeric reconstitution revealed an advantage of KO leukocytes in lymphoid organs, with 80% of BM CD45+ cells deficient in TRIM24 at 10 weeks post-reconstitution. L. donovani infection reduced this skew in spleen and liver but not in BM, identifying a potential role for TRIM24 in BM retention that persists during infection independently of the CXCR4-CXCL12 axis. Immune responses characteristic of VL were unaffected by TRIM24 deletion (IFNγ, TNF, IL-10, IL-6 production, granuloma size and number, Kupffer cell iNOS expression), and hepatic parasite burden was slightly increased. Elevated mRNA abundance of interferon-stimulated genes was observed in KO spleen 24 hours post-infection.Finally, we used scRNA-seq to report a transcriptional landscape of L. donovani-infected WT murine BM, providing evidence for an emergency myelopoiesis-promoting environment. Haematopoietic stem and progenitor cells were directly responding to CD4+ T cell-derived IFNγ, and we identify CD4+ T cells as a major source of Csf1 during infection. Ccl5 was expressed by several cell types, and parasite-permissive metabolic shifts were also observed, all contributing factors to myelopoiesis. These metabolic shifts were exacerbated by TRIM24 deletion, probably through modulation of mTOR signalling. This data therefore provides an interesting avenue for future investigation of TRIM24 in immunometabolism
Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy
No full textTo continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three-year progression of eteplirsen-treated patients was compared to matched historical controls (HC).
METHODS:
Ambulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open-label basis. The primary functional assessment in this study was the 6-Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.
RESULTS:
At 36 months, eteplirsen-treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen-treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.
INTERPRETATION:
Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257-271
Book Review Neurogenetics (Contemporary Neurology Series. 57.) Edited by Stefan-M. Pulst. 482 pp., illustrated. New York, Oxford University Press, 2000. $110. 0-19-512975-X
No full textEarly transition metal complexes of carbene donors linked to cyclopentadienyl ring analogues or amidine/amidinate moieties
No full textThe new indenyl-functionalised NHC potassium salt, 1-[3-(4, 7-dimethylindenylpropyl]-3-(2,6-diisopropylphenyl)imidazol-2-ylidenepotassium, has been synthesised. Complexes oftitanium, zirconium and chromium containing this ligand and the two carbon bridge analogue,1-[2-(4,7-dimethylindenyl)ethyl]-3-(2,6-diisopropylphenyl)imidazol-2 ylidene potassium,have been synthesised and characterised by X-ray crystallographic techniques. The followingcomplexes were tested as catalysts for the oligomerisation of ethylene in the presence ofMAO: 3-(2,6-diisopropylphenyl)-1-[2-(4,7-dimethylindenyl)ethyl]-imidazol-2-ylidene(tertbutylimido)titanium chloride, 3-(2,6-diisopropylphenyl)-1-[3-(4,7-dimethylindenyl)propyl]imidazol-2-ylidene(tert-butylimido)titanium chloride, 3-(2,6-diisopropylphenyl)-1-[3-(4,7-dimethylindenyl)propyl]imidazol-2-ylidenezirconiumtrichloride, 3-(2,6-diisopropylphenyl)-1-[2-(4,7-dimethylindenyl)ethyl]imidazol-2-ylidenezirconium trichloride, 3-(2,6-Diisopropylphenyl)-1-[2-(4,7-dimethylindenyl)ethyl]-imidazol-2-ylidenechromium dichloride, 3-(2,6-diisopropylphenyl)-1-[3-(4,7-(dimethylindenyl)propyl]imidazol-2-ylidene chromium dichloride, 3-(2,6-diisopropylphenyl)-1-[3-(4,7-dimethylindenyl)propyl]-imidazol-2-ylidene chromium methyl chloride and 3-(2,6-diisopropylphenyl)-1-[2-(4,7-dimethylindenyl)ethyl]-imidazol-2-ylidenevanadium dichloride.The following alkyl chromium complexes containing 1-[2-(4,7-dimethylindenyl)ethyl]-3-(2,6-diisopropylphenyl)imidazol-2 ylidene potassium have also been synthesised: 3-(2,6-diisopropylphenyl)-1-[2-(4,7-dimethylindenyl)ethyl]-imidazol-2-ylidene chromium phenylchloride and 3-(2,6-diisopropyl-phenyl)-1-[2-(4, 7-dimethylindenyl)ethyl]-imidazol-2-ylidenechromium dibenzyl. Chromium cations have been synthesised using as starting materials thechromium alkyl complexes. The Cr(II) complex 3-(2,6-diisopropyl-phenyl)-1-[2-(4, 7-dimethylindenyl)ethyl]-imidazol-2-ylidene chromium monochloride and a partially oxidiseddimerised product were also isolated. 5-(2-chloroethyl)- 1, 2, 3, 4-tetramethylcyclopentadieneand 5-(3-chloropropyl) 1, 2, 3, 4-tetramethylcyclopentadiene were synthesised and isolated asgeminal isomers for the first time.The trialkyl chromium complex, tribenzyl chromium tris(tetrahydrofuran) was synthesisedand also it was used as starting material for the complexes di(benzyl)chromium bis(1, 3-diisopropylimidazol-2-ylindene) and tri(benzyl)chromium TACN. All complexes werecharacterised by X-ray crystallography.The imidazolium salt 3-(2.6-diisopropylphenyl)-1-[N, N-bis(2,6-diisopropylphenyl)acetamidyl] imidazolium chloride was synthesised and used as a precursorfor the synthesis of amidinate-functionalised NHC zirconium and amidine-functionalisedNHC silver complexes. Double deprotonation of 3-(2,6-diisopropylphenyl)-1-[N, N’-bis(2,6-diisopropylphenyl)acetamidyl] imidazolium chloride gave the amidinate-functionalised NHCligand, 3-(2.6-diisopropylphenyl)-1-[2-N, N’bis(2,6diisopropylphenylamidinate)ethyl]imidazol-2-ylidenepotassium. Titanium, zirconium andchromium complexes containing this ligand were synthesised and characterised by X-raycrystallographic techniques. Transmetallation of the amidine-functionalised NHC silvercomplex with [Rh(COD)Cl]2 and [Ir(COD)Cl]2 gave the corresponding species. Rh(amidinefunctionalisedNHC)(COD)Cl reacted with Na(BAr)4 (Ar = 3,5-CF3C6H3) to give the cationRh(amidine-functionalised NHC)(COD)]+[BAr4]-. These species were also characterised byX-ray diffraction techniques
The ‘ph’ of English orthography; a digraph or a sequence of separate phonemes?
No full textThe aim of this short article is to offer a belated defense of L. M. Boyd (author of a daily, nationally syndicated column ‘Trivia’ in numerous newspapers throughout the USA) against a critique published in English Today over a decade ago by Alan S. Kaye (2006), and present arguments in support of Boyd's beleaguered claim. Kaye (2006: 54) writes:
I do not mean to be picking on Mr. Boyd, but considering his track record, perhaps the time has come for his quitting pontificating on matters of English grammar, pronunciation, and the history of the language.</jats:p
Ergot of rye - the first specific for migraine
No full textOver the past decade the various triptan derivatives have been accepted as the most effective available agents for relieving migraine attacks. Prior to that, for a period of half a century, ergotamine was the only 'specific' available for this purpose. In 1918, Stoll had isolated it from the various alkaloids present in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow on rye and, to a lesser extent, on other grasses. By 1925 ergotamine was beginning to be used to treat migraine attacks. However, as ergotamine was present in extracts of ergot, which had been used to treat migraine first, In Italy in 1862, and then by Edward Woakes (11868) in England, and after him by Albert Eulenburg in Germany (1883), the drug had actually come into unrecognised use for the disorder more than half a century before ergotamine itself was known to exist. Unfortunately, because of ergotamine's chemical and pharmacokinetic properties, extracts of ergot of rye were incapable of producing consistent therapeutic results, so that general acceptance that the first specific substance for migraine treatment existed had to wait until pure ergotamine was available for administration. (C) 2003 Elsevier Ltd. All rights reserved
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