Nanoscintometry : a pathway to absolute dosimetry of ionising radiations.

It is now accepted that the deleterious effects induced by ionising radiations in mammalian cells are caused by the simultaneous breaking of both strands of the DNA helix by a single track. These effects are optimised when the mean free path of primary ionisation. lambda, matches the 2 nanometre mean chord distribution of DNA. However, there is currently no method of measuring radiation damage in terms of lambda. The aim of this project has been to design and construct a detector with a lambda response function capable of providing a measure of the absolute biological effectiveness of a radiation, independent of radiation type. Organic scintillation molecules, in the condensed phase, have been identified as being most suitable for bio-effectiveness measurements. Tissue equivalent and of comparable interaction cross-section, these nanodetectors are capable of signalling individual interactions with the emission of a scintillation photon, or scinton. Using a 20 mum scintillation film and DEP hybrid photodiode, spectra containing single and plural scinton events were recorded. These spectra reveal unique differences in the radiation quality of photon-emitting radioisotopes. A model of radiation action on scintillators in the condensed phase, analogous to the direct and indirect actions observed in intra-cellular DNA, has been developed and used to predict the characteristic yields of single and plural scinton events. The model was further developed to provide probabilities of paired' scinton events originating from fluor sites with a mean spacing of 2 nm. These critical 'paired' events are representative of double strand breaks and interpretation of these events that will yield bio-effectiveness data. Using Poisson distributions, a scintillator with optimised fluor concentration was developed for use in bio-effectiveness detectors. Loss calculations within the detector revealed an inconsistency in exponential attenuation theory, which appears to be inadequate when applied to light-guides. Consequently a new model of photon transport in light-pipes based on a Monte Carlo simulation has been developed and offers a more rigorous alternative. Calibration of the detector highlighted the need for a simple yet effective technique for photomultiplier tube (PMT) gain calibration in the laboratory. A technique using Cerenkov radiation was developed and provides good correlation with published gain figures. Although this prototype detector has not yet been fully tested, nor the associated bio-effect model fully developed to allow extraction of bio-effectiveness data from the collected spectra, preliminary results suggest this technique to be promising alternative and offers a route towards the measurement of absolute dosimetry with potential application in radiotherapy and radiation protection

Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug

AbstractAnti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling

Who Produces for Whom in the World Economy?

International audienceFor two decades, the share of trade in inputs, also called vertical trade, has been dramatically increasing. In reallocating trade flows to their original input-producing industries and countries, this paper suggests a new measure of international trade: "value-added trade" and makes it possible to answer the question "who produces for whom?". In 2004, 27% of international trade was vertical trade. The industrial and geographic patterns of value-added trade are very different from those of standard trade. Value-added trade is relatively less important in regional trade but the difference is not more important for Asia than for AmericaLa part du commerce en produits intermédiaires dans le commerce international, appelé aussi "commerce vertical", n'a cessé d'augmenter depuis vingt ans. Cet article propose une nouvelle mesure du commerce international "le commerce en valeur ajoutée" qui réalloue les flux commerciaux aux pays et aux secteurs produisant les intrants. Les répartitions géographique et sectorielle du commerce en valeur ajoutée sont très différentes de celles du commerce " standard ". La différence entre le commerce en valeur ajoutée et le commerce standard est plus importante dans le cas du commerce régional mais ce n'est pas plus le cas en Asie qu'en Amérique

Parental experiences and perceptions of infant complementary feeding: a qualitative evidence synthesis

peer-reviewedBackground Interventions to prevent childhood obesity increasingly focus on infant feeding, but demonstrate inconsistent effects. A comprehensive qualitative evidence synthesis is essential to better understand feeding behaviours and inform intervention development. The aim of this study is to synthesize evidence on perceptions and experiences of infant feeding and complementary feeding recommendations. Methods Databases CINAHL, EMBASE, MEDLINE, PsycINFO, Academic Search Complete, SocIndex and Maternity and Infant Care were searched from inception to May 2017. Eligible studies examined parents' experiences of complementary feeding of children (ACCEPTEDpeer-reviewe

Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern

To support efforts to develop a ‘synthetic biology’ based on an artificially expanded genetic information system (AEGIS), we have developed a route to two components of a non-standard nucleobase pair, the pyrimidine analog 6-amino-5-nitro-3-(1′-β-D-2′-deoxyribofuranosyl)-2(1H)-pyridone (dZ) and its Watson–Crick complement, the purine analog 2-amino-8-(1′-β-D-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (dP). These implement the pyDDA:puAAD hydrogen bonding pattern (where ‘py’ indicates a pyrimidine analog and ‘pu’ indicates a purine analog, while A and D indicate the hydrogen bonding patterns of acceptor and donor groups presented to the complementary nucleobases, from the major to the minor groove). Also described is the synthesis of the triphosphates and protected phosphoramidites of these two nucleosides. We also describe the use of the protected phosphoramidites to synthesize DNA oligonucleotides containing these AEGIS components, verify the absence of epimerization of dZ in those oligonucleotides, and report some hybridization properties of the dZ:dP nucleobase pair, which is rather strong, and the ability of each to effectively discriminate against mismatches in short duplex DNA

Crop Updates 2001 - Oilseeds

ABSTRACT This session covers twenty five papers from different authors: FORWARD, Mervyn McDougall, CHAIRMAN, PULSES AND OILSEEDS PARTNERSHIP GROUP PLENARY 1. Implications of the ‘green-bridge’ for viral and fungal disease carry-over between seasons, Debbie Thackray, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 2. Insect pest development in WA via the ‘green-bridge’, Kevin Walden, Agriculture Western Australia VARIETIES 3. Performance of new canola varieties in AGWEST variety trials, G. Walton, Crop Improvement Institute, Agriculture Western Australia 4. New herbicide tolerant varieties in WA, Kevin Morthorpe, Stephen Addenbrooke, Pioneer Hi-Bred Australia P/L 5. IT v’s TT – Head to head, Paul Carmody, Centre for Cropping Systems, Agriculture Western Australia ESTABLISHMENT 6. Effect of stubble, seeding technique and seed size on crop establishment and yield of canola, Rafiul Alam, Glen Riethmuller and Greg Hamilton, Agriculture Western Australia 7. Canola establishment survey 2000, Rafiul Alam, Paul Carmody, Greg Hamilton and Adrian Cox, Agriculture Western Australia 8. Tramline farming for more canola, Paul Blackwell, Agriculture Western Australia NUTRITION 9. Comparing the phosphorus requirement of canola and wheat in WA, M.D.A. Bolland and M.J. Baker, Agriculture Western Australia 10. Will a rainy summer affect nitrogen requirement: Tailoring your fertiliser decisions using the new nitrogen calculator, A.J. Diggle, Agriculture Western Australia 11. Canola – More response to lime, Chris Gazeyand Paul Carmody, Centre for Cropping Systems, Agriculture Western Australia AGRONOMY 12. Hormone manipulation of canola development, Paul Carmody and Graham Walton, Agriculture Western Australia 13. Yield penalties with delayed sewing of canola, Imma Farre, CSIRO Plant Industry, Michael J. Robertson, CSIRO Sustainable Ecosystems, Graham H. Walton, Agriculture Western Australia, Senthold Asseng, CSIRO Plant Industry 14. Dry matter and oil accumulation in developing seeds of canola varieties at different sowing dates, Ping Si1, David Turner1 and David Harris2 , 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2Chemistry Centre of Western Australia 13. Simulating oil concentrations in canola – virtually just the beginning, David Turner1 and Imma Farré2, 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2CSIRO Plant Industry, Centre for Mediterranean Agricultural Research PESTS AND DISEASES 14. Further evidence that canola crops are resilient to damage by aphids, Françoise Berlandier and Christiaan Valentine, Entomology, Agriculture Western Australia 15. Management of Diamondback moth (DBM) in canola, David Cook, Peter Mangano, David Cousins, Françoise Berlandier, and Darryl Hardie, Crop Improvement Institute,Agriculture Western Australia 16. Effect of time of sowing in conjunction with fungicides on blackleg and yield of canola, Ravjit Khangura and Martin Barbetti, Agriculture Western Australia 17. Further developments in forecasting aphid and virus risk in canola, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 18. Efficiency of selected insecticides for the use on Diamondback Moth in canola, Kevin Walden, Agriculture Western Australia 19. Impact® applied ‘in furrow’ controls blackleg in canola, Cameron Weeks and Erin Hasson, Mingenew-Irwin Group Inc. 20. Effect of time of sowing and Impact® on canola yield, Esperance, Dave Eksteen, Agriculture Western Australia 21. Australian Plague Locust Campaign 2000, Kevin Walden, Agriculture Western Australia WEED CONTROL 22. New herbicide options for canola, John Moore and Paul Matson, Agriculture Western Australia HARVESTING 23. Effects of time of swathing and desiccant application on the seed yield and oil content of canola, Carla Thomas and Lionel Martin, Muresk Institute of Agriculture, Curtin University of Technology DECISION SUPPORT AND ADOPTION 24. Using canola monitoring groups to understand factors affecting canola production in Esperance, Dave Eksteen, Agriculture Western Australia 25. Nitrogen and canola, Dave Eksteen, Agriculture Western Australi

Metformin selectively targets redox control of complex I energy transduction

Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled

Soluble FLT1 Gene Therapy Alleviates Brain Arteriovenous Malformation Severity

Background and purposeBrain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. Excessive vascular endothelial growth factor has been implicated in bAVM pathophysiology. Because soluble FLT1 binds to vascular endothelial growth factor with high affinity, we tested intravenous delivery of an adeno-associated viral vector serotype-9 expressing soluble FLT1 (AAV9-sFLT1) to alleviate the bAVM phenotype.MethodsTwo mouse models were used. In model 1, bAVM was induced in R26CreER;Eng2f/2f mice through global Eng gene deletion and brain focal angiogenic stimulation; AAV2-sFLT02 (an AAV expressing a shorter form of sFLT1) was injected into the brain at the time of model induction, and AAV9-sFLT1, intravenously injected 8 weeks after. In model 2, SM22αCre;Eng2f/2f mice had a 90% occurrence of spontaneous bAVM at 5 weeks of age and 50% mortality at 6 weeks; AAV9-sFLT1 was intravenously delivered into 4- to 5-week-old mice. Tissue samples were collected 4 weeks after AAV9-sFLT1 delivery.ResultsAAV2-sFLT02 inhibited bAVM formation, and AAV9-sFLT1 reduced abnormal vessels in model 1 (GFP versus sFLT1: 3.66±1.58/200 vessels versus 1.98±1.29, P<0.05). AAV9-sFLT1 reduced the occurrence of bAVM (GFP versus sFLT1: 100% versus 36%) and mortality (GFP versus sFLT1: 57% [12/22 mice] versus 24% [4/19 mice], P<0.05) in model 2. Kidney and liver function did not change significantly. Minor liver inflammation was found in 56% of AAV9-sFLT1-treated model 1 mice.ConclusionsBy applying a regulated mechanism to restrict sFLT1 expression to bAVM, AAV9-sFLT1 can potentially be developed into a safer therapy to reduce the bAVM severity

Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.</p> <p>Methods</p> <p>We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.</p> <p>Discussion</p> <p>Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.</p

Nonerosive Reflux Disease (NERD) - An Update

Recognizing nonerosive reflux disease (NERD) as a distinct presentation of gastroesophageal reflux disease (GERD) was one of the most important developments in the field of GERD in the last decade. Whilst the definition of NERD has not changed significantly over the years, the disorder accounts for the majority of the GERD patients and those who failed proton pump inhibitor (PPI) treatment. Recent developments in NERD focused primarily on understanding the pathophysiology and natural history. The introduction of esophageal impedance + pH has led to the assessment of other forms of gastroesophageal reflux in causing NERD. Therapeutic modalities still focus on acid suppression, but there is growing recognition that other therapeutic strategies should be considered in NERD