O estudo de processos inflamatórios e infecciosos em Medicina Nuclear apresenta grande relevância para a clínica médica diagnostica. Enquanto em alguns casos o diagnóstico é óbvio, baseado na história clínica e exame físico do paciente, em outros é mais difícil, por serem assintomáticos ou por apresentarem sintomas não específicos. O diagnóstico precoce do processo inflamatório ou infeccioso permite tratamento rápido e também o impedimento de outras complicações. Além disto, a distinção entre inflamação e infecção é de extrema importância, bem como a provável localização. O uso de leucócitos radiomarcados, já estudados e aplicados em várias patologias, é o método de escolha para visualização de focos de infecção e inflamação. A cintilografia de leucócitos radiomarcados foi introduzida em 1976 por McAffe e Thakur e desde então é usada para diagnosticar diferentes patologias que envolvem infiltração leucocitária como distúrbios inflamatórios do intestino, infecção óssea ou prótese-vasculares entre outras. A marcação dos leucócitos in vitro pode ser realizada com 111In utilizando-se oxima ou tropolona como ligante ou com 99mTc, tendo a hexametilpropileno amino oxima (HMPAO) como ligante, resultando em um complexo lipofílico. A melhor disponibilidade, menor tempo de realização do exame, melhor propriedade física e menor dose de radiação para o paciente, resultou na preferência pelo agente HMPAO marcado com 99mTc, ao invés do 111In, para a maioria das indicações na maioria dos países. Entretanto, a marcação empregando o agente HMPAO apresenta como desvantagens a curta estabilidade do reagente marcado, as exigências relacionadas ao processo de marcação (tempo pós-eluição do 99mTc), além do custo elevado, pois se trata de produto importado. Este trabalho visou o desenvolvimento do reagente liofilizado de glucoheptonatoestanho para marcação de leucócitos com 99mTc in vitro pelo método de préestanização. A otimização da técnica de marcação foi realizada através da incubação dos leucócitos, isolados de sangue total, com diferentes volumes do reagente de glucoheptonato-estanho por diferentes tempos à 37°C (préestanização), com posterior marcação com 99mTc (185 MBq), incubados à temperatura ambiente por 20 minutos. O rendimento da marcação foi superior a 90% na condição ótima de marcação. O reagente liofilizado mostrou-se estável por mais de 90 dias. As imagens cintilográficas obtidas 1, 2 e 3 horas após a administração dos leucócitos radiomarcados em coelho New Zeland demonstraram a alta eficiência de marcação de processo inflamatório provocado a partir da administração local de terebentina. O método de marcação de leucócitos desenvolvido apresenta aplicação promissora na clínica médica, com proposta de redução de custo do procedimento, apesar de ser um procedimento mais demorado quando comparado ao procedimento que utiliza o quelante lipofílico de HMPAO. / The study and localization of inflammatory and infection process in Nuclear Medicine represents a relevant tool in diagnostic procedures. In same cases, the diagnostic is easy and based on anamnesis and clinical observation; in other cases, the patients are asymptomatic or present non specific symptoms that difficult the diagnostic. The early diagnostic of inflammatory or infectious process allow the early introduction of therapy and prevents complications. Farther, the differentiation between inflammation and infection is of extreme importance as well as the localization of the focus. The use of labeled leucocytes, studied and applied in much pathologies, is the method of choice for the visualization of inflammation and infection. The scintigraphy using labeled leucocytes was introduced at 1976 by McAffe and Thakur and since of this is used in the diagnostic of different pathologies related to leucocyte infiltration like intestinal inflammatory disease, bone or prosthetic-vascular infections. The in vitro labeling of leucocytes with 111In was performed using oxime or tropolone as ligand and with 99mTc using hexamethylpropylene amine oxime (HMPAO) as ligand, resulting in a lipophilic complex. The 99mTc-HMPAG complex was preferably employed in many indications and countries do to the ideal physical properties of 99mTc that results in low dose to the patient. However, the labeling employing the HMPAO complex results in some disadvantages like the low stability of the complex, and some requirements related to the 99mTc elution (like the time pos elution), beyond the high cost of the compound that is imported. The aim of this work was the development of a tin-glucoheptonate lyophilized kit for in vitro leucocytes labeling with 99mTc using the pre-stannization method. The optimization of the labeling technique was developed using leucocytes isolated from total blood and employing different volumes of the tinglucoheptonate reagent and different incubation times at 37 deg C (pre-stannization), and posterior labeling with 99mTc (185 MBq), after 20 minutes reaction at room temperature. The labeling yield was superior to 90% using the optimized labeling conditions. Lyophilized reagent was stable after 90 days. Scintilographic images obtained 1, 2 e 3 hours after the administration of labeled leucocytes in New Zealand rabbit, showed good uptake on inflammatory focus promoted by tupertine injection. The leucocytes labeling method developed can be probably applied in clinical procedures and represents cost effective method in substitution of the lipophilic complex of HMPAO.

Les isoprénoïdes, présents dans tous les organismes vivants, sont synthétisés selon deux processus: la voie du Mevalonate et la voie Méthylérythritol phosphate (MEP). Cette dernière, absente chez l’humain, est très étudiée car elle représente une cible pour le développement de nouveaux antimicrobiens. Le ME-N3, un analogue du méthylérythritol portant un azoture, a été synthétisé et exploité dans des expériences de marquage métabolique de la voie MEP en utilisant un couplage bioorthogonale suivi d’une analyse par LC/MS. De façon intéressante, nous avons découvert que le MEP-N3, un analogue du MEP, inhibe l'enzyme IspD d’ E. coli (3ème enzyme de la voie MEP). Les études cinétiques ont révélé que le MEP-N3 possède la meilleure activité inhibitrice sur IspD d’ E.coli en comparaison avec les inhibiteurs connus, et que le mécanisme d'inhibition est de type mixte. Une étude détaillée du mécanisme de la réaction catalysée par IspD a été réalisée pour la première fois, en utilisant une analyse cinétique à deux substrats. / Isoprenoids, present in all living organisms, are synthesised according to two routes: the Mevalonate and the Methylerythritol phosphate (MEP) pathways. The MEP pathway, absent in humans, is extensively investigated as it is a target for the development of new antimicrobials. ME-N3 an azide tagged analogue of methylerythritol was synthesised and utilised for metabolic labelling studies of the MEP pathway using bioorthogonal ligation followed by LC-MS analysis. Interestingly, we found that MEP-N3, an analogue of MEP, inhibits E.coli IspD (3rd enzyme of the MEP pathway). Further inhibition kinetic studies revealed that MEP-N3 possesses the highest inhibitory activity on E.coli ispD when compared to known inhibitors. In addition, the mechanism of inhibition of E.coli ispD by MEP-N3 was found to be best described using a mixed type model. Moreover, determination of the IspD reaction mechanism has been carried out for the first time, by virtue of a bisubstrate steady state kinetic analysis.

No description available.

隨著消費者開始意識到自身的購買行為對於環境的影響，環境友善的產品也越來越受歡迎．碳足跡標籤，也就是在標籤上註明一件產品的生命週期所產生的所有碳排放，而其過程就包括了從原料取得到最後被丟棄的整個產品生命週期．產品碳足跡標籤讓消費者了解產品的環境友善程度，也幫助消費者做對環境友善的購買決策．碳足跡標籤也讓消費者成為帶動更永續的未來的主要推力，並激勵企業製造碳足跡較低的產品來維持競爭力． 碳足跡標籤已在全球成為一個越來越普遍的行為，而台灣也正開始推動碳足跡標籤方案．此論文深入研究已發展國家包括英國，美國，法國，日本以及跨國公司包括Walkers，Walmart和Casion Group如何導入碳足跡標籤方案． 接下來將探討台灣以及台灣企業是如何將碳足跡標籤導入到公司以及過程中所碰到的問題與機會． 在台灣企業的部分，宏碁以及泰山為研究對象，由於這兩家企業都是在碳足跡標籤方案的先驅者，並且為不同的產業背景，因此挑選了這兩家深入研究，並探討不同產業導入碳標籤方案的作法． / As consumers become conscious of the impacts of their purchase decision on the environment, environmental friendly products become increasingly popular. By indicating the amount of carbon dioxide produced and emitted throughout a product’s life cycle, from material acquisition to manufacturing to consumption, carbon footprint label give consumers the information to make earth-friendly purchase decisions. Carbon footprint label also makes consumers the driver of a more sustainable future by incentivizing businesses to make lower GHG-content products to increase the competitiveness of products. Carbon footprint label is becoming a popular practice around the world. Taiwan is also learning and doing carbon footprint labelling. This dissertation investigates how carbon footprint labelling is done in advanced countries including the United Kingdom, the United States, France, and Japan and multinational companies including Walkers, Walmart and Casino Group. Then it investigates how carbon footprint labelling is done in Taiwan and how Taiwan businesses approach carbon footprint labelling. Two companies of different industry were interviewed to gain an in-depth understanding of how and why Taiwan businesses implement carbon footprint labelling. From the interviews, insights of the motivation, project planning, execution and questions encountered during the implementation of carbon footprint labelling were revealed. The dissertation then concludes by discussing the limitations that happened during the research and the suggestions for the development of Taiwan’s carbon footprint label.

<p>One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter ¹¹C (t_½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [¹¹C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [¹¹C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and ¹H and ¹³C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed.</p><p>[<i>carbonyl-</i>¹¹C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [<i>carboxyl-</i>¹¹C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [<i>carbonyl-</i>¹¹C]Esters were synthesized using primary and secondary alcohols, <i>tert-</i>butanol, and phenol. Bases were KOH, BuLi, LiHDMS.</p><p>The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases.</p><p>A mild procedure for the ¹¹C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide.</p><p>Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [<i>carbonyl</i>-¹¹C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps.</p><p>In addition, several (¹³C)compounds were synthesised using the described methods.</p><p>Free radical carbonylation may be used for the ¹¹C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.</p>

One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter 11C (t½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [11C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [11C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and 1H and 13C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed. [carbonyl-11C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [carboxyl-11C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [carbonyl-11C]Esters were synthesized using primary and secondary alcohols, tert-butanol, and phenol. Bases were KOH, BuLi, LiHDMS. The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases. A mild procedure for the 11C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide. Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [carbonyl-11C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps. In addition, several (13C)compounds were synthesised using the described methods. Free radical carbonylation may be used for the 11C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.

Chemical biology encompasses the study and manipulation of biological system using chemistry, often by virtue of small molecules or unnatural amino acids. Much insight has been gained into the mechanisms of biological processes with regards to protein structure and function, metabolic processes and changes between healthy and diseased states. As an ever expanding field, developing new tools to interact with and impact biological systems is an extremely valuable goal. Herein, work is described towards the synthesis of a small library of heterocyclic-containing small molecules and the mechanistic details regarding the interesting and unexpected chemical compounds that arose; an alternative set of non-toxic copper catalyzed azide-alkyne click conditions for in vivo metabolic labelling; and the synthesis of an unnatural amino acid for further chemical modification via [3+2] cycloadditions with nitrones upon incorporation into a peptide of interest. Altogether, these projects strive to supplement pre-existing methodology for the synthesis of small molecule libraries and tools for metabolic labelling, and thus provide further small molecules for understanding biological systems.

The 2004 Canadian Community Health Survey (CCHS) revealed many indicators of poor diet quality in Canada which, together with the high rates of obesity and diet-related chronic disease, suggest that shifts in dietary patterns are urgently needed. Given the widespread promotion of foods on the basis of nutrition and health, the aim of this work was to explore the population health implications of voluntary food fortification and nutrition-related marketing in Canada. Using the CCHS, the potential impact of a proposed discretionary food fortification policy on nutrient inadequacies and excesses was examined, in addition to the relationship between consumption of foods eligible to be fortified under this policy and indicators of dietary quality. To better understand the potential risk associated with liberal fortification practices, the National Health and Nutrition Examination Survey (2007-08) was used to examine potential for risk of excess associated with voluntarily fortified food consumption in the US, where these practices have long been permitted. The results suggest that proposed changes to voluntary fortification may reduce inadequacy and increase excess, and may reinforce poor diet patterns. Excessive nutrient intakes were also found to be associated with consumption of voluntarily fortified foods in the US, particularly among children. Therefore, there appears to be real potential for risk associated with voluntary fortification practices in Canada. The extent, nature, and population health implications of nutrition marketing in Canada was examined, using a survey of front-of-package nutrition-related marketing on foods within three large grocery stores in Toronto. Nutrition-related marketing was found on 41% of all foods surveyed, and was widely found on highly processed, often fortified foods. References to nutrients of public health concern (e.g. sodium, vitamin D) were infrequently found. Overall, this practice provides limited nutritional guidance. Current directions in nutrition policy in Canada should be re-evaluated, to ensure that they support healthy diet patterns.

Chemical biology encompasses the study and manipulation of biological system using chemistry, often by virtue of small molecules or unnatural amino acids. Much insight has been gained into the mechanisms of biological processes with regards to protein structure and function, metabolic processes and changes between healthy and diseased states. As an ever expanding field, developing new tools to interact with and impact biological systems is an extremely valuable goal. Herein, work is described towards the synthesis of a small library of heterocyclic-containing small molecules and the mechanistic details regarding the interesting and unexpected chemical compounds that arose; an alternative set of non-toxic copper catalyzed azide-alkyne click conditions for in vivo metabolic labelling; and the synthesis of an unnatural amino acid for further chemical modification via [3+2] cycloadditions with nitrones upon incorporation into a peptide of interest. Altogether, these projects strive to supplement pre-existing methodology for the synthesis of small molecule libraries and tools for metabolic labelling, and thus provide further small molecules for understanding biological systems.

As SMEs transformation to sustainable practices in manufacturing, processing and services, is declared to be the key to a green growth model, the research in this thesis aims to understand in what way eco-labelling can be a part of that. In order to approach this complex issue, the thesis aims to identify the greening potential and the limits of contemporary eco-labelling schemes for SME product within the German coffee-processing sector. With regard to that, the thesis applied the policy evaluation method "Program Theory Evaluation" (PTE), which assesses a policy in place and thus provides information how the introduction and the function of eco-labelling schemes is observed and perceived by German coffee-processing SMEs (GCPS). Hence, based on a policy evaluation from a rational perspective, which has the focus on the policy’s problem-solving process and implementation cycle, the thesis reveals how eco-labelling schemes’ underlying theoretical greening strategy act in practice to German coffee-processing SME (GCPS). Thereby it could be evaluated that eco-labelling schemes imply shortcomings to address and green GCPS high quality coffee products. As the PTE-method aims also on optimizing the policy’s rationalisation, the inappropriate or failed implementation of eco-labelling schemes by GCPS has been further explored. To grasp the eco-labelling schemes extent of limits to green GCPS products, the thesis compares and analyses the policy evaluation results against the backdrop of eco-labelling schemes’ normative theoretical policy conception and in the light of "Environmental Authority of Political Consumerism (Ecological Modernisation Theory)". With regard to that, the thesis fosters a policy learning process and uncovers that eco-labelling scheme eco-labelling schemes potential to green GCPS products is limited and conditioned to this a lower level of sustainable value as they are focused to supply mainly the demand for mainstream coffee products. Hence, the thesis concludes that it is not the underlying rationality of eco-labelling schemes, namely being a consumer-oriented and market-based policy instrument that does not apply to green GCPS products. However, this opens up a new perspective as it points out a sustainable quality gap between products using eco-labelling schemes and non-labelled GCPS high quality products. In return this raises considerations in terms of improving eco-labelling schemes’ contribution to sustainable development. Thus the thesis argues to optimize their rationalization with regard to GCPS high quality products as frontrunners of tomorrow’s sustainability.