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GMOs Across the Atlantic
GMOs Across the AtlanticSacrificing Precaution in the Name of Free Trade?Kofi Annan once said “[…] that arguing against globalisation is like arguing against the laws of gravity”. The world has evolved into a place of omnipresent interconnectivity where people are linked across borders by economic, political, friendly and family ties. Although risks have likewise become globalised in the process, risk management still largely constitutes a national issue. While transnational food scandals as the BSE crisis in 1997 or the horse meat scandal of 2013 have shaken consumers within and beyond the European Union (EU), Member States (MS) nonetheless continue to insist on their sovereignty to approach and handle uncertain risks by themselves. There are a variety of levels related to dealing with uncertain risks that are affected by this controversy. Amongst them are science as in risk assessment, law as in risk regulation and politics as in risk management and the overall coordinating risk governance processes. As neither science or law nor politics are able to provide fully sound and satisfying solutions for coping with uncertain risks, controversy and heated debate remains even long after a political decision has been made on a case. It is striking how all these disciplines attempt to appropriately respond to uncertainty, while they do actually add more complexity and differing opinions. There consequently is no solid ground for policy-makers to base their final decisions on and justify the particular regulation or acceptance of risks. It remains an issue how politics can effectively work in light of uncertainty. This is especially important when considering the effects of globalisation. Through international trade and the flow of goods through the world economy, products associated with uncertain risk cross national borders on a daily basis and need to be regulated. The ongoing negotiations on a free trade agreement between the European Union and the United States of America have highlighted the difficulties regarding this process. If successfully concluded, supposedly by the end of 2014, the Transatlantic Trade and Investment Partnership (TTIP) would constitute the largest free trade zone worldwide and both the EU and the US would benefit tremendously. However, negotiations have not gone so smoothly due to prevailing disagreement over the rules that should apply for the TTIP. With regards to food safety, the EU and the US have already had difficulties in the past to agree on a common denominator. Related differences and incompatibilities become evident in the debate on food safety. Although consumer protection is a highlyranked principle for both parties, there is little agreement on what requires strict protective measures and what should be regulated only mildly. In the past and recently, problematic issues for the EU have included US exports of genetically modified crops into the EU as well as meat imports from American hormone-treated or -fed animals and chicken meat that was treated with chlorine. On the part of the US, concerns have mostly been about EU lactic-acid washed meat, raw milk cheese and dairy imports into the States. Both parties have according precautionary measures in place, but request each other to drop the various bans and ease regulatory practices and processes on other products
BMI1 and KAP1 interaction and function: BMI1 capped by KAP1?
The Polycomb-repressive complex 1 (PRC1) protein BMI1 is of major importance in the epigenetic regulation of gene expression. The repression of important tumour suppressor genes (such a P16INK4a and P14ARF) by means of chromatin remodeling has marked BMI1 as a proto-oncoprotein. We previously found evidence that posttranslational modification by phosphorylation may be implicated in the stability and functioning of BMI1. Furthermore, we found that KAP1, through direct interaction with BMI1, may be implicated in regulation of BMI1 functioning. I here begin to elucidate how phosphorylation affects BMI1 and how KAP1 regulates BMI1. Several U2OS or TIG3ER cell lines were created that overexpressed BMI1 wild type and mutants that either contain phospho-mimic or phospho-null mutations. shRNA’s were used to effectively knockdown KAP1 expression. The effect of BMI1 mutant overexpression and/or KAP1 knock down on proliferation was measured under cell stress conditions induced by arsenite, selenite or etoposide. The effect of KAP1 knock down and mutant KAP1 lacking the RingFinger domain (KAP1-DeltaRF) on sub-cellular localization was assessed in U2OS cells. Finally functional interaction between KAP1 and PRC1 was measured by analysis of transcriptional induction of the PRC1-target gene ATF3 upon mitogenic stimulation. BMI1 overexpression partially rescues arsenite induced senescence; this rescue activity is affected by its phosphorylation status. KAP1 knockdown increases the effect of BMI1 overexpression on proliferation under arsenite induced cell stress but ablates the differences observed between different BMI1 phospho-mutants. KAP1 induced increases of ATF3 induction point towards a functional interaction between KAP1 and PRC1. My experiments provide experimental indication that BMI1 affects proliferation under arsenite induced cell stress condition. This effect was enhanced by KAP1 knockdown suggesting that KAP1 inhibits the pro-proliferative effects of BMI1. Increased ATF3 induction in the presence of KAP1-DeltaRF mutant protein suggests that the KAP1 negatively controls expression of ATF3 in a RF-dependent manner. Further research is required to elucidate the exact molecular mechanisms underlying the function interaction of BMI1 and KAP1.
The paradoxical influence of the pKa on the reactivity of thiols and its biological relevance
Background. Not much is known about the factors that influence thiol reactivity. In this paper we will investigate the paradoxical influence of the acid dissociation constant (pKa). The pKa influences the deprotonation of a compound. This deprotonation gives thiols a negative charge and therefore increases reactivity. Compounds with a low pKa have a higher percentage of deprotonation, this will lead to a higher reactivity. On the other side, thiols with a higher pKa have a higher electron density, and are therefore also more reactive. We want to recognize this paradox and investigate what the exact contribution of these two paradoxical mechanisms is with respect to the reactivity of thiols. Furthermore we will discuss the biological importance of this study with respect to the anti-oxidant system and drug conjugation. Methods. The reactivity of the thiols was determined by calculating the rate constant of these compounds. This was done for different thiols in reaction with 1-chloro-2,4- dinitrobenzene. To do this we created a pseudo first order reaction by adding an excess of CDNB. The thiols we used in this reaction were glutathione, 5-thio-2-nitrobenzoic acid, 2-mercaptoethanol and 2-mercaptobenzothiazole. The reaction rates were measured, using a spectrophotometer and eventually the reaction constant was calculated and transformed into the reactivity of the thiolate ion. Results. The reaction constants from the different thiols are dependent on the fraction thiolate ion. This was converted to the reactivity of the thiolate ion. The reactivity of thiolate ion decreases as pKa value increases. Conclusion. There is indeed a paradoxical influence of the pKa value on the reactivity of thiols. Increases in pKa lead to decreases in reactivity of the thiolate ion but to increases in the fraction of the thiolate ion. Eventually there was no mechanism that had the biggest contribution to the reactivity for all conditions. Apparently this is dependent on the pH. We advice drug researchers to keep this paradox in mind in order to estimate the reactivity of thiols
Preface
This book includes the professional papers that the members of MCT PREMIUM Honours team 2013/2014 have written during the program. Each team member completed an individual professional tax paper. The topics of these individual papers cover a broad range of issues from international commercial tax to transfer pricing, and from VAT to the FTT and the application of the equality principle to the Dutch business succession rules. This wide spectrum of tax issues shows the candidates’ broad professional orientation on taxation and their ability to translate the theory of law to its effects in real life. The team also wrote reports in subteams on the three tax seminars that they attended. Jointly, they wrote a professional conference report on the first Global Tax Policy Conference held at the Royal Academy of Sciences in Amsterdam on 6 March 2014. The results of their work show the broad scope and deep understanding of professional tax matters of these talented young tax experts.
Being kind to my socially anxious mind; A study of the relationship between selfcompassion and social anxiety
Self-compassion is a relatively new construct in Western psychology. It involves a kind and accepting attitude towards oneself during failure, when experiencing difficulties, or disliking an aspect of oneself. In the face of social failure, self-compassion might be particularly useful for people with social anxiety. The present study aimed to examine the relationship between social anxiety and self-compassion. A total of 120 individuals completed online questionnaires measuring self-compassion, social anxiety, fear of negative evaluation, and self-focused attention. Results showed that higher levels of social anxiety, fear of negative evaluation, and self-focused attention were strongly related to less self-compassion. Self-compassion might, therefore, be a useful construct for people with social anxiety and explicit training in self-compassion may give rise to a more caring and kinder attitude towards onesel
The role of fundamental fears in the engagement in health protecting behaviour and the use of health care services
Introduction Fundamental fears have been found to contribute to the engagement in health protective behaviour and the use of health care services before. These behaviours are proposed to contribute to the development of chronic pain. In order to validate these results, anxiety sensitivity (AS), injury/illness sensitivity (IS), and fear of negative evaluation (FNE) were tested in regard to these behaviours and general health concerns. Method Measures of fundamental fears, health protecting behaviour, use of health care services and perceived health were administered online to 121 participants. Correlations were tested with Pearson correlation tests. Predictive values of the fundamental fears were calculated with linear regressions. Results IS correlated positively with all behavioural measures and was the best predictor for all three behavioural measures. AS only correlated with perceived health. FNE showed a trend with perceived health and somewhat predicted health protecting behaviour. Discussion Results partially replicate previous findings, but also contradict other findings. This study further confirms the notion that fundamental fears are involved in pain-related behaviours and recommends further investigation in these relations
Organisatorische kenmerken, factoren en verbetering van samenwerking in de eerstelijnszorg
De Nederlandse gezondheidszorg kent steeds meer problemen zoals aanbod dat niet aansluit op de vraag, te hoge zorgkosten en onvoldoende kwaliteit (Vleugels, 2005). Er worden veel strategieën ontwikkeld om deze knelpunten weg te nemen. Een daarvan is het vormen van een zorgketen, een voorbeeld van integrated care. Integrated care is een meer gecoördineerde en geïntegreerde vorm van zorgverlening en leidt tot verschillende gezondheidszorggerelateerde uitkomsten zoals een hogere kwaliteit van zorg, meer efficiëntie en betere toegankelijkheid (Gröne & Garcia-Barbero, 2002). Samenwerking tussen zorgprofessionals is essentieel voor de levering van integrated care. Zonder afstemming en coördinatie tussen professionals kan er nooit sprake zijn van integrated care. Er zijn veel verschillende organisatorische kenmerken, factoren die samenwerking beïnvloeden en mogelijke maatregelen die samenwerking tussen zorgverleners kunnen verbeteren. Deze kenmerken, factoren en maatregelen moeten in kaart worden gebracht om vast te kunnen stellen waar het bij de samenwerking tussen zorgverleners fout, maar ook goed gaat, om zo de levering van integrated care te kunnen verbeteren. In dit thesisonderzoek zijn deze kenmerken, factoren en verbetermaatregelen onderzocht binnen twee zorgcentra in de eerstelijnszorg. Een secundaire analyse van bestaande data is uitgevoerd. Data zijn verzameld door middel van semi-gestructureerde interviews met zorgprofessionals van verschillende disciplines uit twee zorgcentra. De interviewtranscripten zijn geanalyseerd door middel van een datamatrix. Organisatorische kenmerken van samenwerking in de twee centra zijn: werken met een wijkgerichte samenwerkingsvorm, het hebben van een gezamenlijke organisatie en samen werken in een keten. Factoren die een rol spelen bij de samenwerking zijn: korte lijnen, open deuren, afwezigheid, weinig inhoudelijke overlap, geen overleg, onbekende regelgeving, privacy regelgeving, bureaucratie, elkaar en elkaars werk kennen, vertrouwen en werken met protocollen. Veel voorkomende problemen zijn: hoge werkdruk, geen vast overleg, afwezigheid bij overleg en de ‘eenmanszaak’ cultuur. Verbetermaatregelen zijn: werken met protocollen, structureel overleg en het stimuleren van informeel contact. Inzicht in bovenstaande kenmerken, factoren en verbetermaatregelen van samenwerking leidt tot betere samenwerking tussen zorgprofessionals en dus tot betere levering van integrated care, dat weer leidt tot betere gezondheidszorggerelateerde uitkomsten
Addiction to food: how go/no-go tasks affect appetite
Obesity has an extremely high mortality rate. Most obese people try out several diets, while only a few of them are able to hold on to it and refrain from overeating. A number of studies have been conducted to discover the underlying mechanisms that cause some people not being able to fully commit to a diet. Earlier studies show that people with obesity have much stronger automatic impulses and less inhibitory control over their behavior regarding food intake. This lack in control can be trained by repeating computer tasks focusing on executive functioning. In this study it is hypothesized that a go/no-go training will strengthen impulse control. Sixty-six adolescents were included in this study. The present study was a Randomized Controlled Trial in which thirty-three participants took part in the intervention task and thirty-three were assigned to the control task. The independent variable to train inhibitory control was a go/no-go computer task. The short term dependent variable got measured by the Bogus Taste Test and the long term dependent variable got measured by difference in Body Mass Index between baseline and follow-up measurement after three weeks. Current study does not show any significant difference in food consumption after the intervention which means no short term effect of the training. Weight loss between baseline and follow-up measurement on the other hand, does demonstrate a significant difference, where the intervention condition shows a decrease in body weight compared to the control condition. These outcomes indicate an increased inhibitory control system on the long term which arises as a result of the go/no-go training. Being able to train inhibitory control of food related stimuli makes it an interesting topic to be further explored in combating obesit
Dual-color chromogen In Situ hybridization (CISH) for the determination of Her2 status in breast cancer tissue sections
Background: A factor associated with breast cancer development is the mutation of the Her2/neu gene located on chromosome 17. Chromogen in situ hybridization (CISH) in which the color is generated with an enzymatic reaction is a promising alternative detection method to fluorescence in situ hybridization (FISH) which is nowadays used in clinical practice. The resulting color is stable and therefore usable for permanent storage, the use of a normal brightfield microscope is possible and the morphology of the sample can be evaluated more easily than with a fluorescence microscope. For the visualization of Her2/neu it is however important to also detect chromosome 17 and use it as a reference chromosome. The aim of the study is: to select the best substrates considering color production, background staining, reactivity and localization. Secondly to develop a dualcolor procedure visualizing Her2/neu and chromosome 17 to examine the possibility of using CISH as a standardized method for the detection of Her2 positive tumors and finally to compare these results with FISH. Methods: Single target CISH with eight substrates for the enzyme horseradish peroxidase (PO) and six substrates for alkaline phosphatase (AP) was performed on cervical cancer cell lines with centromere 1 (C1) and 1p36 as targets. The best substrates were subjectively selected with the use of a brightfield microscope. The procedure was expanded to a dual-color detection on cells and formalin-fixed, paraffin embedded (FFPE) breast cancer tissue sections with Her2/neu and centromere 17 (C17) as targets. In this procedure the best conjugate detection systems were worked out. Results: In the single target detection procedure the substrates DAB, Vina Green and Seramun Grün for PO and Ferangi Blue and Vulcan Fast Red for AP were found to give the best color reactions. The dual-color detection on tissue sections showed strong and good distinguishable color reactions when combining the substrates Vina Green for C17 and Vulcan Fast Red for Her2. Results of CISH and FISH were comparable when using immersion oil for the detection of the fluorescent signals. Discussion and Conclusion: Vina Green for C17 and Vulcan Fast Red for Her2/neu are the best substrates considering background staining, color distinguishability and localization and give comparable results to FISH. The study gives a further step in the direction of introducing CISH as a standardized method for the detection of Her2/neu amplification
Local Councillors and Citizens. An exploratory study of the interaction between councillors and citizens in 4 municipalities in the Meuse-Rhine Euregion
The aim of this study is to look into into role behaviour of local councillors and their relation with citizens in their municipality. As little is known about the actual interaction between councillors and citizens in local government the nature of the study is mainly explorative. The research focuses on councillors in 4 different municipalities in the 3 countries of the Meuse-Rhine Euregion: Valkenburg (Netherlands), Riemst (Belgium-Flanders), Visé (Belgium-Wallonia) and Übach-Palenberg (Germany). The study reveals that there are many similarities between the councillors in the different countries. All councillors receive input from citizens, always about specific and often even individual issues of citizens, and surprisingly they leave the initiative mostly to the citizens, instead of actively looking for input. We also found significant differences. We noticed different patterns of contacts between citizens and councillors in the municipalities and it seems that input by citizens is valued differently on the different sides of the border. Several questions for further research were identified.