Brownfield Redevelopment in the European Union

Brownfields not only occur in the United States, but in every industrialized country and region. The European Union is currently confronting the challenge of regulating these sites. This Article offers a comparative survey of different legal approaches within both the European Union and the United States toward dealing with brownfields. As a case study, it outlines important developments in the Flemish region of Belgium. It is clear that more and more Member States are searching for different measures to deal with soil remediation in general, and brownfields in particular. However, the shortage of knowledge and information regarding brownfield development creates myraid difficulties with the start-up and realization of potential brownfield projects. Additionally, and with regard to funding schemes, no consideration is made of the sustainability of the methods used to redevelop these sites

Yin-Yang representation of financial crisis: a Korean perspective

Although the concepts of Western-Eastern integration to optimise management strategies are well-established, investigations on the applicability of these concepts in real-life situations are lacking. This study investigates how integration of (Eastern) Yin-Yang principles of seeking balance into Western concepts benefitted Koreans in combatting financial crises repercussions. Through analysis of 519 South Korean economic magazine covers taken over the period 2007-2012, the study shows the mindset of Korean society during the 2008 financial crisis. The covers provide a balanced interpretation of crisis events as both disastrous and opportunistic. Traditional Yin-Yang values therefore appear to be preserved in Korean management philosophy, even though contemporary Korean business strategies are strongly influenced by Western principles. By comparing these findings with social attitudes during previous crises in Korea, the study provides a real-life example of possible benefits of integrating Eastern and Western philosophy in management strategies

Mental Health Problems and Barriers to Service Use in Dutch Young Adults

Only up to one-third of young adults with a mental disorder seek professional help. The reasons for this low help-seeking rate are largely unclear. The first aim of this thesis is to explain why young adults are unlikely to seek professional help when facing mental health problems. The second aim is to provide insight into problem behaviours that typically first emerge in young adulthood: i.e., psychotic symptoms and problems related to alcohol use

Thermomagnetic Convective Cooling of Hall Effect Thruster

This work proposes and shows that thermomagnetic convection could be used in zero gravity to cool components of a Hall-effect thruster. A ferrofluid cavity was develop in the thermal and geometric model of a Hall-effect thruster. Simulations show that with an Ionic Liquid Ferrofluid after two minutes of thruster operations thermomagnetic convection occurs and in zero gravity will produce a larger velocity then natural convection that occurs in earth gravity. However, experiments did not result in heat transfer enhancement due to the limitation of the ferrofluid. Replacement of the Ferrotec EFH1 dispersant with dodecylbenzene did not result in Ionic Liquid Ferrofluid equivalent ferrofluid and did not lower of vapor pressure as intended and limited test to 60 °C. This limitation did not allow for the fluid to experience the largest difference in magnetic susceptibility that occurs near the Curie temperature

Envelope frequency following responses are stronger for high-pass than low-pass filtered vowels

Background: To assess hearing in response to speech, the envelope frequency following response (FFR) can be observed at the fundamental frequency of a vowel stimulus, and its harmonics. FFRs are complex non-linear phenomena, which require better understanding for allowing robust inferences on the assessment of hearing and hearing aid fitting. Objectives: To evaluate the effect of stimulus bandwidth on FFR detection rates using filtered vowel stimuli with equal sound levels. Design: FFRs were collected whilst presenting repeated vowels (in consonant-vowel-consonant format) filtered into different bandwidths. Eighty stimuli per word were presented at 70 dB SPL LAeq through insert earphones with an inter-stimulus interval of 1s. Responses were detected using frequency-domain Hotelling’s T2 (HT2) tests for individual multiples of the fundamental frequency (F0) and for combinations of F0 multiples. Study Sample: Eleven native English-speaking subjects with normal hearing thresholds. Results: Average detection rates are highest (69%) with stimuli high-pass filtered >1000 Hz, and significantly lower for low-pass filtered stimuli (40%). Conclusion: High-pass filtered vowels elicit stronger FFRs than low-pass filtered vowels at the same dB SPL LAeq. For testing hearing using band-limited speech, filtering effects (due to hearing loss, hearing aid setting or stimulus choice) on responses must be considered

Structure-aided design of inhibitors of Mycobacterium tuberculosis thimydilate kinase

SUMMARY The aim of this work was the search for selective inhibitors of M. tuberculosis thymidine monophosphate kinase (TMPKmt) as leads for the development of new anti-tuberculosis agents. Based on the X-ray structure of TMPKmt, it was decided to establish a preliminary structure-activity relationship by synthesising a series of nucleosides and nucleotides modified at the 2’-, 3’- and 5-positions of the dTMP-scaffold. These analogues were tested for their affinities for TMPKmt. From this, a 2'-chlorine and a 2'-fluorine substituent emerged as the most promising modifications of the dTMP scaffold. Furthermore, the affinities of a series nucleosides and their corresponding nucleotides were compared. The deletion of the phosphate moiety typically resulted in a modest, in many cases negligible affinity loss. In view of the drug delivery problems of phosphorylated compounds, nucleosides seemed more useful leads for further drug design. The goal of the synthesis of a series 3'-C-branched-chain nucleosides and nucleotides (3'-CH2N3, 3'-CH2NH2, 3'-CH2F, 3'-CH2OH) was to occupy a cavity in the enzyme near the 3'-position. Biological results and modeling confirmed this hypothesis. 3'-Azidomethyl- 3'-deoxy-thymidine (4.9), combining a low Ki-value (40 mM) with a high selectivity index for the tuberculosis enzyme (Ki TMPKh/ Ki TMPKmt = 26) emerged as the most promising lead for further optimisation. Attempts were made to combine these favourable 3'-substitution patterns with 2'-halogen substituents (6.9-6.14). However, introduction of the 2'-halogen led to a drastic decrease in affinity compared to the corresponding 2'-deoxy-nucleosides. Probably, the 2'-halogens compete with the 3'-substituents for the same binding pocket. Furthermore, it was tried to supersede the good affinities of the 3'-C-branched-chain nucleosides, by further exploration of the enzyme cavity near the 3'-position with alternative nitrogen-containing substituents. However, attempted simultaneous reduction of the 6'-azido function and the 2'-hydroxyl of compound 19 (chapter 6) failed. Instead three peculiar nucleoside analogues (6.10, 6.11 and 6.12) were isolated that were tested for their affinities for TMPKmt and TMPKh. Dinucleoside 6.12 unexpectedly showed a high affinity (Ki = 37 mM) and selectivity for the tuberculosis enzyme, indicating an exceptional flexibility of TMPKmt towards the orientation of the sugar ring. Also the bicyclic nucleosides 6.10 and 6.11 showed excellent affinities. With its Ki-value of 3.5 mM (exceeding the affinity of the natural substrate) and its selectivity index of 200, 6.10 represents the highest affinity and most selective inhibitor of TMPKmt found so far. The favourable affinities and selectivities of these three inhibitors will form the basis for further drug design, considerably increasing the variety of nucleoside analogues that may be envisaged for future synthesis. Based on the encouraging affinity of anhydro-hexitol nucleotide 7.1, the effects of sixmembered sugar rings for the affinity for TMPKmt were further explored through the synthesis of 1-[2,4-dideoxy-4-C-hydroxymethyl-a-L-lyxopyranosyl]thymine (7.4). This nucleoside indeed showed the predicted equatorial orientation of the thymine ring (4C1). Affinity results were however disappointing. In conclusion, this work yielded some high affinity and selective inhibitors for TMPKmt that open interesting perspectives in the search for new anti-tuberculosis agents. Based on their high selectivity indices, especially dinucleoside 6.12 and bicyclic nucleosides 6.10 and 6.11 will be used as the starting point for the search of inhibitors with an optimal fitting in the active pocket of TMPKmt

Synthesis and conformational analysis of 1-[2,4-dideoxy-4-C-hydroxymethyl-alpha-L-lyxopyranosyl]thymine

Previously different types of nucleosides with a six-membered carbohydrate moiety have been evaluated for their potential antiviral and antibiotic properties and as building blocks in nucleic acid synthesis. However, a pyranose nucleoside with a 1,4-substitution pattern like 1-[2,4-dideoxy-4-C-hydroxymethyl-alpha-L-lyxopyranosyl]thymine (4) has not been studied yet. Modeling suggested that this nucleoside would show the (4)C(1) conformation in contrast to anhydrohexitol nucleosides (1) whose most stable conformation is (1)C(4). The key to the synthesis of 4 involves the stereoselective introduction of the hydroxymethyl group onto the C-4 carbon of the pyranose sugar. Attempts to achieve this via hydroboration/oxidation of a C-4'-exocyclic vinylic intermediate selectively yielded the undesired a-directed hydroxymethyl group. Therefore, we envisaged another approach in which the C-4 substituent was introduced upon treatment of 2,3-O-isopropylidene-1-O-methyl-4-O-phenoxythiocarbonyl-alpha-L-lyxopyranose with beta-tributylstannyl styrene. This allowed stereoselective beta-directed introduction of a 2-phenylethenyl group at C-4, which was converted via oxidation/reduction (OsO(4), NaIO(4)/NaBH(4)) into the desired 4-hydroxymethyl group (20). The resulting 1-O-methyl-2,3,6-tri-O-acetyl-protected sugar was coupled with silylated thymine, using SnCl(2) as Lewis acid (22). After suitable protection, Barton deoxygenation of the 2'-hydroxyl function of the obtained ribo-nucleoside yielded the desired 2'-deoxynucleoside 4, indeed showing the expected equatorial orientation of the thymine ring ((4)C(1))