<p>This thesis describes the design and synthesis of molecules with potential roles in biomedicine, with an emphasis on molecular recognition in complex biological environments. The first chapter describes the synthesis and evaluation of compounds for use in nuclide therapy. Carboranes are frequently used in the development of drugs for Boron Neutron Capture Therapy. New routes for monohydroxylation at the B and C atoms of <i>p</i>-carborane have been developed. The Suzuki-Miyaura reaction has been applied to the cross-coupling of <i>bis</i>(neopentyl glycolato)diboron or <i>bis</i>(pinacolato)diboron and 2-I-<i>p</i>-carborane. The synthesized derivatives are important intermediates in the synthesis of a number of potentially biologically active carborane-containing molecules.</p><p>The DNA intercalator doxorubicin has been functionalized to enable ¹²⁵I labelling. The aim of combining the DNA intercalator with ¹²⁵I was to achieve high delivery of cytotoxic radiation to the nucleus. The DNA-binding ability and cellular uptake of the synthesized compounds have been evaluated. One of the compounds bound strongly to DNA and had similar cellular uptake as daunorubicin, which makes the compound very interesting for further biological evaluation.</p><p>The second chapter describes the use of polypeptide conjugates to broaden our knowledge of molecular recognition. The polypeptides consist of 42 amino acids each and are designed to fold into helix-loop-helix motifs that dimerize due to their amphiphilic character. The polypeptides are combined with a variety of small organic molecules. The incorporation of small aromatic molecules to influence the structure and dynamics of a polypeptide has been investigated. By attaching a dansyl group to the side chain of a lysine residue, the dynamics of the protein’s hydrophobic core where affected to such a degree that a native-like fold was formed. The polypeptide conjugates have also been used to study the binding and recognition of native proteins. High-affinity binders for chitinases and acetylcholine esterase have been developed and evaluated.</p>

This thesis describes the design and synthesis of molecules with potential roles in biomedicine, with an emphasis on molecular recognition in complex biological environments. The first chapter describes the synthesis and evaluation of compounds for use in nuclide therapy. Carboranes are frequently used in the development of drugs for Boron Neutron Capture Therapy. New routes for monohydroxylation at the B and C atoms of p-carborane have been developed. The Suzuki-Miyaura reaction has been applied to the cross-coupling of bis(neopentyl glycolato)diboron or bis(pinacolato)diboron and 2-I-p-carborane. The synthesized derivatives are important intermediates in the synthesis of a number of potentially biologically active carborane-containing molecules. The DNA intercalator doxorubicin has been functionalized to enable 125I labelling. The aim of combining the DNA intercalator with 125I was to achieve high delivery of cytotoxic radiation to the nucleus. The DNA-binding ability and cellular uptake of the synthesized compounds have been evaluated. One of the compounds bound strongly to DNA and had similar cellular uptake as daunorubicin, which makes the compound very interesting for further biological evaluation. The second chapter describes the use of polypeptide conjugates to broaden our knowledge of molecular recognition. The polypeptides consist of 42 amino acids each and are designed to fold into helix-loop-helix motifs that dimerize due to their amphiphilic character. The polypeptides are combined with a variety of small organic molecules. The incorporation of small aromatic molecules to influence the structure and dynamics of a polypeptide has been investigated. By attaching a dansyl group to the side chain of a lysine residue, the dynamics of the protein’s hydrophobic core where affected to such a degree that a native-like fold was formed. The polypeptide conjugates have also been used to study the binding and recognition of native proteins. High-affinity binders for chitinases and acetylcholine esterase have been developed and evaluated.

The main purpose of this study was to develop and administer a four-tier test for assessing Turkish pre-service physics teachers&rsquo / misconceptions about geometrical optics. Sixteen pre-service physics teachers, who were selected by maximum variation and convenience sampling methods from three state universities in Ankara, were interviewed in the contexts of plane mirrors, spherical mirrors, and lenses. From these interviews and the studies in the literature, the Open-Ended Geometrical Optics Test was developed. It was administered to 52 pre-service physics teachers from three state universities selected by purposive and convenience sampling. The responses of each subject for each item were categorized in order to determine the alternatives of the multiple-tier multiple-choice misconception test. The initial form of the test, the Three-Tier Geometrical Optics Test (TTGOT), was administered to 53 pre-service physics teachers from three state universities selected by purposive and convenience sampling as a pilot study. The analysis of the results of the TTGOT was used to revise the test items. Finally, the Four-Tier Geometrical Optics Test (FTGOT) was developed and administered to 243 pre-service physics teachers from 12 state universities in Turkey. The validity of the FTGOT scores was established by means of some qualitative and quantitative methods. The Cronbach alpha reliability coefficients were calculated for different test scores. Those for the total correct scores and standardized misconception scores (SUMM4) were found to be .59 and .42, respectively. Some misconceptions, which were held by more than 10 % of the pre-service teachers, were identified and considered to be significant.

Ett ovårdat språkbruk bland de yngre eleverna är något som har uppmärksammats av studiens författare. Ett ovårdat språkbruk definieras i studien till svordomar och/eller könsord i relation till svordomar. Syften med studien är att undersöka vad erfarna lågstadielärare anser är ett ovårdat språkbruk. Vidare är syftet att ta reda på hur lågstadielärare enligt sina erfarenheter uppfattar orsaker till ett ovårdat språk och hur de bemöter de yngre elever som använder ett sådant språk. Undersökningen har skett genom kvalitativa ostrukturerade intervjuer. Resultatet visade att en lågstadielärare upplever att de yngre eleverna använder ett ovårdat språk medan resterande upplever att eleverna använder ett bra språkbruk. Lågstadielärarna ansåg också att ovårdat språk främst innebär svordomar men även könsord, slanguttryck och grammatiskt felanvända ord. Resultatet i studien har lett fram till slutsatsen att anledningarna till att elever använder ett ovårdat språk är flera. Lågstadielärarna menar att det beror på det språkbruk som föräldrarna använder, samhällsförändringar samt på media. Ett bemötande i lugn ton är att rekommendera samt att man som lärare föregår med gott exempel. / A bad language use among the younger pupils is something that has been paid attention to according to the authors of the study. A bad language use is in the study defined as swearword and/or a use of four-letter words together with swearword. The study aims to examine what experience primary teachers thinks is a bad language. Further more aims the study investigate what primary teachers according to their experience understand reasons of a bad language use and how they answer the younger pupils using such a language.The investigation has been carried out by qualitative unstructured interviews. The results showed that one primary teacher experienced that the younger pupils are using a bad language, the remaining experienced that pupils use a good language. Primary school teachers also found that bad language use mainly means swearword but also four-letter words, slang words and grammatical errors using the word. The result of the study give the conclusion that there are many reasons why pupils use bad language according to the primary teachers. They mean that it depends on which language their parents use, changes in the society and the media. The best way to answer these pupils is in a calm voice and to be a good ideal for them.

The global population can, based on income per capita be divided into three socioeconomic segments of a pyramid where the bottom segment is labeled: base/bottom of the pyramid (BOP). The BOP market has a collective buying power estimated to five trillion dollar per year. The BOP-segment may seem lucrative but it is however risky and challenging to enter a market characterized by poverty. One of the risks that are pointed out in research is minimal local marketing expertise. A key to succeed in a BOP-market is finding innovative ways of building awareness for a product. Earlier research have pointed at local partners as important for creating that awareness. This study aimed to find how companies have enabled and used non-traditional partners as a communication channel. The findings of the study indicate that companies have used enabling efforts and that CSR approaches and NGO partnerships had been important for enabling the communication channel as well as important for delivering a trustworthy message for all investigated cases

Le rejet des nutriments (phosphates et nitrates) issues des eaux usées domestiques entraînent la dégradation des écosystèmes (74 % du territoire français concerné en 2006). Compte tenu de la situation, l'Etat français a promulgué la Loi sur l'Eau et les Milieux Aquatiques le 30décembre 2006 qui vise à atteindre le " bon état écologique des eaux et des milieux aquatiques " d'ici 2015. Cette notion bien que difficilement intégrable a généré des normes plus strictes pour les stations d'épuration en termes de rejet de nutriments vers le milieu récepteur (jusque 15 mg NTOT.L-1 et 2 mg PTOT.L-1). Depuis la fin des années 1990, la technologie des filtres plantés de roseaux (FPR) est de plus en plus employée(> 2500 unités en 2012) pour le traitement des eaux usées domestiques des petites collectivités inférieures à 2000 Equivalent-Habitants. Cependant, des limites de traitement existent sur les concentrations résiduelles en azote (rejet de 70-80 mg NTOT.L-1) et en phosphore (rejet> 10 mg PTOT.L-1), en vue de répondre à la réglementation future. Ce travail a eu pour objectif de mettre en oeuvre des améliorations telles que la recirculation sur un étage de traitement pour le traitement de l'azote d'une part et l'emploi de matériaux réactifs pour piéger le phosphore d'autre part. La démarche scientifique expérimentale déployée a consisté à suivre des pilotes sur site réel et en laboratoire pendant 2 années. Le suivi des performances épuratoires et hydrauliques a été réalisé au cours du temps. Pour l'azote, 2 FPR (2,5 m²) garnis de schiste expansé (Mayennite®) ont été alimentés en effluent brut. L'effet de la hauteur de saturation en eau dans la partie drainante ainsi que l'effet de la recirculation ont été étudiés. Les résultats obtenus ont montré : une couche saturée à 38 % (rapporté à la hauteur totale) et un ratio de recirculation de 100 % permettent une meilleure élimination de la matière particulaire-carbonée (Arrêté du22 juin 2007) et de l'azote (< 20 mg NTK.L-1 ; < 45 mgNTOT.L-1). Deux laitiers de four à arc électrique ont été sélectionnés pour le traitement du phosphore. Ceux-ci ont été mis en œuvre dans 5 colonnes (6 L) en laboratoire alimentées en effluent synthétique en phosphore puis secondaire et dans 4 filtres réactifs pilote (0,3 m² ; 34 L) à flux horizontal sous surfacique alimentés en effluent secondaire. Il ressort de ces expériences: (i) des disparités existent entre les deux échelles en termes de performances (< 2 mg P.L-1 pendant 20 mois en colonne et variation saisonnière des performances en pilote) et mécanismes épuratoires (adsorption/précipitation P-Caen colonne ; P-Ca + P-Fe en pilote), (ii) l'augmentation de la température (> 15 °C) et/ou du temps de séjour (48h et plus) améliore la cinétique d'élimination du phosphore à échelle pilote et (iii) l'implantation d'un filtre réactif garni de laitier de four à arc électrique est limité par le degré de traitement souhaité et la distance du futur chantier (coût du transport).

Preparing all teachers to work with culturally and linguistically diverse (CLD) populations is essential in teacher education (Banks, Cochran-Smith, Moll, Richert, Zeichner, LePage, Darling-Hammond, Duffy, & MacDonald, 2005). Simultaneously, current literacy policy serves to dictate how teachers teach literacy; requiring specific curricula and assessments, particularly in urban and low performing school districts (Woodside-Jiron & Gehsmann, 2009). As new teachers enter classrooms, they are forced to negotiate the realities of teaching in urban, diverse schools with what they learned in their preparation programs (Achinstein & Ogawa, 2006). The purpose of this study was to understand the literacy teaching experiences of three beginning teachers, graduates of an alternative teacher preparation program, who teach at the same CLD, Professional Development School. This naturalistic inquiry explored the intersection of these constructs through the questions; (1)What instructional decisions, resources, and strategies do alternatively certified beginning teachers enact when teaching CLD students? and (2) What are the contextual factors that influence beginning teachers’ literacy pedagogy? Luke and Freebody’s (1999) Four Resources Model, critical theory (McLaren, 1995), sociocultural views of literacy (Street, 1995), and constructivism (Savery & Duffy, 2001) served as theoretical lenses. Data collection took place over nine months and included interviews, observations, questionnaires, and teacher debriefs. The data was analyzed using a constant comparative approach (Merriam, 1998) and elements of Grounded Theory methodology (Strauss & Corbin, 1998). These beginning teachers struggled to negotiate the prescriptive literacy mandates from the county and school. The context of the school challenged many of the theories and strategies teachers learned in their preparation program and caused tension between what they espoused about literacy and their enacted practices. Teachers felt that they were not adequately prepared to work with English Language Learners in particular, thus, they chose to adhere closely to the prescriptive curriculum. Decontextualized literacy activities dominated instruction and constrained CLD students’ opportunities for critical literacy learning. These findings suggest that teachers should be better prepared to work with ELLs and educated about the research behind current literacy policies. A Professional Development School model offers opportunities for continued learning in these areas.

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.

Preparing all teachers to work with culturally and linguistically diverse (CLD) populations is essential in teacher education (Banks, Cochran-Smith, Moll, Richert, Zeichner, LePage, Darling-Hammond, Duffy, & MacDonald, 2005). Simultaneously, current literacy policy serves to dictate how teachers teach literacy; requiring specific curricula and assessments, particularly in urban and low performing school districts (Woodside-Jiron & Gehsmann, 2009). As new teachers enter classrooms, they are forced to negotiate the realities of teaching in urban, diverse schools with what they learned in their preparation programs (Achinstein & Ogawa, 2006). The purpose of this study was to understand the literacy teaching experiences of three beginning teachers, graduates of an alternative teacher preparation program, who teach at the same CLD, Professional Development School. This naturalistic inquiry explored the intersection of these constructs through the questions; (1)What instructional decisions, resources, and strategies do alternatively certified beginning teachers enact when teaching CLD students? and (2) What are the contextual factors that influence beginning teachers’ literacy pedagogy? Luke and Freebody’s (1999) Four Resources Model, critical theory (McLaren, 1995), sociocultural views of literacy (Street, 1995), and constructivism (Savery & Duffy, 2001) served as theoretical lenses. Data collection took place over nine months and included interviews, observations, questionnaires, and teacher debriefs. The data was analyzed using a constant comparative approach (Merriam, 1998) and elements of Grounded Theory methodology (Strauss & Corbin, 1998). These beginning teachers struggled to negotiate the prescriptive literacy mandates from the county and school. The context of the school challenged many of the theories and strategies teachers learned in their preparation program and caused tension between what they espoused about literacy and their enacted practices. Teachers felt that they were not adequately prepared to work with English Language Learners in particular, thus, they chose to adhere closely to the prescriptive curriculum. Decontextualized literacy activities dominated instruction and constrained CLD students’ opportunities for critical literacy learning. These findings suggest that teachers should be better prepared to work with ELLs and educated about the research behind current literacy policies. A Professional Development School model offers opportunities for continued learning in these areas.

A refinement of a minimal model for protein folding originally proposed by Imamura is presented. The representation of the alpha-helix has been improved by adding in explicit modelling of the entire peptide unit. A four-helix bundle consisting of four alpha-helices and three loop regions is generated with the parallel tempering Monte Carlo scheme. Six native states are found for the given sequence, four U-bundle and two Z-bundle states. All six states have energies of E approx -218ε and all appear equally likely to occur in simulation. The highest probability of folding a native state is found to be at a hydrophobic strength of Ch = 0.8 which agrees with the value of Ch = 0.7 used by Imamura in his studies of alpha to beta structural conversions. Two folding stages are observed in the temperature spectrum dependent on the magnitude of the hydrophobic strength parameter. The two stages observed as temperature decreases are 1) the hydrophobic energy causes the random coil to collapse into a compact globule 2) the secondary structure starts forming below a temperature of about T = 0.52ε/kB. The temperature of the first stage, which corresponds to the characteristic collapse temperature Tθ, is highly dependent on the hydrophobic strength. The temperature of the second stage is constant with respect to hydrophobic strength. Attempts to measure the characteristic folding temperature, Tf , from the structural overlap function proved to be difficult due mostly to the presence of six minima and the complications that arose in the parallel tempering Monte Carlo scheme. However, a rough estimate of Tf is obtained at each hydrophobic strength from a native state density analysis. Tf is found to be significantly lower than Tθ.