No description available.

The first enantioselective oxidative rearrangement of indoles to spirooxindoles was developed. A 2,3-disubstituted indole was stereoselectively epoxidized using an in situ-generated chiral dioxirane catalyst. Rearrangement of the transient epoxide intermediate afforded the antipode of the tricyclic spirooxindole present in the marine alkaloid citrinadin A. A mild and rapid entry to 1,4-dioxygenated xanthones from benzocyclobutenones was developed. This method was applied to the construction of the highly aromatic pentacyclic core of IB-00208, a promising antitumor agent with reported nanomolar activity. The requisite angularly-fused benzocyclobutenone was accessed via a novel ring-closing metathesis approach. Lack of success in synthesizing the final ring of IB-00208 from the pentacycle led us to revise our approach and incorporate an extra ring earlier in the synthesis. After constructing a modified benzocyclobutenone, the hexacyclic core of IB-00208 was efficiently accessed using the same key chemistry. An oxidation, deprotection and glycosylation remain to complete the synthesis of the natural product. A total synthesis of antimicrobial and antineoplastic cribrostatin 6 was accomplished in only four steps in the longest linear sequence from commercially available starting materials. The key step employed a tandem 4π-electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence to afford the tricyclic core of the natural product, which was converted to cribrostatin 6 via a subsequent oxidation in one pot. The versatility of this reaction sequence was demonstrated by preparation of analogs of the natural product, which were tested for their anticancer activity. / text

<p>Det här är en jämförande studie av två skolsystem, International Baccalaurate (IB) och den svenska gymnasieskolan. Studien fokuserar på bedömningen av elevers kunskaper i historia. Uppsatsen undersöker hur elever och lärare uppfattar förhållandet mellan kunskap och bedömning. IB har en mer absolut kunskapssyn där det går att göra bedömningar utifrån strikta och konkreta betygskriterier medan det svenska betygssystemet har mer öppna kursplaner och betygskriterier som kräver tolkningar. Elevers och lärares syn på kunskap är lika inom de båda systemen. Däremot finns det skillnader i hur ämnet historia uppfattas. IB-eleverna betonar vikten av källkritik medan eleverna i det svenska systemet lägger större vikt vid värderingar av historiska händelser. IB-eleverna upplever att deras betygssystem är rättvist men är oroliga för att inte all deras kunskap finns med i bedömningen. Eleverna i det svenska systemet ser betygskriterierna som otydliga och anser därför att bedömningen inte blir rättvis. Lärarna i de båda systemen stödjer elvernas synpunkter.</p>

Det här är en jämförande studie av två skolsystem, International Baccalaurate (IB) och den svenska gymnasieskolan. Studien fokuserar på bedömningen av elevers kunskaper i historia. Uppsatsen undersöker hur elever och lärare uppfattar förhållandet mellan kunskap och bedömning. IB har en mer absolut kunskapssyn där det går att göra bedömningar utifrån strikta och konkreta betygskriterier medan det svenska betygssystemet har mer öppna kursplaner och betygskriterier som kräver tolkningar. Elevers och lärares syn på kunskap är lika inom de båda systemen. Däremot finns det skillnader i hur ämnet historia uppfattas. IB-eleverna betonar vikten av källkritik medan eleverna i det svenska systemet lägger större vikt vid värderingar av historiska händelser. IB-eleverna upplever att deras betygssystem är rättvist men är oroliga för att inte all deras kunskap finns med i bedömningen. Eleverna i det svenska systemet ser betygskriterierna som otydliga och anser därför att bedömningen inte blir rättvis. Lärarna i de båda systemen stödjer elvernas synpunkter.

Desde a descoberta da cisplatina várias tentativas têm sido feitas com o objetivo de desenvolver novos quimioterápicos com menor toxicidade e efeitos colaterais melhorados para tratar o câncer. Complexos de coordenação com metais de transição variados vêm sendo estudados buscando melhoras na biodisponibilidade, seletividade e efeitos adversos. Neste sentido, o presente trabalho consiste na síntese e caracterização estrutural de complexos de PdII e PtII com ligantes derivados de tiossemicarbazidas contendo o grupo fluoróforo pireno visando a obtenção de potenciais agentes antitumorais. Os agentes quelantes foram preparados a partir de reações de condensação entre o pirenocarboxaldeído e a tiossemicarbazida desejada resultando em compostos 1-pirenocarboxaldeído-N(3)-R-tiossemicarbazona, H2PrR, onde R = etil ou ciclohexil, Pr = pireno. A partir dos ligantes H2PrR foram realizadas as reações de complexação com os íons metálicos PdII e PtII, sendo possível obter duas classes de complexos com diferentes características: complexos monoméricos contendo ligantes clorido e trifenilfosfano do tipo [MCl(PPh3)(HPrR)] e complexos tetraméricos do tipo [M4(&mu;-S-PrR-&kappa;3-C,N,S)4], onde M = PdII ou PtII, R = etil ou ciclohexil. Nas duas primeiras séries, o grupo R foi modificado por etil e ciclohexil para investigar a correlação entre lipoficilidade e atividade antiproliferativa, enquanto que o grupamento pireno foi incluído pensando que um maior número de unidades aromáticas possivelmente melhoraria a intercalação com o DNA e/ou ser utilizado como um marcador celular. A caracterização dos complexos envolveu técnicas como: análise elementar, espectroscopia na região do infravermelho e do UV-Vis, condutimetria, ressonância magnética nuclear (1H e 13C RMN) e difração de raios X em monocristal. As análises mostraram que os agentes complexantes podem atuar em diferentes modos coordenação tanto com relação à denticidade quanto à carga. A atividade antiproliferativa dos novos compostos de PdII e PtII foi determinada, sendo que vários deles apresentaram IC50 promissores contra células de câncer de ovário e, em muitos casos, as atividades observadas foram melhores do que a da cisplatina. Os dados obtidos indicam efeitos diferentes nos resultados de atividade biológica para os centros metálicos (Pd vs Pt) e ligantes utilizados (Etil vs Ciclohexil). Estudos de captação e distribuição celular mostraram que o complexo [PdCl(PPh3)(HPrCh)] atinge o núcleo celular. Com o intuito de verificar possíveis alvos biológicos, testes de interação com o DNA, ciclo celular e inibição da enzima Top IB foram realizados para os compostos. Os resultados do ciclo celular, mostraram uma maior inibição nos estádios S e G2/M para os complexos do tipo [PdCl(PPh3)(HPrR)]. Diante dos resultados obtidos, verificou-se que a Top IB é um dos alvos moleculares para os complexos do tipo [MCl(PPh3)(HPrR)], um mecanismo diferente da cisplatina. Estes resultados preliminares são bastante promissores e mostram que alguns dos complexos estudados neste trabalho apresentam-se como potenciais agentes para serem usados na terapia do câncer em combinação com os demais fármacos em uso clínico. / Since the discovery of cisplatin, many attepemts have been made to prepare new drugs with less cytotoxicity and side effects. Coordination complexes based on a variety of transition metals have been developed in the search for improved bioavailability, selectivity and reduced adverse side-effects. This work consists on the synthesis and structural characterization of PdII and PtII complexes with chelating compounds derived from thiosemicarbazides containing the pyrene fluorophore group aiming to obtain potential antitumor compounds. The chelating agents were prepared from condensation reactions between the pyrenocarboxaldehyde and the desired thiosemicarbazide resulting in 1-pyrenocarboxaldehyde-N (3) -R-thiosemicarbazone compounds, H2PrR, where R = ethyl or cyclohexyl. Complexation reactions with the metal ions PdII and PtII were carried out with the H2PrR ligands. It was possible to obtain two main classes of complexes with different characteristics: i) monomeric complexes containing chlorido and triphenylphosphane ligands of the type [MCl(PPh3)(HPrR)] and (ii) tetramer complexes of the type [{M(PrR)}4], where M = PdII or PtII and R = etyl ou cyclohexyl. In both series the R group was modified by ethyl and cyclohexyl in order to investigate the correlation between lipophilicity and antiproliferative activity, while the pyrene group was attached to the ligands with the belief that a higher number of aromatic units would improve DNA intercalation and/or to be used as an intracellular probe. The characterization of the complexes involved techniques such as: elemental analysis, infrared and UV-Vis spectroscopy, conductimetry, nuclear magnetic resonance (1H and 13C NMR) and single crystal X-ray diffraction. The antiproliferative activity of the novel PdII and PtII compounds have been determined, several of them showed promising IC50 against ovarian cancer cells, and in many cases the observed activities are better than that of cisplatin. The data obtained indicate different effects for the metal centers (Pd vs Pt) and the ligands used (ethyl vs cyclohexyl). Uptake and cellular distribution studies proved that the palladium complex [PdCl(PPh3)(HPrCh)] achieved the cell nucleus. In order to verify possible biological targets, interaction with DNA, cell cycle and inhibition experiments of the topoisomerase IB (Top IB) enzyme were performed for some compounds. Cell cycle results showed an inhibition at the S and G2/M stages for the complexes [PdCl(PPh3)(HPrR)]. Overall, the results indicated the Top IB enzyme as one of the targets of the complexes. These preliminary results are quite promising and show that some of the complexes studied here can be used in cancer therapy in combination with other anticancer drugs.

Desde a descoberta da cisplatina várias tentativas têm sido feitas com o objetivo de desenvolver novos quimioterápicos com menor toxicidade e efeitos colaterais melhorados para tratar o câncer. Complexos de coordenação com metais de transição variados vêm sendo estudados buscando melhoras na biodisponibilidade, seletividade e efeitos adversos. Neste sentido, o presente trabalho consiste na síntese e caracterização estrutural de complexos de PdII e PtII com ligantes derivados de tiossemicarbazidas contendo o grupo fluoróforo pireno visando a obtenção de potenciais agentes antitumorais. Os agentes quelantes foram preparados a partir de reações de condensação entre o pirenocarboxaldeído e a tiossemicarbazida desejada resultando em compostos 1-pirenocarboxaldeído-N(3)-R-tiossemicarbazona, H2PrR, onde R = etil ou ciclohexil, Pr = pireno. A partir dos ligantes H2PrR foram realizadas as reações de complexação com os íons metálicos PdII e PtII, sendo possível obter duas classes de complexos com diferentes características: complexos monoméricos contendo ligantes clorido e trifenilfosfano do tipo [MCl(PPh3)(HPrR)] e complexos tetraméricos do tipo [M4(&mu;-S-PrR-&kappa;3-C,N,S)4], onde M = PdII ou PtII, R = etil ou ciclohexil. Nas duas primeiras séries, o grupo R foi modificado por etil e ciclohexil para investigar a correlação entre lipoficilidade e atividade antiproliferativa, enquanto que o grupamento pireno foi incluído pensando que um maior número de unidades aromáticas possivelmente melhoraria a intercalação com o DNA e/ou ser utilizado como um marcador celular. A caracterização dos complexos envolveu técnicas como: análise elementar, espectroscopia na região do infravermelho e do UV-Vis, condutimetria, ressonância magnética nuclear (1H e 13C RMN) e difração de raios X em monocristal. As análises mostraram que os agentes complexantes podem atuar em diferentes modos coordenação tanto com relação à denticidade quanto à carga. A atividade antiproliferativa dos novos compostos de PdII e PtII foi determinada, sendo que vários deles apresentaram IC50 promissores contra células de câncer de ovário e, em muitos casos, as atividades observadas foram melhores do que a da cisplatina. Os dados obtidos indicam efeitos diferentes nos resultados de atividade biológica para os centros metálicos (Pd vs Pt) e ligantes utilizados (Etil vs Ciclohexil). Estudos de captação e distribuição celular mostraram que o complexo [PdCl(PPh3)(HPrCh)] atinge o núcleo celular. Com o intuito de verificar possíveis alvos biológicos, testes de interação com o DNA, ciclo celular e inibição da enzima Top IB foram realizados para os compostos. Os resultados do ciclo celular, mostraram uma maior inibição nos estádios S e G2/M para os complexos do tipo [PdCl(PPh3)(HPrR)]. Diante dos resultados obtidos, verificou-se que a Top IB é um dos alvos moleculares para os complexos do tipo [MCl(PPh3)(HPrR)], um mecanismo diferente da cisplatina. Estes resultados preliminares são bastante promissores e mostram que alguns dos complexos estudados neste trabalho apresentam-se como potenciais agentes para serem usados na terapia do câncer em combinação com os demais fármacos em uso clínico. / Since the discovery of cisplatin, many attepemts have been made to prepare new drugs with less cytotoxicity and side effects. Coordination complexes based on a variety of transition metals have been developed in the search for improved bioavailability, selectivity and reduced adverse side-effects. This work consists on the synthesis and structural characterization of PdII and PtII complexes with chelating compounds derived from thiosemicarbazides containing the pyrene fluorophore group aiming to obtain potential antitumor compounds. The chelating agents were prepared from condensation reactions between the pyrenocarboxaldehyde and the desired thiosemicarbazide resulting in 1-pyrenocarboxaldehyde-N (3) -R-thiosemicarbazone compounds, H2PrR, where R = ethyl or cyclohexyl. Complexation reactions with the metal ions PdII and PtII were carried out with the H2PrR ligands. It was possible to obtain two main classes of complexes with different characteristics: i) monomeric complexes containing chlorido and triphenylphosphane ligands of the type [MCl(PPh3)(HPrR)] and (ii) tetramer complexes of the type [{M(PrR)}4], where M = PdII or PtII and R = etyl ou cyclohexyl. In both series the R group was modified by ethyl and cyclohexyl in order to investigate the correlation between lipophilicity and antiproliferative activity, while the pyrene group was attached to the ligands with the belief that a higher number of aromatic units would improve DNA intercalation and/or to be used as an intracellular probe. The characterization of the complexes involved techniques such as: elemental analysis, infrared and UV-Vis spectroscopy, conductimetry, nuclear magnetic resonance (1H and 13C NMR) and single crystal X-ray diffraction. The antiproliferative activity of the novel PdII and PtII compounds have been determined, several of them showed promising IC50 against ovarian cancer cells, and in many cases the observed activities are better than that of cisplatin. The data obtained indicate different effects for the metal centers (Pd vs Pt) and the ligands used (ethyl vs cyclohexyl). Uptake and cellular distribution studies proved that the palladium complex [PdCl(PPh3)(HPrCh)] achieved the cell nucleus. In order to verify possible biological targets, interaction with DNA, cell cycle and inhibition experiments of the topoisomerase IB (Top IB) enzyme were performed for some compounds. Cell cycle results showed an inhibition at the S and G2/M stages for the complexes [PdCl(PPh3)(HPrR)]. Overall, the results indicated the Top IB enzyme as one of the targets of the complexes. These preliminary results are quite promising and show that some of the complexes studied here can be used in cancer therapy in combination with other anticancer drugs.

This thesis explores the extent to which the pedagogical intentions of a social science subject introductory workshop at an International Baccalaureate (IB) Diploma school align with the participating students’ experienced learning. The purpose is to gain an in-depth understanding of how well the IB faculty were able to implement the IB’s Approaches to Learning (ATL), a comprehensive pedagogical initiative. The research is guided by the question of the extent to which the workshop’s intended learning outcomes, constructed by the social science faculty at the particular IB school in focus, correspond with the perceived learning experienced by the students attending the workshop. The study initially introduces a theoretical framework including philosophy of the IB and the ATL initiative. It also describes the school setting and the teacher and student participants. Secondly, previous research is presented in order to situate the study in an academic context. Furthermore, the thesis discusses and evaluates the methods used. The results of the study indicate that the participating students’ understanding of the social science subjects’ interdisciplinary nature aligns well with the teachers’ intentions, and that the students are able to grasp and critically engage with the workshop’s focus on global issues in a local context. However, student lack understanding of the relationship between social science theories and the workshop’s case study which indicate a lack of implementation of the IB:s core pedagogical approach.

No description available.

Abstract A range of di®erent high-quality single crystal diamonds synthesized under high pressure and high temperature (HPHT) conditions have been studied in view of their potential as candidates for specialized electronic devices with emphasis on particle detectors. The studies incorporated a long range of spectroscopic and electronic characterization techniques. Special attention was given to electronic properties and device performance re- lated to the electrical contacts applied, the type and the concentration of impur- ities and the crystallographic defects present. The electronic response of a dia- mond detector as far as impurities are concerned is predominantly determined by the single substitutional nitrogen (SSN) and boron acceptors. Di®erent tech- niques were used to assess the role of such impurities in the diamond crystals stud- ied, as well as to study the dynamics due to the interaction of such impurities with each other (compensation). Hence, the electron spin resonance (ESR) and the current-deep level transient spectroscopy (I-DLTS) techniques were used in this re- spect to extract the information concerning activation energies, nitrogen-boron dy- namics, and the nitrogen and boron concentrations. ii iii It was found that the SSN content was below 1013 cm¡3 with this result giving the approximate concentration of boron acceptors, being the same value as of that of the SSN, or slightly above. Maximum activation energies of boron acceptors were extracted from three di®erent regions in the bulk of the diamond. The values were approximately 0.311 eV § 0.0027 eV in the center region, 0.308 eV § 0.007 eV in the intermediate region and 0.29 eV § 0.007 eV at the edge region, respectively. The maximum activation energy when boron is fully compensated is about 0.37 eV. Properties of ohmic and Schottky contacts as a function of concentration of SSN and boron acceptors were investigated using Current-Voltage characteristic and photo- current measurements. Di®erent surface treatment conditions and di®erent types of diamonds (IIa, IIb and Ib) were used. Electronic properties as a function of contacts were assessed for high purity synthetic type IIa diamond detector, incorporating a time of °ight (TOF) UV laser set-up. The maximum hole collection distance at room temperature was found to be 91.00 cm, the maximum transient time for holes was about 1.00 ms and the e±ciency was approximately 41%, with contacts made of Ti/Pt/Au-Ru. When Ru-Ru contacts are applied, the maximum hole mobility and the velocity were extracted at room temperature to be about 17963.44 cm2V¡1s¡1 and 5.02 £107 cms¡1, respectively, and the e±ciency of the device is about 30%. The maximum applied external electric ¯elds with Ru-Ru contacts were increased to about 1.32 times that at low temperature and to about 1.84 times that at room temperature. iv Large signals generated by ®-particles from 228Th were obtained without using amp- li¯cation. However, a full analysis of the pulse was not possible due to the narrow bandwidth of the electronic probes used. In a detector made of type Ib diamond, with SSN concentrations of about 50 ppm, it was found that regions in the bulk exhibiting better charge collection properties contained small concentrations of uncompensated boron impurity. On the other hand, the di®erence in the concentrations of SSN between the two type Ib diamonds, with about 50 ppm and about 200 ppm of SSN concentrations, respectively, resulted in approximately 70 ps di®erence in the transit time between two detectors made of these diamonds. Keywords: Synthetic diamond, detector, HPHT, type Ib, type IIa, single substitutional ni- trogen, SSN, ESR, ARP, I-DLTS, metallization, uncompensated boron impurity, crystallographic defects, rise and decay times, charge carrier life time, charge carrier mobility, carrier mean free path , charge collection distance, carrier Schubweg.

In thermal spraying, semi-molten (or partially-melted) particles are likely to form when the sprayed particles are insufficiently heated, or when a composite material is deposited. The present 2D model serves to begin to assess the spreading behavior of a semi-molten particle when impacting a solid substrate. An Immersed-Boundary (IB) scheme was implemented in an axisymmetric fluid model to simulate fluid flow in the presence of a solid core. The IB method calculates a forcing term, which is added to the momentum equation, to enforce the no-slip boundary condition at the core surface. Results are presented for the impact of a semi-molten tin droplet of radius R for a wide range of solid core radii r, varying the drop size ratio r/R, and the impact velocity Uo.