Thesis (Ph.D.)--Indiana University, 2010. / Title from screen (viewed on April 1, 2010). Department of Pharmacology and Toxicology, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Theodore R. Cummins, Grant D. Nicol, Gerry S. Oxford, Andy Hudmon, John H. Schild. Includes vitae. Includes bibliographical references (leaves 232-266).

Substance IEM 1460 is an antagonist of AMPA receptors in the brain. It is a derivative of adamantine, which has already been tested in several studies as a potential age-related anticonvulsant. In the research part of the thesis there is a summary of the knowledge about receptors, focusing on AMPA receptors, IEM 1460, epilepsy and ontogenetic development of laboratory rat. The research section evaluates the effect of IEM 1460 on motor skills of a rat in a few postnatal days of its life. To evaluate spontaneous animal motor skills, Open-Field tracking was used, and several specific tests were used to evaluate provoked motor skills. A total of 30 animals were included in the research. Substances (IEM 1460 at 3 mg / kg, IEM 1460 at 10 mg / kg or 2 ml / kg saline) were infused intraperitoneally on five consecutive days (ages P7-P11) and the animals were repeatedly tested at age 12, 15, 18, 21, 25, 31 and 60 days. In this study, IEM 1460 has not been shown to have significant effect on the gross rat motor skills and therefore the substance remains as a serious candidate for age-specific antiepileptic drugs.

No description available.

Building/creating the learning of the oboe: Experimental implementation of improvisation and creation in Chamber Music and Group Music in a conservatory. Strategic Actions (2014-2017) An oboe's class in the music conservatory can be summed up in the practicing of the studies and of the instrument's own repertoire. In order to future oboists are able to perform scores along their life, this is the way required technique and musicality are addressed. However, we have noticed a far too large number of students who cannot find motivation in that way of approaching the class. Low performance, lack of motivation and premature abandonment are very components occurrence especially in adolescence. With this work, we expect to tackle that problem. By including improvisation and composition in the class, we expect to create in the student a need of self-expression through music that will encourage their technical and interpretative learning process. On the basis of the elements provided by Action-Research (Cain, 2008) (Kemmis & McTaggart, 1988), we have implemented two strategic actions which have helped us to understand and transform our practice within the class. Strategic Action I (school year 2014-2015) was applied to a Professional Education four-student group in Ribarroja del Turia Conservatory (Valencia); specifically, to the Music Chamber subject, in which students had to design their own repertoire and to set both technical and specific goals according to regulations for conservatoires. Short-term changes were very encouraging, though not so very a longer period of time. That took us to reflect deeply which led to Strategic Action II (school year 2016- 2017) which consisted of the didactic material design according to IEM Methodology (Instituto de Educación Musical) developed by Dr. Emilio Molina. His methodology is based on the "Improvisation as a Pedagogic System", which we have transferred and applied to the learning of the oboe. The Strategic Action II was implemented in an Elementary Education three-student group in Ribarroja de Turia Conservatory (Valencia) in an attempt to create, from the beginning, a more significant relationship between the instrument and its study. We cannot say that the results are definitive because they need the perspective of time, but they are being very motivating. Students see oboe as an instrument to express their musical ideas, not as a purpose in itself. From this perspective, difficulties are approached as personal challenges that make students feel motivated to solve. We consider this is one of the keys to make progress in any instrument learning in general and particularly in oboe's. / Haciendo/creando el aprendizaje del Oboe: Aplicación experimental de la improvisación y la creación en la clase de Música de Cámara y de Conjunto en el conservatorio. Acciones Estratégicas (2014-2017). Una clase de Oboe en el conservatorio se resume en la práctica de los estudios y el repertorio propio del instrumento. Con ello abordamos la técnica y el desarrollo de la musicalidad necesarias para interpretar las partituras que los futuros oboístas irán encontrándose a lo largo de su vida. Sin embargo, hemos observado que un número demasiado amplio del alumnado no encuentra motivación con esta forma de conducirnos en las clases. Especialmente durante la adolescencia aparecen problemas de bajo rendimiento en el estudio, desmotivación y abandono prematuro. Con este trabajo hemos pretendido dar respuesta a dicho problema incluyendo la improvisación y la composición en las clases, creando en el alumno una necesidad de autoexpresión mediante la música que alentara su aprendizaje técnico e interpretativo. Basándonos en los elementos que nos ofrecía la Investigación-Acción (Cain, 2008) (Kemmis & McTaggart, 1988) hemos puesto en marcha dos acciones estratégicas que nos han ayudado a comprender y trasformar nuestra práctica dentro del aula. La Acción Estratégica I (curso 2014-2015) fue aplicada a un grupo de cuatro alumnos de oboe cursando Enseñanzas Profesionales dentro de la asignatura de Música de Cámara en el Conservatorio de Riba Roja del Turia (Valencia). En ella los alumnos han creado su propio repertorio sobre el cual trabajar, tanto los objetivos técnicos como los objetivos específicos de la asignatura según la normativa para los conservatorios. Los cambios en el corto plazo fueron muy estimulantes, no obstante no se mantuvieron en el tiempo, lo cual nos llevó a una profunda reflexión que desembocó en la Acción Estratégica II (curso 2016-2017), consistente en el diseño de un material didáctico según la Metodología IEM, (Instituto de Educación Musical) impulsada por el Dr. Emilio Molina, basada en la "Improvisación como Sistema Pedagógico", que hemos aplicado y trasladado al aprendizaje del oboe. Se puso en marcha dentro de la asignatura de Conjunto, con un grupo de tres alumnos de oboe, esta vez cursando las Enseñanzas Elementales en el Conservatorio de Riba Roja de Turia (Valencia), con el ánimo de crear una relación con el instrumento, y su estudio, más significativa desde los inicios. Los resultados, sin poder anunciar que sean definitivos puesto que necesitan de la perspectiva del tiempo, están siendo más que alentadores. Los alumnos ven el oboe como un instrumento a través del cual expresar sus ideas musicales y no como un fin en sí mismo. Desde esta perspectiva las dificultades se plantean como retos personales que el estudiante se ve motivado a solucionar. Consideramos que esta es una de las claves para que se produzcan los avances en el aprendizaje de cualquier instrumento en general y del oboe en particular. / Construint/creant l'aprenentatge de l'Oboè: Aplicació experimental de la improvisació i la creació a la classe de Música de Cambra i de Conjunt en el conservatori. Accions estratègiques (2014-2017). Una classe d'Oboè al conservatori es resumeix en la pràctica dels estudis i el repertori propi de l'instrument. Amb açò abordem la tècnica i el desenvolupament de la musicalitat necessàries per a interpretar les partitures que els futurs oboistes es trobaran al llarg de la seua vida. Tanmateix, hem observat que un nombre excessivament ampli de l'alumnat no troba motivació amb eixa forma de conduir-nos a les classes. Especialment durant l'adolescència apareixen problemes de baix rendiment en l'estudi, desmotivació i abandó prematur. Amb aquest treball hem volgut donar resposta al problema incloent la improvisació i la composició dins la classe, amb la intenció de crear en l'alumne una necessitat d'auto expressió mitjançant la música, que encoratge el seu aprenentatge tècnic i interpretatiu. Basant-nos en els elements que ens oferia la Investigació-Acció (Cain, 2008) (Kemmis & McTaggart, 1988), hem posat en marxa dues accions estratègiques que ens han ajudat a comprendre i transformar la nostra pràctica dins l'aula. L'Acció Estratègica I (curs 2014-2015), va ser aplicada a un grup de quatre alumnes d'oboè, cursant els Ensenyaments Professionals dins de l'assignatura de Música de Cambra al Conservatori de Riba Roja de Túria (València). En ella, els alumnes han creat el seu propi repertori amb el qual treballar, tant els objectius tècnics com els específics de l'assignatura segons la normativa per als conservatoris. Els canvis a curt termini van ser molt estimulants, malgrat això cal dir que no es van mantindre en el temps, la qual cosa ens va portar a fer una reflexió profunda que ens abocà a l'Acció Estratègica II (curs 2016-2017), basada en el disseny d'un material didàctic segons la Metodologia IEM ("Instituto de Estudios Musicales"), impulsada pel Dr. Emilio Molina i fonamentada en la improvisació com a sistema pedagògic, que hem aplicat i traslladat a l'aprenentatge de l'oboè. Es va posar en marxa dins l'assignatura de Conjunt, amb un grup de tres alumnes d'oboè, aquesta vegada cursant els Ensenyaments Elementals al Conservatori de Riba Roja de Túria (València), amb la voluntat de construir una relació amb el instrument, i el seu estudi, més significativa des dels inicis. Els resultats, sense poder anunciar que siguen definitius, ja que necessiten de la perspectiva del temps, estan resultant més que encoratjadors. Els alumnes veuen l'oboè com un instrument amb el qual expressar les seues idees musicals, i no com un fi en ell mateix. Des d'aquesta perspectiva les dificultats es plantegen com a reptes personals que l'estudiant es veu motivat a solucionar. Considerem que aquesta és una de les claus per a que es produeixen els avanços en l'aprenentatge de qualsevol instrument en general i de l'oboè en particular. / Cotolí Miguel, MV. (2017). Haciendo/creando el aprendizaje del Oboe: Aplicación experimental de la improvisación y la creación en la clase de Música de Cámara y de Conjunto en el conservatorio. Acciones Estratégicas (2014-2017) [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/89089

The perception is that inborn errors of metabolism (IEM) are rare, but the reality is that more than 600 lEMs are now recognized. The organic aciduria, 3-methylcrotonyl-CoA carboxylase (MCC) deficiency arises when 3-methylcrotonyl-Coenzyme A (CoA) carboxylase that participates in the fourth step of the leucine catabolism is defective. Tandem mass spectrometry (MS/MS) based screening programmes in North America, Europe and Australia, showed that MCC deficiency is the most frequent organic aciduria detected, with an average frequency of 1:50 000. Therefore MCC deficiency is considered an emerging disease in these regions. The incidence of MCC deficiency in the Republic of South Africa (RSA) is not yet known. However, one 48 year old male Caucasian individual (HGS) was diagnosed suffering from mild MCC deficiency, since elevated levels of 3-hydroxyisovaleric acid, 3- hydroxyisovalerylcarnitine, 3-methylcrotonylglycine was present in his urine. Several groups are currently working on various aspects of this emerging disease with the focus on the molecular characterisation of MCC deficiency. In the RSA no molecular based diagnostic method which complements MS/MS screening programmes have yet been implemented. Therefore, the aim of this study was to implement the necessary techniques for the molecular characterisation of MCC deficiency, the determination of the sequence of the open reading frame (ORF) of mccA and mccB subunits to determine which mutation(s) are present in the South African MCC deficient patient. For the implementation of the molecular characterisation, a two-pronged approached was used to characterize MCC of a MCC non-deficient individual (CFC). This approach included the reverse transcriptase polymerase chain reaction (RT-PCR) amplification of the ORFs of the associated genes [mccA (19 exons) and mccB (17 exons] and the PCR amplification of selected (genomic deoxyribonucleic acid (gDNA) regions (exons mccA8, mccA11 , mccB5, mccB6 and mccB5-intron 5-6 exon 6 (mccB5-6) which have been found to have mutations associated with MCC deficiency in Caucasians. The sequence analyses produced surprising results of the amplified ORFs (CFCmccA and CFCmccB) of the MCC non-deficient individual CFC. A non-synonymous single nucleotide polymorphism (SNP) (1391C→A, H464P) associated with MCC deficiency (Gallardo et al., 2001) was identified in the CFCmccA subunit. Another SNP (1368G→A, A456A) recently listed in GenBank was observed in the amplified CFCmccB ORF. No significant novel variations or described mutations were identified in the amplified genomic regions mccA8, mccA11 ,mccB5, mccB6 and mccB5-6. The implemented molecular approach was used to characterise MCC of our MCC deficient patient (HGS). The patient did not have any mutation in the four selected exons mccA8, mccA11, mccB5, mccB6 or the genomic region mccB5-6. The RT-PCR amplification of both ORFs (HGSmccA and HGSmccB) resulted in multiple amplicons. Gel extracted amplicons of the expected size were sequenced. Of the 36 exons, 34 exons were sequenced. This includes all 19 exons of HGSmccA and 15 of 17 exons of HGSmccB (exons 1-6 and exons 9-17). The non-synonymous SNP (1391C→A, H464P) detected in CFCmccA (MCC non-deficient individual), seems to be present in the HGSmccA subunit of the MCC deficient individual, HGS. The HGSmccB amplicons could not be entirely sequenced. However, the region exon 1-6 and 9-17 was sequenced but no described or novel mutations were identified. The lack of sequence data of region exon 7-8 led to an incomplete molecular characterisation of the MCC deficiency in HGS. In conclusion, the basic methods and techniques for the molecular characterisation of MCC deficient patients have been implemented locally. A few additional sequencing primers need to be designed to cover mccB7 and mccB8 as well as the entire coding and non-coding strands of each MCC gene (mccA and mccB). The primers for RT-PCR of both mccA and mccB need to be further refined to ensure better specificity. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

The IEM 1460 is a potential age-specific anticonvulsant and an indicator of the distribution of AMPA receptor subtypes among rat brain cells. It is a derivative of adamantane, that was tested in previous studies on models of human myoclonic and generalized tonic-clonic seizures with promising results. In this thesis we evaluated its effect on the motor activity of rat offspring in the age of 12, 18 and 25 days, we used 90 animals in total . The effect was evaluated 30 minutes after intraperitoneal administration of IEM 1460 in two doses, 10 mg/kg or 20 mg/kg, and was compared to the control animals with physiological solution applied intraperitoneally in amount of 20 mg/kg. To test the animals we used Open field test, righting reflex, negative geotaxis, horizontal bar test, rope climbing test, regular and irregular horizontal ladder test. The tests were applied to animals in mentioned order. There were found significant changes influencing motor behaviour, primarily in the 12 days old animals with the dose of 20 mg/kg IEM 1460 and in the 25 days old animals with both doses of IEM 1460, 10 and 20 mg/kg. In the 18 days old animals the results were less significant. Powered by TCPDF (www.tcpdf.org)

Le problème de la modélisation de la diffusion d'une onde électromagnétique par une surface rugueuse naturelle (océan, sable...) ou artificielle (routes...) intervient dans de nombreuses applications radar. La nature géométrique et physique des contributeurs ainsi que leur répartition sur la surface entraînent souvent des interactions difficiles à quantifier par des méthodes exactes et/ou asymptotiques numériques. <br />D'autre part, nous avons établi, à partir de nos recherches bibliographiques dans le domaine des surfaces rugueuses, que la diffusion totale par de telles surfaces est la somme d'une diffusion de surface (fonction des irrégularités sur la surface) et d'une diffusion de volume (due aux inclusions dans le sol).<br /><br />Au cours de cette thèse, nous avons développé une méthode analytique rigoureuse de calcul de la puissance totale diffusée par des sols rugueux basée sur l'utilisation conjointe de la Méthode de l'Equation Intégrale ou IEM (diffusion de surface) et de la Théorie du Transfert Radiatif (diffusion de volume). <br /><br />Dans nos applications, nous nous sommes intéressés à des surfaces rugueuses en asphalte et en béton. Nous avons évalué le coefficient de rétrodiffusion en considérant aussi le cas rarement traité de l'incidence rasante (pour des applications radar d'assistance à la conduite). Nous avons ensuite généralisé cette étude au comportement de la diffusion bistatique (diffusion dans des directions autres que la direction d'incidence).<br /><br />Une autre partie intéressante de ces travaux a concerné l'évaluation du comportement d'un objet dans son environnement proche. Il s'avère en effet nécessaire, sous certaines incidences, de prendre, de plus, en compte la contribution du couplage entre un objet et son environnement immédiat. Les interactions directes onde électromagnétique - objet sont évaluées par les modules de calcul de la surface équivalente radar (SER) d'objets complexes 3D réalisés au laboratoire. L'environnement (surface rugueuse dans notre cas) est caractérisé par son coefficient de diffusion bistatique déterminé par les méthodes électromagnétiques étudiées et précitées. Ainsi, il a été possible d'élaborer une méthode de calcul de la SER d'un objet complexe 3D en tenant compte de l'influence de son environnement naturel.

The perception is that inborn errors of metabolism (IEM) are rare, but the reality is that more than 600 lEMs are now recognized. The organic aciduria, 3-methylcrotonyl-CoA carboxylase (MCC) deficiency arises when 3-methylcrotonyl-Coenzyme A (CoA) carboxylase that participates in the fourth step of the leucine catabolism is defective. Tandem mass spectrometry (MS/MS) based screening programmes in North America, Europe and Australia, showed that MCC deficiency is the most frequent organic aciduria detected, with an average frequency of 1:50 000. Therefore MCC deficiency is considered an emerging disease in these regions. The incidence of MCC deficiency in the Republic of South Africa (RSA) is not yet known. However, one 48 year old male Caucasian individual (HGS) was diagnosed suffering from mild MCC deficiency, since elevated levels of 3-hydroxyisovaleric acid, 3- hydroxyisovalerylcarnitine, 3-methylcrotonylglycine was present in his urine. Several groups are currently working on various aspects of this emerging disease with the focus on the molecular characterisation of MCC deficiency. In the RSA no molecular based diagnostic method which complements MS/MS screening programmes have yet been implemented. Therefore, the aim of this study was to implement the necessary techniques for the molecular characterisation of MCC deficiency, the determination of the sequence of the open reading frame (ORF) of mccA and mccB subunits to determine which mutation(s) are present in the South African MCC deficient patient. For the implementation of the molecular characterisation, a two-pronged approached was used to characterize MCC of a MCC non-deficient individual (CFC). This approach included the reverse transcriptase polymerase chain reaction (RT-PCR) amplification of the ORFs of the associated genes [mccA (19 exons) and mccB (17 exons] and the PCR amplification of selected (genomic deoxyribonucleic acid (gDNA) regions (exons mccA8, mccA11 , mccB5, mccB6 and mccB5-intron 5-6 exon 6 (mccB5-6) which have been found to have mutations associated with MCC deficiency in Caucasians. The sequence analyses produced surprising results of the amplified ORFs (CFCmccA and CFCmccB) of the MCC non-deficient individual CFC. A non-synonymous single nucleotide polymorphism (SNP) (1391C→A, H464P) associated with MCC deficiency (Gallardo et al., 2001) was identified in the CFCmccA subunit. Another SNP (1368G→A, A456A) recently listed in GenBank was observed in the amplified CFCmccB ORF. No significant novel variations or described mutations were identified in the amplified genomic regions mccA8, mccA11 ,mccB5, mccB6 and mccB5-6. The implemented molecular approach was used to characterise MCC of our MCC deficient patient (HGS). The patient did not have any mutation in the four selected exons mccA8, mccA11, mccB5, mccB6 or the genomic region mccB5-6. The RT-PCR amplification of both ORFs (HGSmccA and HGSmccB) resulted in multiple amplicons. Gel extracted amplicons of the expected size were sequenced. Of the 36 exons, 34 exons were sequenced. This includes all 19 exons of HGSmccA and 15 of 17 exons of HGSmccB (exons 1-6 and exons 9-17). The non-synonymous SNP (1391C→A, H464P) detected in CFCmccA (MCC non-deficient individual), seems to be present in the HGSmccA subunit of the MCC deficient individual, HGS. The HGSmccB amplicons could not be entirely sequenced. However, the region exon 1-6 and 9-17 was sequenced but no described or novel mutations were identified. The lack of sequence data of region exon 7-8 led to an incomplete molecular characterisation of the MCC deficiency in HGS. In conclusion, the basic methods and techniques for the molecular characterisation of MCC deficient patients have been implemented locally. A few additional sequencing primers need to be designed to cover mccB7 and mccB8 as well as the entire coding and non-coding strands of each MCC gene (mccA and mccB). The primers for RT-PCR of both mccA and mccB need to be further refined to ensure better specificity. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

Indiana University-Purdue University Indianapolis (IUPUI) / Voltage-gated sodium channels (VGSCs) are dynamic membrane-spanning proteins crucial for determining the electrical excitability in nerve and muscle. VGSCs transition, or gate, between opened, closed, and inactivated states, in response to changes in transmembrane potential. Altered VGSC gating can affect electrical communication and is implicated in numerous channelopathies. Nav1.7, a VGSC isoform highly expressed in the peripheral nervous system, plays a unique role in pain perception as evidenced by single point missense mutations causing a spectrum of pain syndromes (inherited erythromelalgia; IEM and paroxysmal extreme pain disorder; PEPD) and nonsense mutations resulting in human insensitivity to pain (CIP). These studies indicate Nav1.7 is critical in pain transduction and, as such, structural perturbations to Nav1.7 affecting conformational stability and response to changes in transmembrane potential have the potential to cause pain. Therefore, the aims of this dissertation were to (1) examine the effects of PEPD mutations on the voltage-dependent properties Nav1.7; (2) investigate the effects Nav1.7 alternative splicing has on the impact of IEM and PEPD mutations; (3) evaluate the effects channelopathies, resulting from slowed inactivation, have on modulating an unusual type of sodium current that flows during membrane repolarization; and (4) determine the structural components involved in stabilizing Nav1.7 inactivation. Standard patch-clamp electrophysiology was used to study changes in channel properties. Results from this dissertation demonstrate that (1) PEPD mutations significantly shift the voltage-dependent properties of Nav1.7 channels, destabilize an inactivated state in a residue specific manner, and render nociceptive neurons hyperexcitable; (2) alternative splicing can functionally impact PEPD; (3) channelopathies, resulting from slowed inactivation in neuronal and muscle VGSC isoforms, increase an unusual sodium conductance that flows during repolarization; and (4) specific residues located in distinct regions of Nav1.7 serve as docking sites to stabilize inactivation at different membrane potentials. Overall, this dissertation answers key questions regarding the molecular mechanics required during inactivation and the biophysical consequences of Nav1.7 mutations implicated in painful disorders. The results of this dissertation are important for a more detailed understanding of pain perception and validate the applicability of studying Nav1.7 for discovery of therapeutic targets for treatment of pain. – Theodore R. Cummins, Chair

The need for public participation in the development of policies, programmes or actions has been widely accepted by both government and private sectors because of the benefits of such involvement. Involving the public in the development of any policy, programme or action is, however, a daunting task. Public involvement in the development of a policy or action often leads to protest, legal litigation, criticism and delay in carrying out the project. The main objectives of this research are to examine the process of public participation in the Gautrain project and to interrogate how public involvement in the decision-making processes of environmental concerns can be improved. A quantitative study was conducted to describe and explore the process of public participation in the Gautrain environmental impact assessment procedure. The purposive sampling method was used. Thereafter, the data generated was analysed using statistical tools such as charts, tables and the Wilcoxon Mann Whitney U test to examine the similarities and differences in the response patterns of the public and the project proponent. Cronbach alpha statistical methodology was also used to test the reliability of the measurement. The findings are discussed in relation to the objectives of the study and research hypotheses. The results indicate that (1) the public were not involved early enough during the project planning and design phases; (2) adequate information was not provided to the public; and (3) public input does not have much impact on decisionmaking processes. The study does, however, indicate that the process has enhanced the participants’ learning and that the process of participation has improved in recent time as compared to the 2002-2003 periods. The study concludes by providing relevant solutions and recommendations. / Environmental Sciences / M. Sc. (Environmental Management)