SOI-based micro-ring resonators can be ultra-compact and highly sensitive for sensing applications. In order to obtain deeper notches and enlarge the detection area, the concentric double-ring resonators have been proposed. To further increase the sensing area and promote the sensing sensitivity, we add one more inner ring into the double-ring structure to form the triple-ring resonator. In this thesis, we have derived the transfer functions of the multi-ring structures and calculated the resonance properties of the triple-ring resonators by using the 3-D FDTD method. We have investigated the effects of the ring radius on the transmission spectra and discussed the variations of spectral response between the double-ring and triple-ring resonators. We also demonstrate the applications of the triple-ring resonator as the refractive index sensors. The triple-ring resonator can obtain deeper dips and higher detection sensitivity of 12.85 nm/RIU. Enlarging the gap can increase the sensing area and is shown to be able to promote the sensing sensitivity. Besides, the influences of the light polarization and the optical absorption on the spectral responses have been discussed as well.

Adolescence is a stage that brings about multiple developmental changes for an individual. Parents of adolescent children often find these changes challenging. Parenting programmes have been created however, to help alleviate some of these problems. The review of the literature in this article selects and reviews a few parenting programmes that focus on the adolescent population. The current study then focuses specifically on one in particular; Teen Triple P and its use with 4 families. The participants included were a community sample with identifiable, but non-diagnosable, behavioural problems between the ages of 12-13 years old. Using a triangulation method of results; including a multiple-baseline of behaviour monitoring, parental and youth self-reports, and an observational task, the current study evaluates the effectiveness of Teen Triple P. The results indicate that notable changes were observed and reported in young person and parental behaviour for three of the four families. The other family encountered a crisis prior to the measures being completed at post-intervention which may have influenced their findings. Conclusions regarding this study, limitations, and future focuses for research are also discussed.

This study investigated the effectiveness of the Triple P Programme to reduce stealing behaviour in three preadolescent children. Using behavioural monitoring and self-report questionnaires, outcome measures included stealing behaviour, parenting practices, parenting efficacy, and parental mental health. A measure of change was also included to identify change points in the therapeutic process. Results suggest that parent training is effective in the reduction of stealing behaviours, as positive changes were found across all the measures employed. This early intervention has the potential to disrupt an antisocial developmental trajectory for children who steal. Limitations of the study and directions for future research are discussed.

It is well known that for any Steiner triple system (STS) one can define a binary operation · upon its base set by assigning x·x = x for all x and x·y = z, where z is the third point in the block containing the pair {x, y}. The same can be done for Mendelsohn triple systems (MTS), directed triple systems (DTS) as well as hybrid triple systems (HTS), where (x, y) is considered to be ordered. In the case of STSs and MTSs the operation yields a quasigroup, however this is not necessarily the case for DTSs and HTSs. A DTS or an HTS which induces a quasigroup is said to be Latin. The quasigroups associated with STSs and MTSs satisfy the flexible law x · (y · x) = (x · y) · x but those associated with Latin DTSs and Latin HTSs need not. A DTS or an HTS is said to be pure if when considered as a twofold triple system it contains no repeated blocks. This thesis focuses on the study of Latin DTSs and Latin HTSs, in particular it aims to examine flexibility, purity and other related properties in these systems. Latin DTSs and Latin HTSs which admit a cyclic or a rotational automorphism are also studied. The existence spectra of these systems are proved and enumeration results are presented. A smaller part of the thesis is then devoted to examining the size of the centre of a Steiner loop and the connection to...

The RAB guanosine triphosphates (RAS-related in brain) belong to the Ras superfamily of GTPases, and loss of RAB 25 expression has been reported in a number of breast cancer cases containing H-Ras point mutations, particularly triple negative breast cancers (TNBC), one of the most aggressive subtypes of breast cancer and associated with a poor prognosis. The mechanism involved in the progression of these tumors is poorly understood. In this study, we are trying to understand if loss of RAB25 expression in Human Mammary Epithelial Cell (HMEC) lines co-operates with H-Ras mutations and contributes to tumorigenesis. HMEC were immortalized by transduction with LXSN CDK4 R24C, a mutant form of cyclin-dependent kinase, followed by transduction with hTERT, catalytic subunit of the telomerase enzyme that permits the cells to exceed the Hayflick Limit and become immortal. We have found that with loss of RAB25 and over expression of mutant H-Ras61L, immortal HMEC undergo transformation. We have looked into the co-operativity between loss of Rab25 and H-Ras61L mutant by in-vitro studies to show their anchorage independent growth and increased ability to migrate. Furthermore, cells express low CD24, high CD44, and very low levels of Claudin indicating that cells acquire stem-like properties upon transformation. Loss of RAB25 and over-expression of H-ras61L resulted in increased expression of transcription markers Snail and Slug that drive these cells to lose E-cadherin and undergo Epithelial Mesenchymal Transition (EMT). This study shows that loss of RAB25 and over-expression of mutant H-Ras can transform HMEC and give rise to mesenchymal stem-like tumors. Our findings reveal that RAB25 functions as a tumor suppressor gene, and loss of RAB25 could serve as a novel biomarker in the prognosis of Claudin-low type of TNBC.

[EN] Aims of the thesis Aims: A - To identify and justify in a reasonable way, providing corroborated historical data, why saxophone players do not use the technique of the double/triple staccato. B - To locate the books (method books) dealing with the study of the double staccato in the saxophone and to do a comparative study analyzing the content of them. C - To offer this collective a reasoned collection of phrases appearing in the classical repertoire for saxophone which imply the use of this technique, in order to get a better quality of interpretation. D - To show, by means of methodological praxis in the classroom, that saxophone players can achieve quite a good command of the double/triple staccato, and to make the students who take part in this experiment get aware of the importance of studying and applying the lingual-guttural technique, when necessary, making thus the other saxophone players aware of its usefulness, both in an individual and a collective way. E - To offer the access, for those who are interested, before the publication of this work, to the most relevant biographical data of all the composers whose works for saxophone have been selected for containing phrases where the application of the double staccato is required. (This last part (E) will be included as an annex) Materials used The materials that have been used are: For the theoretical part (history, analysis) the ones described in bibliography, such as books, method books for saxophone, method books for flute, scores for both instruments, the Internet, etc. For the praxis in the classroom we have used the book "Muy picado", dealing completely with the study of the double/triple staccato and divided into three volumes that are distributed all along the four years of study. Planning The planning of this work does not start after the approval of this project. The praxis in the classroom actually starts, applying the selected methodology, in the school year 2003/04. The initial idea was to develop the experiment in class during 8 years so that it covered several generations of students and, this way, we would be able to verify if the achieved average level was similar every year and, also, if it was high enough. Thus, after seeing the results, we could affirm if the methodology used had been the right one and, if it was so, we could conclude by saying that, at first, it would be possible to extend to all the students of the specialization, no matter of their school, the result of the experiment, generalizing thus the use of the lingual-guttural technique. In order to get more reliable results, the research has been extended up to 11 years. Results We must admit that not all our aims finish here. Specially, the last part of the aim "D" will take some time to be generalized. The aim "E" will finish when the corresponding publication appears. In order to get the generalization of our aims, it will be necessary to develop an important information campaign both in conservatories and in bands, with conferences/speeches for professionals including practical demonstrations. In these future presentations, professionals will be provided with the experience and results obtained in the classroom with the study of the double/triple staccato and its application to the phrases included in this work. / [ES] Objetivos de la tesis Objetivos: A - Identificar y justificar, razonadamente y con datos históricos contrastados, por qué los saxofonistas no utilizan la técnica del doble/triple picado. B - Localizar libros (métodos) dedicados al estudio del doble picado en el saxofón y realizar un estudio comparativo analizando el contenido de los mismos. C - Ofrecer a este colectivo una recopilación razonada de frases del repertorio clásico de saxofón donde sea necesario aplicar esta técnica para una mejor resolución interpretativa de las mismas. D - Demostrar, mediante la praxis metódica en el aula, que los saxofonistas pueden alcanzar el suficiente dominio del doble/triple picado, intentando que al menos los alumnos que participan en esta experimentación se conciencien de la necesidad de estudiar y aplicar la técnica linguo - gutural, cuando proceda, y contribuir con ello a que el resto de saxofonistas vean la utilidad de usarla, tanto a nivel individual como en agrupaciones. E - Poner a disposición de los interesados, previa publicación de este trabajo, los datos biográficos más relevantes de todos los compositores cuyas obras de saxofón hayan sido seleccionadas por contener frases para la aplicación del doble picado. (Este último apartado (E) se incluirá como anexo) Medios utilizados Los medios utilizados han sido: Para la parte teórica (historia, análisis) los reseñados en bibliografía, como libros, métodos para saxofón, métodos para flauta, partituras para ambos instrumentos, Internet, etc. Para la praxis en el aula se ha utilizado el libro "Muy picado" dedicado en su totalidad al estudio del doble/triple picado, y dividido en tres volúmenes distribuidos a lo largo de los cuatro años de carrera. Planificación temporal La planificación de este trabajo no arranca a partir de la aprobación del presente proyecto. En realidad la praxis en el aula, aplicando la metodología seleccionada, comienza en el curso 2003/04. La idea inicial era desarrollar la experimentación en clase durante 8 años, de manera que hubiesen pasado por las aulas diversas generaciones de alumnos y así, por un lado, poder comprobar si el nivel medio alcanzado en cada una de las promociones era similar, y por otro lado si era suficiente. De esta forma, a la vista de los resultados, se podría constatar si la metodología empleada había sido la adecuada, y caso de serlo podríamos llegar a la conclusión de que, en principio, sería factible extender a todos los alumnos de la especialidad, de cualquier otro centro, el resultado de la experiencia realizada, generalizando así la utilización de la técnica linguo-gutural. Para asegurar más los resultados la investigación se ha prolongado hasta 11 años. Resultados Debemos admitir que no todos los objetivos concluyen aquí. Sobre todo la última parte del objetivo "D" llevará tiempo conseguir que se generalice. El objetivo "E" quedará concluido en el momento salga la publicación correspondiente. Para lograr la generalización de los objetivos, será necesario desarrollar una amplia campaña divulgativa, tanto en conservatorios como en las bandas de música, mediante conferencias/charlas para profesionales con demostraciones prácticas. En estas futuras presentaciones, a los profesionales de la especialidad se aportará la experiencia y resultados obtenidos en el aula con el estudio del doble/triple picado y la aplicación del mismo a las frases incluidas en el presente trabajo / [CAT] Objectius de la tesi Objectius: A - Identificar i justificar, raonadament i amb dades històriques contrastades, per què els saxofonistes no utilitzen la tècnica del doble/triple picat. B - Localitzar llibres (mètodes) dedicats a l'estudi del doble picat en el saxofon i realitzar un estudi comparatiu analitzant-ne el contingut. C - Oferir a aquest col·lectiu una recopilació raonada de frases del repertori clàssic de saxofon on calga aplicar aquesta tècnica per millorar-ne la resolució interpretativa. D - Demostrar, mitjançant la praxi metòdica a l'aula, que els saxofonistes poden aconseguir prou domini del doble/triple picat, amb la intenció que almenys els alumnes que participen en aquesta experimentació es consciencien de la necessitat d'estudiar i aplicar la tècnica linguogutural quan escaigui, i contribuir amb això al fet que la resta de saxofonistes vegin la utilitat d'usar-la, tant individualment com en agrupacions. E - Posar a la disposició dels interessats, prèviament a la publicació d'aquest treball, les dades biogràfiques més rellevants de tots els compositors les obres de saxofon dels quals s'hagen seleccionat per contenir frases per a l'aplicació del doble picat. (Aquest últim apartat (E) s'inclourà com a annex) Mitjans utilitzats Els mitjans utilitzats han sigut: Per a la part teòrica (història, anàlisi), els ressenyats en bibliografia, com llibres, mètodes per a saxofon, mètodes per a flauta, partitures per a tots dos instruments, Internet, etc. Per a la praxi a l'aula s'ha utilitzat el llibre Muy picado, dedicat íntegrament a l'estudi del doble/triple picat, i dividit en tres volums distribuïts al llarg dels quatre anys de carrera. Planificació temporal La planificació d'aquest treball no arranca a partir de l'aprovació del present projecte. En realitat, la praxi a l'aula, aplicant la metodologia seleccionada, comença en el curs 2003/04. La idea inicial era desenvolupar l'experimentació en classe durant 8 anys, de manera que hagueren passat per les aules diverses generacions d'alumnes i així, d'una banda, poder comprovar si el nivell mitjà aconseguit en cadascuna de les promocions era similar, i d'altra banda, si era suficient. D'aquesta manera, a la vista dels resultats, es podria constatar si la metodologia emprada havia sigut l'adequada, i cas de ser-ho podríem arribar a la conclusió que, en principi, seria factible estendre a tots els alumnes de l'especialitat, de qualsevol altre centre, el resultat de l'experiència realitzada, i generalitzar així la utilització de la tècnica linguogutural. Per assegurar més els resultats, la investigació s'ha perllongat fins a 11 anys. Resultats Hem d'admetre que no tots els objectius conclouen ací. Sobretot l'última part de l'objectiu D costarà temps aconseguir que es generalitze. L'objectiu E quedarà conclòs així que isca la publicació corresponent. Per aconseguir la generalització dels objectius, caldrà desenvolupar una àmplia campanya divulgativa, tant en conservatoris com en les bandes de música, mitjançant conferències/xarrades per a professionals amb demostracions pràctiques. En aquestes presentacions futures, als professionals de l'especialitat s'aportarà l'experiència i resultats obtinguts a l'aula amb l'estudi del doble/triple picat i l'aplicació d'aquest a les frases incloses en el present treball. / Pérez Morell, E. (2016). Análisis histórico de la utilización del doble/triple picado en el saxofón y su enseñanza en la actualidad [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/62319 / TESIS

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A Steiner triple system of order ν, denoted STS(ν), is said to be tricyclic if it admits an automorphism whose disjoint cyclic decomposition consists of three cycles. In this paper we give necessary and sufficient conditions for the existence of a tricyclic STS(ν) for several cases. We also pose conjectures concerning their existence in two remaining cases.

Les cancers du sein triple-négatif (TNBC) (RE-, RP-, HER2) représentent 15% des cas de cancer du sein. Les patientes atteintes de TNBC sont traitées uniquement par chimiothérapie. A l’heure actuelle, il n’existe aucune thérapie ciblée efficace. Malgré une chimiosensibilité initiale, les rechutes sont fréquentes. Ainsi de nouveaux traitements sont nécessaires pour soigner ces patientes. Dans le cancer du sein, l’aspartyl protéase cathepsine D (cath-D), un marqueur de mauvais pronostic, est surexprimée par les cellules cancéreuses et est hyper-secrétée dans le microenvironnement tumoral. La cath-D stimule la prolifération des cellules cancéreuses, la croissance invasive des fibroblastes, la croissance tumorale, l’angiogenèse tumorale et la formation des métastases. Différentes études ont mis en exergue le rôle oncogénique de la cath-D extracellulaire dans le cancer du sein, suggérant qu’elle serait une cible thérapeutique d’intérêt. Afin de neutraliser sélectivement la forme sécrétée de la cath-D, le laboratoire a généré des anticorps humains IgG1 dirigés contre la cath-D par un crible de phage display (International patent N° PCT/EP2016/061454).Les principaux objectifs de ma thèse ont été i) de valider la cath-D comme une cible extracellulaire d’intérêt pour les patientes atteintes de TNBC, ii) d’évaluer les effets thérapeutiques et iii) de caractériser les mécanismes d’action des anticorps humains anti-cath-D.Nous avons montré que des niveaux élevés d'ARNm de CTSD sont corrélés à une survie sans récidive plus courte. Par analyse protéomique et étude immunohistochimique anti-cath-D réalisée sur Tissue Micro-Array, nous avons observé que la cath-D extracellulaire est détectée dans le microenvironnement tumoral des TNBC contrairement au tissu mammaire normal. Nos résultats mettent ainsi en exergue que la cath-D serait un biomarqueur tumoral extracellulaire, suggérant que les patientes atteintes de TBNC pourraient bénéficier d’une thérapie par des anticorps anti-cath-D. Par des analyses de SPECT-CT (Single Photon Emission Computed Tomography) et de biodistribution, nous avons validé que les anticorps humains anti-cath-D, F1 et E2, s’accumulent dans les xénogreffes de la lignée TNBC MDA-MB-231 chez la souris athymique. Les anticorps F1 et E2 inhibent la croissance tumorale des xénogreffes MDA-MB-231 et améliorent la survie des souris athymiques. Notre meilleur anticorps anti-cath-D, F1, inhibe également la croissance tumorale de deux lignées de TNBC PDX (patient-tumor derived xenografts). Au niveau mécanistique, l’anticorps F1 module le microenvironnement immunitaire dans les tumeurs issues des xénogreffes MDA-MB-231. L’ensemble de nos résultats suggèrent qu’une immunothérapie avec des anticorps humains anti-cath-D pourrait être une nouvelle approche thérapeutique pour les patientes atteintes de TNBC. / Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer cases, and chemotherapy is the only available treatment. Thus identification of new therapeutic targets is required to improve TNBC outcome. In breast cancer, the aspartic protease cathepsin D (cath-D) is a marker of poor prognosis associated with metastatic risk. This protease is overexpressed by breast cancer cells and is abnormally hypersecreted into the tumor microenvironment. Cath-D affects both cancer and stromal cells in the breast tumor microenvironment by increasing the proliferation of breast cancer cells, fibroblast invasive outgrowth, tumor growth and angiogenesis, and metastasis formation. Many studies indicated that extracellular cath-D displays oncogenic activities, suggesting it could represent a novel therapeutic target in TNBC. In order to block its oncogenic actions, the laboratory generated human IgG1 antibodies against extracellular cath-D by phage display (International patent N° PCT/EP2016/061454). The aims of my PhD project was i) to validate the potential value of cath-D as a tumor-specific extracellular target in TNBC, ii) to evaluate the therapeutic activity, and iii) to characterize the mechanisms of action of these anti-cath-D human antibodies.We showed that elevated CTSD mRNA levels correlated with shorter recurrence-free survival. Using proteomics analysis and anti-cath-D immunohistochemistry performed on Tissue Micro-Array, we observed that extracellular cath-D was detected in the tumor microenvironment of TNBC, but not in matched normal breast stroma samples. Our results thus indicate that cath-D is a tumor cell-associated extracellular biomarker and strongly suggest that it could be a good candidate for antibody-based therapy in TNBC. We found that anti-cath-D human antibodies, F1 and E2, accumulated in TNBC MDA-MB-231 tumor xenografts in athymic mice by SPECT-CT (Single Photon Emission Computed Tomography) and biodistribution analysis. F1 and E2 antibodies inhibited tumor growth of MDA-MB-231 tumor xenografts and improved mice survival without apparent toxicity. F1, the best antibody candidate, inhibited tumor growth of two TNBC patient-derived xenografts (PDX). Mechanistically, F1 treatment modulates immune tumor microenvironment in the MDA-MB-231 tumor cell xenograft model. Together, our results indicate that antibody-based targeting of cath-D may have therapeutic efficacy for TNBC treatment.

Conventionally, the focus during supplier evaluation has been to assess cost, quality and delivery effectiveness due to their impact on profitability. In recent years, there has been increased emphasis on promoting more sustainable business practices that focus on reducing environmental impact and improve societal well-being, in addition to economic benefits. However, most of the existing supplier evaluation methods in literature as well as those used by leading companies fall short of comprehensively assessing suppliers from a Triple Bottom Line (TBL) perspective. TBL defined as holistically looking at the economic, environmental, and societal aspects of an entity. This paper presents a review and selection of metrics for economic, environmental and societal sustainability evaluation. In addition, this work proposes a methodology for combining the scores into a comprehensive score that can be used to compare two entities performance relative to the TBL.