No / The duocarmycins belong to a class of agent that has fascinated scientists for over four decades. Their exquisite potency, unique mechanism of action, and efficacy in multidrug-resistant tumour models makes them attractive to medicinal chemists and drug hunters. However, despite great advances in fine-tuning biological activity through structure-activity relationship studies (SARS), no duocarmycin-based therapeutic has reached clinical approval. In this review, we provide an overview of the most promising strategies currently used and include both tumour-targeted prodrug approaches and antibody-directed technologies.

This study serves to collate and evaluate measures of self-directed learning (SDL), with the goal of guiding the measurement and discussion of SDL. Used in a variety of settings, many applications of SDL have been proposed, but a consistent definition has yet to be formulated. Despite the lack of a cohesive definition, several tools exist to measure SDL. Within this study, which implemented the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) protocols, 157 articles were analyzed for content and themes were identified. An important finding of this study was a definite lack of cohesion in application and understanding of SDL as a framework. While some regard it as a stand-alone learning intervention, others address it as a personality trait. Close examination of the instruments used to measure SDL led to the conclusion that it is both inappropriate and ineffective to continue using, as they broadly lack construct validity and generalizability. Limitations of this study are single subject research, number studies available within databases used, and lack of raw data from studies covered. Future research surrounding the conceptual framework and instrumentation is indicated to further develop the field's understanding of SDL's value and implications.

This study examined the relationship between the sub-components of Holland's Self-Directed Search and independent, objective measures of ability using a comprehensive battery of well-validated tests of primary abilities corresponding to each of Holland's six vocational interest types. The sample consisted of 149 female undergraduate students, ages 18-25. Correlation of the ability measure test scores with the four Self-Directed Search subcomponents revealed that the subtests were not related to corresponding measures of ability in a consistent fashion. Implications for the use of the Self-Directed Search in assessing abilities are discussed along with suggestions for future research investigating the relationhip between interest in ventories and the measurement of primary abilities.

Approved for public release, distribution is unlimited / An investigation of how fuel cells, an integrated power system, and directed energy weapons will affect the shipboard command and control process. The focus is on the implementation of the new technologies onboard near-term and far-term destroyer variants and the resulting changes to the command and control process. / Ensign, United States Naval Reserve

This thesis is an autoethnography of an elementary art teacher who has transitioned from a traditional, teacher-led curriculum to a choice-based model where more freedom and responsibilities are given to the students. It is an account of the challenges and obstacles faced during the implementation of a choice-based curriculum and offers possible solutions, teaching strategies, and tips utilized to navigate the transition.

Pseudomonas aeruginosa (PA) est la troisième bactérie impliquée dans les maladies nosocomiales et est la principale cause de mortalité des patients atteints de la mucoviscidose. PA est résistante à la plupart des traitements antibiotiques. Trouver de nouvelles stratégies thérapeutiques est devenu un enjeu majeur de santé publique, l’une d’entre elles est l’inhibition de facteurs de virulence. Parmi ceux-ci, les lectines sont des protéines impliquées dans l’adhésion et la formation de biofilm via des interactions avec des sucres (PA-IL, PA- IIL, FliC, FliD, PilA, PilY1 et CupB6).Le but de ce travail est donc de trouver des leurres moléculaires ayant une forte affinité pour ces lectines. Ceux-ci sont des motifs saccharidiques présentés de façon multivalente : glycoclusters. De part leur grande diversité structurale et leur faible quantité, un outil de criblage innovant a été développé qui consiste en une lame de verre microstructurée : le glycocluster-microarray. Les glycoclusters sont immobilisés de manière ordonnée par DNA Directed Immobilization (DDI). Deux méthodes de criblage ont été développées grâce à cet outils : 1) le criblage en solution et par compétition d’une bibliothèque de motifs saccharidiques et 2) le criblage d’une bibliothèque de glycoclusters immobilisés sur le microarray. Avec cet outil, des protocoles de mesures d’IC50 et de Kd ont aussi été fiabilisés pour caractériser les meilleurs candidats inhibiteurs des lectines. Le glycocluster- microarray présente l’avantage de n’utiliser qu’une très faible quantité de matériel (quelques picomoles) et permet de réaliser diverses analyses en parallèle.Afin de valider cet outil, une étude sur l’impact de la densité de surface en glycocluster a été menée. Le criblage de plus de 150 motifs saccharidiques a permis de sélectionner ceux ayant une forte affinité pour les lectines. L’analyse sur microarray complétée par de la modélisation moléculaire d’une bibliothèque de glycoclusters, possédant ces motifs et différentes topologies, valences et propriétés (aromaticité, charge,…), a permis d’identifier les paramètres clés dirigeant les relations structure-affinité. Une activité anti-biofilm chez PA a été démontrée avec les meilleurs glycoclusters ciblant PA-IL.Tester l’activité in vivo, chez l’animal, des meilleurs candidats est une voie à explorer. Cibler d’autres lectines comme celles présentes sur le flagelle et les pili de PA et notamment impliquées dans son adhésion précoce est aussi une voie à développer. Pour cela, des tests préliminaires ont été présentés et d’autres sont en cours faisant appel à l’utilisation de bactéries entières ainsi qu’à une détection sans marquage des lectines. / Summary: Pseudomonas aeruginosa (PA) is the third pathogen involved in nosocomial diseases and the major cause of mortality of cystic fibrosis patients. PA develops resistance to antibiotics treatments. And so, developing new therapeutic strategies is a public health issue. One of the promising strategies is to inhibit virulence factors involved in the adhesion and the biofilm formation of PA. Some of these virulence factors are lectins which interact with sugars (PA-IL, PA-IIL, FliC, FliD, PilA, PilY1 and CupB6).The goal of this work is to find molecular decoys which have a strong affinity for these lectins. These are saccharidic units with a multivalent display: glycoclusters. An innovative screening tool has been developed: the glycocluster-microarray, to study lectin/glycocluster interactions. It is a microstructured glass slide where glycoclusters are immobilized by DNA Directed Immobilization (DDI). Two screening methods have been developed with this microarray: 1) the screening in solution and by competition of a saccharidic units library and2) the screening of a glycoclusters library immobilized on the microarray. Protocols of IC50 and Kd measurements have also been developed with this tool to characterize the best lectins inhibitors. This tool allows to use few amount of material (few picomoles) and to do parallel analysis.To validate the microarray, a study of the impact of glycoclusters surface density has been done. The screening of more than 150 saccharidic units allowed the selection of the ones that display the best affinity forlectins. The analysis, on microarray and molecular simulations, of the glycoclusters library displaying thesesaccharidic units and several topologies, valences and properties (aromaticity, charge,…) enable to identify key parameters of structure-affinity relationships. An anti-biofilm activity has been observed for the best glycoclusters targeting PA-IL.Testing in vivo activity of these best candidates will be explored. Targeting others lectins such as the ones on the flagella and pili of PA and involved in the early adhesion needs also to be developed. To this end, preliminary tests have been showed and some are in progress.

The relationships between community college students’ sense of community, student self-directed learning readiness, and successful completion of online courses were investigated using a correlational research design. Rovai’s Classroom Community Scale was used to measure classroom community, and the Fisher Self-directed Learning Readiness Scale was used to measure self-directed learning readiness, including three subscales of self-management, desire for learning, and self-control. The study participants were 205 students (49 males, 156 females; 131 White, 39 Black, 15 Asian, 10 Latino, 10 Multi-racial, 1 Native American) taking online courses during a summer term at a Texas community college. The research hypotheses were tested using Pearson r correlation coefficients between each of the seven independent variables (student learning, connectedness, classroom community, self-management, desire for learning, self-control, and self-directed learning readiness) and student successful course completion data. Contrary to prior study results, no association was found between students’ sense of community in online courses and student successful course completion. Although statistically significant differences were found between successful course completion and self-management (r = .258), desire for learning (r = .162), and self-directed learning readiness (r = .184), effect sizes were small suggesting a lack of practical significance. Possible reasons for the outcome of this study differing from prior research include relatively shorter semester length (summer term) during which data were collected and relatively smaller sample size.

The aim of this study was to discover whether a value-based typology could be established that was applicable to all South African adults. It was predicated on the basis of a literature review and previous research findings that there were two major underlying dimensions of values: collectivism versus individualism and inner- versus outer-directed. The parameters of these dimensions were hypothesised within the framework of a common social structure, based on a number of related propositions. It was also hypothesised that the South African adult population consisted of five types. Five value measures were examined and found to have disadvantages for South Africa. A value measurement technique had been developed in South Africa for an on-going study titled Sociomonitor. The core of this study was the measurement of values of relevance to marketing and media. Over the period 1976 to 1993 separate value based typologies were identified for urban Blacks and Whites. In 1995 both races were covered in the same year and a common typology was found. In 1997/8 Sociomonitor was extended to the total adult population of South Africa. Respondents were sub-divided into Collectivism, Individualism, Inner- and Outer-directed groups. The characteristics of which were found to be substantially as had been expected. South African adults were categorised into five value types. Three of which were as had been hypothesised, two were in place of one of the five anticipated and one wasn't found. It is concluded that the values of adults from all ethnic groups fall within the parameters of collectivism versus individualism and inner- versus outer-directed. Furthermore, there are five different value types in the South African adult population that transcend ethnic boundaries. The implications of a multi-ethnic typology for marketing, social and political decision-making, research and the formulation of scenarios are outlined. It is recommended that this type of research be extended to other African countries and small communities. / Dissertation (PHD)--University of Pretoria, 2003. / Psychology / unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(文学) / 甲第21285号 / 文博第773号 / 新制||文||662(附属図書館) / 京都大学大学院文学研究科行動文化学専攻 / (主査)教授 板倉 昭二, 教授 蘆田 宏, 准教授 森口 佑介 / 学位規則第4条第1項該当 / Doctor of Letters / Kyoto University / DGAM

Ultrasound directed self-assembly (DSA) relies on the acoustic radiation force associated with a standing ultrasound wave to organize particles dispersed in a fluid medium into specific patterns. State-of-the-art ultrasound DSA methods can only organize particles into (quasi-)periodic patterns, limited by the use of single-frequency ultrasound wave fields. Acoustic holography and acoustic waveguides provide alternatives to assembling complex patterns of particles, but generally provide low spatial accuracy and are not re-configurable because they require custom hardware for each specific pattern of particles, which is impractical. We introduce multi-frequency ultrasound wave fields to organize particles in non-periodic patterns. We theoretically derive and experimentally validate a solution methodology to determine the operating parameters (frequency, amplitude, phase) of any number and spatial arrangement of ultrasound transducers, required to assemble spherical particles dispersed in an inviscid fluid medium into any specific two-dimensional pattern. The results show that multi-frequency ultrasound DSA enables the assembly of complex, non-periodic patterns of particles with substantially fewer ultrasound transducers than single-frequency ultrasound DSA, and without incurring a penalty in terms of accuracy. The results of this work fundamentally transform the state-of-the-art knowledge of ultrasound DSA. Multi-frequency ultrasound wave fields enable a near-unlimited complexity of patterns of particles that can be assembled, increasing the relevance of the technology to practical implementation in engineering applications such as manufacturing of engineered composite materials that derive their properties from the spatial organization of the filler in the matrix material. Although this work focuses specifically on ultrasound wave fields, the theoretical model is valid for all wave phenomena. / Master of Science / Ultrasound directed self-assembly (DSA) is the process where particles dispersed in a fluid medium assemble into specific patterns due to their interactions with a sound wave and/or other particles. Current ultrasound DSA methods use a single-frequency ultrasound wave to assemble particles into specific patterns, which creates repeating patterns within the fluid medium. Other methods of assembling particles that allow for more complex, non-repeating patterns generally provide low spatial accuracy and do not allow dynamically changing the pattern as they require custom hardware for each specific pattern of particles, rendering these methods impractical. We use many ultrasound waves each with a different frequency to organize particles into complex, non-repeating patterns, which we call multi-frequency ultrasound DSA. We theoretically derive and experimentally validate a method that allows us to assemble any specific two-dimensional pattern of particles using multi-frequency ultrasound DSA. The results show that multi-frequency ultrasound DSA enables the assembly of complex, non-repeating patterns of particles with substantially resources than single-frequency ultrasound DSA, and without incurring a penalty in terms of accuracy. Multi-frequency ultrasound DSA enables a near-unlimited complexity of patterns of particles that can be assembled, increasing the relevance of the technology to practical implementation in engineering applications.