Dissertations / Theses on the topic 'High note effect'

The purpose of this research is to compare the effects two different teaching techniques-rote and note--have upon high school chorus. Rote instruction involves teaching students who do not have music in front of them. Note instruction involves teaching students who do have music in front of them. The methodology counterbalanced two different high school choirs. Rote and note taught groups were taught four of the same 3-part SAB chorale settings type music. Two recordings were made of each song for each group - once after 30 minutes of instruction and second 24 hours later to test retention. Recordings were randomized and mastered onto CD and given to experts for evaluation. Across the board results were that rote taught groups scored higher than note taught groups on intonation, note accuracy and rhythm. This research does not recommend doing away entirely with note instruction. Rather, this research gives credence to rote as a valid music learning technique, often misunderstood because of the conflicting reports found in the professional literature.

The Take Flight Program in Albion, NY had 20 students who took the Living Environment science class. This study examined the use of a guided note strategy to replace the traditional science notebook for these students. Over the course of three weeks the effectiveness of the guided note packet was measured with quiz scores, concept map preparation, student attitude and final test scores. Results suggested an improvement in attitude and improved test scores.

Numerous trim, control requirements and mission generalizations have been made to our previous multidisciplinary design methodology for a high speed civil transport. We optimize the design for minimum take off gross weight, including both aerodynamics and structures to find the wing planform and thickness distribution, fuselage shape, engine placement and thrust, using 29 design variables. While adding trim and control it was found necessary to simultaneously consider landing gear integration. We include the engine-out and crosswind landing requirements, as well as engine nacelle ground strike for lateral-directional requirements. For longitudinal requirements we include nose-wheel lift-off rotation and approach trim as the critical conditions. We found that the engine-out condition and the engine nacelle ground strike avoidance were critical conditions. The addition of a horizontal tail to provide take-off rotation resulted in a signiffcant weight penalty, and that penalty proved to be sensitive to the position of the landing gear. We include engine sizing with thrust during cruise and balanced field length conditions. Both the thrust during cruise and balanced field length constraints were critical. We include a subsonic leg in our mission analysis. The addition of a subsonic mission requirement also results in a large weight penalty.
Master of Science

Svensk militär verksamhet organiseras och leds i ett normalläge, för att snabbt kunna möta och hantera en hastigt uppkommen påfrestning. På motsvarande sätt finns annan verksamhet i samhället som verkar under liknande förutsättningar. Vad kännetecknar en militär organisation som skall hantera påfrestningar med hög operativ effekt, och vad utmärker metoden för att leda verksamheten vid påfrestning? Vilka utmaningar och lösningar kan identifieras? I syfte att vidga perspektiven gjordes en jämförelse i kontrasterande syfte mellan ett militärt förband och ett akutsjukhus. Genom en induktivt driven ansats och kvalitativ metod, genomfördes sju semistrukturerade djupintervjuer vid Luftstridsskolan i Uppsala och Lokal katastrofledning vid Gävle sjukhus. Likheterna mellan de undersökta enheterna avseende organisation och ledningsmetod samt utmaningar och lösningar kopplade till detta var stor. Med utgångspunkt i begreppen High Reliability Organizations och Ambidextrous Organizations diskuteras resultaten, som ger förutsättningar att utveckla organisation och ledningsmetod främst vid författarnas förband Luftstridsskolan. För att nå detta är författarnas konkreta rekommendationer, med stöd i empiri och litteratur, bl.a. att i högre utsträckning nyttja tvärfunktionellt sammansatta ledningsgrupper för att hantera påfrestningar eller komplexa planeringsuppgifter och därigenom minska stuprörstänkande, att sträva mot förbättrad gemensam lägesbild vid flottiljstab och att avkräva lojalitet mot beslutad organisation och ledningsmetod. Detta bedöms leda till ökad operativ effekt vid förbandet.
Swedish armed forces are normally organized for education and training on a daily basis, for the purpose of rapidly being able to deal with sudden events or strains. What signifies a military organization and command dealing with these kinds of strains whilst maintaining a high level of operational effect? What challenges do they face and what kinds of solutions are available? In order to expand the perspective a comparison was made with a military unit and an emergency hospital. This study was carried out withan inductive and qualitative method, and seven semi-structured interviews were conducted. By the perspectives of High Reliability Organizations and Ambidextrous Organizations, the results are discussed. The resemblances between the two researched units are surprisingly striking in the investigated areas of interest. In order to improve organization and command at the researched military unit, the authors recommend the following actions: the use of joint functions command groups to a greater extent in order to enhance the ability to handle strains and sudden events, to strive for a greater level of situational awareness on all levels in the organization and the demand for loyalty to organization and structure of management decided by the commander. These actions are deemed to increase the level of operational effect at the unit.

The majority of schools use punitive and reactive strategies to deal with maladaptive behaviors. This descriptive study was a replication of Wilmott (2012) and occurred in a multi-tiered system of supports (MTSS) high school. Professional development was provided to 22 teachers from a high school located in the western United States. This included 61% males and 39% females. Measures included the frequency of praise notes and ODRs, the quality of praise notes based on a praise note rubric, and a social validity questionnaire. The ODR and praise note frequencies were compared using the Spearman correlational coefficient that resulted in a weak correlation (r (2) = .-385, p > .05). Results were not significant in the ODR baseline to treatment (t(3)=-1.849, p <.05). The baseline praise note frequency compared to praise note frequency during treatment was significant (t(3)=-4.115, p<.05). Implications for educators suggested that the problem-solving process is feasible and essential when implementing evidenced based practices (EBPs), such as praise notes. The study concluded that ongoing professional development is integral to maintaining MTSS and EBPs. Limitations of this study include the lack of precise definitions in ODR reporting and minimal baseline data.

Research shows that students may be proficient in solving physics problem mathematically but still lack a fundamental understanding of the phenomena in question. One reason may be that a traditional approach to physics instruction emphasises instructors transfer of material to the students and problem-solving, sometimes at the expense of conceptional understanding. This master thesis combines socio-cultural and behaviouristic perspectives to analyse the effects of audience response systems in learning environments, in particular physics instruction. An audience response system is a tool that collects responses from the participants. It is commonly used to create interaction, thus moderating the approach of pure transmission of information. The current state of research shows that the effects of audience response systems depend on how it is used by the instructor. Audience response systems have been popular for use in peer instruction in physics and part of this study was to evaluate the design of conceptual problems. Using a mix-methods approach with interviews, observations, and tests, this thesis explores teachers’ experiences from using audience response systems to stimulate thinking and discussion on conceptual questions. Different modalities of systems are also compared. The study was affected by the school closure due to the COVID-19 pandemic, however the remote teaching situation also makes the topic even more important. The findings confirm what is previously established about the role of the instructor and that the effects depend on their intention. This study demonstrates that an audience response system can be used for formative assessment, initiate discussions, simultaneously engage multiple participants, prompt instructors to reconsider their methods and support a productive learning environment. Important features of an audience response system are ease of use, clear display of responses, synchronous participation, and anonymity.
Tidigare forskning visar att studenter kan vara skickliga i att lösa fysikproblem matematiskt men ändå sakna en grundläggande förståelse för fenomenen i fråga. En möjlig förklaring är att fysikundervisning traditionellt fokuserar på överföring av material från lärare till elev med ett fokus på problemlösning, ibland på bekostnad av den konceptuella förståelsen. Detta examensarbete kombinerar sociokulturella och beteendemässiga perspektiv för att analysera effekterna av publiksvarssystem i lärande miljöer, primärt i fysikundervisning. Ett publiksvarssystem är ett verktyg som samlar in respons från deltagarna. Det används vanligen för att skapa interaktion, och därmed reducera fokuset på ren överföring av material i undervisningen. Det aktuella forskningsläget visar att effekterna av publiksvarssystem beror på hur det tillämpas av läraren. Publiksvarssystem har populärt använts i peer instruction (kamratlärande) i fysik och en del i denna studie har varit att utvärdera design av konceptuella frågor. Med hjälp av kvalitativa och kvantitativa metoder (intervjuer, observationer och tester) undersöker detta arbete lärares erfarenheter av att använda publiksvarssystem för att stimulera tänkande och diskussioner om konceptuella frågor. Vidare jämförs modaliteten hos olika system. Studiens utformning påverkades av skolstängningarna till följd av COVID-19-pandemin, dock ger de förutsättningar som kommer med distansundervisning ytterligare relevans för ämnet. Resultaten bekräftar vad som tidigare har fastställts om lärarens roll och att effekterna beror på dennes intentioner. Studien visar att ett publiksvarssystem kan användas för formativ bedömning, initiera diskussioner, engagera flera deltagare simultant, uppmuntra lärare att ompröva sina metoder och hjälpa till att skapa förutsättningar för en produktiv inlärningsmiljö. Viktiga funktioner i ett publikresponssystem är användarvänlighet, tydlig presentation av svar, möjlighet till synkront deltagande för många personer samt anonymitet.

La réhabilitation respiratoire (RR) est recommandée dans la prise en soin des patients atteints d’un handicap ventilatoire afin d’améliorer leur qualité de vie. Malgré une efficacité clairement établie, très peu de patients en bénéficient et les modalités optimales d’entrainement restent à définir. L’utilisation des outils existants et des nouveaux outils pour optimiser l’accès au programme et ses effets représentent des développements majeurs qui méritent d’être évalués. Dans le cadre de cette thèse, nous avons cherché à aborder ces deux problématiques (1) en tentant de proposer un modèle de RR délocalisée hors des centres tout en évaluant les freins à ce modèle et (2) en explorant la place de différents adjuvants à la RR afin d’en optimiser les bénéfices. Dans la première partie, nous avons montré, à travers plusieurs études rétrospectives et une contribution originale prospective multicentrique, que le test stepper de six minutes peut être utilisé pour prescrire l’entrainement en endurance, particulièrement pour les patients présentant une forme légère à modérée de bronchopneumopathie chronique obstructive (BPCO), mais pas pour prescrire le renforcement musculaire. Par ailleurs, nous avons montré dans une population de 105 patients adressés en RR que l’utilisation d’un dispositif de telemonitoring était faisable, valide et largement accepté. Enfin, nous avons exploré la prévalence des dysfonctions cognitives, autre conséquence systémique de la BPCO qui pourrait compromettre la délocalisation du programme, et avons montré que cette prévalence était très élevée (environ 75% des patients) mais que ces troubles cognitifs pouvaient s’améliorer après la RR et ne semblaient pas influencer l’utilisation d’un dispositif de telemonitoring. Dans la seconde partie, nous avons évalué la place de différents adjuvants à la RR utilisés pour en potentialiser les bénéfices. Dans une étude en cross-over menée chez 21 patients atteints de BPCO, nous avons montré que la ventilation non invasive ne permettait pas d’améliorer la capacité à l’exercice en endurance en raison d’une limitation technologique du ventilateur. A travers une étude contrôlée randomisée multicentrique menée chez 73 patients atteints de BPCO sévère à très sévère, nous avons montré que la stimulation électrique excito-motrice à domicile, réalisée en plus d’un programme de RR, n’apportait pas davantage de bénéfices sur la qualité de vie ou la capacité à l’exercice. Enfin, à travers une étude randomisée en cross-over et en double aveugle menée chez 10 patients, nous n’avons pas pu montrer l’intérêt de la stimulation électrique nerveuse transcutanée pour améliorer leur capacité à l’exercice en endurance. Enfin, dans la dernière partie, nous avons présenté les recherches actuellement menées au sein de notre laboratoire, faisant suite aux contributions originales décrites au cours de cette thèse, ainsi que de nouvelles pistes de recherche afin de poursuivre les thématiques explorées. Ainsi, deux revues de littérature et méta-analyses (l’une d’elle portant sur le haut débit nasal et l’autre sur l’utilisation des technologies de santé avancées pour réaliser la RR respiratoire à domicile) serviront de base pour de futurs travaux
Pulmonary rehabilitation (PR) is recommended in the management of subjects with ventilatory impairment to improve their quality of life. Although a large body of evidence support its use, only few subjects benefit from it and the optimal training modality has not been determined yet. In this context, the use of new and existing tools to optimize access as well as the effects of the program are major developments that deserve to be studied. As part of this thesis, we sought to explore these two major issues (1) by considering a rehabilitation model relocated outside the PR centres while assessing the obstacles to this model and (2) exploring the effectiveness of different add-on to PR in further optimizing the benefits of the program. In the first part, we have shown, through several retrospective studies and an original prospective multicentre contribution, that the six-minute stepper test can be used to prescribe endurance training, particularly for those patients with a mild to moderate chronic obstructive pulmonary disease (COPD), but not to prescribe muscle strengthening. Furthermore, we have shown in a cohort of 105 subjects referred for PR that the use of a remote tele monitoring device was feasible, valid and widely accepted. Finally, we explored the prevalence of cognitive dysfunction, another systemic impairment of COPD that could compromise the relocation of the program, and showed that it was a very common condition (around 75% of the subjects) but that it could improve following PR and did not seem to influence the use of a remote tele monitoring device. In the second part, we evaluated the effects of different add-on used to potentiate the benefits of the PR program. In a cross-over study of 21 COPD patients, we showed that non-invasive ventilation did not improve endurance exercise capacity due to technological limitation of the ventilator. Through a multicentre randomized controlled study carried out in 73 patients with severe to very severe COPD, we have shown that neuromuscular electrical stimulation at home, performed in addition to a PR program, did not provide further benefits on quality of life or exercise capacity. Finally, through a randomized cross-over double-blind study carried out in 10 patients, we were unable to show the effectiveness of transcutaneous nerve electrical stimulation in improving their endurance exercise capacity. Finally, in a last part, we highlighted the research currently carried out in our laboratory following the original contributions described during this thesis, as well as new area of research in order to pursue the themes explored. Thus, two systematic reviews and meta-analysis (the first about nasal high flow therapy in subjects with stable COPD and the second about the use of advanced telehealth technologies to deliver PR) will serve as a basis for future research

L'hypoxie intermittente (HI), induite par les apnées du sommeil, conduit à des altérations de la sensibilité à l'insuline et de l'homéostasie glucidique mais les mécanismes impliqués restent mal connus. L'objectif de ce travail était d'étudier les effets et les mécanismes sous jacents d'une exposition chronique à l'HI sur l'homéostasie glucidique. L'HI induit une résistance à l'insuline à la fois systémique et tissulaire, ainsi qu'une amélioration de la tolérance au glucose associée à une activation de l'AMPK musculaire. L'HI cause également des altérations du foie et du tissu adipeux associées à un changement du pattern d'expression des gènes dans ces tissus et à un risque accru de développement de pathologies vasculaires comme l'athérosclérose. Enfin, la délétion de PHD1, une des protéines régulatrices de HIF-1, entraîne une résistance à l'insuline associée une stéatose hépatique, faisant de HIF-1 une cible potentielle impliquée dans les altérations metaboliques induites par l'HI
Intermittent hypoxia (IH), induced by sleep apnea, leads to alterations in insulin sensitivity and glucose homeostasis but the mechanisms involved remains poorly understood. The objective of this work was to study the effects and the underlying mechanisms of chronic exposure to IH on glucose homeostasis. IH induces both systemic and tissue-specific insulin resistance , as well as improved glucose tolerance associated with an activation of muscle AMPK. IH also causes a change in the pattern of gene expression in liver and adipose tissue and an increased risk of vascular pathologies such as atherosclerosis development. Finally, the deletion of PHD1, a regulatory protein of HIF-1, leads to insulin resistance associated with hepatic steatosis, making HIF-1 a possible target involved in the metabolic changes induced by IH

Testing is the most common way to assess student learning at all ages and grade levels. Testing is traditionally viewed as a measure of knowledge, and not as a way to enhance learning. Nonetheless, a large body of literature demonstrates that testing is actually an effective way to facilitate learning and enhance long-term memory for information. This finding, that retrieval of information from memory leads to better retention than re-studying or re-reading the same information, has been termed the testing effect. The benefit of testing compared to review of material is typically seen after a delay between practice and final test, with review being a better strategy when the test is given immediately or after a short delay. This phenomenon has been shown across a variety of contexts, test formats, retention intervals, and ranges of ages and abilities. However, one domain in which the testing effect has not been shown to work is in the review of student-produced lecture notes. Lecture note-taking is a ubiquitous learning strategy and notes have been shown to be highly correlated with academic outcomes such as test performance and GPA. Note-taking in itself is a cognitively demanding process, and students often struggle to take accurate and complete notes from lecture, thus limiting the benefits of note-taking and review. There is limited research on ways to improve the review function of notes. Thus, this dissertation sought to understand the effect of integrating the testing effect into the context of lecture note-taking on memory for information compared to review of notes and a lecture-only control. A sample of 59 high school students watched a video lecture and took notes on the information. The lecture was divided into three sections with two-minute pauses in between each segment. During each pause, students were asked to either reread their notes from the previous section (review group), recall and write down what they remembered to be the most important ideas from the lecture they were just shown (self-testing group), or complete a distractor word search puzzle for the duration of the pause (lecture-only control group). Participants were given a written recall test of lecture information following a one-day delay. Comparisons were made between lecture groups on test performance and note quantity. Measures of sustained attention and mind-wandering during lecture were examined as covariates. While participants in the self-testing group scored higher on the written recall test, this difference did not reach statistical significance. Self-testing and reviewing notes during lecture pauses were both significantly better than lecture note-taking alone. Results also showed that it was actually the students in the review group who took significantly more notes than those in the lecture-only control. There was a main effect for time, indicating that students in all lecture groups took increasingly more notes as the lecture progressed. Note quantity was found to be a significant predictor of test performance. Examination of attentional variables showed that students who reported lower instances of mind-wandering took significantly more notes and did significantly better on the recall test. Further, students in the self-testing group reported less of an increase in mind-wandering as the lecture progressed compared to those in the control group. Differences between the results of this study and other studies in the testing effect literature are hypothesized to be due several factors, including complexity of lecture information, encoding difficulties, and the presentation of new information at each self-testing time point. Future research should continue to explore the testing effect in conjunction with note taking.

碩士
國立臺灣大學
翻譯碩士學位學程
107
After the College Entrance Examination Center introduced the Test of English Listening Comprehension (TELC) in 2012, more attention has been given to listening strategy instruction in senior high schools. Although previous studies have explored the benefits of various listening strategies, few studies have looked into the effect of conference interpreting strategies on listening comprehension tests. The consecutive interpreting notes commonly used in interpreting teaching are an important tool that assist interpreters in listening to and remembering the source speech, but whether consecutive interpreting note-taking can be applied to high school English listening comprehension tests remains unknown. This study thus attempted to fill the research gap by exploring the effects of consecutive interpreting note-taking on the Test of English Listening Comprehension. The materials for this study included a pre-study questionnaire, a pre-test and a post-test, 8 listening mock tests, a post-study questionnaire, and CINT handouts. The CINT instruction designed by the researcher was based on the principles on consecutive interpreting note-taking, and the lesson procedures were drawn up using the Cognitive Academic Language Learning Approach (CALLA) proposed by Chamot et al. (1999). A total of 60 students from two intact classes in a senior high school in Taiwan were recruited for the study, and they were divided into an experimental group and a control group accordingly. Both groups received eight weeks of listening training, during which the experimental group received CINT instruction and was urged to apply the CINT skills to the TELC practice tests, whereas the control group received the same listening exposure without any instructions in note-taking. Both groups were asked to fill out the post-study questionnaires which investigated their perception of the CINT instruction. Data collected from the pre-test and post-test were analyzed statistically to determine the effectiveness of the CINT instruction, and the qualitative data from the pre-study and post-study questionnaires were also analyzed to find out how senior high school students perceived the CINT instruction. The results of the present study imply that the CINT instruction developed by the researcher failed to improve students’ performance on the Short Talk section of the TELC. Both groups scored worst on the post-test, but the difference between their impaired performances were nonetheless not significant. This could be attributed to insufficient practice during the short training course, which did not allow the participants in the experimental group to achieve meaningful levels of competency in CINT, or even resulted in poor effort distribution that disrupted listening. Another plausible reason is that the nature of the TELC short talk rendered CINT superfluous, as the talks were not long enough to cause cognitive overload in the first place. However, the participants in the experimental group generally held a positive attitude toward CINT. The study has arrived at two pedagogical implications. Firstly, CINT may be helpful in terms of improving concentration, memory, and efficiency, but rigorous practice is needed to overcome the difficulties encountered at the initial stages of acquisition. Secondly, linguistic abilities are still a prerequisite in effective listening comprehension. Without basic understanding of the aural input, any form of note-taking would be pointless.

碩士
國立臺北科技大學
機電整合研究所
100
MOSFETs use HfO2 as the gate dielectrics in the new generation, but they still have hot-carrier problem, and more studies are need. Our team invented the Power Transform Model to study hot-carrier reliability of 65 nm MOSFETs in the past, and the results of the study were good. Hence, Power Transform Model applied in 45 nm nMOSFETs is studied in this work. In this research, the tested devices were 45 nm nMOSFETs from United Micro-electronics Corporation (UMC). The device channel width/length (W/L) = 10/0.1um and (W/L) = 10/0.05um. All tests were conducted at temperatures 55℃. and the stress voltage of VD and VG were (2.7 ; 2.7)、(2.7 ; 2.9)、(2.7 ; 3.1)、(2.9 ; 2.7)、(2.9 ; 2.9)、(2.9 ; 3.1)、(3.1 ; 2.7)、(3.1 ; 2.9)、(3.1 ; 3.1), respectively. Stress modes were DC and AC on channel hot-carrier (CHC) conditions. From the CHC test results, it is found that the power transform model can successfully describe device damage.

Beta-gallium oxide (β-Ga₂O₃) is an emerging wide bandgap semiconductor for next generation power devices which offers the potential to replace GaN and SiC. It has an ultra-wide bandgap (UWBG) of 4.8 eV and a corresponding E_br of 8 MV/cm. β-Ga₂O₃ also possesses a decent intrinsic electron mobility limit of 250 cm²/V·s, yielding high Baliga’s figure of merit of 3444. In addition, the large bandgap of β-Ga₂O₃ gives stability in harsh environment operation at high temperatures.

Although low-cost large-size β-Ga₂O₃ native bulk substrates can be realized by melt growth methods, the unique property that (100) surface of β-Ga₂O₃ has a large lattice constant of 12.23 Å allows it to be cleaved easily into thin and long nano-membranes. Therefore, β-Ga₂O₃ FETs on foreign substrates by transferring can be fabricated and investigated before β-Ga₂O₃ epitaxy technology becomes mature and economical viable. Moreover, integrating β-Ga₂O₃ on high thermal conductivity materials has an advantage in terms of suppressing self-heating effects.

In this dissertation, structural and material innovations to overcome and improve critical challenges are summarized as follows: 1) Top-gate nano-membrane β-Ga₂O₃ FETs on a high thermal conductivity diamond substrate with record high maximum drain current densities are demonstrated. The reduced self-heating effect due to high thermal conductivity of the substrate was verified by thermoreflectance measurement. 2) Local electro-thermal effect by electrical bias was applied to enhance the electrical performance of devices and improvements of electrical properties were shown after the annealing. 3) Thin thermal bridge materials such as HfO₂ and ZrO₂ were inserted between β-Ga₂O₃ and a sapphire substrate to reduce self heating effects without using a diamond substrate. The improved thermal performance of the device was analyzed by phonon density of states plots of β-Ga₂O₃ and the thin film materials. 4) Nano-membrane tri-gate β-Ga₂O₃ FETs on SiO₂/Si substrate fabricated via exfoliation have been demonstrated for the first time. 5) Using the robustness of β-Ga₂O₃ in harsh environments, β-Ga₂O₃ ferroelectric FETs operating as synaptic devices up to 400 °C were demonstrated. The result offers the potential to use the novel device for ultra-wide bandgap logic applications, specifically neuromorphic computing exposed to harsh environments.

Young football players are hypothesized to experience damage to the brain and brain function from repeated subconcussive head acceleration events (HAEs) during practices and games. Such damage may cause delayed cognitive and mental problems. Resting state fMRI (rs-fMRI) is an effective non-invasive method to detect alterations in brain functional connectivity. Seed-based rsfMRI analysis using the central node of the default mode network (DMN) as the seed is a common approach to measuring intrinsic changes of the DMN, accepted as a key network in brain function. Seed-based rs-fMRI analysis of the DMN was used to explore how age, HAE intensity, and HAE counts influence brain connectivity in youth athletes (ages 12-18). Middle school and high school football players and peer controls were studied using rs-fMRI before and after one season of competition. An identifiability matrix was generated from the seed-based connectivity matrix, allowing measurement of similarity between pre-season and post-season functional connectivity. The consistency of seed-based brain functional connectivity we observed across the season of play for players has no statistically significant difference from controls. The identifiability matrix exhibited no relation to the number and magnitude of any subset of HAEs experienced which rejected our hypothesis. Another finding is that high school football players exhibited the largest percentage increase in identification from middle school football players in the somatomotor network over other resting-state networks.

AIMS/HYPOTHESIS: We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity. METHODS: Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n = 24), standard chow (SC; n = 16), HF + metformin (144 mg/kg in diet; n = 20) or SC + metformin (144 mg/kg in diet; n = 16) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. RESULTS: HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. CONCLUSIONS/INTERPRETATION: Metformin prevented the metabolic but not cognitive alterations associated with HF feeding. The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.

Various organic reactions, including important synthetic reactions involving C–C, C–N, and C–O bond formation as well as reactions of biomolecules, are known to be accelerated when the reagents are present in confined volumes such as sprayed or levitated microdroplets or thin films. This phenomenon of reaction acceleration and the key role of interfaces played in it are of intrinsic interest and potentially of practical value as a simple, rapid method of performing small-scale synthesis. This dissertation has three focusing subtopics in the field of reaction acceleration: (1) application of reaction acceleration in levitated droplets and mass spectrometry to accelerate the reaction-analysis workflow of forced degradation of pharmaceuticals at small scale; (2) fundamental understanding of mechanisms of accelerated reactions at air/solution interfaces; (3) discovery the use of glass particles as a `green' heterogeneous catalysts in solutions and systematical study of solid(glass)/solution interfacial reaction acceleration as a superbase for synthesis and degradation using high-throughput screening.

Reaction acceleration in confined volumes could enhance analytical methods in industrial chemistry. Forced degradation is critical to probe the stabilities and chemical reactivities of therapeutics. Typically performed in bulk followed by LC-MS analysis, this traditional workflow of reaction/analysis sequence usually requires several days to form and measure desirable amount of degradants. I developed a new method to study chemical degradation in a shorter time frame in order to speed up both drug discovery and the drug development process. Using the Leidenfrost effect, I was able to study, over the course of seconds, degradation in levitated microdroplets over a metal dice. This two-minute reaction/analysis workflow allows major degradation pathways of both small molecules and therapeutic peptides to be studied. The reactions studied include deamidation, disulfide bond cleavage, ether cleavage, dehydration, hydrolysis, and oxidation. The method uses microdroplets as nano-reactors and only require a minimal amount of therapeutics per stress condition and the desirable amount of degradant can be readily generated in seconds by adjusting the droplet levitation time, which is highly advantageous both in the discovery and development phase. Built on my research, microdroplets can potentially be applied in therapeutics discovery and development to rapidly screen stability of therapeutics and to screen the effects of excipients in enhancing formulation stabilities.

My research also advanced the fundamental understanding of reaction acceleration by disentangles the factors controlling reaction rates in microdroplet reactions using constant-volume levitated droplets and Katritzky transamination as a model. The large surface-to-volume ratios of these systems results in a major contribution from reactions at the air/solution interface where reaction rates are increased. Systems with higher surface-active reactants are subject to greater acceleration, particularly at lower concentrations and higher surface-to-volume ratios. These results highlight the key role that air/solution air/solution interfaces play in Katritzky reaction acceleration. They are also consistent with the view that reaction increased rate constant is at least in part due to limited solvation of reagents at the interface.

While reaction acceleration at air/solution interfaces has been well known in microdroplets, reaction acceleration at solid/solution interfaces appears to be a new phenomenon. The Katritzky reaction in bulk solution at room temperature is accelerated significantly by the surface of a glass container compared to a plastic container. Remarkably, the reaction rate is increased by more than two orders of magnitude upon the addition of glass particles with the rate increasing linearly with increasing amounts of glass. A similar phenomenon is observed when glass particles are added to levitated droplets, where large acceleration factors are seen. Evidence shows that glass acts as a ‘green’ heterogeneous catalyst: it participates as a base in the deprotonation step and is recovered unchanged from the reaction mixture.

Subsequent to this study, we have systematically explored the solid/solution interfacial acceleration phenomena using our latest generation of a high-throughput screening system which is capable of screening thousands of organic reactions in a single day. Using desorption electrospray ionization mass spectrometry (DESI-MS) for automated analysis, we have found that glass promotes not only organic reactions without organic catalysts but also reactions of biomolecules without enzymes. Such reactions include Knoevenagel condensation, imine formation, elimination of hydrogen halide, ester hydrolysis and/or transesterification of acetylcholine and phospholipids, as well as oxidation of glutathione. Glass has been used as a general `green' and powerful heterogeneous catalyst.