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Lab-on-a-chip platform for high throughput drug discovery with DNAencoded chemical librariesGrünzner, S., Reddavide, F. V., Steinfelder, C., Cui, M., Busek, M., Klotzbach, U., Zhang, Y., Sonntag, F. 09 August 2019 (has links)
The fast development of DNA-encoded chemical libraries (DECL) in the past 10 years has received great attention from pharmaceutical industries. It applies the selection approach for small molecular drug discovery. Because of the limited choices of DNA-compatible chemical reactions, most DNA-encoded chemical libraries have a narrow structural diversity and low synthetic yield. There is also a poor correlation between the ranking of compounds resulted from analyzing the sequencing data and the affinity measured through biochemical assays. By combining DECL with dynamical chemical library, the resulting DNA-encoded dynamic library (EDCCL) explores the thermodynamic equilibrium of reversible reactions as well as the advantages of DNA encoded compounds for manipulation/detection, thus leads to enhanced signal-to-noise ratio of the selection process and higher library quality. However, the library dynamics are caused by the weak interactions between the DNA strands, which also result in relatively low affinity of the bidentate interaction, as compared to a stable DNA duplex. To take advantage of both stably assembled dual-pharmacophore libraries and EDCCLs, we extended the concept of EDCCLs to heat-induced EDCCLs (hi-EDCCLs), in which the heat-induced recombination process of stable DNA duplexes and affinity capture are carried out separately. To replace the extremely laborious and repetitive manual process, a fully automated device will facilitate the use of DECL in drug discovery. Herein we describe a novel lab-on-a-chip platform for high throughput drug discovery with hi-EDCCL. A microfluidic system with integrated actuation was designed which is able to provide a continuous sample circulation by reducing the volume to a minimum. It consists of a cooled and a heated chamber for constant circulation. The system is capable to generate stable temperatures above 75 °C in the heated chamber to melt the double strands of the DNA and less than 15 °C in the cooled chamber, to reanneal the shuffled library. In the binding chamber (the cooled chamber) specific retaining structures are integrated. These hold back beads functionalized with the target protein, while the chamber is continuously flushed with library molecules. Afterwards the whole system can be flushed with buffer to wash out unspecific bound molecules. Finally the protein-loaded beads with attached molecules can be eluted for further investigation
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ARCH4HEALTH - Notaufnahme: Student Research Lab: Wintersemester 2021/22Büter, Kathrin, Kolodziej, Carolina, Schoß, Anne-Sophie, Marquardt, Gesine 08 July 2022 (has links)
Im Wintersemester 2020/21 haben sich 12 Architekturstudierende im Rahmen des ARCH4HEALTH Student Research Lab an der Professur für Sozial- und Gesundheitsbauten der TU Dresden mit der architektonischen Gestaltung von Notaufnahmen beschäftigt. Im Rahmen von eigenen Forschungsprojekten sind sie aktuellen Fragestellungen zu Nutzerbedürfnissen, der Gestaltung von einzelnen Bereichen einer Notaufnahme oder Planungsmethoden nachgegangen und haben aus ihren Erkenntnissen erste Ideen und Konzepte abgeleitet. In diesem Buch werden die Ergebnisse der studentischen Forschungsprojekte präsentiert.:1. Vorwort
2. Einleitung
3. Forschungsartikel
4. Poster
5. Rückblick & Ausblick
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ARCH4HEALTH - Strahlentherapie: Student Research Lab: Sommersemester 2022Kolodziej, Carolina, Büter, Kathrin, Schoß, Anne-Sophie, Marquardt, Gesine 11 October 2023 (has links)
Im Sommersemester 2022 haben sich 14 Architekturstudierende im Rahmen des ARCH4HEALTH - Student Research Lab an der Professur für Sozial- und Gesundheitsbauten der TU Dresden mit der architektonischen Gestaltung von Abteilungen der Strahlentherapie beschäftigt. Im Rahmen von eigenen Forschungsprojekten und kurzen Entwurfsaufgaben sind sie aktuellen Fragestellungen zu Nutzerbedürfnissen, der Gestaltung von einzelnen Bereichen der Strahlentherapie nachgegangen und haben aus ihren Erkenntnissen erste Ideen und Konzepte abgeleitet. In diesem Buch werden die Ergebnisse der studentischen Forschungsprojekte präsentiert.:1. Vorwort
2. Einleitung
3. Forschungsartikel
4. Poster
5. Stegreifentwürfe
6. Rückblick & Ausblick
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Impact of Green Design and Technology on Building EnvironmentXiong, Liang 12 1900 (has links)
Currently, the public has a strong sense of the need for environment protection and the use of sustainable, or “green,” design in buildings and other civil structures. Since green design elements and technologies are different from traditional design, they probably have impacts on the building environment, such as vibration, lighting, noise, temperature, relative humidity, and overall comfort. Determining these impacts of green design on building environments is the primary objective of this study. The Zero Energy Research (ZOE) laboratory, located at the University of North Texas Discovery Park, is analyzed as a case study. Because the ZOE lab is a building that combines various green design elements and energy efficient technologies, such as solar panels, a geothermal heating system, and wind turbines, it provides an ideal case to study. Through field measurements and a questionnaire survey of regular occupants of the ZOE lab, this thesis analyzed and reported: 1) whether green design elements changed the building’s ability to meet common building environmental standards, 2) whether green design elements assisted in Leadership in Energy and Environmental Design (LEED) scoring, and 3) whether green design elements decreased the subjective comfort level of the occupants.
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Screening, identification and characterisation of bacteriocins produced by the wine isolated LABNdlovu, Joseph Buyani 03 1900 (has links)
Thesis (MSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Lactic acid bacteria (LAB) play a vital role in reducing wine acidity and also contributing to its
aroma and flavour. However, they can also be responsible for many wine spoilage problems that
compromise the quality and value of wine. While Oenococcus oeni contributes positive characteristics to
the sensory properties of wine, certain species of the genera, Lactobacillus and Pediococcus can affect the
wholesomeness of wine by producing undesirable compounds, such as biogenic amines and ethyl
carbamate.
Chemical preservatives like sulphur dioxide (SO2) are used to prevent the growth of spoilage
micro-organisms during the winemaking process. SO2 also acts as a reducing agent and maintains the
benefits of antioxidant properties of the polyphenols of wine. However, there is a worldwide demand to
reduce SO2 levels due to the increasing health related risks and other factors.
All these considerations have increased the interest in research to look for new preservation
strategies, and LAB-produced bacteriocins seem to be a potential alternative that has been explored in the
last decade. Various types of bacteriocins have been identified and characterized. However, there are few
reports on bacteriocins produced by LAB of oenological origin or on bacteriocins present in the finished
wine.
The present study screened 155 LAB isolates from the IWBT culture collection for bacteriocin
production. The isolates originated from South African red wines undergoing spontenous malolactic
fermentation (MLF). Eight strains (5%) were identified to be producers, as evidenced by strong inhibition
zones formed against sensitive organisms on agar plates. The producers demonstrated a broad spectrum of
antimicrobial activity by inhibiting Lactobacillus spp., Leuconostoc mesenteroides, Listeria
monocytogenes and Pediococcus pentosaceus strains. Some of these bacterial genera are important in
winemaking since they are potential wine spoilage bacteria. Hence these strains and/or the bacteriocins
they produce could possibly find application in the food fermentation industry. The physiological results, biochemical tests and sugar fermentation profiles all gave the same
results for the seven isolates, which were indicative of enterococci. The identification through 16S rRNA
gene sequencing revealed that the seven tested isolates were all Enterococccus faecium. RAPD-PCR
fingerprinting gave the same profile for the seven strains confirming that they were all identical on
genetic level. Determining the molecular weight using SDS-PAGE showed the peptides to be below
4.6 kDa in size. PCR amplification of the enterocin P gene, sequencing and BLAST search results
confirmed that all eight strains contained the enterocin P gene from Ent. faecium.
The enterocin tested in this study was heat stable at 100°C (30 min), but lost 50% of its activity at
121°C (15 min). Factors such as bacteriocin production and heat resistance are among many that enable
enterococci to be dominant in fermented products such as dairy foods or meat. Therefore, enterococci
producing bacteriocins have potential applications in various foods and fermented products. The pH tests
showed enterocin to be active over a broad pH range (2-10). Enterocin activity over a wide pH range make them potentially more suitable as natural preservatives of foods and fermented products where
products are acidified or pH decreases due to natural LAB present. They also have potential applications
in oenological process where pH levels are as low as 3 and 4.
Proteolytic enzyme treatments with lysozyme, lipase, lyticase and catalase could not inhibit
enterocin activity. This indicated that their antimicrobial activity was independent of lipid or carbohydrate
moieties or hydrogen peroxide. α-Chymotrypsin and proteinase K inactivated enterocin, which indicated
that the compound was proteinaceous in nature.
Bacteriocin production tested in two of the isolates, #16.3 and 128.1, coincided with the
exponential growth phase which occurred after 6 hours of incubation at 30°C, which was an indication of
primary metabolite kinetics. The highest production of 400 AU/ml was observed after eight hours and
was maintained for several hours (46 hours) in the stationery phase. The bactericidal effect of the cell free
supernatants from #16.3 and 128.1 against the sensitive culture of Lactobacillus pentosus DSM 20314
was clearly demonstrated by complete inhibition of growth for most of the experimental period, while the
control increased exponentially throughout the experiment.
In conclusion, this study has confirmed the isolation and identification of Ent. faecium strains
from wine, a genus that is rarely found in the wine environment. Although one can speculate on the origin
of this bacterium in the wine e.g. human handling and contaminated water, these bacterial isolates
produced enterocin P which have antimicrobial action against wine-related LAB genera and therefore
have a potential role in wine spoilage control. / AFRIKAANSE OPSOMMING: Melksuurbakterieë (MSB) speel ‘n belangrike rol in die redusering van die suurgehalte van wyn
en dra ook by tot die aroma en smaak daarvan. Hulle kan egter ook verantwoordelik wees vir vele
wynbederfprobleme wat die gehalte en waarde van wyn negatief beïnvloed. Hoewel Oenococcus oeni
positiewe karaktertrekke aan die sensoriese eienskappe van wyn verleen, kan sekere spesies van die
genus, Lactobacillus en Pediococcus, die heilsaamheid van wyn beïnvloed deur ongewenste verbindings,
soos biogeniese amienes en etielkarbamaat, te produseer.
Chemiese preserveermiddels, soos swaweldioksied (SO₂), word gebruik om die groei van
bederfmikro-organismes tydens die wynbereidingsproses te voorkom. SO₂ fungeer ook as ‘n
reduseermiddel en onderhou die voordele van die antioksidant eienskappe van die poli-fenole van wyn.
Daar is egter ‘n wêreldwye vraag na die redusering van SO₂-vlakke as gevolg van die toename in
gesondheidsverwante risiko’s en ander faktore.
Al hierdie oorwegings het belangstelling in die navorsing van nuwe preserveringstrategieë laat
toeneem en MSB-geproduseerde bakteriosiene lyk na ‘n potensiële alternatief wat in die laaste dekade
ondersoek word. Verskeie tipes bakteriosiene is geïdentifiseer en getipeer. Daar is egter nog weinig
gerapporteer oor bakteriosiene wat deur MSB van wynkundige oorsprong geproduseer is of oor
bakteriosiene wat in afgeronde wyn teenwoordig is.
Die huidige studie het 155 MSB isolate van die Instituut vir Wynbiotegnologie se
kultuurversameling vir bakteriosien-produsering gegradeer. Agt stamme (5%) is as produseerders
geïdentifiseer, soos gestaaf is deur sterk inhibisiesones wat teen sensitiewe organismes op agarplate
gevorm het. Die produseerders het ‘n breë spektrum van antimikrobiese aktiwiteit by inhiberende
Lactobacillus spp., Leuconostoc mesenteroides, Listeria monocytogenes en Pediococcus pentosaceus
stamme gedemonstreer. Sommige van hierdie bakteriese genera is belangrik in wynbereiding, omdat dit
potensiële wynbederfbakterieë is. Hierdie isolate en/of die bakteriosiene wat dit produseer, kan dus moontlik toepassing in die voedselfermentasiebedryf vind.
Die fisiologiese resultate, biochemiese toetse en suikerfermentasieprofiele het almal dieselfde
resultate vir die sewe isolate, wat indikatief van enterococci was, gelewer. Die identifisering deur 16S
rRNA-basispaaropeenvolging het onthul dat die sewe getoetste isolate almal Enterococccus faecium was.
RAPD-PKR-vingerafdrukke het dieselfde profiel vir die sewe rasse gelewer, wat bevestig dat die
rasse almal identies op genetiese vlak was. Deur die molekulêre gewig vas te stel deur middel van SDSPAGE,
het dit getoon dat die peptiede kleiner as 4.6 kDa in grootte is. PKR-amplifikasie van die
enterosien-P geen, die bepaling van basispaaropeenvolging en BLAST-soekresultate het bevestig dat al
agt rasse die enterosien-Pgeen van Ent. faecium bevat.
Die enterosien wat in hierdie studie getoets is, was hitte-stabiel teen 100°C (30 min), maar het
50% van sy aktiwiteit teen 121°C (15 min) verloor. Faktore soos bakteriosienproduksie en
hittebestandheid, is van die vele faktore wat enterococci in staat stel om dominant in gefermenteerde produkte, soos suiwelprodukte of vleis te wees. Enterococci wat bakteriosiene produseer het dus
potensiële toepassings in verskeie kossoorte en gefermenteerde produkte. Die pH-toetse het getoon dat
enterosien-P oor ‘n breë pH spektrum (2-10) aktief was. Enterosienaktiwiteit oor ‘n wye pH spektrum
maak dit potensieel meer geskik as natuurlike preserveermiddels vir kossoorte en gefermenteerde
produkte waar produkte versuur word of die pH afneem as gevolg van natuurlike MSB wat teenwoordig
is. Dit het ook potensiële toepassings in enologiese prosessering waar pH-vlakke so laag as 3 en 4 is.
Proteolitiese ensiembehandelings met lisosiem, lipase, litikase en katalase kon nie
enterosienaktiwiteit inhibeer nie. Daar is getoon dat hul antimikrobiese aktiwiteit onafhanklik was van
lipiede, koolhidraatdele óf waterstofperoksied. α-Chymotripsien en proteïenase-K het enterosien onaktief
gemaak, wat getoon het dat die samestelling proteïenagtig van nature is.
Bakteriosienproduksie wat in twee van die stamme #16.3 en 128.1 getoets is, het ooreengestem
met die eksponensiële groeifase wat na 6 ure van inkubasie teen 30°C plaasgevind het, en wat ‘n
aanduiding is van primêre metabolitiese kinetika. Die hoogste produksie van 400 AU/ml is na agt ure
waargeneem en is vir etlike ure (46 uur) in die stasionêre fase gehandhaaf. Die bakterie-dodende effek
van die selvrye supernatant van #16.3 en 128.1 teenoor die sensitiewe kultuur van Lactobacillus pentosus
DSM 20314 is duidelik gedemonstreer deur totale inhibisie van groei vir die grootste deel van die
eksperimentele periode, terwyl die kontrole eksponensieel deur die hele eksperiment toegeneem het.
Hierdie studie het dus die isolering en identifisering van Ent. faecium-stamme, ‘n genus wat baie
selde gevind word in ‘n wynomgewing, vanuit wyn bevestig. Alhoewel daar gespekuleer kan word oor
die oorsprong van hierdie bakterie in wyn bv. menslike hantering en besmette water, het hierdie rasse wel
enterosien geproduseer en daarom die potensiaal om ‘n rol te speel in beheer teen verskeie bederf-MSB-genera. / TIA, NRF and THRIP
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Lab work in science education : Instruction, inscription, and the practical achievement of understanding / Interaktivitet, instruktion och förståelse i naturvetenskapliga laborationerLindwall, Oskar January 2008 (has links)
Taking an analytical perspective founded on ethnomethodology and conversation analysis, the four studies presented in this thesis provide detailed analyses of video recorded lab work in mechanics at secondary and university level. The investigated activities all build on educational design afforded by a technology called probeware. The aim of the thesis is to investigate how teachers, task formulations, and technology make mechanics visible and learnable, and how students and teachers witnessably orient towards the practical achievement of understanding in the setting. The first study investigates how students use the technology in the interpretation and production of graphs: how they produce increasingly precise interpretations, how they fluently switch between different modes of meaning, and how the interpretations are both prospectively and retrospectively oriented. With a starting point in the analysis, the relevance of technology and task structure for the students’ interaction and learning are discussed. In the second study, the use of probeware is contrasted with the use of a simulation software. The study shows that some important differences between the local enactment of the two technologies are to be found in the practical work of the students; more specifically, in the ways that students orient to the subject matter content. The third study demonstrates an intimate interplay between how students display their problems and understandings and how instructors try to make the subject matter content visible and learnable. The analyzed episodes are illuminating with regard to the analytical notion of disciplined perception as applied to graph interpretation, the cognitive and practical competencies involved in producing, recognizing, and understanding graphs in mechanics, and the interactive work by which these competencies are made into objects of learning and instruction. The fourth study investigates episodes where explicit references to students’ understanding are made through formulations such as, “I don’t understand” or “do you get it?” The analysis focuses on the use, reference, interactional significance, and positioning of these formulations, and is followed by a discussion on the relation between the many and varied ways references to understanding are used and the concrete conditions of lab work. In sum, all four studies contribute to a detailed understanding of lab work as an educational practice and how learning and instruction are practically achieved. / Avhandlingen baseras på fyra empiriska studier av laborationsarbete i mekanik. Den analytiska utgångspunkten hämtas från etnometodologi och angränsande ansatser. Materialet består av videoinspelad interaktion från en tematisk lärarutbildning, en teknisk gymnasieutbildning samt en högskoleingenjörsutbildning. I laborationerna använder studenterna en specifik teknologi kallad probeware, som består av kraft- och rörelsedetektorer kopplade till en dator. Gemensamt för laborationerna är också att uppgifterna bygger på ett likartat pedagogiskt upplägg, vilket i korthet innebär att studenterna först ska ställa upp en hypotes, sedan genomföra ett experiment och slutligen diskutera relationen mellan hypotes och resultat. Avhandlingens övergripande syfte är att undersöka lärandets konkreta villkor i laborationsarbetet: hur studenternas arbete, tillsammans med teknologi, uppgiftsformuleringar och lärarstöd, skapar vissa möjligheter för lärande och förståelse. Detta syfte specificeras i de fyra delstudierna. I den första studien undersöks hur två studenter, genom verbala tolkningar, gester och rörelser, gradvis får en större förståelse av en graf som representerar tid och hastighet. I artikeln diskuteras teknologins och uppgiftsformuleringens roll för sättet som studenterna interagerar och lär. Den andra studien jämför studenters användning av probeware med användningen av en simulering. Ett syfte med studien är att visa hur två aktiviteter som vid första anblick kan verka vara lika, samtidigt kan vara väldigt olika om man i detalj studerar vad studenterna gör och hur de angriper ämnesinnehållet. I den tredje studien analyseras interaktionen mellan två studenter och en lärare. Artikeln fokuserar på det täta samspelet mellan de sätt studenterna visar sina problem, i detta fall oförmågan att se något relevant i en graf, och de sätt som läraren försöker lösa dessa problem genom att visa vad och hur man kan se något i grafen. I den avslutande artikeln analyseras ett större antal sekvenser som innehåller explicita referenser till studenternas förståelse, såsom ”vi fattar inte”, ”förstår du?” och ”jag förstår den men inte den”. Analysen används sedan som utgångspunkt för en diskussion av relationen mellan de många och varierade sätt som förståelse refereras och laborationens praktiska villkor.
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Distributed deployment of Therminators in the networkCheng, Kah Wai 12 1900 (has links)
Approved for public release; distribution in unlimited. / The idea of deploying a distributed network intrusion system using Therminator is explored in this thesis. There are many advantages in having a distributed system compared to a standalone network intrusion system. The underlying principle of Therminator is modeling network traffic on conversation exchange models. Using Zippo, a new implementation of Therminator, the experimental setup consisted of multiple sensors reporting individual findings to a central server for aggregated analysis. Different scenarios of network attacks and intrusions were planned to investigate the effectiveness of the distributed system. The network attacks were taken from the M.I.T Lincoln Lab 1999 Data Sets. The distributed system was subjected to different combinations of network attacks in various parts of the network. The results were then analyzed to understand the behavior of the distributed system in response to the different attacks. In general, the distributed system detected all attacks under each scenario. Some surprising observations also indicated attack responses occurring in unanticipated scenarios. These results are subject to further investigation. / Defence Science & Technology Agency Singapore
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Exploring the Impact of a Visuo-Haptic Simulation for the Conceptual Understanding of PulleysShreya Digambar Randive (6818642) 02 August 2019 (has links)
<p>Recently, exploration to develop creative and technology-centered learning techniques have become popular. Researchers work on non-traditional tools to help students understand abstract concepts and reduce misconceptions in physics education. Studies have been performed to explore the influence computer simulations can make on learning as compared to the traditional methods. Simulations with dynamic moving images which engage visual senses have helped improve learning, while haptic channels are unexplored in comparison tactile senses are crucial in the case of embodied cognitive learning.</p><p><br></p><p>This thesis takes an opportunity to explore the research area of haptic technology combined with visual simulation. It tests the efficiency of the learning environment developed as a part of this thesis called the Visuo-Haptic Pulley Simulation (ViHaPS) in learning concepts of when compared to traditional learning tools. ViHaPS consists of six different scenarios and is designed to address common misconceptions of pulleys and has two different modes - minimal visual cues and added visual cues. Undergraduate students enrolled at Purdue University participated in this research. They were formed into two groups - an experimental group (ViHaPS) and control group (physical manipulatives) and were compared for learning gains.</p><p> </p><p><br></p><p>Results indicate that ViHaPS is useful in learning concepts of pulleys; however, the results are not significant in comparison to the real experimentation with pulleys.</p>
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Noise Analysis of Computer Chassis and Secondary Sound Source Noise ReductionZheng, Haosheng, Zhang, Kaichun January 2019 (has links)
This article focuses on computer noise analysis and noise reduction processing. With the popularity of computers, people are increasingly demanding the comfort of using computers. Solving the noise problem of the computer case can make the working environment more comfortable. People working in a noisy environment for a long time can cause anxiety and the quality of work is not high. The main purpose of this paper is to analyse the characteristics of computer noise and to reduce the noise of the chassis through the secondary sound source. Through the comparison of the experimental and simulation results, the noise reduction effect of the secondary sound source on the computer case is obtained. This paper can provide a scientific reference for the manufacture of computer chassis and improvement of noise.
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Utilização de objetos de aprendizagem para melhoria da qualidade do ensino de hierarquia de memória / Use of learning objects to improve the quality of the memory hierarchyTiosso, Fernando 24 March 2015 (has links)
O ensino e a aprendizagem do tema hierarquia de memória não são tarefas simples, pois muitos assuntos que são abordados em teoria podem desmotivar a aprendizagem em virtude de sua complexidade. Este projeto de mestrado apresenta a transformação do módulo de memória cache da ferramenta Amnesia em um objeto de aprendizagem, que visa facilitar a construção do conhecimento através da simulação da estrutura e da funcionalidade da hierarquia de memória na arquitetura von Neumann de uma maneira mais prática e didática. Este processo permitiu que funcionalidades existentes na ferramenta fossem readequadas e novas funcionalidades desenvolvidas. Aliado a isso, planos de aula e questionários de avaliação e usabilidade também foram concebidos, validados e implementados junto à elaboração de um tutorial para descrever o funcionamento do novo objeto. Os estudos experimentais realizados analisaram dois aspectos: o primeiro, se o objeto de aprendizagem melhorou, de fato, a aprendizagem dos alunos no assunto memória cache; o segundo, a opinião dos alunos em relação à utilização do objeto. Após a análise e avaliação dos resultados obtidos nos experimentos, foi possível demonstrar uma evolução na aprendizagem quando se fez o uso do objeto, além de se perceber que a motivação dos alunos em utilizar outros objetos de aprendizagem aumentou. / The teaching and learning of memory hierarchy are not simple tasks, because many subjects that are covered in theory may demotivate learning because of its complexity. This Master\'s thesis presents the process of transformation of the cache memory module of Amnesia tool in a learning object, aiming to facilitate the construction of knowledge by simulating the structure and functionality of memory hierarchy of von Neumann architecture in a more practice and didactic way. This process allowed existing features in the tool to be adequate and new features developed. In addition, lesson plans and questionnaires of assessment and usability have also been designed, validated and implemented and a tutorial to describe the operation of the new object was developed. Experimental studies have examined two aspects: the first, if the learning object improved, in fact, the students\' learning in the subject cache memory; the second, students\' opinions regarding the use of the object. After the analysis and evaluation of the results obtained in the experiments, was possible show an evolution in learning when it made the use of the object, and also to perceive that students\' motivation to use other learning objects increased.
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