<p> Students who achieve their long-term goal of graduating from college are models of persistence and grit. Grit is the self-regulatory construct defined as “passion and perseverance for long-term goals despite setbacks, failures, and competing pursuits” (Eskreis-Winkler, Gross, Duckworth, 2016) and has been associated with both academic and workplace success (Eskreis-Winkler, Duckworth, Shulman, & Beal, 2014). Unfortunately, 37% of freshmen drop out of college by the end of their freshmen year (Almeida, 2016; Snyder, de Brey, & Dillow, 2018). The college classroom provides an optimal environment for institutions of higher learning to foster the grit-to-graduate<i> </i>in college freshmen, to enhance learning and academic success, and to increase goal commitment to graduation, degree achievement, and career readiness.</p> <p> The purpose of this study was to investigate whether six pedagogical interventions and project adaptations would increase student grit in an entry-level communication class heavily comprised of freshmen. Four class sections were administered the 12-item grit scale (Duckworth, 2019) during the first and last week of first semester at a Midwestern University (<i>N</i>=79). The experimental group received the pedagogical grit interventions throughout the semester; the control group did not. A repeated measures ANOVA computed the variance of grit scores between the groups. Students in the experimental group also provided quantitative and qualitative data about which pedagogical instruments they found most effective.</p> <p> While the hypothesis was not supported, student feedback on the six grit interventions was largely positive. Ideas for improving the interventions and for fostering grit and college persistence in freshmen are included.</p> <br>

O adenocarcinoma de ducto pancreático (PDAC) é a quarta causa de morte em decorrência de neoplasias nos países ocidentais. Atualmente, a cirurgia ressectiva é a única possibilidade de cura para a doença, porém, a recidiva tumoral acontece em menos de um ano após a intervenção cirúrgica, mesmo com a quimioterapia adjuvante. A terapia fotodinâmica (PDT) é uma alternativa promissora no tratamento do câncer. No entanto, pouco se sabe sobre o uso da PDT em tumores pancreáticos. Portanto, o objetivo deste trabalho foi avaliar a eficiência da PDT com o azul de metileno (MB) como fotossensibilizador (MB-PDT) em induzir a morte de linhagens de PDAC humanas (AsPC-1, Panc-1, MIAPaCa-2 e BxPC-3) e estudar a contribuição de vias de necrose regulada nos efeitos citotóxicos da terapia sobre estes modelos. Os resultados obtidos mostraram que a MB-PDT foi capaz de induzir a morte massiva das células de PDAC. Além disso, eles indicaram que há dois perfis de susceptibilidade entre as quatro linhagens estudadas quando submetidas a MBPDT com 4,5 J/cm2 de energia e 6min de irradiação. De acordo com os dados apresentados, a diferença nas sensibilidades das linhagens à terapia não está associada à diferenças na capacidade de incorporação do MB ou na localização sub-celular do fotossensibilizador nas diferentes células, uma vez que a localização é, predominantemente, lisossomal em todas elas. Adicionalmente, mostrou-se que as linhagens menos susceptíveis ao tratamento, MIAPaCa-2 e Panc-1, apresentam níveis significativamente menores de RIPK3 e MLKL, dois dos componentes do necrossomo, essenciais para a execução da necroptose. Além disso, foi visto que a MB-PDT induz um aumento de fosforilação de MLKL em AsPC-1, demonstrando a ativação da necroptose após a terapia nestas células, mas não em MIAPaCa-2 (menos responsiva à terapia com 4,5 J/cm2 deenergia e 6min de tempo de irradiação). Ainda, a inibição da via de sinalização necroptótica diminuiu significativamente as porcentagens de morte das células mais susceptíveis (BxPC-3 e AsPC-1), não alterando a resposta de Panc-1 e MIAPaCa-2, corroborando a ativação e importância da necroptose para a citotoxicidade da MB-PDT. Finalmente, neste trabalho foi mostrado que o aumento do tempo de irradiação, mantendo-se a quantidade total de energia aplicada no tratamento, melhora a eficiência da MB-PDT em induzir a morte das células que apresentam limitações para executar a necroptose, sugerindo que mais de uma via de morte esteja sendo ativada após a terapia e que o tempo de irradiação atuaria modulando esta ativação. Complementarmente, foi mostrado que os tempos maiores de irradiação aumentam o estresse oxidativo intracelular que é acompanhado por uma diminuição significativa do conteúdo intracelular de glutationa reduzida (GSH), indicando, preliminarmente, que a ferroptose pode estar sendo acionada após os protocolos mais longos de irradiação. Coletivamente, os resultados apresentados neste trabalho confirmam a eficiência da MB-PDT no tratamento de diferentes linhagens de PDAC, indicando que a necroptose está sendo ativada e contribuindo para a citotoxicidade da terapia sobre as células que não apresentam resistência à esta via de morte. Ainda, eles demonstram que o aumento do tempo de irradiação pode transpor a barreira de resistência de algumas linhagens à terapia, provavelmente por induzir a ativação de outras vias de necrose regulada, mostrando a importância da otimização do protocolo de tratamento no aumento da eficiência da MB-PDT sobre os tumores de pâncreas. Finalmente, os resultados confirmam a MB-PDT como alternativa eficaz no tratamento do PDAC, apresentando um amplo espectro de atuação sobre subtipos tumorais resistentes à vias clássicas de morte celular, uma característica importante no contexto de uma terapia anti-cancer. / Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death due to neoplasms in western countries. Currently, resective surgery is the only therapetical approach to cure this disease, but tumor´s recurrence occurs less than one year after the surgery, even with adjuvant chemotherapy. Photodynamic therapy (PDT) is a promising alternative for the cancer treatment. However, the efficacy of PDT to treat pancreatic tumors as well as the mechanisms involved in the induction of tumorigenic cell death remain unclear. For this purpose, in this study, we set out to evaluate the efficacy of PDT using methylene blue (MB) as a photosensitizer (MB-PDT), in inducing death of human PDAC derived cell lines (AsPC-1, Panc-1, MIAPaCa-2 and BxPC-3) and to deeper investigate the contribution of necroptosis to the cytotoxic effects of the therapy. We observed that MB-PDT was able to induce massive death of PDAC cells. Moreover, our results indicated that upon MB-PDT (4.5 J/cm2 energy and 6min of irradiation time), there were two susceptibility profiles among the four cell lines studied. Data also showed that this differential profile of cell response was neither associated with the differences in the MB incorporation capacity nor with the subcellular location of the photosensitizer, since the localization was predominantly lysosomal in all of tested cell lines. In addition, less susceptible cells, MIAPaCa-2 and Panc-1, showed significantly lower levels of RIPK3 and MLKL, two of the necrosome components, essential for triggering necroptosis. Furthermore, while MB-PDT (4.5 J/cm2 and 6min of irradiation) has been able to increase MLKL´s phosphorylation levels, an essential step in necroptosis induction, in AsPC-1cells, less responsive MIAPaCa-2 cells presented no variations on the phosphorylation state of this pseudokinase. Moreover, pharmacological inhibition of the necroptotic signaling pathway significantly decreased cell death percentages of the most susceptible cells (BxPC-3 andAsPC-1), without altering the response of Panc-1 and MIAPaCa-2, corroborating that activation of necroptosis was strongly involved in the cytotoxicity of MB-PDT. Finally, this work showed that increasing the irradiation time improved the efficacy of MB-PDT in killing cells which display limitations to perform necroptosis, suggesting that the irradiation time would be modulating the degree of oxidative stress generated and this stimuli would in turn, be responsible for triggering other regulated cell death pathways in a RIKP3 and MLKL independent way. Indeed, this increase in oxidative stress was accompanied by a significant decrease in GSH, a global indicatior of less antioxidant cell capacity, preliminarily pointing at the induction of ferroptosis by longer irradiation protocols. In summary, we demonstrated that MB-PDT is able to induce cell death in different PDAC cell lines and that different regulated cell death mechanisms are being activated upon MB-PDT induction. Furthermore, it was demonstrated that increased irradiation time may overcome the resistance barrier of some cell lines, probably inducing the activation of other regulated cell death pathways, showing the importance of optimizing the irradiation protocol in order to maximize the efficacy of the therapy. Finally, our observations point MB-PDT as an alternative and effective therapy for pancreatic cancer treatment, displaying a broad-spectrum action on tumors displaying different resistance mechanisms to classic cell death pathways, a desired property for improving an anticancer therapy.

The Thesis intends to introduce business in government regulated Water Industry, accurately the area of Water Supply and Sewerage. Its aim is to describe the business market of this field. Moreover, to find out whether the companies in private multinational corporation ownership don't burden their customers with too high price of water supply and find if there is any relationship between the price of water and the profitability of these enterprises. To achieve this aim, companies are categorized into five groups and compared. These groups are created on the basis of the shares of private foreign corporation. A separate group is made of companies that are in ownership of municipalities that means without the influence of private foreign corporations. Firstly the one component prices are compared, then two-component ones. In conclusion, these prices are compared to profitability of these enterprises.

O presente trabalho investiga estratégias para aperfeiçoar o estudo individual do violonista com base no conceito de autorregulaçaao da aprendizagem e nas informações da literatura musical. Nas últimas décadas, pesquisas tem enfatizado a importância do aspecto qualitativo no estudo individual (Barry, 1992; Nielsen, 1999 e 2001; Williamon e Valentine, 2000; Hallam, 2001) e destacam que saber como estudar eí uma habilidade fundamental para sustentar o contínuo aperfeiçoamento musical. Essa capacidade de regular o próprio estudo se relaciona com o mecanismo da autor regulação, conjunto de processos psicológicos pelos quais o ser humano regula seu comportamento. Como referencia principal para o estudo desse conceito eí utilizado Barry J. Zimmerman (2000, 2002) e também Mcpherson e Zimmerman (2011) que discutem a autor regulação na prática do músico. Da literatura musical as principais referências são os livros de Gerald Klickstein (2009) e dos violonistas Ricardo Iznaola (2000), Richard Provost (1992) e Lee F. Ryan (1991), que discutem viários aspectos relacionados à prática individual do músico. As informações trazidas pelos autores da aéra musical foram discutidas e organizadas de forma a trazer um panorama das estratégias para o aperfeiçoamento da prática e para estimular o comportamento autorregulado do estudante (de universidade ou conservatório superior). O trabalho incluiu também uma etapa prática, na qual as informações levantadas na parte teórica foram aplicadas na rotina de estudos pessoal. A experiência teve o objetivo de observar as implicações desta abordagem e foi registrada como um memorial de estudo através de relatórios e vídeos. Em suma, a análise dessa etapa se alinha com as evidências da pesquisa empírica, de que o engajamento do estudante em procedimentos como analise prévia da tarefa, estabelecimento de metas, planejamento, escolha de estratégias adequadas e reflexão sobre o estudo tem um impacto positivo na eficiência do aprendizado e no desenvolvimento musical. / This research explores strategies to improve the classical guitarist\'s individual practice based on the concept of self-regulated learning and resources from musical literature. During the last decades, a great amount of research has emphasized the relevance of qualitative aspect in music practice (Barry, 1992; Nielsen, 1999 e 2001; Williamon e Valentine, 2000; Hallam, 2001) and suggest that knowing how to practice is an essential ability to support constant musical improvement. The skill of regulating one\'s study is related to self-regulation mechanisms, which is a set of psychological procedures in which the human being regulates his own behavior. It is chosen, as main reference to the self-regulation study, Barry J. Zimmerman (2000, 2002) and also Mcpherson e Zimmerman (2011), that discusses the self-regulation in the musical activity. The main references from the musical literature are the books of Gerald Klickstein (2009) and the classical guitarists Ricardo Iznaola (2000), Richard Provost (1992), Lee F. Ryan (1991), that presents several aspects related to the musician individual practice. The knowledge brought from the authors in musical field were debated and organized in order to provide a panorama of strategies to enhance music practice and to stimulate students\' self-regulated behavior (at university or conservatory level). This paper includes a practical stage as well, in which the collected information from the theoretical stage was applied to my study routine. The experiment has had the aim of observing and discussing the implications of self-regulation strategies, and it was registered as a study report through daily logs, audio recordings and videos. Lastly, the analysis and reflection of this practical process relates to the empirical research evidences, which show that the student\'s commitment in some procedures, such as task analysis, goal setting, planning, the choice of suitable strategies and reflection about the study, leads to a positive impact in practice efficiency and musical development.

Heparan sulphate proteoglycans (HSPGs) are cell surface/secreted molecules expressed by all cells. HSPGs consist of carbohydrate side-chains attached to a core protein and are involved in regulating key signalling pathways in the developing mammalian brain via sugar-protein interactions. It has been hypothesized, in the ‘heparan sulphate (HS) code hypothesis’, that the specificity for the interaction between the HSPGs and particular signalling pathways is encoded by its HS side-chain. HS has an enormous variety of structures due to postsynthetic modification. Hs2st and Hs6st1 are enzymes involved in generating different HS structures by sulphating the 2-carbon or 6-carbon molecule of the sugar backbone respectively. Fibroblast growth factors (Fgfs) are a family of signalling molecules crucial for forebrain development. Some of its members such as Fgf8 are morphogens which pattern the forebrain via regulated gradient formation while others such as Fgf2 drive neurogenesis and cell proliferation. One of the main molecular consequences of Fgf signalling is activation of extracellular signal-regulated kinase (Erk) where the activation of Erk then drives developmental events such as neurogenesis or cell migration. Based on previous studies on the HS code hypothesis, we hypothesized that differential sulphation regulates Fgf signalling in a specific manner depending on the HS sulphation pattern. We performed binding assays on Hs2st-/- mice to ascertain the molecular mechanism behind the role of differential sulphation in Erk signalling through Fgf2 in the forebrain. We found that differential sulphation also has an important role to play in regionally targeting Fgf2/Erk signalling through regulating the formation of active signalling complexes. Studying the Fgf8/Erk signalling axis at E14.5 developing mouse corticoseptal boundary (CSB) revealed increased Fgf8 levels and Erk hyperactivation in both Hs2st and Hs6st1 null mutants. The dysregulation of Fgf8/Erk signalling at the CSB also highly correlates with the high expression of Hs2st and Hs6st1 at the CSB. A closer look into the molecular phenotypes of Hs2st-/- and Hs6st1-/- CSB revealed differences between them in which Hs6st1-/- CSB has higher Fgf8 levels compared to Hs2st-/- CSB. To elucidate the mechanisms underlying Hs2st and Hs6st1 role at the CSB, we investigated the formation and interpretation of Fgf8/Erk signalling gradient using Fgf8 bead assays in mice with Hs2st and Hs6st1 loss of function throughout development. We found that differential sulphation has a complex effect on Fgf8 gradient formation and interpretation in the forebrain in which Hs2st acts to stabilise the Fgf8 distribution through regulating Fgf8 levels through time while Hs6st1 acts to stabilise the Fgf8 distribution by maintaining the shape of the Fgf8 gradient through restricting Fgf8 levels during the formation of the Fgf8 distribution. In addition, we found Hs2st and Hs6st1 both function to increase the sensitivity of the CSB to Fgf8 for an Erk response although through different modes of action. Therefore, we conclude that differential HS sulphation plays a specific role in Fgf/Erk signalling depending on the HS sulphation pattern.

Due to its unsupervised nature, undergraduate education requires students to manage their own learning. They need to use self-regulated learning (SRL) strategies in order to achieve academic success. However, college students often have insufficient regulatory skills and strategies, suggesting the need for substantive and practical support. Supplemental Instruction (SI) is a well-recognized academic intervention that utilizes peer-led study groups for difficult college courses, through which students can develop their SRL abilities. This study focuses on the role of the SI program in college students’ development of SRL from a person-centered perspective. First, this study examines the heterogeneous effects of the SI intervention on students’ development of SRL by combining latent profile modeling and propensity score matching. Second, it explores the changes in student SRL profiles over the intervention period and determines factors affecting the prediction of such changes using latent transition modeling. Results identify three distinct student profiles: competent regulator, self-confident regulator, and goal-oriented regulator. Within the competent regulator profile, both SI and non-SI attendees’ overall SRL scores significantly decreased over time, though non- SI attendees showed a greater downturn. For the self-confident regulator profile, only SI attendees’ overall SRL scores increased. Both SI and non-SI attendees in the goal-oriented regulator profile had small decreases in scores, which were not statistically significant. Regarding students’ longitudinal transitions between SRL profiles, students in the most desirable profile (competent regulator) remained most stable over time. Students’ SRL in the goal-oriented regulator profile was most malleable in a positive way; approximately 40% of these students moved into the competent regulator profile. In addition, students whose decision to attend the SI sessions was more mastery-oriented tended to fall into more positive transition groups. Furthermore, students whose levels of self-confidence in learning, critical thinking skills, and group work skills increased as a result of their participation in SI sessions were more likely to become members of more positive transition groups. The findings of this study extend previous work by longitudinally examining individual differences in college students’ SRL development. They also provide significant implications for the future design of more targeted interventions.

Process skills, such as critical thinking, communication, and problem solving, are sometimes referred to as soft skills or professional skills and have been identified by instructors and employers alike as being desirable skills for students to acquire before they graduate. The development and assessment of process skills in students were important learning objectives for both the ANA-POGIL (Analytical Process Oriented Guided Inquiry Learning) and ELIPSS (Enhancing Learning by Improving Process Skills in STEM) projects. The ANA-POGIL project consisted of a faculty consortium that was comprised of chemistry faculty. The ELIPSS project currently consists of a faculty consortium that includes representation from multiple STEM disciplines, including biology, chemistry, anatomy & physiology, math, engineering, and physics. In order to optimize the student development of process skills there should be alignment between the instructors’ goals for their courses and what they assess. The faculty members associated with both of these projects wanted to enhance students’ development of process skills by providing them with feedback, and a problem solving rubric was developed to meet those needs. The rubric categories were constructed based on faculty definitions and literature that described characteristics of successful problem solvers. To the test the rubric’s validity, it was piloted by both faculty and students. The rubric was then used in an advanced analytical instrumental laboratory course to assess the extent to which evidence of students’ process skills changed over the course of a semester. Students from the laboratory course were interviewed to gather their insights into the rubric and how they used the feedback. Findings suggest that instructors should emphasize the importance of process skills and incorporate them directly into their courses if they want students to value them. Even though students were provided regular feedback, their problem solving scores did not change appreciably throughout the semester. While students found the rubric feedback useful on the surface, they did not use the feedback in any significant way to improve on their laboratory reports because there was no grade or incentive tied to the rubrics. If faculty want students to obtain process skills, they should place some incentive on the acquisition and development of them. Another goal of the ANA-POGIL project was to develop multi-part, open-ended questions to assess process skills. To analyze evidence of the process skills that were present in the student responses, a qualitative coding scheme focused on three process skills (information processing, problem solving, and critical thinking) was used. There was overall good alignment between the process skills the faculty had identified for the exam questions and the evidence that was found in the student responses. Findings show that if instructors value eliciting a certain process skill in students’ responses, then they should be extremely explicit in how the exam structure is worded to elicit that skill. Well-designed laboratories help students develop skills in experimental design, data analysis, and communication in addition to critical technical skills. A common course structure that presents challenges for both the students and instructional staff is in upper-level undergraduate chemistry laboratories where students perform experiments in a rotational style, with each group of students working on one instrument per week. As a solution to this challenge, a set of pre-laboratory videos were generated for each experiment. Laboratory observations and student interviews were conducted to investigate how students were using the resources and to characterize their experiences in the laboratory. Findings show that students used the resources to come more prepared to complete the laboratory experiments more independently with less instructional intervention. Findings from the student observations and experiences in the laboratory show that students enjoyed working with both their peers and the instructional team to successfully complete the experiments.

Task interpretation is a critical first step in the process of self-regulated learning and a key determinant of the goals students set while learning and the criteria used in selecting the strategy in their work. Laboratory activities have been proposed to improve students' conceptual understanding when working independently and alongside peers while integrating new experiences in a lab setting. The purpose of this study was to investigate how the explicit and implicit aspects of student's interpretation of the task assigned during laboratory work may change during the task process, and how that interpretation may influence the student's coregulation and conceptual understanding. One-hundred and forty-three sophomore students enrolled in the course of Fundamental Electronics for Engineers participated in this study. Instruments designed to measure task interpretation and conceptual understanding were created and validated in a pilot study. They were applied before and after selected laboratory activities during the semester. The instrument used to measure correlation was applied at the end of every selected laboratory activity. Statistical analysis indicated differences between the student's task interpretation before and after the laboratory activity. Students improved in approximately 15% in the level of task interpretation. From the 143 students, only 37 of them were identified with high levels of task interpretation and coregulation. Moreover, Pearson correlations identified a positive correlation between the students' task interpretation and conceptual understanding of the students during the laboratory work. Findings suggested students' task interpretation changed during the task process and increased after the completion of laboratory activity. Overall, the findings showed a low level of task interpretation. However, students with a high level of task interpretation reached high levels of coregulation. Findings confirmed previous research that round students generally have an incomplete understanding of the assigned tasks, and struggle to establish a connection between laboratory activities and theory. Lastly, this study reported a significant relationship between students' task interpretation and conceptual understanding in laboratory work which has not been reported in the most recent published reports. Further investigation is necessary to unveil other factors related to these constructs in order to engage students in laboratory work.

Dam releases increase river stage and can reverse groundwater movement into and out of the river. As the flood, thermal, and solute waves travel downstream in a regulated river, the size of the waves is anticipated to be affected both by river processes and exchanges with near river groundwater. This study established a modeling framework to quantify the influences of the groundwater exchanges on the temperatures and solute concentration dynamics along regulated rivers. The wave properties, volume of exchanges, conservative solute mass exchanges, and heat energy exchanges were calculated as a function of time and distance downstream. Results show that the temperature and solute concentrations are influenced by the arrival of flood waves. Groundwater exchanges were found to affect temperatures along the river with a minimal effect on solute concentration. These findings provide insight regarding the influences of hydropeaking occurring in a large fraction of rivers in the world which has important implications for water quality and the ecology of regulated rivers.

Effective practice determines the quality of a performance and it is essential to improving a musician's overall level of playing. Studies show that experts in the field of music display superior metacognitive skills, or the ability to think about one's thinking. Metacognition is an important skill that needs to be developed in order for a student to become a self-regulated, or independent learner. Effective practice can be improved by learning and developing metacognitive and self-regulated learning skills. An important component of self-regulated learning is reflective thinking. Reflective thinking is a mental process that contributes to deeper learning experiences, improves problem solving skills, and enhances creativity. Reflective thinking can be stimulated with writing activities. Research and theories of reflective practices informed the creation of the Reflective Writing Prompts. The Reflective Writing Prompts stimulate reflective thinking as they teach and develop metacognitive and self-regulated learning skills to make practice more effective. Each exercise prompts the student to think and write a response to questions focused on a specific skill. These prompts are based on research in music psychology and reflective thinking, with special focus on metacognition, self-regulated learning, practice habits, and reflective journaling. The pertinent studies and theories in these areas will be examined and explained in relation to each other. With this foundational knowledge in place, the Reflective Writing Prompts will be presented. The prompts are designed to support first or second year music students in their development as independent learners who practice effectively.