Enhancing mRNA stability through the addition of stabilizing untranslated regions

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 20).Messenger-RNA (mRNA) therapy, in which mRNA is introduced to cells or tissues to cause a transient expression of specific genes, has applications ranging from tissue engineering to neural regeneration. This transient nature of mRNA, however, limits the duration of gene upregulation, and potentially reduces the efficacy of mRNA therapy. In this paper, various mRNA constructs were studied to identify stable designs which could be used for long-lasting mRNA therapies. Specifically, the GFP gene was prepared with four different hemoglobin untranslated regions (UTR's), which are known for their stabilization effects on mRNA. Each mRNA template was created through the digestion and ligation of a cDNA template, reversed transcribed from total RNA, and transfected into fibroblasts. The resulting fluorescence was measured as a surrogate for translation efficiency and duration. It was determined that the human beta-globin B UTR resulted in a fluorescence level that was tenfolds brighter than human alpha-globin 1 (HBA1), which was the least effective stabilizing untranslated region. This highlights the importance of UTR selection for future mRNA therapies.by Thi Tran.S.B

MICROSTRUCTURAL CHARACTERIZATION OF ULTRASONIC IMPACT TREATED AL-MG ALLOY

Aluminum 5456-H116 has high as-welded strength, is formable, and highly corrosion resistant, however, it can become sensitized when exposed to elevated temperatures for a prolonged time. Sensitization results in the formation of a continuous β phase at the grain boundaries that is anodic to the matrix. Thus the grain boundaries become susceptible to stress corrosion cracking (SCC) and intergranular corrosion cracking (IGC). Cracking issues on aluminum superstructures have prompted the use of a severe plastic deformation processes, such as ultrasonic impact treatment (UIT), to improve SCC resistance. This study correlated the effects of UIT on the properties of 5456-H116 alloy to the microstructural evolution of the alloy and helped develop a fundamental understanding of the mechanisms that cause the microstructural evolution. Ultrasonic impact treatment produces a deformed layer at the surface ~ 10 to 18 µm thick that is characterized by micro-cracks, tears, and voids. Ultrasonic impact treatment results in grain refinement within the deformation layer and extending below the deformed layer. The microstructure exhibits weak crystallographic texture with larger fraction of high angle grain boundaries. Nanocrystalline grains within the deformation layer vary in size from 2 to 200 nm in diameter and exhibit curved or wavy grain boundaries. The nanocrystalline grains are thermally stable up to 300°C. Above 300°C, grain growth occurs with an activation energy of ~ 32 kJ/mol. Below the deformation layer, the microstructure is characterized by submicron grains, complex structure of dislocations, sub-boundaries, and Moiré fringes depicting overlapping grains. The deformation layer does not exhibit the presence of a continuous β phase, however below the deformation layer; a continuous β phase along the grain boundaries is present. In general the highest hardness and yield strength is at the UIT surface which is attributed to the formation of nanocrystalline grains. Although the highest hardness and yield strength was observed at the UIT surface, the results were mixed with some lower values. The lower hardness and yield strength values at the UIT surface are attributed to the voids and micro cracking/micro voids observed in the deformation layer. The fracture mode was transgranular ductile fracture with micro void coalescence and dimples. Both UIT and untreated material exhibit similar levels of intergranular corrosion susceptibility. Corrosive attack was intergranular with slightly deeper attack in the untreated material. Numerical simulation modeling showed that the calculated residual stress under the tool, ~80 MPa, is of the same order of magnitude as the compressive residual stresses measured by XRD measurements near the surface. Modeling also showed that high effective strains were induced almost immediately. The UIT process also resulted in rapid localized heating to a maximum temperature of ~32°C during the first eleven pin tool cycles. The model also showed that during UIT processing, the material undulates as the pin tool impacts and retracts from the surface of the material. The undulations represent the elastic response of the surface to the compressive stresses built up during a pin tool cycle

The Factors Affecting Entrepreneurial Intention With Self Confidence as a Moderator - Based on Elderly People as an Example

Purpose: This study aims to determine the factors affecting the entrepreneurial intention of young people in Vietnam, thereby assessing the level of these influencing factors to propose solutions and entrepreneurship orientations effectively in the future.   Theoretical framework:  After synthesizing previous studies, the study has found some studies that mention the impact on the entrepreneurial intention of students and young people while finding a research gap that has not been studied on this issue among elderly people. Therefore, the authors proposed a research model with factors as follows: Family support, government policy, self-confidence, and capital, which affect entrepreneurial intention.   Design/methodology/approach: This study uses SPSS software to test the hypothesis by linear regression method and to test the research hypothesis with survey samples conducted in 5 months 1310 votes were collected, including 972 valid votes. The age of survey participants is between 45 and 65 years old..   Findings:  The results show that the capital factor does not affect the entrepreneurial intention while the entrepreneurial experience factor has the strongest impact on the start-up intention. Next, it is support from the government and support from family. Finally, it is self-confidence. That proves that capital is not an essential issue for elderly people because they have already accumulated capital before. Whereas, the experience factor refers to a long process of working. The longer they work, the more experienced they get, thereby increasing their ability to be confident and successful in doing business in their old age.   Research, Practical & Social implications:  The proposal of this study will be an important reference for start-ups and related government agencies. It aims to promote breakthrough business ideas and exploit the essence of experienced people who have retired. This object needs special attention to develop the country's economy sustainably.   Originality/value:  Identified a research gap from previous studies there are no studies into the object of elderly people. The research results have been through a methodical and professional data acquisition process in two forms, such as quantitative and qualitative methods, thereby proposing research models. The research results are to find out the difference with the previous topics. Also, it is proposed to be an important reference for agencies and organizations related to start-up activities in Vietnam

Some Solutions to Help Students Enjoy Learning English More

When teaching a large class of students, the teacher's biggest concern is which method to use to partially satisfy the learning needs of the majority of students. Each class has its unique characteristics, different learning needs, and the same level of students between classes at Tan Trao University. Some methods work well for one class, but not for another. This concern becomes much greater when the level of the student and the level of the curriculum has quite a big difference. Teachers often have to add the function of "curriculum designer" for a particular class. In addition to teaching according to the school's general curriculum, teachers must prepare more types of exercises and support activities to help students become more interested in learning and learn English more effectively. In this research paper, the writer of this article would like to mention some solutions that I have applied to students of Kindergarten Class C K8 and their feedback on my solution

Utilizing Visual Stimuli to Foster Engagement Among English Speaking Skill Learners During Instructional Sessions

The utilization of imagery proves highly effective in stimulating interest and fostering motivation for learners during the process of honing English speaking skills. Through this approach, not only does it facilitate learners in easily conceptualizing and comprehending concepts visually, but it also provides a platform for them to discuss and articulate ideas with confidence and creativity. Imagery serves as a bridge between language and real-life experiences, thereby igniting learners' passion and curiosity, aiding in their rapid and effective progress in language acquisition. In the journey of refining English speaking skills, imagery transcends mere static pictures to become gateways to myriad worlds. When educators incorporate images into the classroom, they bring not only pictures but also emotions, stories, and even dreams. Each detail within an image serves as a key, unlocking the door to imagination, enabling learners to step into a rich world where language extends beyond words on paper to vibrant images within the mind. Through the integration of imagery, the learning process becomes vivid and captivating, transforming each lesson into an adventure, a voyage filled with exploration and anticipation.&nbsp

CHOOSE REMEMBERSHIP REMEDIES TO IMPROVE THE HAPPINESS OF FEMALE OFFICERS AND OFFICERS UNIVERSITY OF FITNESS AND SPORTS DA NANG, VIETNAM

Happiness has long been a veritable area of scientific research in most industrialized countries. Using the method of synthesis of documents and interview method, the study investigates the current state of happiness of 30 female officers and employees of Danang University of Physical Education and Sports using the author's happiness scale. Michael Argyle and Peter Hills (2002) have shown: 30.0% less are happy; 43.33% are happy on average; 26.67% are moderately happy; the most important factor in happiness is health. Subject-selected measures that can increase happiness are finding moments with loved ones in the family; practising more positive thinking; accepting the reality of the situation; join arts and sports clubs

SIMULTANEOUS REMOVAL OF AMMONIA AND ORGANIC MATTERS FROM GROUND WATER BY COMBINATION OF ADSORPTION AND BIOLOGICAL TREATMENT PREPARATION OF BIOPOROUS ACTIVATED CARBON FROM RICE HUSKS AND ITS CHARACTERIZATION

Joint Research on Environmental Science and Technology for the Eart