Inhibition of glucocorticoid-induced apoptosis by targeting splice variants of \u3ci\u3eBIM\u3c/i\u3e mRNA with small interfering RNA and short hairpin RNA.

Glucocorticoids (GCs) induce apoptosis in lymphocytes and are effective agents for the treatment of leukemia. The activated glucocorticoid receptor (GR) initiates a transcriptional program leading to caspase activation and cell death, but the critical signaling intermediates in GC-induced apoptosis remain largely undefined. We have observed that GC induction of the three major protein products of the Bcl-2 relative Bim (BimEL, BimS and BimL) correlates with GC sensitivity in a panel of human pre-B acute lymphoblastic leukemia (ALL) cell lines. To test the hypothesis that Bim facilitates GC-induced apoptosis, we reduced BIM mRNA levels and Bim protein levels by RNA interference (RNAi) in highly GC-sensitive pre-B ALL cells. Reducing Bim proteins by either electroporation of synthetic siRNA duplexes or lentiviral-mediated stable expression of shRNA inhibited activation of caspase-3 and increased cell viability following GC exposure. We also observed that the extent of GC resistance correlated with siRNA silencing potency. siRNA duplexes that reduced only BimEL or BimEL and BimL (but not BimS) exhibited less GC resistance than a potent siRNA that silenced all three major isoforms, implying that induction of all three Bim proteins contributes to cell death. Finally, the modulation of GC-induced apoptosis caused by Bim silencing was independent of Bcl-2 expression levels, negating the hypothesis that the ratio of Bim to Bcl-2 regulates apoptosis. These results offer evidence that induction of Bim by GC is a required event for the complete apoptotic response in pre-B ALL cells

Learning Abaqus for Master\u27s thesis project

I am writing to notify the results of the independent study that I have been performing over the semester of Fall 2016. The objective of this study was to lay a foundation of a Master’s thesis project at which the end goal would be to improve the repair rate of the human rotator cuff tear repairs. The experimental plots of the most recent models will be further attached

Feedback (F) Fueling Adaptation (A) Network Growth (N) and Self-Organization (S): A Complex Systems Design and Evaluation Approach to Professional Development

This paper reports on the efficacy of a professional development framework premised on four complex systems design principles: Feedback, Adaptation, Network Growth and Self-organization (FANS). The framework is applied to the design and delivery of the first two years of a three-year study aimed at improving teacher and student understanding of computational modeling tools. We demonstrate that structuring a professional development program around the FANS framework facilitates the development of important strategies and processes for program organizers such as the identification of salient system variables, effectively distributing expertise, adaptation and improvement of professional development resources and activities and building technological, human and social capital. For participants, there is evidence to show that the FANS framework encourages: professional goal setting, engagement in a strong professional community and personal autonomy by enabling individualized purpose—all fundamental components in promoting self-organization. We discuss three meta-level themes that may account for the success of the FANS framework: structure vs. agency, exploration vs. exploitation and short-term vs. long-term goals. Each illustrates the tension that exists between competing variables that need to be considered in order to work effectively in real world complex educational systems

An advanced course on finite element analysis, with application to the stress distribution in teeth

The overall goal of my work is to gain insight into how tooth shape relates to its function. As a step towards this, I undertook an independent study project to further improve my skills on finite element analysis (FEA) this semester, and to combine this into my Master’s thesis project work. Continuing from the previous independent study course, the tooth model was improved to eliminate singularities and a contact surface model was included to simulate contact stress problems. I believe that these series of problems will be useful to my research. This report contains an overview of some literature that I studied, and a summary of several finite element output plots that I found to be particularly instructive

Development of Global Operational Snow Analysis at the US Air Force 557th Weather Wing

The outdated SNODEP snow depth retrieval algorithm is replaced by the Foster et al. (1997; 2005) approach, which considers the effects of variations in forest cover. The simple blending algorithm (IDW) is replaced by the Bratseth scheme, a successive correction algorithm that converges to the solution provided by Optimal Interpolation (OI). Outdated quality control datasets are updated and quality control algorithms are reorganized to ensure the performance of the snow analysis. The spatial resolution of snow and ice estimates are increased from 25-km to 10-km.USAF-SI are fully integrated into the global operational land analysis configuration at the USAF 557th WW

Smart exercise application to improve leg function and short-term memory through game- like lunge exercises: development and evaluation

The purpose of this study was to evaluate the functionality, accuracy, and usability of a novel smart exercise application (SEA). The functionality such as counting lunges, providing task-related auditory feedback, and testing short-term memory was examined while thirteen young adults (six men, age 25.4 ± 8.3 years) performed the lunge exercise with the SEA. The accuracy of logged motion data including angles and accelerations were also tested. Another twenty-five participants (11 men, age 23.2 ± 5.7 years) evaluated the usability of the SEA interest, motivation, convenience, and strength/cognitive benefit via a questionnaire. The SEA assessed the lunge motion correctly, provided auditory feedback, and tested users’ short-term memory as required. High correlations (r = 0.90 to 0.99) with low RMSE (4.85 ̊ for direction angle, 0.13 to 0.22 m/ s2 for acceleration) were observed between the sensor output and the reference output. Bland-Altman plot also showed a low discrepancy between each of the two measures. Most participants positively answered all questions about interest (60%), motivation (40%), convenience (80%), strength benefits (92%), and cognitive benefits (88%) of the SEA. The SEA demonstrated accurate kinematic assessment of accelerations and directions, assessed the lunge motion correctly, and created the appropriate auditory feedback on the short- term memory task. The high rate of positive responses suggested the potential of the application in future use

DifferentMRF4Knockout Alleles Differentially Disrupt Myf-5 Expression:cis-Regulatory Interactions at theMRF4/Myf-5Locus

AbstractThree different null alleles of the myogenic bHLH geneMRF4/herculin/Myf-6were created recently. The three alleles were similar in design but were surprisingly different in the intensity of their phenotypes, which ranged from complete viability of homozygotes to complete lethality. One possible explanation for these differences is that each mutation altered expression from the nearbyMyf-5gene to a different extent. This possibility was first raised by the observation that the most severeMRF4knockout allele expresses no Myf-5 RNA and is a developmental phenocopy of theMyf-5null mutation. Furthermore, initial studies of the two weaker alleles had shown that their differences in viability correlate with the intensity of rib skeletal defects, and the most extreme version of this rib defect is the hallmark phenotype ofMyf-5null animals. In the present study we tested this hypothesis for the two milderMRF4alleles. By analyzing compound heterozygous animals carrying either the intermediate or the weakestMRF4knockout allele on one chromosome 10 and aMyf-5knockout allele on the other chromosome, we found that both of theseMRF4alleles apparently downregulate Myf-5 expression by acis-acting mechanism. Compound heterozygotes showed increased mortality of the normally viableMRF4allele, together with intensified rib defects for bothMRF4alleles and increased deficits in myotomal Myf-5 expression. The allele-specific gradation in phenotypes also suggested that rib morphogenesis is profoundly sensitive to quantitative differences in Myf-5 function if Myf-5 products drop below hemizygous levels. The mechanistic basis forcisinteractions at theMRF4/Myf-5locus was further examined by fusing a DNA segment containing the entireMRF4structural gene, including all sequences deleted in the threeMRFknockout alleles, with a basal promoter and alacZreporter. Transgenic embryos showed specific LacZ expression in myotomes in a pattern that closely resembles the expression of Myf-5 RNA.cis-acting interactions betweenMyf-5andMRF4may therefore play a significant role in regulating expression of these genes in the early myotomes of wildtype embryos