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Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin. We analyzed naturally occurring and synthetic cyclotides (Cycloviolacin O3, Cycloviolacin O19, natural Kalata B1, synthetic Kalata B1, and Vitri E) alone and in co-exposure treatments with the drug temozolomide (TMZ) in human glioblastoma cells. The cyclotides were identified by UPLC-PDA and HPLC-UV. The synthetic Kalata B1 sequence was verified with orbitrap LC-MS, and structural confirmation was provided by NMR spectroscopy. The cyclotides displayed dose-dependent cytotoxicity (IC50 values 2.4–21.1 µM) both alone and as chemosensitizers of U-87 MG and T 98 cells to TMZ. In fact, a 16-fold lower concentration of TMZ (100 µM) was needed for significant cytotoxicity in U-87 MG cells co-exposed to synthetic Kalata B (0.5 µM). Similarly, a 15-fold lower concentration of TMZ (75 µM) was required for a significant reduction in cell viability in T 98 cells co-exposed to synthetic Kalata B1 (0.25 µM). Kalata B1 remained stable in human serum stability assays. The data support the assertion that cyclotides may chemosensitize glioblastoma cells to TMZ. 

It is challenging to effectively educate in large classes with students from a multitude of backgrounds. Many introductory engineering courses in universities have hundreds of students, and some online classes are even larger. Instructors in these circumstances often turn to online homework systems, which help greatly reduce the grading burden; however, they come at the cost of reducing the quality of feedback that students receive. Since online systems typically can only automatically grade multiple choice or numeric answer questions, students predominately do not receive feedback on the critical skill of sketching free-body diagrams (FBD). An online, sketch-recognition based tutoring system called Mechanix requires students to draw free-body diagrams for introductory statics courses in addition to grading their final answers. Students receive feedback about their diagrams that would otherwise be difficult for instructors to provide in large classes. Additionally, Mechanix can grade open-ended truss design problems with an indeterminate number of solutions. Mechanix has been in use for over six semesters at five different universities by over 1000 students to study its effectiveness. Students used Mechanix for one to three homework assignments covering free-body diagrams, static truss analysis, and truss design for an open-ended problem. Preliminary results suggest the system increases homework engagement and effort for students who are struggling and is as effective as other homework systems for teaching statics. Focus groups showed students enjoyed using Mechanix and that it helped their learning process. 

In plant cytokinesis, de novo formation of a cell plate evolving into the new cell wall partitions the cytoplasm of the dividing cell. In our earlier chemical genomics studies, we identified and characterized the small molecule endosidin-7, that specifically inhibits callose deposition at the cell plate, arresting late-stage cytokinesis in arabidopsis. Endosidin-7 has emerged as a very valuable tool for dissecting this essential plant process. To gain insights regarding its mode of action and the effects of cytokinesis inhibition on the overall plant response, we investigated the effect of endosidin-7 through a nuclear magnetic resonance spectroscopy (NMR) metabolomics approach. In this case study, metabolomics profiles of arabidopsis leaf and root tissues were analyzed at different growth stages and endosidin-7 exposure levels. The results show leaf and root-specific metabolic profile changes and the effects of endosidin-7 treatment on these metabolomes. Statistical analyses indicated that the effect of endosidin-7 treatment was more significant than the developmental impact. The endosidin-7 induced metabolic profiles suggest compensations for cytokinesis inhibition in central metabolism pathways. This study further shows that long-term treatment of endosidin-7 profoundly changes, likely via alteration of hormonal regulation, the primary metabolism of arabidopsis seedlings. Hormonal pathway-changes are likely reflecting the plant’s responses, compensating for the arrested cell division, which in turn are leading to global metabolite modulation. The presented NMR spectral data are made available through the Metabolomics Workbench, providing a reference resource for the scientific community. 

Large class sizes in engineering programs often prevent instructors from providing detailed and meaningful feedback to students on their homework problems. While the literature shows that frequent and immediate formative feedback has several benefits in terms of knowledge gain and academic motivation, several instructors struggle to provide any feedback. Motivated by this inability, a sketch-based virtual tutoring system, named Mechanix, has been developed and implemented. Mechanix lets the students to sketch their freebody diagram on a virtual interface and the process involved is very close to using a pencil and paper. The system provides real-time feedback on the accuracy of their Freebody diagrams and the solution to the problem. This paper reports the implementation of Mechanix at two large public universities in the United States – Georgia Institute of Technology and Texas State University. Mechanix is used to solve specific assignments from each school that involve the use of freebody diagrams. Pre- and post- concept inventories are used to measure the improvements in the conceptual understanding of the students. The results show that students who solve their homework using Mechanix outperform their peers who do not in one school, whereas the results are similar across the two groups in the second school. The evaluation of the concept inventories shows that the students who used Mechanix has the same level of improvement in their conceptual knowledge compared to the control group.