Metabolic Engineering of Cyanobacteria for Production of Chemicals

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge of using cyanobacteria for chemical production is their low productivities compared to that of conventional heterotrophic hosts. More research is needed to improve the photosynthetic conversion of CO2 to desired compounds. In this dissertation, cyanobacteria were engineered to produce two commercially-used products, limonene and sucrose, which use distinct substrates for biosynthesis. To identify the metabolic bottlenecks for enhancing the production of limonene and sucrose, various genes and pathways were expressed in cyanobacteria, and further optimized using synthetic biology tools. Their productivities were significantly improved compared to those reported in previous studies. The findings in this dissertation provide knowledge to improve cyanobacterial production of limonene and sucrose, and facilitate a deeper understanding of the terpene and sugar metabolism in these photosynthetic microorganisms

Rhythm-Flexible Voice Conversion without Parallel Data Using Cycle-GAN over Phoneme Posteriorgram Sequences

Speaking rate refers to the average number of phonemes within some unit time, while the rhythmic patterns refer to duration distributions for realizations of different phonemes within different phonetic structures. Both are key components of prosody in speech, which is different for different speakers. Models like cycle-consistent adversarial network (Cycle-GAN) and variational auto-encoder (VAE) have been successfully applied to voice conversion tasks without parallel data. However, due to the neural network architectures and feature vectors chosen for these approaches, the length of the predicted utterance has to be fixed to that of the input utterance, which limits the flexibility in mimicking the speaking rates and rhythmic patterns for the target speaker. On the other hand, sequence-to-sequence learning model was used to remove the above length constraint, but parallel training data are needed. In this paper, we propose an approach utilizing sequence-to-sequence model trained with unsupervised Cycle-GAN to perform the transformation between the phoneme posteriorgram sequences for different speakers. In this way, the length constraint mentioned above is removed to offer rhythm-flexible voice conversion without requiring parallel data. Preliminary evaluation on two datasets showed very encouraging results.Comment: 8 pages, 6 figures, Submitted to SLT 201

Noninvasive technique for measurement of heartbeat regularity in zebrafish (Danio rerio) embryos

<p>Abstract</p> <p>Background</p> <p>Zebrafish (<it>Danio rerio</it>), due to its optical accessibility and similarity to human, has emerged as model organism for cardiac research. Although various methods have been developed to assess cardiac functions in zebrafish embryos, there lacks a method to assess heartbeat regularity in blood vessels. Heartbeat regularity is an important parameter for cardiac function and is associated with cardiotoxicity in human being. Using stereomicroscope and digital video camera, we have developed a simple, noninvasive method to measure the heart rate and heartbeat regularity in peripheral blood vessels. Anesthetized embryos were mounted laterally in agarose on a slide and the caudal blood circulation of zebrafish embryo was video-recorded under stereomicroscope and the data was analyzed by custom-made software. The heart rate was determined by digital motion analysis and power spectral analysis through extraction of frequency characteristics of the cardiac rhythm. The heartbeat regularity, defined as the rhythmicity index, was determined by short-time Fourier Transform analysis.</p> <p>Results</p> <p>The heart rate measured by this noninvasive method in zebrafish embryos at 52 hour post-fertilization was similar to that determined by direct visual counting of ventricle beating (<it>p </it>> 0.05). In addition, the method was validated by a known cardiotoxic drug, terfenadine, which affects heartbeat regularity in humans and induces bradycardia and atrioventricular blockage in zebrafish. A significant decrease in heart rate was found by our method in treated embryos (<it>p </it>< 0.01). Moreover, there was a significant increase of the rhythmicity index (p < 0.01), which was supported by an increase in beat-to-beat interval variability (<it>p </it>< 0.01) of treated embryos as shown by Poincare plot.</p> <p>Conclusion</p> <p>The data support and validate this rapid, simple, noninvasive method, which includes video image analysis and frequency analysis. This method is capable of measuring the heart rate and heartbeat regularity simultaneously via the analysis of caudal blood flow in zebrafish embryos. With the advantages of rapid sample preparation procedures, automatic image analysis and data analysis, this method can potentially be applied to cardiotoxicity screening assay.</p

Measuring Taiwanese Mandarin Language Understanding

The evaluation of large language models (LLMs) has drawn substantial attention in the field recently. This work focuses on evaluating LLMs in a Chinese context, specifically, for Traditional Chinese which has been largely underrepresented in existing benchmarks. We present TMLU, a holistic evaluation suit tailored for assessing the advanced knowledge and reasoning capability in LLMs, under the context of Taiwanese Mandarin. TMLU consists of an array of 37 subjects across social science, STEM, humanities, Taiwan-specific content, and others, ranging from middle school to professional levels. In addition, we curate chain-of-thought-like few-shot explanations for each subject to facilitate the evaluation of complex reasoning skills. To establish a comprehensive baseline, we conduct extensive experiments and analysis on 24 advanced LLMs. The results suggest that Chinese open-weight models demonstrate inferior performance comparing to multilingual proprietary ones, and open-weight models tailored for Taiwanese Mandarin lag behind the Simplified-Chinese counterparts. The findings indicate great headrooms for improvement, and emphasize the goal of TMLU to foster the development of localized Taiwanese-Mandarin LLMs. We release the benchmark and evaluation scripts for the community to promote future research.Comment: Preprint. Under revie

Construction and verification of digital electronics contestants' indicators for vocational education in Taiwan

No AbstractKeywords: competency indicator, digital electronics, important-performance analysis, skill competitio

Food Supplement 20070721-GX May Increase CD34+ Stem Cells and Telomerase Activity

Few rejuvenation and antiaging markers are used to evaluate food supplements. We measured three markers in peripheral blood to evaluate the antiaging effects of a food supplement containing placental extract. Samples were evaluated for CD34+ cells, insulin-like growth factor 1 (IGF1), and telomerase activity, which are all markers related to aging. To control the quality of this food supplement, five active components were monitored. In total, we examined 44 individuals who took the food supplement from 1.2 months to 23 months; the average number of CD34+ cells was almost 6-fold higher in the experimental group compared with the control group. Food supplement intake did not change serum IGF1 levels significantly. Finally, the average telomerase activity was 30% higher in the subjects taking this food supplement. In summary, our results suggest that the placental extract in the food supplement might contribute to rejuvenation and antiaging