Development of novel separation techniques for biological samples in capillary electrophoresis

This dissertation includes three different topics, general introduction of capillary electrophoresis (CE), gradient in CE and CE in biological separations, and capillary gel electrophoresis (CGE) for DNA separation;Factors such as temperature, viscosity, pH and the surface of capillary wall affecting the separation performance have been well demonstrated in Chapters 2 to 4. A pH gradient between 3.0 and 5.2 is useful to improve the resolution among eight different organic acids. Flow gradient due to the change in the concentration of surfactant which is able to coat to the capillary wall to change the flow rate and its direction is also shown as a good way to improve the resolution for organic compounds. Temperature gradient caused by joule heat has been shown by voltage programming to enhance the resolution and shorten the separation time for several phenolic compounds. We also showed that self-regulating dynamic control of electroosmotic flow in CE by simply running separation in different concentration of surfactant has less matrix effect on the separation performance. One of the most important demonstrations in this dissertation is that we proposed on-column reaction which gives several advantages including the use of small amount of sample, low risk of contamination, time saving and kinetic feature. We used this idea with laser induced fluorescence (LIF) as a detection mode to detect an on-column digestion of sub-ng of protein. This technique also has been applied to single cell analysis in our group;An entangled polymer, poly(ethylene oxide), was used to separate 11 fragments of Hae III digest of [phi]X174RF DNA. The effects of voltage, gel concentration and molecular weight of polymer are well studied. Also, the effects of the nature and concentration of labeling dyes, and the capillary length on the resolution of DNA fragments has been studied with different lasers. DNA sequence of PGEM/U with four different terminal dyes has been shown. Mixed gel matrices provides single-base resolution and better separation performance for DNA fragments up to 500 base pairs have been shown;Lastly, CE with LIF has been shown as a powerful technique to detect attomol levels of amine compounds, which are neurotransmitters. This method also has been used to determine the norepinephrine and epinephrine at femtomole level in single adrenomedullary cells

Effects of Ambient Ozone Exposure on Mail Carriers’ Peak Expiratory Flow Rates

The extent to which occupational exposure to ozone in ambient air can affect lung function remains unclear. We conducted a panel study in 43 mail carriers by measuring their peak expiratory flow rates (PEFRs) twice daily for 6 weeks in 2001. The daily exposure of each mail carrier to O(3), particulate matter < 10 μm in aerodynamic diameter (PM(10)), and nitrogen dioxide was estimated by one air monitoring station in the center of the mail carrier’s delivery area. Hourly concentrations of air pollutants during their exposure periods were 6–96 ppb for O(3), 11–249 μg/m(3) for PM(10), and 14–92 ppb for NO(2). Linear mixed-effects models were used to estimate the association between air pollution exposures and PEFR after adjusting for subject’s sex, age, and disease status and for temperature and humidity. We found that night PEFR and the deviation in night PEFR were significantly decreased in association with 8-hr O(3) exposures with a lag 0–2 days and by daily maximum O(3) exposures with a lag of 0–1 day in our multipollutant models. By contrast, neither PM(10) nor NO(2) was associated with a PEFR reduction. Daily 8-hr mean concentrations of O(3) had greater reduction effects on PEFR than did daily maximum concentrations. For a 10-ppb increase in the 8-hr average O(3) concentration, the night PEFR was decreased by 0.54% for a 0-day lag, 0.69% for a 1-day lag, and 0.52% for a 2-day lag. We found that an acute lung function reduction occurs in mail carriers exposed to O(3) concentrations below current ambient air quality standards and occupational exposure limits

Compressing Transformer-based self-supervised models for speech processing

Despite the success of Transformers in self- supervised learning with applications to various downstream tasks, the computational cost of training and inference remains a major challenge for applying these models to a wide spectrum of devices. Several isolated attempts have been made to compress Transformers, but the settings and metrics are different across studies. Trade-off at various compression rates are also largely missing in prior work, making it difficult to compare compression techniques. In this work, we aim to provide context for the isolated results, studying several commonly used compression techniques, including weight pruning, head pruning, low-rank approximation, and knowledge distillation. We report trade- off at various compression rate, including wall-clock time, the number of parameters, and the number of multiply-accumulate operations. Our results show that compared to recent approaches, basic compression techniques are strong baselines. We further present several applications of our results, revealing properties of Transformers, such as the significance of diagonal attention heads. In addition, our results lead to a simple combination of compression techniques that improves trade-off over recent approaches. We hope the results would promote more diverse comparisons among model compression techniques and promote the use of model compression as a tool for analyzing models. Our code of compressing speech self-supervised model is available at https://github.com/nervjack2/Speech-SSL-Compression/.Comment: Submitted to IEEE Transactions on Audio, Speech and Language Processing (TASLP

Fluorescence detection of single nucleotide polymorphisms using a universal molecular beacon

We present a simple and novel assay—employing a universal molecular beacon (MB) in the presence of Hg2+—for the detection of single nucleotide polymorphisms (SNPs) based on Hg2+–DNA complexes inducing a conformational change in the MB. The MB (T7-MB) contains a 19-mer loop and a stem of a pair of seven thymidine (T) bases, a carboxyfluorescein (FAM) unit at the 5′-end, and a 4-([4-(dimethylamino)phenyl]azo)benzoic acid (DABCYL) unit at the 3′-end. Upon formation of Hg2+–T7-MB complexes through T–Hg2+–T bonding, the conformation of T7-MB changes from a random coil to a folded structure, leading to a decreased distance between the FAM and DABCYL units and, hence, increased efficiency of fluorescence resonance energy transfer (FRET) between the FAM and DABCYL units, resulting in decreased fluorescence intensity of the MB. In the presence of complementary DNA, double-stranded DNA complexes form (instead of the Hg2+–T7-MB complexes), with FRET between the FAM and DABCYL units occurring to a lesser extent than in the folded structure. Under the optimal conditions (20 nM T7-MB, 20 mM NaCl, 1.0 μM Hg2+, 5.0 mM phosphate buffer solution, pH 7.4), the linear plot of the fluorescence intensity against the concentration of perfectly matched DNA was linear over the range 2–30 nM (R2 = 0.991), with a limit of detection of 0.5 nM at a signal-to-noise ratio of 3. This new probe provides higher selectivity toward DNA than that exhibited by conventional MBs

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Development of novel separation techniques for biological samples in capillary electrophoresis

This dissertation includes three different topics, general introduction of capillary electrophoresis (CE), gradient in CE and CE in biological separations, and capillary gel electrophoresis (CGE) for DNA separation;Factors such as temperature, viscosity, pH and the surface of capillary wall affecting the separation performance have been well demonstrated in Chapters 2 to 4. A pH gradient between 3.0 and 5.2 is useful to improve the resolution among eight different organic acids. Flow gradient due to the change in the concentration of surfactant which is able to coat to the capillary wall to change the flow rate and its direction is also shown as a good way to improve the resolution for organic compounds. Temperature gradient caused by joule heat has been shown by voltage programming to enhance the resolution and shorten the separation time for several phenolic compounds. We also showed that self-regulating dynamic control of electroosmotic flow in CE by simply running separation in different concentration of surfactant has less matrix effect on the separation performance. One of the most important demonstrations in this dissertation is that we proposed on-column reaction which gives several advantages including the use of small amount of sample, low risk of contamination, time saving and kinetic feature. We used this idea with laser induced fluorescence (LIF) as a detection mode to detect an on-column digestion of sub-ng of protein. This technique also has been applied to single cell analysis in our group;An entangled polymer, poly(ethylene oxide), was used to separate 11 fragments of Hae III digest of [phi]X174RF DNA. The effects of voltage, gel concentration and molecular weight of polymer are well studied. Also, the effects of the nature and concentration of labeling dyes, and the capillary length on the resolution of DNA fragments has been studied with different lasers. DNA sequence of PGEM/U with four different terminal dyes has been shown. Mixed gel matrices provides single-base resolution and better separation performance for DNA fragments up to 500 base pairs have been shown;Lastly, CE with LIF has been shown as a powerful technique to detect attomol levels of amine compounds, which are neurotransmitters. This method also has been used to determine the norepinephrine and epinephrine at femtomole level in single adrenomedullary cells.</p