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Coenzyme Q10 (CoQ10) is a component of the respiratory chain with antioxidant properties that has in recent years been advocated as a therapy for heart disease. In the cases of hypertrophic cardiomyopathy and congestive heart failure, the evidence supporting CoQ10 use is diminished by experimental design flaws, while that opposing its use is based on relatively solid planning. Although critical analysis of studies up to date suggests that CoQ10 does not have a significant effect on relieving aspects of heart disease, technical difficulties in delivering the supplement to human myocytes may have more to do with this observation than an inability of CoQ10 to alleviate symptoms. Further exploration of the subject is needed.

Cover page: Coenzyme Q10 as a Treatment for Heart Disease

Thesis
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Estimating Student Competence in Engineering Statics From a Lexical Analysis of Handwritten Equations

Lin, Han-Lung
Advisor(s): Stahovich, Thomas F

UC Riverside Electronic Theses and Dissertations (2014)

We present a technique that examines handwritten equations from a student's solution to an engineering statics problem and estimates the correctness of the work. The solution is recorded with a smartpen that digitizes the writing with time stamps. Our technique first separates equation pen strokes from other content, such as diagrams. Then the equation pen strokes are grouped first into individual equations, then into individual characters. A character recognizer is used to recognize each character, and then a Hidden Markov Model is used to correct recognition errors. The equation text is characterized by a set of features. Some of these describe the frequency of various symbols and symbol combinations, such as a letter following a mathematical operator. One feature describes the frequency with which units of measure (e.g., "kg") appear, while another describes inter-character pauses. This set of features is used to construct SVM regression models to predict the correctness of the work. We tested our approach on a corpus of solutions to exam problems from an undergraduate statics course. The SVM models predicted the grade assigned by the instructor with an average coefficient of determination of 36%. We also combined our features with an existing set of features that describe the temporal and spatial organization of a handwritten solution a statics problem. Using both sets of features, the SVM models predicted the grade on the exam problems with an average coefficient of determination of 56%. This is a surprising result given that none of the features consider the semantic content of the writing, or even the correctness of a student's final answer.

Cover page: Estimating Student Competence in Engineering Statics From a Lexical Analysis of Handwritten Equations

Article
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Domain Knowledge and False Memory

Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 24 (2002)

Article
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Combining Hadoop with MPI to Solve Metagenomics Problems that are both Data- and Compute-intensive

LBL Publications (2018)

Metagenomics, the study of all microbial species cohabitants in an environment, often produces large amount of sequence data varying from several GBs to a few TBs. Analyzing metagenomics data includes both data-intensive and compute-intensive steps, making the entire process hard to scale. Here we aim to optimize a metagenomics application that partitions the shortgun metagenomics sequences based on their species of origin. Our solution combines MapReduce-based BioPig analytic toolkit with MPI to provide scalability in respective to both data and compute. We also made some improvements to the existing BioPig toolkit by using simplified data types and compressed k-mer storage. These optimizations leads up to 193× speedup for the computing-intensive step and 9.6× speedup over the entire pipeline. Our optimized application is also capable of processing datasets that are 16 times larger on the same hardware platform. These results suggest integrating heterogeneous technologies such as Hadoop and MPI is quite efficient to solve large genomics problems that are both data-intensive and compute-intensive.

Cover page: Combining Hadoop with MPI to Solve Metagenomics Problems that are both Data- and Compute-intensive

Article
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Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma

UCLA Previously Published Works (2017)

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced antineoplastic activities both in vitro and in vivo An integrative analysis using both whole-transcriptome sequencing and chromatin immunoprecipitation sequencing pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2, and the long noncoding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK, and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease. Cancer Res; 77(23); 6614-26. ©2017 AACR.

Cover page: Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma

Article
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Light‐limited photosynthesis under energy‐saving film decreases eggplant yield

UC Santa Cruz Previously Published Works (2020)

Abstract: Glasshouse films with adjustable light transmittance and energy‐efficient designs have the potential to reduce (up to 80%) the high energy cost for greenhouse horticulture operations. Whether these films compromise the quantity and quality of light transmission for photosynthesis and crop yield remains unclear. A “Smart Glass” film ULR‐80 (SG) was applied to a high‐tech greenhouse horticulture facility, and two experimental trials were conducted by growing eggplant (Solanum melongena) using commercial vertical cultivation and management practices. SG blocked 85% of ultraviolet (UV), 58% of far‐red, and 26% of red light, leading to an overall reduction of 19% in photosynthetically active radiation (PAR, 380–699 nm) and a 25% reduction in total season fruit yield. There was a 53% (season mean) reduction in net short‐wave radiation (radiometer range, 385–2,105 nm upward; 295–2,685 nm downward) that generated a net reduction of 8% in heat load and reduced water and nutrient consumption by 18%, leading to improved energy and resource use efficiency. Eggplant adjusted to the altered SG light environment via decreased maximum light‐saturated photosynthetic rates (Amax) and lower xanthophyll de‐epoxidation state. The shift in light characteristics under SG led to reduced photosynthesis, which may have reduced source (leaf) to sink (fruit) carbon distribution, increased fruit abortion and decreased fruit yield, but did not affect nutritional quality. We conclude that SG increases energy and resource use efficiency, without affecting fruit quality, but the reduction in photosynthesis and eggplant yield is high. The solution is to re‐engineer the SG to increase penetration of UV and PAR, while maintaining blockage of glasshouse heat gain.

Cover page: Light‐limited photosynthesis under energy‐saving film decreases eggplant yield

Creative Commons 'BY-NC-ND' version 4.0 license

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Critical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.

UC Irvine Previously Published Works (2024)

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.

Cover page: Critical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.

Article
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Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease

UC San Francisco Previously Published Works (2017)

Hallmarks of chronic neurodegenerative disease include progressive synaptic loss and neuronal cell death, yet the cellular pathways that underlie these processes remain largely undefined. We provide evidence that dual leucine zipper kinase (DLK) is an essential regulator of the progressive neurodegeneration that occurs in amyotrophic lateral sclerosis and Alzheimer's disease. We demonstrate that DLK/c-Jun N-terminal kinase signaling was increased in mouse models and human patients with these disorders and that genetic deletion of DLK protected against axon degeneration, neuronal loss, and functional decline in vivo. Furthermore, pharmacological inhibition of DLK activity was sufficient to attenuate the neuronal stress response and to provide functional benefit even in the presence of ongoing disease. These findings demonstrate that pathological activation of DLK is a conserved mechanism that regulates neurodegeneration and suggest that DLK inhibition may be a potential approach to treat multiple neurodegenerative diseases.

Cover page: Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease

Article
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Pistachio genomes provide insights into nut tree domestication and ZW sex chromosome evolution

UC Davis Previously Published Works (2023)

Pistachio is a nut crop domesticated in the Fertile Crescent and a dioecious species with ZW sex chromosomes. We sequenced the genomes of Pistacia vera cultivar (cv.) Siirt, the female parent, and P. vera cv. Bagyolu, the male parent. Two chromosome-level reference genomes of pistachio were generated, and Z and W chromosomes were assembled. The ZW chromosomes originated from an autosome following the first inversion, which occurred approximately 8.18 Mya. Three inversion events in the W chromosome led to the formation of a 12.7-Mb (22.8% of the W chromosome) non-recombining region. These W-specific sequences contain several genes of interest that may have played a pivotal role in sex determination and contributed to the initiation and evolution of a ZW sex chromosome system in pistachio. The W-specific genes, including defA, defA-like, DYT1, two PTEN1, and two tandem duplications of six VPS13A paralogs, are strong candidates for sex determination or differentiation. Demographic history analysis of resequenced genomes suggest that cultivated pistachio underwent severe domestication bottlenecks approximately 7640 years ago, dating the domestication event close to the archeological record of pistachio domestication in Iran. We identified 390, 211, and 290 potential selective sweeps in 3 cultivar subgroups that underlie agronomic traits such as nut development and quality, grafting success, flowering time shift, and drought tolerance. These findings have improved our understanding of the genomic basis of sex determination/differentiation and horticulturally important traits and will accelerate the improvement of pistachio cultivars and rootstocks.

Cover page: Pistachio genomes provide insights into nut tree domestication and ZW sex chromosome evolution

Article
Peer Reviewed

SN 2017gmr: An Energetic Type II-P Supernova with Asymmetries

UC Davis Previously Published Works (2019)

We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN 2017gmr from hours after discovery through the first 180 days. SN 2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ∼500 R o progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130 ± 0.026 M o of 56Ni are present, if the light curve is solely powered by radioactive decay, although the 56Ni mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of Hα and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.

Cover page: SN 2017gmr: An Energetic Type II-P Supernova with Asymmetries