Sensitive and Makeable Computational Materials for the Creation of Smart Everyday Objects

The vision of computational materials is to create smart everyday objects using the materi- als that have sensing and computational capabilities embedded into them. However, today’s development of computational materials is limited because its interfaces (i.e. sensors) are unable to support wide ranges of human interactions , and withstand the fabrication meth- ods of everyday objects (e.g. cutting and assembling). These barriers hinder citizens from creating smart every day objects using computational materials on a large scale. To overcome the barriers, this dissertation presents the approaches to develop compu- tational materials to be 1) sensitive to a wide variety of user interactions, including explicit interactions (e.g. user inputs) and implicit interactions (e.g. user contexts), and 2) makeable against a wide range of fabrication operations, such cutting and assembling. I exemplify the approaches through five research projects on two common materials, textile and wood. For each project, I explore how a material interface can be made to sense user inputs or activities, and how it can be optimized to balance sensitivity and fabrication complexity. I discuss the sensing algorithms and machine learning model to interpret the sensor data as high-level abstraction and interaction. I show the practical applications of developed computational materials. I demonstrate the evaluation study to validate their performance and robustness. In the end of this dissertation, I summarize the contributions of my thesis and discuss future directions for the vision of computational materials

A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2–3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4–8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation

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

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Abnormalities of Neurotransmission in Drug Addiction

Substance use disorders are prevalent and severe conditions associated with numerous health, social, and economic harms. While the neurobiological mechanisms are still not fully understood, adaptations in multiple neurotransmitter systems have been implicated in the development and maintenance of substance use disorders. The advent of molecular imaging techniques has provided a unique opportunity to better understand abnormalities of neurotransmission in humans with substance use disorders, and this insight may ultimately lead to improved treatment options in the future. This chapter provides a summary of positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies in humans with alcohol, tobacco, cannabis, opioid, and stimulant use disorders. Studies to date provide consistent evidence that the dopaminergic system is disrupted in populations with substance use disorders, although there has been little research in other neurotransmitter systems and findings of existing studies have been mixed. Many PET and SPECT studies investigating abnormalities of neurotransmission in substance use disorder are limited by small sample sizes and over-reliance on male samples without comorbid conditions. In addition, the use of cross-sectional study designs does not make it possible to draw conclusions about causality