碩士
國立交通大學
電子研究所
83
Electron cyclotron resonance plasma oxide (ECR oxide) for the
inter-metal dielectric (IMD) application has been well
characterized for sub-half-micron technology. The void-free
...gap- filling capability of the ECR CVD process is demonstrated.
Good planarity was obtained by combining ECR CVD process with
either SOG etchback or chemical mechanical polishing (CMP)
technique. The major concern for the implementation of ECR CVD
process into sub-half-micron technology is device damage. In
this thesis, hot-carrier stress and Fowler-Nordheim (F-N)
tunneling stress were performed to detect device damage.
Experiments were designed to evaluate the influence of various
process parameters on device damage. In our study, the
microwave power input shows the most significant effect. As the
microwave power reduced down to 1400 watts, the reliability
performance of devices with ECR oxide is comparable to that of
devices with the conventional IMD process (SOG sandwich
structure). The ECR CVD process with lower etch-to-deposition
ratio (E/D ratio) is also helpful in alleviating the device
degradation. In addation, the impact from RF power and other
process parameters were extensively investigated as well.
In this paper we describe the first reported blanket removal properties of various dielectric films. Based on material selectivity, We deposited thin PEOX, thick BPSG and a hard dielectric film with ...lower removal rate on top of a patterned wafer. Initial polishing removed the top hard dielectric level completely, exposing the BPSG, but the lower hard material remains less polished, BPSG polishes faster than hard dielectric film, resulting that the BPSG level was selectively polished. After the completion of the process with over etch, the height variation of 5mm scan range is less than 60 nm.
The passive stiffness and strength of periscapular muscles may affect scapulohumeral control, especially in overhead athletes due to sports-specific training. This study tried to assess the ...relationship between the passive stiffness and strength of periscapular muscles, scapulohumeral kinematics and neuromuscular control during scaption in swimmers. Ten male adolescent competitive front-crawl swimmers were recruited. The passive stiffness and strength of periscapular muscles were measured in standard postures by a hand-held myotonometer and dynamometer, respectively. Surface electromyography and electromagnetic tracking systems were synchronized to record the muscle activities and scapulohumeral kinematics during scaption. Correlations between the passive stiffness or strength of periscapular muscles and the kinematics or muscle activity were examined by Spearman's rank correlation coefficient. The maximal strength of periscapular muscles correlated positively with the ranges of upward and external rotation of the scapula and negatively with muscle activity during scaption. Passive stiffness of periscapular muscles was associated with the downward rotation of the scapula and triggered an increase in muscle activity. Increased passive stiffness or decreased strength in the periscapular muscles may affect their role in controlling the scapular rotation and contribute to compensation from adjacent muscles. Our findings suggest that when attempting to evaluate scapular behavior, it may be beneficial to examine muscle strength and passive stiffness of periscapular muscles.
Summary
Steroidal oestrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors and group ...1 carcinogens. Microbial degradation is a naturally occurring mechanism that mineralizes oestrogens in the biosphere; however, the corresponding genes in oestrogen‐degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative oestrogen‐degrading genes (aed; actinobacterial oestrogen degradation) in actinobacterium Rhodococcus sp. strain B50. Among them, the aedA and aedB genes involved in oestrogenic A‐ring cleavage were identified through gene‐disruption experiments. We demonstrated that actinobacterial oestrone 4‐hydroxylase (AedA) is a cytochrome P450‐type monooxygenase. We also detected the accumulation of two extracellular oestrogenic metabolites, including pyridinestrone acid (PEA) and 3aα‐H‐4α(3'‐propanoate)‐7aβ‐methylhexahydro‐1,5‐indanedione (HIP), in the oestrone‐fed strain B50 cultures. Since actinobacterial aedB and proteobacterial edcB shared < 40% sequence identity, 4‐hydroxyestrone 4,5‐dioxygenase genes (namely aedB and edcB) could serve as a specific biomarker to differentiate the contribution of actinobacteria and proteobacteria in environmental oestrogen degradation. Therefore, 4‐hydroxyestrone 4,5‐dioxygenase genes and the extracellular metabolites PEA and HIP were used as biomarkers to investigate oestrogen biodegradation in an urban estuarine sediment. Interestingly, our data suggested that actinobacteria are active oestrogen degraders in the urban estuarine sediment.
We identified a gene cluster encoding several putative estrogen‐degrading genes (aed; actinobacterial estrogen degradation) in actinobacterium Rhodococcus sp. strain B50. Among them, the aedA and aedB genes involved in estrogenic A‐ring cleavage were identified through gene‐disruption experiments.
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly ...understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.
Display omitted
•Pan-cancer resource of comprehensively annotated intra-tumor heterogeneity (ITH)•ITH is pervasive across cancers and shows cancer type-specific patterns•Branching phylogenies are common•Dynamic changes in mutational processes between subclonal expansions
Dentro et al. provide a comprehensive annotation of intra-tumor heterogeneity and its drivers in cancer evolution.
Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that ...gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT - qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.
Objectives
This study aimed to evaluate the feasibility of automatic Stanford classification of classic aortic dissection (AD) using a 2-step hierarchical neural network.
Methods
Between 2015 and ...2019, 130 arterial phase series (57 type A, 43 type B, and 30 negative cases) in aortic CTA were collected for the training and validation. A 2-step hierarchical model was built including the first step detecting AD and the second step predicting the probability (0–1) of Stanford types. The model’s performance was evaluated with an off-line prospective test in 2020. The sensitivity and specificity for Stanford type A, type B, and no AD (Sens
A, B, N
and Spec
A, B, N
, respectively) and Cohen’s kappa were reported.
Results
Of 298 cases (22 with type A, 29 with type B, and 247 without AD) in the off-line prospective test, the Sens
A
, Sens
B
, and Sens
N
were 95.45% (95% confidence interval CI, 77.16–99.88%), 79.31% (95% CI, 60.28–92.01%), and 93.52% (95% CI, 89.69–96.25%), respectively. The Spec
A
, Spec
B
, and Spec
N
were 98.55% (95% CI, 96.33–99.60%), 94.05% (95% CI, 90.52–96.56%), and 94.12% (95% CI, 83.76–98.77%), respectively. The classification rate achieved 92.28% (95% CI, 88.64–95.04%). The Cohen’s kappa was 0.766 (95% CI, 0.68–0.85;
p
< 0.001).
Conclusions
Stanford classification of classic AD can be determined by a 2-step hierarchical neural network with high sensitivity and specificity of type A and high specificity in type B and no AD.
Key Points
•
The Stanford classification for aortic dissection is widely adopted and divides it into Stanford type A and type B based on the ascending thoracic aorta dissected or not
.
•
The 2-step hierarchical neural network for Stanford classification of classic aortic dissection achieved high sensitivity (95.45%) and specificity (98.55%) of type A and high specificity in type B and no aortic dissection (94.05% and 94.12%, respectively) in 298 test cases
.
•
The 2-step hierarchical neural network demonstrated moderate agreement (Cohen’s kappa: 0.766, p < 0.001) with cardiovascular radiologists in detection and Stanford classification of classic aortic dissection in 298 test cases
.
Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most ...comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data mining and results visualization. Our findings provide new insights into the role of inherited variation in blood metabolic diversity and identify potential new opportunities for drug development and for understanding disease.
Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic ...disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of ＂stable CAD＂ may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.
Steroidal estrogens are ubiquitous contaminants that have garnered attention worldwide due to their endocrine-disrupting and carcinogenic activities at sub-nanomolar concentrations. Microbial ...degradation is one of the main mechanisms through which estrogens can be removed from the environment. Numerous bacteria have been isolated and identified as estrogen degraders; however, little is known about their contribution to environmental estrogen removal. Here, our global metagenomic analysis indicated that estrogen degradation genes are widely distributed among bacteria, especially among aquatic actinobacterial and proteobacterial species. Thus, by using the Rhodococcus sp. strain B50 as the model organism, we identified three actinobacteria-specific estrogen degradation genes, namely aedGHJ, by performing gene disruption experiments and metabolite profile analysis. Among these genes, the product of aedJ was discovered to mediate the conjugation of coenzyme A with a unique actinobacterial C17 estrogenic metabolite, 5-oxo-4-norestrogenic acid. However, proteobacteria were found to exclusively adopt an α-oxoacid ferredoxin oxidoreductase (i.e., the product of edcC) to degrade a proteobacterial C18 estrogenic metabolite, namely 3-oxo-4,5-seco-estrogenic acid. We employed actinobacterial aedJ and proteobacterial edcC as specific biomarkers for quantitative polymerase chain reaction (qPCR) to elucidate the potential of microbes for estrogen biodegradation in contaminated ecosystems. The results indicated that aedJ was more abundant than edcC in most environmental samples. Our results greatly expand the understanding of environmental estrogen degradation. Moreover, our study suggests that qPCR-based functional assays are a simple, cost-effective, and rapid approach for holistically evaluating estrogen biodegradation in the environment.
Display omitted
•Estrogen degradation genes are distributed among actinobacteria and proteobacteria.•We identified three actinobacteria-specific estrogen degradation genes, namely aedGHJ.•Actinobacterial aedJ and proteobacterial edcC can be used as specific biomarkers.•Quantitative PCR-based functional assays are a simple, rapid and cost-effective.
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