Phase-based regional oxygen metabolism in magnetic resonance imaging at high field

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.Includes bibliographical references (p. 45-48).Venous oxygen saturation (Yv) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO₂) are important indicators for brain function and disease. Phase-susceptibility measurements in magnetic resonance imaging (MRI) have been used to quantify Yv in candidate cerebral veins. However, currently there is no method to quantify regional CMRO₂ using MRI. Here we propose a novel technique to quantify CMRO₂ from independent MRI estimates of Yv and cerebral blood flow (CBF). Our approach used standard gradient-echo (GRE) and arterial spin labeling (ASL) to make these measurements. Results for in vivo Y, and CMRO₂ estimates on human subjects are presented from application of our technique at 3 Tesla (3T). We also extended our method to high-field human imaging at 7 Tesla (7T), which allows us to take advantage of improved signal-to-noise ratio (SNR) for the same scan duration to achieve higherresolution analysis of vessels of interest. While the higher field strength poses additional challenges, such as increased main field and excitation field inhomogeneities as well as more severe susceptibility artifacts, initial results suggest that substantial benefits can be realized with phase-based regional oxygen metabolism in MRI at high field.by Audrey Peiwen Fan.S.M

Increased co-expression of TIM-3 with TIGIT or 2B4 on CD8+ T cells is associated with poor prognosis in locally advanced nasopharyngeal carcinoma

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma

Complete genome sequence of Echinicola rosea JL3085, a xylan and pectin decomposer.

Marine Bacteroidetes are well known for their functional specialization on the decomposition of polysaccharides which results from a great number of carbohydrate-active enzymes. Here we represent the complete genome of a Bacteroitedes member Echinicola rosea JL3085T that was isolated from surface seawater of the South China Sea. The genome is 6.06 Mbp in size with a GC content of 44.1% and comprises 4613 protein coding genes. A remarkable genomic feature is that the number of glycoside hydrolase genes in the genome of E. rosea JL3085T is high in comparison with most of the sequenced members of marine Bacteroitedes. E. rosea JL3085T genome harbored multi-gene polysaccharide utilization loci (PUL) systems involved in the degradation of pectin, xylan and arabinogalactan. The large diversity of hydrolytic enzymes supports the use of E. rosea JL3085T as a candidate for biotechnological applications in enzymatic conversion of plant polysaccharides

Complete genome sequence of Echinicola rosea JL3085, a xylan and pectin decomposer

Abstract(#br)Marine Bacteroidetes are well known for their functional specialization on the decomposition of polysaccharides which results from a great number of carbohydrate-active enzymes. Here we represent the complete genome of a Bacteroitedes member Echinicola rosea JL3085 T that was isolated from surface seawater of the South China Sea. The genome is 6.06 Mbp in size with a GC content of 44.1% and comprises 4613 protein coding genes. A remarkable genomic feature is that the number of glycoside hydrolase genes in the genome of E. rosea JL3085 T is high in comparison with most of the sequenced members of marine Bacteroitedes . E. rosea JL3085 T genome harbored multi-gene polysaccharide utilization loci (PUL) systems involved in the degradation of pectin, xylan and arabinogalactan. The large diversity of hydrolytic enzymes supports the use of E. rosea JL3085 T as a candidate for biotechnological applications in enzymatic conversion of plant polysaccharides

Increased co-expression of 4-1BB with PD-1 on CD8+ tumor-infiltrating lymphocytes is associated with improved prognosis and immunotherapy response in cervical cancer

BackgroundThe combination of agonistic antibodies with immune checkpoint inhibitors presents a promising avenue for cancer immunotherapy. Our objective is to explore the co-expression of 4-1BB, ICOS, CD28, with PD-1 on CD8+ T cells in the peripheral blood and tumor tissue of cervical cancer(CC) patients, with a specific focus on the association between the co-expression levels of 4-1BB with PD-1 and clinical features, prognosis as well as immunotherapy response. The goal is to offer valuable insights into cervical cancer immunotherapy.MethodsIn this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer.ResultsThe co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy.ConclusionPD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer

Development, testing, and application of quantitative oxygenation imaging from magnetic susceptibility by MRI

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014.Cataloged from PDF version of thesis.Includes bibliographical references (pages 101-133).The healthy brain consumes 20% of total oxygen used by the body under normal conditions. Continuous oxygen delivery to neural tissue is needed to maintain normal brain function and viability. Reliable measurements of brain oxygenation can provide critical information to diagnose and manage diseases in which this oxygen supply is disturbed, including stroke and tumor. In acute stroke, for instance, metabolic biomarkers such as local oxygen extraction fraction (OEF) have been shown to identify tissue at risk of infarction by positron emission tomography. This knowledge can then be used to identify patients who are candidates for reperfusion therapies or to avoid thrombolytic therapy in futile situations. Unfortunately, there is currently no clinically feasible method for radiologists to assess brain oxygenation in patients. My thesis aims to address this need through development of a clinically viable tool to examine regional OEF in the brain with magnetic resonance imaging (MRI). We have designed a novel imaging and analysis method to quantify oxygenation in cerebral veins. MRI phase images are sensitive to local, oxygenation-dependent magnetic field variations in brain vessels, due to the presence of paramagnetic deoxyhemoglobin molecules in venous blood. Our method was developed on a 3 Tesla MRI scanner and tested in 10 healthy volunteers during hypercapnia, i.e. breathing of low levels of CO₂. This respiratory challenge changes the baseline oxygenation state of the brain, enabling us to test whether our MRI method can detect different levels of OEF in vivo. We also show that OEF is reduced in 23 patients with multiple sclerosis, an autoimmune disease of the central nervous disease, and relates to their performance on cognitive tasks.by Audrey P. Fan.Ph. D

珠寶產業演變與商業模式研究

本研究主要探討珠寶黃金產業在台灣市場中，隨著經濟環境的改變之下中小型的珠寶銀樓產業的挑戰隨著時代演變，前期面對外商進入市場的競爭，近期面對新興電子商務市場發展以及資訊透明化影響，文中以市場調查及消費者趨勢分析以找尋未來發展脈絡。 本研究探討的個案外商公司，在進入台灣市場的過程中如何在品牌及行銷的溝通調整，通路發展策略調整以及商品設計符合本地市場喜好，在這些過程中可以看到品牌在地溝通以及深入文化的重要性，如何利用本身的資源優勢，在競爭的市場找到策略合作夥伴，並且利用擁有的優勢資源，規劃拓展市場的資源策略、競爭策略。研究主要採用個案研究法，透過訪問市場相關人員的訪談中蒐集相關資訊，並彙整產業相關資料及報告，加以整合分析，並同步探討外部環境變化，如何因應進行調整迎合市場。 藉由本研究之相關分析、探討，希冀能在台灣黃金珠寶產業發展的脈絡軌跡中作為未來經營規劃參考