高脂饮食引起的血中氧化低密度脂蛋白(oxidized low-density lipoprotein,Ox-LDL)升高是动脉粥样硬化（atherosclerosis，AS）的重要危险因素，其所致的内皮细胞功能障碍是AS早期病理变化的关键环节。孤儿核受体NR4A2（nuclear receptor subfamily 4 group Amember 2, NR4A2）和NF-κB是调节AS相关基因表达的重要转录因子，但两者对Ox-LDL致内皮细胞功能障碍的分子机理尚不明确。本项目采用细胞培养和动物模型研究NR4A2和NF-κB的交互作用对ICAM-1、VCAM-1、MCP-1、IL-1、IL-6、IL-8、eNOS的转录和翻译的影响，从而进一步阐明AS过程中Ox-LDL致内皮细胞功能障碍的分子机理。本研究将为进一步阐明动脉粥样硬化的机制和制订防治新策略提供科学依据。

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC), the most prevalent malignant liver cancer, has seen an increasing incidence rate over the last decade. Segmental liver resection and liver transplantation are curative options shown to be effective when the patient meets certain criteria, which rely on a sensitive and early detection and characterization of HCC lesions with imaging. Because the liver may be too diseased to tolerate a large resection or due to insufficient numbers of donor livers, these treatments are not available for a major part of the patient population. For these patients, other treatment options are considered including systemic chemotherapy. While treatment response is conventionally measured based on tumor size change, this may take several months to occur. A sensitive and early measurement of treatment response is therefore expected to significantly impact treatment as well. It is in this context that quantitative MR imaging plays an increasing role. High temporal and spatial resolution dynamic imaging has been introduced into contrast-enhanced liver MRI to overcome bolus-timing problems and to capture the desired enhancement phases traditionally used for diagnosis. However, current methods are still limited to breath-holds or very moderate amounts of respiratory motion. Additionally, the reader is presented with a large number of images, from which a manual selection of the typical arterial, portal-venous and delayed phases is necessary. Our long-term goal is to develop MRI into a robust method for the diagnosis of liver disease. As part of this goal, it is the objective of this application is to transform dynami liver contrast enhanced MRI into a quantitative measure of liver cancer presence and progression. Our central hypothesis is that a quantitative kinetic parametric map (KPM) of hepatic arterial blood flow and bolus arrival time estimated directly from the raw MRI data will have a better diagnostic performance for detecting HCC than conventional multiple phase MRI. The rationale for the proposed research is that the resulting KPMs enable a compact representation of the contrast enhancement behavior that is reproducible and lends itself to intra- and inter-patient comparisons. We plan to test our hypothesis by pursuing the following aims: (1) develop an imaging method that maps the acquired MR data directly onto quantitative kinetic parametric maps, and (2) evaluate the diagnostic performance of the developed quantitative method in patients undergoing liver transplantation. The expected outcome of this research of this research is a better method for characterizing liver tumors during initial detection and follow-up. Such a technique is likely to have a positive impact, since it is expected to allow a quantitative measure of cancer burden, allow an early measurement of treatment success or failure and reduce the need for liver biopsy.

BSTRACT Breast cancer is the second leading cause of cancer-deaths in women in the United States and early detection can help improve survival. While mammography is the current first-line imaging technique for early breast cancer detection, its diagnostic accuracy is limited in women with dense breast tissue. Ultrasound is often performed as a second line test in women with dense breast tissue. However, due to its low specificity, it results in many false positive findings with unnecessary biopsies with increased associated health care costs. Dr. Willmann and his group at Stanford have recently identified and validated B7-H3 as a novel, highly specific neoangiogenesis marker in patients with breast cancer that allows differentiation of breast cancer from benign breast lesions with an AUC of up to 0.96. In a preliminary study, they tested an ultrasound contrast agent bearing antibodies to B7-H3 and showed in a transgenic mouse model that contrast-enhanced ultrasound could detect small foci of breast cancer. They have identified a peptide that binds to both murine and human B7-H3. Dr. Unger and his group at NuvOx Pharma developed the world?s #1 selling microbubble (MB) ultrasound contrast agent and have industry-leading expertise in targeting MB technologies. The overall goal of this grant proposal is to develop a novel clinical grade B7-H3-targeted ultrasound contrast agent that allows detection and characterization of breast cancer with both high sensitivity and specificity. In this collaborative effort we will create bioconjugates of the already identified peptide to B7-H3, incorporate them into newly designed clinical grade ultrasound contrast microbubbles (MB), confirm their binding to B7-H3 in vitro under flow shear stress conditions, and then confirm efficacy in a transgenic mouse model of breast cancer development. We will label the molecularly targeted MB with a fluorescent dye to allow in situ confirmation of in vivo B7-H3 target binding using microscopy. Successful completion of the Aims of this project may subsequently support formal development of B7-H3-targeted MB as a new drug candidate in Phase II.

Проект направлен на решение фундаментальной проблемы,связанной с устойчивостью и гомеостазом генома,а также приобретением им новых структурных элементов и свойств,и посвящен изучению молекулярных механизмов регуляции транспозиции ретротранспозонов-эндогенных ретровирусов беспозвоночных(эррантивирусов).На модельном объекте-Drosophila melanogaster-исследуется влияние ретроэлементов на функционирование и эволюцию хозяйского генома,саморегуляция активности ретроэлементов и регуляция за счет хозяйских генов,а также исследуется вопрос о роли доместицированных генов ретроэлементов в хозяйском геноме.

Цели данного проекта непосредственно связаны с решением фундаментальных задач современной лексикографии с использованием методов искусственного интеллекта и с активным применением компьютерных технологий.Эти методы и технологии позволят：(1)на основе моделей искусственного интеллекта для эффективного хранения и представления данных обеспечить быстрый доступ к огромным объёмам материала-как собственно языкового,так и уже готового-лексикографического;(2)на основе алгоритмов искусственного интеллекта обеспечить автоматическое структурирование полученного материала,с учётом приоритетности заданных разделов;(3)с помощью поисковых интеллектуальных алгоритмов упростить доступ к лингвистической и иллюстративной частям того или иного словаря,к их разделам,которые в полном виде как правило не доступны обычному пользователю.Одной из важнейших задач проекта является преобразование множества текстов словарных статей онлайн-словаря в чёткую взаимосвязанную структуру,которая будет храниться в реляционной базе данных машинно-читаемого словаря.На данный момент построены машинно-читаемые словари на основе русского и английского онлайн-словарей,из которых извлекается только часть словарных статей(толкование,парадигматические отношения,переводы).Для решения задачи необходимо：1.Выполнить анализ существующих научных работ и составить список задач(определить какой тип информации должен быть извлечён из интернет словарей в первую очередь,например цитаты к значениям слов,пометы к толкованиям и т.д.).2.Расширить структуру базы данных машинно-читаемого словаря таблицами для хранения данных,извлечённых из интернет словарей,связать эти новые таблицы с уже существующими таблицами.3.Разработать математическую модель и список правил для извлечения данных из Русского Викисловаря и сохранения в машинно-читаемый словарь.4.На основе полученной структуры данных разработать интеллектуальный поисковый механизм для машинно-читаемого словаря.Реализовать визуальный интерфейс для удобной работы лексикографа.5.В ходе совместной работы лингвистов и специалистов по интеллектуальным системам выявить ошибки и доработать функциональность и визуальный интерфейс программы,в случае необходимости внести изменения в структуру данных машинно-читаемого словаря.Созданный машинно-читаемый словарь можно будет использовать как самостоятельно,так и в составе какой-либо большой компьютерной системы,связанной с обработкой текста,например,в виде словаря в корпусе текстов или словаря в системе машинного перевода и т.д.

The color barrier-free conversion is studied and it is the conversion to arrange colors in an image for color vision deficiencies.The color-to-gray conversion can be considered as an elemental technology of the color barrier-free conversion.New color-to-gray conversions and a color barrier-free conversion are proposed in this study.In the color barrier-free conversion,visibility improvement and naturalness preservation should be considered.Although the proposed color barrier-free method has restriction on object images,it simultaneously achieves visibility improvement and naturalness preservation.

Development and measurement for dense plasma and Warm Dense Matter state generation and measurement system using an intense pulsed power generator, development and analysis of a calculation code were performed. The emission spectrum measurement from the generated sample was realized by designing and constructing the transfer optical system. It is difficult to perform synchronized measurement under strong noise environment like this experimental system, and research and development of the measurement system was also conducted. In order to adjust the energy input into the sample, we equipped an input energy control system using an electron beam diode, and confirmed that the sample reached the target temperature or higher. The calculation code development based on the heat conduction equation and the numerical analysis according to the experimental conditions were conducted, and the cautions etc. were clarified for the experimental conditions.