Aspisol inhibits tumor growth and induces apoptosis in breast cancer

Nonsteroidal anti-inflammatory drugs inhibit cell proliferation and induce apoptosis in various cancer cell lines, which is considered to be an important mechanism for their anti-tumor activity and cancer prevention. However, the molecular mechanisms through which these compounds induce apoptosis are not well understood. Aim: to determine the effects of nonselective cyclooxygenase-2 (COX-2) inhibitor, aspisol on breast cancer cells in vitro and in vivo. Methods: The cytotoxic activity of aspisol was evaluated by MTT assay. The apoptosis index of cells was measured by flow cytometry. Immunohistochemical staining was used to detect expressions of COX-2 and caspase-3 in MDA-MB-231 cells. The expression of bcl-2 and bax was analyzed by Western blot analysis. The content of prostaglandin E2 (PGE2) in MDA-MB-231 cells was estimated by ELISA. In vivo apoptosis of the tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results: Our results showed that aspisol reduced viability of MDA-MB-231 cells in time- and dose- dependent fashions and induced apoptosis by increase of caspase-3 and bax expressions while decrease of COX-2 and bcl-2 expression in vitro. In addition, exposure to aspisol decreased the basal release of PGE2. In vivo, aspisol also inhibited the proliferation of breast cancer cells and induced their apoptosis. Conclusions: Our in vitro and in vivo data indicated that the antitumor effects of aspisol on breast cancer cells was probably mediated by the induction of apoptosis, and it could be linked to the downregulation of the COX-2 or bcl-2 expression and up-regulation of caspase-3 or bax expression.Нестероидные противовоспалительные препараты ингибируют пролиферацию клеток и вызывают апоптоз во многих опухолевых клеточных линиях, что считается важным механизмом их противоопухолевой активности и профилактики развития рака. Тем не менее молекулярные механизмы апоптотического действия этих препаратов изучены недостаточно. Цель: изучить действие неспецифического ингибитора циклогексиназы-2 (COX-2) — аспизола — на злокачественные клетки рака молочной железы in vitro и in vivo. Методы: выживаемоть клеток MDA-MB-231 определяли с помощью MTT-теста. Апоптотический индекс измеряли с помощью проточной цитометрии и иммуногистохимическим окрашиванием с антителами против COX-2 и каспазы-3. Экспрессию bcl-2 и bax изучали с помощью Вестерн-блот-анализа. Содержание простагландина E2 (PGE2 ) в клетках MDA-MB-231 оценивали методом ELISA. In vivo апоптоз опухолевых клеток определяли путем выявления разрывов ДНК с помощью концевой дезоксинуклеот-идилтранферазы (метод TUNEL). Результаты: показано, что в зависимости от времени инкубации и дозы аспизол угнетал рост клеток MDA-MB-231 in vitro и вызывал их апоптоз на фоне повышения экспрессии каспазы-3 и bax, а также снижения экспрессии COX-2 и bcl-2. В условиях in vivo аспизол также ингибировал пролиферацию злокачественных клеток рака молочной железы и вызывал их апоптоз. Выводы: данные, полученные in vitro и in vivo, свидетельствуют о противоопухолевом эффекте аспизола на клетки рака молочной железы, что скорее всего опосредовано его проапоптотическим действием и может быть связано со снижением экспрессии COX-2 и bcl-2, а также повышением экспрессии каспазы-3 и bax

Numerical Analysis of Crack Propagation Path Using an Advanced Element Cracking Method

The determination of the crack path is important for predicting the unexpected failures or assessing fatigue life in engineering material. To simulate the crack path under mixed mode loading using a finite element model, a new local element cracking technique was proposed. The waiting cracking element was divided into two units along crack propagation direction based on the maximum circumference ( 0) KII criterion. Then, the information of element number and nodal number was also modified and singular elements were avoided by the transfixion method. With advantages of small remeshing only on a local region, this method also examined three classic problems of stationary crack growth, i.e., edge crack propagation in double cantilever beam, mode I cracking in an asphalt concrete beam, a crack in typical longitudinal connection of large natural gas carriers. The calculated stress intensity factors and the predicted crack trajectories using this method agree well with the theoretical solutions existing in literature. Optimal design of structure against failure by fast fracture is discussed.Определение траектории трещины является важным при прогнозировании непредвиденного разрушения или при оценке усталостной долговечности конструкционного материала. Предложен новый метод моделирования траектории локальной трещины при нагружении смешанного типа с помощью модели, основанной на методе конечных элементов. Элемент, моделирующий трещину, разбивают на два вдоль распространения трещины с использованием критерия максимальных касательных напряжений (KII 0). Затем изменяется информация о номерах элемента и узла, поскольку метод трансфикции исключает использование сингулярных элементов. Преимущества незначительного перестроения конечноэлементной сетки только в локальной зоне позволили исследовать с помощью предложенного метода три классические проблемы роста стационарной трещины, т.е. распространение краевой трещины в двухконсольной балке, моделирование трещинообразования в асфальтобетонных балках и трещина в стандартном продольном соединении в газопроводе. Расчетный коэффициент интенсивности напряжений и траектория трещины, спрогнозированная с помощью описанного метода, хорошо соответствуют теоретическим данным, представленным в литературных источниках. Рассмотрена оптимальная конструкция структуры, которой несвойственно быстрое разрушение.Визначення траєкторії тріщини є важливим при прогнозуванні непередбачуваного руйнування або при оцінці довговічності від утомленості конструкційного матеріалу. Запропоновано новий метод моделювання траєкторії локальної тріщини під час навантаження змішаного типу за допомогою моделі, що базується на методі скінченних елементів. Елемент, що моделює тріщину, розбивають на два вздовж поширення тріщини з використанням критерію максимальних дотичних напружень ( ). KII 0 Далі змінюється інформація щодо номерів елемента і вузла, оскільки метод трансфікції виключає використання сингулярних елементів. Переваги незначної перебудови скінченноелементної сітки тільки в локальній зоні дозволили за допомогою запропонованого методу дослідити три класичні проблеми росту стаціонарної тріщини: поширення краєвої тріщини в двоконсольній балці, моделювання тріщиноутворення в асфальтобетонних балках і тріщина в стандартному поздовжньому з’єднанні у газопроводі. Розрахунковий коефіцієнт інтенсивності напружень і траєкторія тріщини, спрогнозована за допомогою описаного методу, добре відповідають теоретичним даним, представленим у літературних джерелах. Розглянуто оптимальну конструкцію структури, якій невластиве швидке руйнування

Analysis of changes in climate and river discharge with focus on seasonal runoff predictability in the Aksu River Basin

The River Aksu is the principal tributary to the River Tarim, providing about three quarters of its discharge. It originates in Kyrgyzstan and flows into the arid areas of the Xinjiang Uyghur Autonomous Region in China, where an extensive irrigated agriculture has been developed in the river oases. The aim of the present contribution is to review the current trends in temperature, precipitation, and river discharge and links between these variables. The temperature in the region and the river discharge have been rising. Changes were studied using multiple trend analyses with different start and end years. Correlations between daily temperature and discharge are high and statistically significant for two headwater subcatchments of the Aksu for most of the time. However, there are episodes in late summer or beginning of autumn when correlations between temperature and discharge for the Xiehela station are absent. This can only be explained by Glacial Lake Outburst Floods from the Lake Merzbacher that are not routinely monitored. On an annual time scale, changes in summer discharge in the highly glacierized Xiehela subcatchment are dominated by changes in temperature. In contrast, in the subcatchment Shaliguilanke, variations in summer streamflow are more strongly influenced by variations in precipitation. A comparison of links between climatic variables and streamflow at different temporal scales is offered. Perspectives for seasonal forecasting are examined

Integrating risks of climate change into water management

[No abstract available

Integrating risks of climate change into water management

The Working Group II contribution to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change critically reviewed and assessed tens of thousands of recent publications to inform about the assess current scientific knowledge on climate change impacts, vulnerability and adaptation. Chapter 3 of the report focuses on freshwater resources, but water issues are also prominent in other sectoral chapters and in the regional chapters of the Working Group II report as well as in various chapters of Working Group I. With this paper, the lead authors, a review editor and the chapter scientist of the freshwater chapter of the WGII AR5 wish to summarize their assessment of the most relevant risks of climate change related to freshwater systems and to show how assessment and reduction of those risks can be integrated into water management

An analysis of the time course of attention in preview search.

We used a probe dot procedure to examine the time course of attention in preview search (Watson and Humphreys, 1997). Participants searched for an outline red vertical bar among other new red horizontal bars and old green vertical bars, superimposed on a blue background grid. Following the reaction time response for search, the participants had to decide whether a probe dot had briefly been presented. Previews appeared for 1,000 msec and were immediately followed by search displays. In Experiment 1, we demonstrated a standard preview benefit relative to a conjunction search baseline. In Experiment 2, search was combined with the probe task. Probes were more difficult to detect when they were presented 1,200 msec, relative to 800 msec, after the preview, but at both intervals detection of probes at the locations of old distractors was harder than detection on new distractors or at neutral locations. Experiment 3A demonstrated that there was no difference in the detection of probes at old, neutral, and new locations when probe detection was the primary task and there was also no difference when all of the shapes appeared simultaneously in conjunction search (Experiment 3B). In a final experiment (Experiment 4), we demonstrated that detection on old items was facilitated (relative to neutral locations and probes at the locations of new distractors) when the probes appeared 200 msec after previews, whereas there was worse detection on old items when the probes followed 800 msec after previews. We discuss the results in terms of visual marking and attention capture processes in visual search

Effect of Initial Disturbance on The Detonation Front Structure of a Narrow Duct

The effect of an initial disturbance on the detonation front structure in a narrow duct is studied by three-dimensional numerical simulation. The numerical method used includes a high resolution fifth-order weighted essentially non-oscillatory scheme for spatial discretization, coupled with a third order total variation diminishing Runge-Kutta time stepping method. Two types of disturbances are used for the initial perturbation. One is a random disturbance which is imposed on the whole area of the detonation front, and the other is a symmetrical disturbance imposed within a band along the diagonal direction on the front. The results show that the two types of disturbances lead to different processes. For the random disturbance, the detonation front evolves into a stable spinning detonation. For the symmetrical diagonal disturbance, the detonation front displays a diagonal pattern at an early stage, but this pattern is unstable. It breaks down after a short while and it finally evolves into a spinning detonation. The spinning detonation structure ultimately formed due to the two types of disturbances is the same. This means that spinning detonation is the most stable mode for the simulated narrow duct. Therefore, in a narrow duct, triggering a spinning detonation can be an effective way to produce a stable detonation as well as to speed up the deflagration to detonation transition process.Comment: 30 pages and 11 figure

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011