Binding characteristics of novel nonsteroidal antiestrogens to the rat uterine estrogen receptors

Tamoxifen (TAM), the only antiestrogen currently available for the endocrine therapy of breast cancer behaves as a mixed agonist/antagonist of estrogen action, thus limiting its therapeutic potential. We report the binding characteristics of a novel series of nonsteroidal antiestrogens to the rat uterine estrogen receptor. As measured by competition studies, the affinity of EM-652, the active metabolite of the prodrug EM-800, for the estrogen receptor is 7-11 times higher than that of 17beta-estradiol (E2), ICI 182780, and hydroxy-tamoxifen (OH-TAM), the active metabolite of Tamoxifen. EM-652 is 20x more potent than ICI 164384 and Droloxifene while it is 400 times more potent than Toremifene in displacing [3H]E2 from the rat uterine estrogen receptor. On the other hand, the prodrug EM-800 and Tamoxifen have respectively 150-fold and 410-fold less affinity for the estrogen receptor than the pure antiestrogen EM-652. No significant binding of EM-652, EM-800, TAM or OH-TAM was observed to the rat uterine progesterone receptor at concentrations up to 10,000 nM except for TAM that caused a 50% displacement of labeled R5020 at 4000 nM. No significant binding of EM-652 or EM-800 was observed on the rat ventral prostate androgen receptor or the rat uterine progesterone receptor. The present data demonstrate the high affinity and specificity of the new antiestrogen, EM-652, for the rat uterine estrogen receptor. The antiestrogen EM-652 thus becomes the compound having the highest known affinity for the estrogen receptor. Due to its unique potency and its pure antiestrogenic activity already demonstrated in many systems, this antiestrogen could well offer an important advance for the endocrine therapy of breast cancer, uterine cancer, and other estrogen-sensitive diseases in women.     

Performance analysis of the forgetting factor RLS algorithm

An analysis is given of the performance of the standard forgetting factor recursive least squares (RLS) algorithm when used for tracking time-varying linear regression models. Three basic results are obtained: (1) the ‘P-matrix’ in the algorithm remains bounded if and only if the (time-varying) covariance matrix of the regressors is uniformly non-singular; (2) if so, the parameter tracking error covariance matrix is of the order O(μ + γ²/μ), where μ = 1 - λ, λ is the forgetting factor and γ is a quantity reflecting the speed of the parameter variations; (3) this covariance matrix can be arbitrarily well approximated (for small enough μ) by an expression that is easy to compute.     

Adaptive control of permanent magnet synchronous machines with disturbance estimation

In this paper,an adaptive control scheme is introduced for permanent magnet synchronous machines (PMSMs)as an alternative to classical control techniques.The adaptive control strategy capitalizes on the machine’s inverse dynamics to achieve accurate tracking by using an observer to approximate disturbance in the form of friction and load torque.The controller’s output is then fed to a space vector pulse width modulation(SVPWM)algorithm to produce duty cycles for the inverter.The control scheme is validated through a set of simulations on an experimentally validated PMSM model.Results for different situations highlight its high speed tracking accuracy and high performance in compensating for friction and load disturbances of various magnitudes.     

EASEA: specification and execution of evolutionary algorithms on GPGPU

EASEA is a framework designed to help non-expert programmers to optimize their problems by evolutionary computation. It allows to generate code targeted for standard CPU architectures, GPGPU-equipped machines as well as distributed memory clusters. In this paper, EASEA is presented by its underlying algorithms and by some example problems. Achievable speedups are also shown onto different NVIDIA GPGPUs cards for different optimization algorithm families.     

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H₂S) is a cardioprotector. Previous research proposed a positive role of H₂S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H₂S, which decreases the expression of adenosine A_2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.     

Oxidation of hafnium carbide and hafnium carbide with additions of tantalum and praseodymium

The oxidation behavior of HfC, HfC-25 wt. % TaC, and HfC-7 wt.% PrC₂ has been studied between 1200–2200° C. Parabolic growth of the oxide layer has been observed for both HfC and HfC-TaC over the entire temperature range. A break in the temperature dependence of the oxidation kinetics occurs around 1600°C. At lower temperatures, the kinetics are limited by gaseous diffusion via pores in the oxide. Above 1800°C, gaseous diffusion through pores becomes less important as scale-growth kinetics are dominated by bulk (ambipolar) diffusion of oxygen and electrons through the oxide.     

An accelerated algorithm for full band electron–phonon scattering rate computation

Computing scattering rates of electrons and phonons stands at the core of studies of electron transport properties. In the high field regime, the interactions between all electron bands with all phonon bands need to be considered. This full band interaction implies a huge computational burden in calculating scattering rates. In this study, a new accelerated algorithm is presented for this task, which speeds up the computation by two orders of magnitude (100 times) and dramatically simplifies the coding. At the same time, it visually demonstrates the physical process of scattering more clearly.     

阳极氧化铝的表面参数对硅酮结构的装锒密封胶长期黏结性的影响(连载一)

硅酮密封胶对阳极氧化铝的黏结质量千差万别.影响黏结性的关键因素是铝材表面的封孔程度、氧化层的着色情况、清洁剂的特性以及基材表面清洁与打胶之间允许的时间间隔.由于清洁剂将有机污染物从阳极氧化铝表面去除的效果不同,所以此效果并不和黏结质量有必然联系.据猜测,吸附在阳极氧化铝表面的清洁溶剂会改善基材表面从而提高硅酮胶的黏结性,但这种改善效果会随着清洁溶剂随时间的的挥发而降低.对于给定的溶剂,最佳的黏结效果取决于材料表面的封孔程度.依照ISO 2143酸刻蚀方法测量材料表面的封孔程度,可以预测未着色的阳极氧化铝基材的黏结性.对于着色的阳极氧化铝表面,依照ISO 2931的测试标准,用电相位漂移方法可以用来预测黏结质量.一种控制阳极氧化铝表面的方法被提了出来,此方法是测量不同频率下基材的电阻抗并将它成功地和硅酮密封胶与该材料表面的长期黏接性联系起来.     

Stability of ruthenium catalysts supported on TiO2 or ZrO2 in catalytic wet air oxidation

The stability of ruthenium catalysts supported on TiO₂ and ZrO₂ were studied in the wet air oxidation of aqueous solution of succinic and p-hydroxybenzoic acids taken as model effluent and on real effluents from the paper-pulp industry. Catalyst recycling experiments were conducted in batch reactor and long-term stability tests were conducted in trickle-bed reactor. In all experiments, ruthenium and support materials were perfectly stable to leaching, sintering and fouling. Ruthenium catalysts experienced a weak deactivation as they were exposed to air, e.g., in recycling experiments however the loss of activity occurred only after the first exposure and was completely reversible upon catalyst reduction. The deactivation was attributed to an over-oxidation of the catalyst surface particularly noticeable in the case of very small Ru-clusters (1 nm).