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.     

Prevalence of osteoporosis in the Czech Republic

BACKGROUND: The objective of this study was to evaluate the prevalence of osteoporosis and osteopenia in Czech women and men aged 50 to 75 years. METHODS AND RESULTS: Bone mineral density was assessed in an age-stratified random sample of 713 women and 429 men from two cities (Prague and Litom?rice) in the lumbar spine, proximal femur and total body by dual X-ray absorptiometry and in the distal forearm by single X-ray absorptiometry. The proportion of women and men in each age group with bone density below specified levels at any of these skeletal sites was projected to the population structure of the Czech Republic. With advancing age, in women at 55 years and in men at 65 years of age the population with normal bone mineral density becomes smaller, and a greater proportion has osteopenia or osteoporosis. Overall, an estimated 428,000 women and 195,000 men over age 50 have osteoporosis and another 680,000 women and 435,000 men have osteopenia. CONCLUSIONS: The results of this first population-based cross sectional study in the Czech Republic document a high prevalence of osteoporosis and osteopenia which is comparable with that published for the Netherlands and the United States. The results offer a basis for economical considerations in diagnosis, treatment and consequences of osteoporosis.     

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.