Effects of SERM (selective estrogen receptor modulator) treatment on growth and proliferation in the rat uterus

BACKGROUND: Selective estrogen receptor modulators (SERMs) have been developed in order to create means to control estrogenic effects on different tissues. A major drawback in treatment of estrogen receptor (ER) positive breast cancer with the antagonist tamoxifen (TAM) is its agonistic effect in the endometrium. Raloxifene (RAL) is the next generation of SERMs where the agonistic effect on the endometrium has been reduced. METHODS: The aim of the present study was to determine the effect of SERM treatment on the uterus, as assessed by proliferation markers and several factors involved in uterine growth. Ovariectomized (ovx) rats were treated with estradiol (E(2)), tamoxifen (TAM), RAL, ICI182780 (ICI) or vehicle (OVX-controls). We studied the effects on mRNA levels of the growth hormone (GH) receptor, insulin-like growth factor-I (IGF-I), ERα and ERβ. In addition, by immunohistochemistry the proliferation markers PCNA and Ki-67, as well as ERα and ERβ, were detected. RESULTS: The uterine weight of the rats treated with E(2 )or TAM was increased as compared to OVX-controls. The uterine GH-receptor mRNA level was highest in the E(2 )treated animals. In ICI treated rats no GH-receptor mRNA could be detected. The IGF-I mRNA level increased 16-fold in uteri of the TAM treated group and 9-fold in the E(2 )treated rats as compared to OVX-controls. The ERα mRNA level was increased in the E(2 )treated rats, while the ERβ mRNA level was increased after TAM treatment. The proliferation, as assessed by PCNA, was lowest in ICI treated animals. CONCLUSIONS: The uterine wet weight, the LE height and the GH-receptor mRNA levels showed similar patterns, indicating that GH is involved in the regulation of uterine weight. Tamoxifen, which has been related to increased incidence of endometrial carcinoma in women, dramatically increased IGF-I mRNA levels in rat uterus. Since proliferation was not higher in TAM and E(2 )treated rats than in OVX controls, this assay of simple, early proliferation does not give the full explanation of why TAM should enhance the risk of developing endometrial cancer

Stark Effect Control of the Scattering Properties of Plasmonic Nanogaps Containing an Organic Semiconductor

The development of actively tunable plas-monic nanostructures enables real-time reconfigurable and on demand enhancement of optical signals. This is an essential requirement for a wide range of applications such as sensing and nanophotonic devices, for which electrically driven tunability is required. By modifying the transition energies of a material via the application of an electric field, the Stark effect offers a reliable and practical approach to achieve such tunability. In this work, we report on the use of the Stark effect to control the scattering response of a plasmonic nanogap formed between a silver nanoparticle and an extended silver film separated by a thin layer of the organic semiconductor PQT-12. The plasmonic response of such nano-scattering sources follows the quadratic stark shift. Additionally, our approach allows to experimentally determine the polarizability of the semiconductor material embedded in the nanogap region, offering a new approach to probe the excitonic properties of extremely thin semi-conducting materials such as 2D materials under applied external electric field with nanoscale resolution

Econometric Models for Forecasting Innovative Development of the Country

The purpose of this study is to develop models to predict the level of innovative development of countries, as well as to identify the most significant factors influencing innovative development.The scientific novelty consists in applying a systematic, integrated approach to the selection of statistically significant factors that are drivers of innovative development, with the subsequent construction of econometric models and their testing. When developing models, both resources (“input parametersâ€) and results (“output parametersâ€) were taken into account, which also allows evaluating the effectiveness of innovative development and developing scenario forecasts taking into account the existing possibilities and limitations, optimizing innovative development strategies.The main methods of research and approaches were used: statistical summary and grouping of information, trend analysis, regression and correlation analysis, testing of statistical hypotheses, factor analysis. The procedure for detecting multicollinearity was performed using the VIF test (Variance Inflation Factor, incremental regression method). In determining the set of explanatory variables (the choice of "short" or "long" regression), the following criteria were used: Akaike criterion and Bayesian Schwarz information criterion. To estimate the parameters of econometric models, the Least Squares Method was used with a preliminary check of the fulfillment of all conditions of the Gauss-Markov theorem. In addition, various tests for checking the constructed models and their parameters for significance, adequacy were applied: Durbin-Watson test, Sved-Eisenhart series method and Breush-Godfrey test, Helvig agreement test, Shapiro-Wilk test, Goldfeld-Quandt test and Spearman's rank correlation test. To determine the influence of explanatory factors on the explained factor, the average elasticity coefficients were calculated on the basis of linear regression as the best model based on the results of all tests.Data and Empirical Analysis: The main components included in the calculation of the Global Innovation Index (GII) were selected for the study. Statistical data on them are published annually, which allows us to estimate the country's place in international innovation development. The study identified four multiple econometric models: one linear and three non-linear. The value of the Global Innovation Index was chosen as an explained factor, and the indicators for the main groups in accordance with the GII structure were chosen as explanatory factors.To achieve this goal, the following work was carried out, as reflected in this article: 1) an econometric analysis was performed based on a sample of 30 countries based on the 2018 Global Innovation Index report; 2) multiple regression models were built - linear, polynomial, hyperbolic and power; 3) with the use of special tests, a check for heteroscedasticity and autocorrelation of random residues was implemented; 4) the parameters and the obtained regressions were estimated for statistical significance and adequacy.According to the results of the study, the model that best approximates the initial data was chosen. Using this regression, one can form scenario forecasts of the country's innovative development, for example, by predicting the values of individual factors using various modern methods of macroeconomic planning and forecasting. The principle is the expediency of the most optimal combination of resources for innovative development in order to ensure the maximum effect on the "output"

Plasmon-enhanced fluorescence in gold nanorod-quantum dot coupled systems

Plasmon-exciton coupling is of great importance to many optical devices and applications. One of the coupling manifestations is plasmon-enhanced fluorescence. Although this effect is demonstrated in numerous experimental and theoretical works, there are different particle shapes for which this effect is not fully investigated. In this work electrostatic complexes of gold nanorods and CdSe/CdZnS quantum dots were studied. Double-resonant gold nanorods have an advantage of the simultaneous enhancement of the absorption and emission when the plasmon bands match the excitation and fluorescence wavelengths of an emitter. A relationship between the concentration of quantum dots in the complexes and the enhancement factor was established. It was demonstrated that the enhancement factor is inversely proportional to the concentration of quantum dots. The maximal fluorescence enhancement by 10.8 times was observed in the complex with the smallest relative concentration of 2.5 quantum dots per rod and approximately 5 nm distance between them. Moreover, the influence of quantum dot location on the gold nanorod surface plays an important role. Theoretical study and experimental data indicate that only the position near the nanorod ends provides the enhancement. At the same time, the localization of quantum dots on the sides of the nanorods leads to the fluorescence quenching

Magnetic Mode Coupling in Hyperbolic Bowtie Meta-Antennas

Hyperbolic metaparticles have emerged as the next step in metamaterial applications, providing tunable electromagnetic properties on demand. However, coupling of optical modes in hyperbolic meta-antennas has not been explored. Here, we present in detail the magnetic and electric dipolar modes supported by a hyperbolic bowtie meta-antenna and clearly demonstrate the existence of two magnetic coupling regimes in such hyperbolic systems. The coupling nature is shown to depend on the interplay of the magnetic dipole moments, controlled by the meta-antenna effective permittivity and nanogap size. In parallel, the meta-antenna effective permittivity offers fine control over the electrical field spatial distribution. Our work highlights new coupling mechanisms between hyperbolic systems that have not been reported before, with a detailed study of the magnetic coupling nature, as a function of the structural parameters of the hyperbolic meta-antenna, which opens the route toward a range of applications from magnetic nanolight sources to chiral quantum optics and quantum interfaces

Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study

Acute respiratory failure (ARF) is responsible for about one-third of intensive care unit (ICU) admissions and is associated with adverse outcomes. Predictors of short- and long-term outcomes in unselected ICU-patients with ARF are ill-defined. The purpose of this analysis was to determine predictors of in-hospital and one-year mortality and assess the effects of oral beta-blockers in unselected ICU patients with ARF included in the BASEL-II-ICU study. The BASEL II-ICU study was a prospective, multicenter, randomized, single-blinded, controlled trial of 314 (mean age 70 (62 to 79) years) ICU patients with ARF evaluating impact of a B-type natriuretic peptide- (BNP) guided management strategy on short-term outcomes. In-hospital mortality was 16% (51 patients) and one-year mortality 41% (128 patients). Multivariate analysis assessed that oral beta-blockers at admission were associated with a lower risk of both in-hospital (HR 0.33 (0.14 to 0.74) P = 0.007) and one-year mortality (HR 0.29 (0.16 to 0.51) P = 0.0003). Kaplan-Meier analysis confirmed the lower mortality in ARF patients when admitted with oral beta-blocker and further shows that the beneficial effect of oral beta-blockers at admission holds true in the two subgroups of patients with ARF related to cardiac or non-cardiac causes. Kaplan-Meier analysis also shows that administration of oral beta-blockers before hospital discharge gives striking additional beneficial effects on one-year mortality. Established beta-blocker therapy appears to be associated with a reduced mortality in ICU patients with acute respiratory failure. Cessation of established therapy appears to be hazardous. Initiation of therapy prior to discharge appears to confer benefit. This finding was seen regardless of the cardiac or non-cardiac etiology of respiratory failure. ClinicalTrials.gov Identifier: NCT00130559

Using adsorption kinetics to assemble vertically aligned nanorods at liquid interfaces for metamaterial applications

Vertically aligned monolayers of metallic nanorods have a wide range of applications as metamaterials or in surface enhanced Raman spectroscopy. However the fabrication of such structures using current top-down methods or through assembly on solid substrates is either difficult to scale up or have limited possibilities for further modification after assembly. The aim of this paper is to use the adsorption kinetics of cylindrical nanorods at a liquid interface as a novel route for assembling vertically aligned nanorod arrays that overcomes these problems. Specifically, we model the adsorption kinetics of the particle using Langevin dynamics coupled to a finite element model, accurately capturing the deformation of the liquid meniscus and particle friction coefficients during adsorption. We find that the final orientation of the cylindrical nanorod is determined by their initial attack angle when they contact the liquid interface, and that the range of attack angles leading to the end-on state is maximised when nanorods approach the liquid interface from the bulk phase that is more energetically favorable. In the absence of an external field, only a fraction of adsorbing nanorods end up in the end-on state (<=40% even for nanorods approaching from the energetically favourable phase). However, by pre-aligning the metallic nanorods with experimentally achievable electric fields, this fraction can be effectively increased to 100%. Using nanophotonic calculations, we also demonstrate that the resultant vertically aligned structures can be used as epsilon-near-zero and hyperbolic metamaterials. Our kinetic assembly method is applicable to nanorods with a range of diameters, aspect ratios and materials and therefore represents a versatile, low-cost and powerful platform for fabricating vertically aligned nanorods for metamaterial applications