Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

No temperature fluctuations in the giant HII region H 1013

While collisionally excited lines in HII regions allow one to easily probe the chemical composition of the interstellar medium in galaxies, the possible presence of important temperature fluctuations casts some doubt on the derived abundances. To provide new insights into this question, we have carried out a detailed study of a giant HII region, H 1013, located in the galaxy M101, for which many observational data exist and which has been claimed to harbour temperature fluctuations at a level of t^2 = 0.03-0.06. We have first complemented the already available optical observational datasets with a mid-infrared spectrum obtained with the Spitzer Space Telescope. Combined with optical data, this spectrum provides unprecedented information on the temperature structure of this giant HII region. A preliminary analysis based on empirical temperature diagnostics suggests that temperature fluctuations should be quite weak. We have then performed a detailed modelling using the pyCloudy package based on the photoionization code Cloudy. We have been able to produce photoionization models constrained by the observed Hb surface brightness distribution and by the known properties of the ionizing stellar population than can account for most of the line ratios within their uncertainties. Since the observational constraints are both strong and numerous, this argues against the presence of significant temperature fluctuations in H 1013. The oxygen abundance of our best model is 12 + log O/H = 8.57, as opposed to the values of 8.73 and 8.93 advocated by Esteban et al. (2009) and Bresolin (2007), respectively, based on the significant temperature fluctuations they derived. However, our model is not able to reproduce the intensities of the oxygen recombination lines . This cannot be attributed to observational uncertainties and requires an explanation other than temperature fluctuations.Comment: accepted in Astronomy & Astrophysic

Green's Relations in Finite Transformation Semigroups

We consider the complexity of Green's relations when the semigroup is given by transformations on a finite set. Green's relations can be defined by reachability in the (right/left/two-sided) Cayley graph. The equivalence classes then correspond to the strongly connected components. It is not difficult to show that, in the worst case, the number of equivalence classes is in the same order of magnitude as the number of elements. Another important parameter is the maximal length of a chain of components. Our main contribution is an exponential lower bound for this parameter. There is a simple construction for an arbitrary set of generators. However, the proof for constant alphabet is rather involved. Our results also apply to automata and their syntactic semigroups.Comment: Full version of a paper submitted to CSR 2017 on 2016-12-1

Uniaxial pressure dependence of magnetic order in MnSi

We report comprehensive small angle neutron scattering (SANS) measurements complemented by ac susceptibility data of the helical order, conical phase and skyrmion lattice phase (SLP) in MnSi under uniaxial pressures. For all crystallographic orientations uniaxial pressure favours the phase for which a spatial modulation of the magnetization is closest to the pressure axis. Uniaxial pressures as low as 1kbar applied perpendicular to the magnetic field axis enhance the skyrmion lattice phase substantially, whereas the skyrmion lattice phase is suppressed for pressure parallel to the field. Taken together we present quantitative microscopic information how strain couples to magnetic order in the chiral magnet MnSi.Comment: 23 pages, includes supplemen

Technological Challenges of Ambient Serious Games in Higher Education

Naturally, university courses should be designed to attract students, engaging them to achieve learning goals. Toward this end, the use of Serious Games has been proposed in the literature. To address positive effects, such as content memorability and attendance rates, we propose Ambient Serious Games as games embedded in a computer-enriched environment, which is only partially perceived mentally by players. In this paper, we describe five technological key challenges that must be overcome to seamlessly and beneficially integrate an Ambient Serious Game into teaching. These challenges, derived from a scenario, focus on the technological provision and conduct of such games based on a software platform. They include (1) the integration of physical smart learning objects in heterogeneous environments under dynamic constraints, (2) the representation of abstract subject matter using smart learning objects, (3) the guided or automatic connection of all involved components, (4) the explanation of the components, their interaction, as well as the serious game itself, and (5) feedback on the game state.Comment: 6 page

Wild zebra finches do not use social information from conspecific reproductive success for nest site choice and clutch size decisions

Information about the quality of local habitat can greatly help to improve an individual’s decision-making and, ultimately, its fitness. Nevertheless, little is known about the mechanisms and significance of information use in reproductive decisions, especially in unpredictable environments. We tested the hypothesis that perceived breeding success of conspecifics serves as a cue for habitat quality and hence influences breeding decisions (nest site choice and clutch size), using the zebra finch (Taeniopygia guttata) as a model species. Zebra finches breed opportunistically in the unpredictable, arid zone of Australia. They often inspect the nests of conspecifics, potentially to prospect on conspecific reproductive success, i.e., to collect social information. We conducted a clutch and brood size manipulation to experimentally create the perception of high and low quality areas. In six areas, clutch sizes of almost 300 zebra finch nests were either all increased (N = 3 areas) or reduced (N = 3 areas) throughout one breeding season. The number of breeding pairs and sizes of newly laid clutches were not significantly affected by the manipulated reproductive success of the areas. Thus, zebra finches did not use social cues for their reproductive decisions, which contrasts with findings of species in temperate zones, and could be an adaptation to the high unpredictability of their habitat. Even the personal experience of rebreeding birds did not directly affect their clutch size. Our study suggests that zebra finches employ a high level of opportunism as a key strategy for reproduction. Further, this is the first study to our knowledge using an experimental approach in the wild to demonstrate that decision-making in unpredictable natural environments might differ from decision-making in temperate environments with seasonal breeding

Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease

Band structure of helimagnons in MnSi resolved by inelastic neutron scattering

A magnetic helix realizes a one-dimensional magnetic crystal with a period given by the pitch length $\lambda_h$. Its spin-wave excitations -- the helimagnons -- experience Bragg scattering off this periodicity leading to gaps in the spectrum that inhibit their propagation along the pitch direction. Using high-resolution inelastic neutron scattering the resulting band structure of helimagnons was resolved by preparing a single crystal of MnSi in a single magnetic-helix domain. At least five helimagnon bands could be identified that cover the crossover from flat bands at low energies with helimagnons basically localized along the pitch direction to dispersing bands at higher energies. In the low-energy limit, we find the helimagnon spectrum to be determined by a universal, parameter-free theory. Taking into account corrections to this low-energy theory, quantitative agreement is obtained in the entire energy range studied with the help of a single fitting parameter.Comment: 5 pages, 3 figures; (v2) slight modifications, published versio

A First Estimate Of The X-Ray Binary Frequency As A Function Of Star Cluster Mass In A Single Galactic System

We use the previously-identified 15 infrared star-cluster counterparts to X-ray point sources in the interacting galaxies NGC 4038/4039 (the Antennae) to study the relationship between total cluster mass and X-ray binary number. This significant population of X-Ray/IR associations allows us to perform, for the first time, a statistical study of X-ray point sources and their environments. We define a quantity, \eta, relating the fraction of X-ray sources per unit mass as a function of cluster mass in the Antennae. We compute cluster mass by fitting spectral evolutionary models to K_s luminosity. Considering that this method depends on cluster age, we use four different age distributions to explore the effects of cluster age on the value of \eta and find it varies by less than a factor of four. We find a mean value of \eta for these different distributions of \eta = 1.7 x 10^-8 M_\sun^-1 with \sigma_\eta = 1.2 x 10^-8 M_\sun^-1. Performing a \chi^2 test, we demonstrate \eta could exhibit a positive slope, but that it depends on the assumed distribution in cluster ages. While the estimated uncertainties in \eta are factors of a few, we believe this is the first estimate made of this quantity to ``order of magnitude'' accuracy. We also compare our findings to theoretical models of open and globular cluster evolution, incorporating the X-ray binary fraction per cluster.Comment: 20 pages, 6 figures, accepted by Ap