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

The Physical Hazards of Police Work Revisited

This study examines the extent to which injuries to police officers have changed from 1996-1998 to 2006-2008. Data were obtained from injury reports filed by sworn officers of the Milwaukee (Wisconsin) Police Department. Results indicated that the frequency and rate (injury incidents per officer) of officer assaults, other suspect-related injuries, and accidents declined during the study period. While the specification of the reasons for these changes remains a topic for future research, the decline in assaults and suspect-related injuries may well be a function of the increased availability and more routine use of less lethal technology, enhanced training, and the more common use of protective equipment

The Role of Officer Attributes, Job Characteristics, and Arrest Activity in Explaining Police Use of Force

While numerous studies have examined the causes, correlates, and control of police use of force, many questions remain. This study contributes to the literature on police use of force by examining the role of officers’ background characteristics, job characteristics (patrol area and shift assignment), and arrest activity in explaining variation in the frequency with which officers use force. Analyses were conducted on 1,084 police officers employed in a large municipal police department. Use of force data were obtained from 477 official departmental reports from 2010. Results suggest that a small proportion of officers are responsible for a large proportion of force incidents, and that officers who frequently use force differ in important and significant ways from officers who use force less often (or not at all). Policy implications and directions for future research are discussed

Investigation of the origin and distribution of heavy metals around Ebenezer Dam, Limpopo Province, South Africa

This study was based on the outcome of the soil geochemical survey which was conducted by the Council for Geoscience around Ebenezer Dam during 1995-1996, the results of which indicated high concentrations of lead (Pb), zinc (Zn) and arsenic (As). The current study therefore focused on the origin and distribution patterns of Pb, Zn, Cu, As and Cr withinthe environs of Ebenezer Dam and their potential impacts on the environment and human health. The work involved soil, sediment, rock and water sampling and analysis. Atomic absorption and x-ray fluorescence spectrometry were used to determine the metal concentrations. The occurrence of anomalous concentrations of these metals in the study area was established. The anomalies registered maximum concentrations of (mg/g): 57 for Pb, 157 for Zn, 313 for Cu, 73 for As and 888 for Cr. The concentrations of these metals in sediments along the streams were high near the anomalies, but decreaseddownstream. Concentrations of heavy metals in water around the Ebenezer Dam were found to be less than 0.01 mg/g ,except for As which was less than 1.0 mg/g. Thus Pb, Zn, Cu and Cr values were below the target water quality ranges for domestic, irrigation, livestock watering and aquatic ecosystem use. The study confirmed that the distribution of heavymetals in this area is localised within and around the source rocks that are felsic in nature, namely; granites and pegmatites that formed domes in the area