Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Support Vector machine and duration-aware conditional random field for identification of spatio-temporal activity patterns by combined indoor positioning and heart rate sensors

Tracking the spatio-temporal activity is highly relevant for domains like security, health, and quality management. Since animal welfare became a topic in politics and legislation locomotion patterns of livestock have received increasing interest. In contrast to the monitoring of pedestrians cattle activity tracking poses special challenges to both sensors and data analysis. Interesting states are not directly observable by a single sensor. In addition, sensors must be accepted by cattle and need to be robust enough to cope with a rough environment. In this article, we introduce the novel combination of heart rate and positioning sensors. Attached to neck and chest they are less interfering than accelerometers at the ankles. Exploiting the potential of such combined sensor system that records locomotion and non-spatial information from the heart rate sensor however is challenging. We introduce a novel two level method for the activity tracking focused on the duration and sequence of activity states. We combine Support Vector Machine (SVM) with Conditional Random Field (CRF) and extend Conditional Random fields by an explicit representation of duration. The SVM characterizes local activity states, whereas the CRF addresses sequences of local states to sequences incorporating spatial and non-spatial contextual knowledge. This combination provides a reliable and comprehensive identification of defined activity patterns, as well as their chronology and durations, suitable for the integration in an activity data base. This data base is used to extract physiological parameters and promises insights into internal states such as fitness, well-being and stress. Interestingly we were able to demonstrate a significant correlation between resting pulse rate and the day of pregnancy.     

Connecting the Empire: New Research Perspectives on Infrastructures and the Environment in the (Post)Colonial World

In the academic debate on infrastructures in the Global South, there is a broad consensus that (post)colonial legacies present a major challenge for a transition towards more inclusive, sustainable and adapted modes of providing services. Yet, relatively little is known about the emergence and evolution of infrastructures in former colonies. Until a decade ago, most historical studies followed Daniel Headrick’s (1981) “tools of empire” thesis, painting—with broad brush strokes—a picture of infrastructures as instruments for advancing the colonial project of exploitation and subordination of non-European peoples and environments. This paper explores new research perspectives beyond this straightforward, ‘diffusionist’ perspective on technology transfer. In order to do so, it presents and discusses more recent studies which focus on interactive transfer processes as well as mechanisms of appropriation, and which increasingly combine approaches from imperial history, environmental history, and history of technology.There is much to gain from unpacking the changing motives and ideologies behind technology transfer; tracing the often contested and negotiated flows of ideas, technologies and knowledge within multilayered global networks; investigating the manifold ways in which infrastructures reflected and (re)produced colonial spaces and identities; critically reflecting on the utility of large (socio)technical systems (LTS) for the Global South; and approaching infrastructures in the (post)colonial world through entangled histories of technology and the environment. Following David Arnold’s (2005) plea for a “more interactive, culturally-nuanced, multi-sited debate” on technology in the non-Western world, the paper offers fresh insights for a broader debate about how infrastructures work within specific parameters of time, place and culture.     

An algorithm for generalizing topography to grids while preserving subscale morphologic characteristics—creating a glacier bed DEM for Jakobshavn trough as low-resolution input for dynamic ice-sheet models

The objective of this paper is to derive an algorithm for preserving important subscale morphologic characteristics at grids of lower-resolution, in particular for linear features such as canyons and ridge lines. The development of such an algorithm is necessitated by applications that require reduced spatial resolution, as is common in cartographic generalization, GIS applications, and geophysical modeling. Since any algorithm that results in weighted averages, including optimum interpolation and ordinary kriging, cannot reproduce correct depths, a new algorithm is designed based on principles of mathematical morphology. The algorithm described here is applied to derive a subglacial bed of the Greenland Ice Sheet that includes the trough of Jakobshavn Isbræ as a continuous canyon at correct depth in a low-resolution (5-km) digital elevation model (DEM). Data from recent airborne radar measurements of the elevation of the subglacial bed as part of the CReSIS project are utilized. The morphologic algorithm is designed with geophysical ice-sheet modeling in mind, in the following context. Currently occurring changes in the Earth's climate and the cryosphere cause changes in sea level, and the societal relevance of these natural processes motivates estimation of maximal sea-level rise in the medium-term future. The fast-moving outlet glaciers are more sensitive to climatic change than other parts of the Greenland ice sheet. Jakobshavn Isbrae, the fastest-moving ice stream in Greenland, follows a subglacial geologic trough. Since the existence of the trough causes the acceleration of the slow-moving inland ice in the Jakobshavn region and the formation of the ice stream, correct representation of the trough in a DEM is essential to model changes in the dynamics of the ice sheet and resultant sea-level predictions, even if current ice-sheet models can typically be run only at 5-km resolution. The DEM resultant from this study helps to bridge the conceptual gap between data analysis and geophysical modeling approaches. It is available as SeaRISE Greenland bed data set dev1.2 at http://websrv.cs.umt.edu/isis/index.php/SeaRISE_Assessment.     

The interplay of memory and judgment processes in effects of aging on hindsight bias.

Hindsight bias is the phenomenon that after people are presented with the correct answer to a question, their judgment regarding their own past answer to this question is biased toward the correct answer. In three experiments, younger and older adults gave numerical responses to general-knowledge questions and later attempted to recall their responses. For some questions, the correct answer was provided during recall (Experiment 1) or before recall (Experiments 2 and 3). Multinomial model-based analyses show age differences in both recollection bias and reconstruction bias when the correct judgment was in working memory during the recall phase. The authors discuss implications for theories of cognitive aging and theories of hindsight bias. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral Inhibition and Amplification During Emotional Arousal: A Comparison of Two Age Groups.

This study investigated age differences in the ability to suppress and amplify expressive behavior during emotional arousal. Young and old participants viewed 3 film clips about medical procedures while their behavioral, autonomic, and subjective responses were recorded. Half of the participants viewed all 3 films without additional instructions; the other half was asked to suppress and amplify their behavioral expression during the 2nd and 3rd films. Except for heart rate, suppression and amplification produced similar patterns of autonomic activation. Neither suppression nor amplification had effects on self-reported emotion. There were no age differences in the ability to suppress or amplify emotional expression or in their physiological or subjective consequences. Considering that older people's unregulated reactivity was lower than that of young adults, suppression may have been easier and amplification more difficult for older adults. Voluntary emotion regulation might be one domain of human performance that is spared from age-related losses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)