Wer hat die Wahl? Robin Markwicas „Emotional Choices. How the Logic of Affect Shapes Coercive Diplomacy“ – Eine Reflexion

Robin Markwicas Monografie erforscht, welche Rolle Emotionen in der Geschichte von (außen-)politischen Prozessen und Beziehungen spielen können. Entsprechend setzen die Autorinnen der Rezension Markwicas Arbeit in Beziehung zur Emotionsgeschichte als Forschungsparadigma. Zudem referieren sie anhand ausgewählter Arbeiten, welchen Erkenntnisgewinn eine Berücksichtigung der Emotionen in der Geschichte der internationalen Beziehungen liefert. Im Anschluss daran evaluieren sie die theoretischen und methodischen Überlegungen des Autors, die Ergebnisse seiner Analyse und seine Vorschläge zur konstruktiven Anwendung dieser Resultate in der internationalen Diplomatie. Die Autorinnen kommen zu dem Schluss, dass Markwicas Ansatz aufgrund seines Fokus auf Emotion als eine weitere Variable in (außen-)politischen Prozessen, sowie wegen der relativen Offenheit, Pluralität und Flexibilität des Analysemodells die Diskussion um Entscheidungsfindungzprozesse nachhaltig inspirieren könne

Playin’ the city : artistic and scientific approaches to playful urban arts

An Theorien und Diskussionen über die Stadt mangelt es nicht, denn Städte dienen uns u.a. als Projektionsfläche zur Auseinandersetzung mit unserer Vergangenheit, der Gegenwart und unserer Zukunft. Diese Ausgabe 1 (2016) der Navigationen untersucht spielerische Formen dieser Auseinandersetzung in und mit der Stadt durch die sogenannten playful urban arts.The city has been discussed and theorized widely, and it continues to serve as a space in which our sense of the present, past, and future is constantly negotiated. This issue 1 (2016) of Navigationen examines new ways of engaging with cities through what are called the playful urban arts. Playful engagements with the urban environment frequently strive to create new ways of imagining and experiencing the city. In and through play, city spaces can become playgrounds that have the potential to transform people’s sense of themselves as human actors in an urban network of spatially bound and socio-economically grounded actions. Emerging from the playin’siegen urban games festival 2015, the essays and panel discussions assembled in this issue provide an interdisciplinary account of the contemporary playful urban arts. Wiht contributions by Miguel Sicart, Andreas Rauscher, Daniel Stein, Judith Ackermann and Martin Reiche, Michael Straeubig and Sebastian Quack, Marianne Halblaub Miranda and Martin Knöll, and Anne Lena Hartman

Relating the shape of protein binding sites to binding affinity profiles: is there an association?

<p>Abstract</p> <p>Background</p> <p>Various pattern-based methods exist that use <it>in vitro </it>or <it>in silico </it>affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values) and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs) were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses.</p> <p>Results</p> <p>PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors.</p> <p>Conclusions</p> <p>This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that, except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.</p

Direct myosin-2 inhibition enhances cerebral perfusion resulting in functional improvement after ischemic stroke

Acute ischemic stroke treatment faces an unresolved obstacle as capillary reperfusion remains insufficient after thrombolysis and thrombectomy causing neuronal damage and poor prognosis. Hypoxia-induced capillary constriction is mediated by actomyosin contraction in precapillary smooth muscle cells (SMCs) therefore smooth muscle myosin-2 could be an ideal target with potentially high impact on reperfusion of capillaries. Methods: The myosin-2 inhibitor para-aminoblebbistatin (AmBleb) was tested on isolated human and rat arterioles to assess the effect of AmBleb on vasodilatation. Transient middle cerebral artery occlusion (MCAO) was performed on 38 male Wistar rats followed by local administration of AmBleb into the ischemic brain area. Development of brain edema and changes in cerebrovascular blood flow were assessed using MRI and SPECT. We also tested the neurological deficit scores and locomotor asymmetry of the animals for 3 weeks after the MCAO operation. Results: Our results demonstrate that AmBleb could achieve full relaxation of isolated cerebral arterioles. In living animals AmBleb recovered cerebral blood flow in 32 out of the 65 affected functional brain areas in MCAO operated rats, whereas only 8 out of the 67 affected areas were recovered in the control animals. Animals treated with AmBleb also showed significantly improved general and focal deficit scores in neurological functional tests and showed significantly ameliorated locomotor asymmetry. Conclusion: Direct inhibition of smooth muscle myosin by AmBleb in pre-capillary SMCs significantly contribute to the improvement of cerebral blood reperfusion and brain functions suggesting that smooth muscle myosin inhibition may have promising potential in stroke therapies as a follow-up treatment of physical or chemical removal of the occluding thrombus.Published versio

National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium

Purpose To establish performance benchmarks for modern screening digital mammography and assess performance trends over time in U.S. community practice. Materials and Methods This HIPAA-compliant, institutional review board-approved study measured the performance of digital screening mammography interpreted by 359 radiologists across 95 facilities in six Breast Cancer Surveillance Consortium (BCSC) registries. The study included 1 682 504 digital screening mammograms performed between 2007 and 2013 in 792 808 women. Performance measures were calculated according to the American College of Radiology Breast Imaging Reporting and Data System, 5th edition, and were compared with published benchmarks by the BCSC, the National Mammography Database, and performance recommendations by expert opinion. Benchmarks were derived from the distribution of performance metrics across radiologists and were presented as 50th (median), 10th, 25th, 75th, and 90th percentiles, with graphic presentations using smoothed curves. Results Mean screening performance measures were as follows: abnormal interpretation rate (AIR), 11.6 (95% confidence interval [CI]: 11.5, 11.6); cancers detected per 1000 screens, or cancer detection rate (CDR), 5.1 (95% CI: 5.0, 5.2); sensitivity, 86.9% (95% CI: 86.3%, 87.6%); specificity, 88.9% (95% CI: 88.8%, 88.9%); false-negative rate per 1000 screens, 0.8 (95% CI: 0.7, 0.8); positive predictive value (PPV) 1, 4.4% (95% CI: 4.3%, 4.5%); PPV2, 25.6% (95% CI: 25.1%, 26.1%); PPV3, 28.6% (95% CI: 28.0%, 29.3%); cancers stage 0 or 1, 76.9%; minimal cancers, 57.7%; and node-negative invasive cancers, 79.4%. Recommended CDRs were achieved by 92.1% of radiologists in community practice, and 97.1% achieved recommended ranges for sensitivity. Only 59.0% of radiologists achieved recommended AIRs, and only 63.0% achieved recommended levels of specificity. Conclusion The majority of radiologists in the BCSC surpass cancer detection recommendations for screening mammography; however, AIRs continue to be higher than the recommended rate for almost half of radiologists interpreting screening mammograms. © RSNA, 2016 Online supplemental material is available for this article

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Gesture and naming therapy for people with severe aphasia: a group study

In this study, the authors (a) investigated whether a group of people with severe aphasia could learn a vocabulary of pantomime gestures through therapy and (b) compared their learning of gestures with their learning of words. The authors also examined whether gesture therapy cued word production and whether naming therapy cued gestures