Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina

Photopharmacology has yielded compounds that have potential to restore impaired visual responses resulting from outer retinal degeneration diseases such as retinitis pigmentosa. Here we evaluate two photoswitchable azobenzene ion channel blockers, DAQ and DAA for vision restoration. DAQ exerts its effect primarily on RGCs, whereas DAA induces light-dependent spiking primarily through amacrine cell activation. Degeneration-induced local field potentials remain a major challenge common to all vision restoration approaches. These 5-10 Hz rhythmic potentials increase the background firing rate of retinal ganglion cells (RGCs) and overlay the stimulated response, thereby reducing signal-to-noise ratio. Along with the bipolar cell-selective photoswitch DAD and second-generation RGC-targeting photoswitch PhENAQ, we investigated the effects of DAA and DAQ on rhythmic local field potentials (LFPs) occurring in the degenerating retina. We found that photoswitches targeting neurons upstream of RGCs, DAA (amacrine cells) and DAD (bipolar cells) suppress the frequency of LFPs, while DAQ and PhENAQ (RGCs) had negligible effects on frequency or spectral power of LFPs. Taken together, these results demonstrate remarkable diversity of cell-type specificity of photoswitchable channel blockers in the retina and suggest that specific compounds may counter rhythmic LFPs to produce superior signal-to-noise characteristics in vision restoration

Timing of Optical Maturation of Recently Exposed Material on Ceres

On Ceres, multispectral imaging data from the Dawn spacecraft show a distinct bluish characteristic for recently exposed material from the subsurface in, for example, crater ejecta. Ejecta blankets of presumably old craters show a more reddish spectrum. We selected areas in which fresh material from the Cerean subsurface was exposed at a specific time in the past, and no later geologic process is expected to have changed its surface composition or its cratering record. For each area, we determined two color ratios and the crater retention age. The measured color ratios show an exponential diminishment of the bluish characteristic over time. Although the cause of the color change remains uncertain, the time-dependent change in spectral properties is evident, which could help identify the process

High-resolution large-scale onshore wind energy assessments : A review of potential definitions, methodologies and future research needs

Funding Information: KG, MK, JS, OT and SW gratefully acknowledge support from the European Research Council (’‘reFUEL’’ ERC-2017-STG 758149). JL has received funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 715132). MJ and IS were funded by the Engineering and Physical Sciences Research Council [ EP/R045518/1 ] through the IDLES programme. JW is funded through an ETH Postdoctoral Fellowship and acknowledges support from the ETH foundation and the Uniscientia foundation. The authors gratefully acknowledge the helpful comments of three anonymous reviewers on an earlier version of this paper.Peer reviewedPublisher PD

Structural basis for type VI secreted peptidoglycan DL-endopeptidase function, specificity and neutralization in <em>Serratia marcescens</em>

Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2a orthologues suggest that the specificity of these immunity proteins for neutralizing effectors is fold-dependent and that in cases where the fold is conserved sequence differences contribute to the specificity of effector–immunity protein interactions

the geomorphology of ceres

### INTRODUCTION Observations of Ceres, the largest object in the asteroid belt, have suggested that the dwarf planet is a geologically differentiated body with a silicate core and an ice-rich mantle. Data acquired by the Dawn spacecraft were used to perform a three-dimensional characterization of the surface to determine if the geomorphology of Ceres is consistent with the models of an icy interior. ### RATIONALE Instruments on Dawn have collected data at a variety of resolutions, including both clear-filter and color images. Digital terrain models have been derived from stereo images. A preliminary 1:10 M scale geologic map of Ceres was constructed using images obtained during the Approach and Survey orbital phases of the mission. We used the map, along with higher-resolution imagery, to assess the geology of Ceres at the global scale, to identify geomorphic and structural features, and to determine the geologic processes that have affected Ceres globally. ### RESULTS Impact craters are the most prevalent geomorphic feature on Ceres, and several of the craters have fractured floors. Geomorphic analysis of the fracture patterns shows that they are similar to lunar Floor-Fractured Craters (FFCs), and an analysis of the depth-to-diameter ratios shows that they are anomalously shallow compared with average Ceres craters. Both of these factors are consistent with FFC floors being uplifted due to an intrusion of cryomagma. Kilometer-scale linear structures cross much of Ceres. Some of these structures are oriented radially to large craters and most likely formed due to impact processes. However, a set of linear structures present only on a topographically high region do not have any obvious relationship to impact craters. Geomorphic analysis suggests that they represent subsurface faults and might have formed due to crustal uplift by cryomagmatic intrusion. Domes identified across the Ceres surface present a wide range of sizes ( 100 km), basal shapes, and profiles. Whether a single formation mechanism is responsible for their formation is still an open question. Cryovolcanic extrusion is one plausible process for the larger domes, although most small mounds (<10-km diameter) are more likely to be impact debris. Differences in lobate flow morphology suggest that multiple emplacement processes have operated on Ceres, where three types of flows have been identified. Type 1 flows are morphologically similar to ice-cored flows on Earth and Mars. Type 2 flows are comparable to long-runout landslides. Type 3 flows morphologically resemble the fluidized ejecta blankets of rampart craters, which are hypothesized to form by impact into ice-rich ground. ### CONCLUSION The global trend of lobate flows suggests that differences in their geomorphology could be explained by variations in ice content and temperature at the near surface. Geomorphic and topographic analyses of the FFCs suggest that cryomagmatism is active on Ceres, whereas the large domes are possibly formed by extrusions of cryolava. Although spectroscopic analysis to date has identified water ice in only one location on Ceres, the identification of these potentially ice-related features suggests that there may be more ice within localized regions of Ceres' crust. ![Figure][1] Dawn high-altitude mapping orbit imagery (140 meters per pixel) of example morphologic features. ( A ) Occator crater; arrows point to floor fractures. ( B ) Linear structures, denoted by arrows. ( C ) A large dome at 42° N, 10° E, visible in the elevation map. ( D ) A small mound at 45.5° S, 295.7° E. ( E ) Type 1 lobate flow; arrows point to the flow front. Analysis of Dawn spacecraft Framing Camera image data allows evaluation of the topography and geomorphology of features on the surface of Ceres. The dwarf planet is dominated by numerous craters, but other features are also common. Linear structures include both those associated with impact craters and those that do not appear to have any correlation to an impact event. Abundant lobate flows are identified, and numerous domical features are found at a range of scales. Features suggestive of near-surface ice, cryomagmatism, and cryovolcanism have been identified. Although spectroscopic analysis has currently detected surface water ice at only one location on Ceres, the identification of these potentially ice-related features suggests that there may be at least some ice in localized regions in the crust. [1]: pending:ye

Affective Reactions Influence Investment Decisions: Evidence from a Laboratory Experiment With Taxation

We investigate the effect of taxation on gains and losses on the investment behavior of investors. Based on the insights of both economic research on the influence of taxation on investment behavior and psychological concepts dealing with the descriptive decision behavior of investors we expect investors to react to taxation of investment alternatives they face with behavioral and affective changes. By conducting a laboratory experiment with a total of 72 participants based on the experimental design of Fochmann, Kiesewetter, and Sadrieh (2012) that allows to quantify the reactions of investors to taxation on gains and loss deduction independent of their individual risk preferences and additionally measuring the affective reactions of our participants, we explore the role of affect in the relation of taxation and decision making. Hence, we are able to show that affective reactions to the taxation situations, in particular the perceived valence of these situations, influence the change in behavior of investors when confronted with taxation on gains and limited loss deduction

Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis

Background Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF

The Dualism of Contemporary Traditional Governance and the State

In many parts of the world, people live in “dual polities”: they are governed by the state and organize collective decision making within their ethnic community according to traditional rules. We examine the substantial body of works on the traditional–state dualism, focusing on the internal organization of traditional polities, their interaction with the state, and the political consequences of the dualism. We find the descriptions of the internal organization of traditional polities scattered and lacking comparative perspective. The literature on the interaction provides a good starting point for theorizing the strategic role of traditional leaders as intermediaries, but large potentials for inference remain underexploited. Studies on the consequences of “dual polities” for democracy, conflict, and development are promising in their explanatory endeavor, but they do not yet allow for robust conclusions. We therefore propose an institutionalist research agenda addressing the need for theory and for systematic data collection and explanatory approaches