Public policy in the United States is marked by a contradiction between the American ideal of equality and the reality of an underclass of marginalized and disadvantaged people who are widely viewed ...as undeserving and incapable. Deserving and Entitled provides a close inspection of many different policy arenas, showing how the use of power and the manipulation of images have made it appear both natural and appropriate that some target populations benefit from policy, while others do not. These social constructions of deservedness and entitlement, unless challenged, become amplified over time and institutionalized into permanent lines of social, economic, and political cleavage. The contributors here express concern that too often public policy sends messages harmful to democracy and contributes significantly to the pattern of uneven political participation in the United States.
Jacques Stephen Alexis takes a sorority approach to the place of women in two of his works: L’Espace d’un cillement and L’Étoile Absinthe. Analyzing questions of desire, couple and domination from ...the angle of the woman’s duality and the systemic nature of the relationships that the sister-women maintain with each other as prostitutes at the ‘Sensation Bar’, he puts forward the idea of a spatial and temporal orientation to be found in order to free oneself from prostitution and be fully one’s own, thus demonstrating a great modernity. Returning to the onomastics that separate Églantine from La Niña Estrellita, he analyzes the relationship between El Caucho and La Niña via the recognition scene that places them on the same plane. Therefore, Jacques Stephen Alexis’s work can be labelled ‘avant-garde’, as it raises questions of lesbianism, transsexuality and intersectionality. The novel indeed places sisterhood at the heart of the intrigue and the author choose to put women’s lives at the forefront.
Exon skipping compounds restoring the dystrophin transcript reading frame have received regulatory approval for Duchenne muscular dystrophy (DMD). Recently, focus shifted to developing compounds to ...skip additional exons, improving delivery to skeletal muscle, and to genome editing, to restore the reading frame on DNA level.
We outline developments for reading frame restoring approaches, challenges of mutation specificity, and optimizing delivery. Also, we highlight ongoing efforts to better detect exon skipping therapeutic effects in clinical trials. Searches on relevant terms were performed, focusing on recent publications (<3 years).
Currently, 3 AONS are approved. Whether dystrophin levels are sufficient to slowdown disease progression needs to be confirmed. Enhancing AON uptake by muscles is currently under investigation. Gene editing is an alternative, but one that involves practical and ethical concerns. Given the field's momentum, we believe the efficiency of frame-restoring approaches will improve.
Progressive familial intrahepatic cholestasis type 3 is caused by biallelic variations of ABCB4, most often (≥70%) missense. In this study, we examined the effects of 12 missense variations ...identified in progressive familial intrahepatic cholestasis type 3 patients. We classified these variations on the basis of the defects thus identified and explored potential rescue of trafficking‐defective mutants by pharmacological means. Variations were reproduced in the ABCB4 complementary DNA and the mutants, thus obtained, expressed in HepG2 and HEK293 cells. Three mutants were either fully (I541F and L556R) or largely (Q855L) retained in the endoplasmic reticulum, in an immature form. Rescue of the defect, i.e., increase in the mature form at the bile canaliculi, was obtained by cell treatments with cyclosporin A or C and, to a lesser extent, B, D, or H. Five mutations with little or no effect on ABCB4 expression at the bile canaliculi caused a decrease (F357L, T775M, and G954S) or almost absence (S346I and P726L) of phosphatidylcholine secretion. Two mutants (T424A and N510S) were normally processed and expressed at the bile canaliculi, but their stability was reduced. We found no defect of the T175A mutant or of R652G, previously described as a polymorphism. In patients, the most severe phenotypes appreciated by the duration of transplant‐free survival were caused by ABCB4 variants that were markedly retained in the endoplasmic reticulum and expressed in a homozygous status. Conclusion: ABCB4 variations can be classified as follows: nonsense variations (I) and, on the basis of current findings, missense variations that primarily affect the maturation (II), activity (III), or stability (IV) of the protein or have no detectable effect (V); this classification provides a strong basis for the development of genotype‐based therapies. (Hepatology 2016;63:1620‐1631)
ABCB4 (MDR3) is an adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. ...Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding. Five disease‐causing variations in these motifs have been identified in ABCB4 (G535D, G536R, S1076C, S1176L, and G1178S), three of which are homologous to the gating mutations of cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7; i.e., G551D, S1251N, and G1349D), that were previously shown to be function defective and corrected by ivacaftor (VX‐770; Kalydeco), a clinically approved CFTR potentiator. Three‐dimensional structural modeling predicted that all five ABCB4 variants would disrupt critical interactions in the binding of ATP and thereby impair ATP‐induced nucleotide‐binding domain dimerization and ABCB4 function. This prediction was confirmed by expression in cell models, which showed that the ABCB4 mutants were normally processed and targeted to the plasma membrane, whereas their PC secretion activity was dramatically decreased. As also hypothesized on the basis of molecular modeling, PC secretion activity of the mutants was rescued by the CFTR potentiator, ivacaftor (VX‐770). Conclusion: Disease‐causing variations in the ATP‐binding sites of ABCB4 cause defects in PC secretion, which can be rescued by ivacaftor. These results provide the first experimental evidence that ivacaftor is a potential therapy for selected patients who harbor mutations in the ATP‐binding sites of ABCB4. (Hepatology 2017;65:560‐570)
•We evaluated the role of two garden types for habitat connectivity for hedgehogs.•Private gardens contribute most, but allotment gardens occupy key locations.•Gardens should play a bigger role in ...green infrastructure plans.•Circuit-theory based modeling is a valuable tool for green infrastructure planning.
Preserving and expanding green infrastructure (GI) is key to biodiversity conservation in cities, but a significant share of urban land is commonly underutilized in GI plans: gardens. This is despite the fact that gardens can support diverse wildlife communities by providing habitat and by functioning as corridors. In this article, we apply circuit theory-based modeling in order to quantify the contribution of two types of gardens to connectivity in the city of Braunschweig, Germany: private gardens and allotment gardens. We ran four permeability scenarios: 1.) all green spaces including private and allotment gardens are permeable; 2.) private gardens are non-permeable; 3.) allotment gardens are non-permeable; 4.) only public green spaces but no gardens are permeable. We based our modeling on the European hedgehog (Erinaceuseuropaeus), a common, relatively well-understood and well-liked urban species. Observations by citizen scientists were used for a plausibility analysis and interpreting the results. Our results confirm the importance of gardens for providing habitat and connectivity. The overall landscape permeability to the movement of hedgehogs would decrease by 75% and the area of core habitats would decline by 63% without private and allotment gardens. While private gardens contribute most to landscape connectivity, some allotment gardens occupy key areas for the overall connectivity in the city. In conclusion, circuit theory-based modeling is a promising tool for urban GI planning and the output of those models can inform decision makers and gardeners.
•Spatial distribution of cold-air paths was estimated using machine learning.•Models were estimated for three German cities with different topography and land use.•Most important predictors for ...cold-air paths distribution were analyzed.•Model transferability from a training city to the other study cities was tested.
Ensuring the transport of colder air masses from rural surroundings or inner urban open spaces into the dense urban center is a vital approach for reducing nocturnal warming of urban areas in summer, i.e. the urban heat island (UHI) effect. Hence, cold-air paths are an important mitigation aspect in urban planning. The identification of cold-air paths by field measurements, however, is time-consuming and it is difficult to cover larger spatial domains (e.g. entire cities). Therefore, we used a machine learning technique, boosted regression trees (BRT), for estimating the spatial distribution of cold-air paths in three German cities (Braunschweig, Freiburg, Stuttgart). We identified the most important predictor variables for cold-air path occurrence and tested the spatial transferability of BRT models from one training city to the other study cities.
Three variables explaining differences in surface elevation indicated strongest influence on spatial distribution of cold-air paths: relative surface elevation, topographic position index, and topographic wind index. We achieved predictions for the spatial distribution of cold-air paths for cities the model was trained on, resulting in model performances of 0.85 < AUC < 0.96 (AUC: area under the receiver operating characteristic curve). Model transfers to other cities, however, achieved only poor to moderate results (0.5 < AUC < 0.8). The city of Freiburg tended to be the most suitable basis for a general model, since it covers the largest range of conditions. Transfer works best for ‘similar’ cities, i.e. cities with a comparable range of predictor variables and morphological structure. Cold-air path identification via BRT modelling appeared to be a promising method delivering helpful information for urban planning.
Elected leaders adopt “anticipatory feedback strategies” in designing public policies that generate support and forestall opposition. This contention is at the core of a social construction theory of ...feedback. Officials anticipate approval when policies allocate benefits to powerful groups socially constructed as deserving and allocate costs or punishment to groups viewed as undeserving, particularly if these groups lack political power. Designs for powerful groups that are widely viewed as unworthy provide mainly benefits in ways that are hidden from the general public who would not approve. For politically weak groups regarded as deserving, legislators generally design policies that provide promises, but not much in terms of material benefits. Often, deception will be used to protect or enhance this particular allocation pattern, including the reinforcement, perpetuation, or change in the social constructions along with the stereotypes, labels, stigma, and accompanying narratives. Using data from legislation introduced by the 2016 Arizona Legislature, we find that most policy is directed toward providing benefits to positively viewed target populations, as expected by the theory, and legislators employ deceptive feedback strategies that protect themselves. Feedback from the general public, which otherwise might be expected, may be precluded by the deceptive strategies being used.
当选领导人在制定公共政策时采用“预期反馈策略”以获得支持力量，而防范反对势力。该论点是反馈效应社会建构理论的核心。官员们预计会批准符合如下叙述的政策：将利益分配给社会建构意义上需要被帮持的势力群体，而将成本或处罚分配给那些被视为不值得帮助的群体，特别是当这些群体缺乏政治权力时。对于被广泛认为不值得的势力群体，为它们提供利益的政策会被设计为以一种隐藏的方式来进行，以瞒过那些不会批准它们的更广泛的公众。对于被视为应得的政治弱势群体，立法者通常会制定一些提供承诺的政策，而这种政策在实质利益方面所提供的却不多。欺骗策略常常与模板、标签、污名和伴随叙事一起被用于保护或者增强某种特定的分配模式，包括社会结构的强化、延续或改变。根据2016年亚利桑那州立法机构推行的立法的数据，我们发现，正如理论所预期的那样，大多数政策旨在为那些被明确视为目标人群的群体提供福利，但与此同时，我们也发现，立法者会采用欺骗性的反馈策略来保护这些政策。预期之中本应出现的来自普通公众的反馈，可能会被立法者以欺骗性的策略排除在外。
What's on the horizon for macroecology? Beck, Jan; Ballesteros-Mejia, Liliana; Buchmann, Carsten M. ...
Ecography (Copenhagen),
August 2012, Volume:
35, Issue:
8
Journal Article
Peer reviewed
Open access
Over the last two decades, macroecology — the analysis of large-scale, multi-species ecological patterns and processes — has established itself as a major line of biological research. Analyses of ...statistical links between environmental variables and biotic responses have long and successfully been employed as a main approach, but new developments are due to be utilized. Scanning the horizon of macroecology, we identified four challenges that will probably play a major role in the future. We support our claims by examples and bibliographic analyses. 1) Integrating the past into macroecological analyses, e.g. by using paleontological or phylogenetic information or by applying methods from historical biogeography, will sharpen our understanding of the underlying reasons for contemporary patterns. 2) Explicit consideration of the local processes that lead to the observed larger-scale patterns is necessary to understand the fine-grain variability found in nature, and will enable better prediction of future patterns (e.g. under environmental change conditions). 3) Macroecology is dependent on large-scale, high quality data from a broad spectrum of taxa and regions. More available data sources need to be tapped and new, small-grain large-extent data need to be collected. 4) Although macroecology already lead to mainstreaming cutting-edge statistical analysis techniques, we find that more sophisticated methods are needed to account for the biases inherent to sampling at large scale. Bayesian methods may be particularly suitable to address these challenges. To continue the vigorous development of the macroecological research agenda, it is time to address these challenges and to avoid becoming too complacent with current achievements.
L’Algérie est un pays dont l’imaginaire multiple irrigue les souvenirs des immigrés qui l’ont quitté, souvent avec beaucoup de déchirement. Dans les albums contemporains qui évoquent l’Algérie ...(corpus de 2001 à 2010), douze albums ont été retenus pour leurs caractéristiques graphiques et esthétiques qui mettent en valeur la question des enjeux dans la transmission mémorielle. Le genre de l’album permet de créer un discours riche, complexe et dense sur l'immigration algérienne en France. Ces albums sont centrés sur le parcours migratoire d'enfants, tiraillés entre pays d'origine et d’accueil. Ils renouvellent la littérature de jeunesse migrante grâce aux images culturelles véhiculées, au sens anthropologique et humaniste, images archétypales, stéréotypées ou tout simplement historiques. Cette culture de l’image reconfigure les imaginaires en les mixant. La question du voyage et de l’exil traumatique sera étudiée à travers un motif majeur, celui du bateau qui part, symbole du tragique du trop tard, puis l’omniprésence de l’écriture de l’histoire centrée sur la colonisation et la guerre d'indépendance en Algérie sera évoquée, et enfin, l’analyse de l’iconographie fondée sur la carte postale et la photographie montrera les tentatives de mise à distance de l'exotisme.
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