The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers.

We show here that the element which was previously characterized as a retinoid X receptor (RXR)-specific response element (RXRE) in the rat cellular retinol-binding protein II (CRBPII) gene is not conserved in the mouse gene. However, two conserved cis-acting elements (RE2 and RE3) located in the promoter region of the mouse and rat CRBPII genes mediate transactivation by retinoic acid receptors (RARs) and RXRs in transfected Cos-1, CV-1, and HeLa cells. The element RE3 which is the major retinoic acid (RA) response element also binds the transcription factors HNF-4 and ARP-1. HNF-4 constitutively activates the mouse CRBPII promoter, whereas ARP-1 represses the activation mediated by RARs, RXRs, and HNF-4. In contrast, RA has no effect on the activity of the mouse CRBPII promoter in the human colon carcinoma cell line CaCo-2 which constitutively expresses RAR alpha, RAR gamma, RXR alpha, HNF-4, and ARP-1, under conditions where the activity of the RAR beta 2 gene promoter is readily induced by RA. Our results suggest that the CRBPII gene may not be RA-inducible in tissues expressing HNF-4 and ARP-1, and that the RA inducibility of the CRBPII gene promoter observed in transfection experiments reflects the promiscuous binding of RARs/RXRs to HNF-4 and ARP-1 response elements

Adapting Pretrained Vision-Language Foundational Models to Medical Imaging Domains

Multi-modal foundation models are typically trained on millions of pairs of natural images and text captions, frequently obtained through web-crawling approaches. Although such models depict excellent generative capabilities, they do not typically generalize well to specific domains such as medical images that have fundamentally shifted distributions compared to natural images. Building generative models for medical images that faithfully depict clinical context may help alleviate the paucity of healthcare datasets. Thus, in this study, we seek to research and expand the representational capabilities of large pretrained foundation models to medical concepts, specifically for leveraging the Stable Diffusion model to generate domain specific images found in medical imaging. We explore the sub-components of the Stable Diffusion pipeline (the variational autoencoder, the U-Net and the text-encoder) to fine-tune the model to generate medical images. We benchmark the efficacy of these efforts using quantitative image quality metrics and qualitative radiologist-driven evaluations that accurately represent the clinical content of conditional text prompts. Our best-performing model improves upon the stable diffusion baseline and can be conditioned to insert a realistic-looking abnormality on a synthetic radiology image, while maintaining a 95% accuracy on a classifier trained to detect the abnormality.Comment: 17 pages, 8 figure

Sense of control depends on fluency of action selection, not motor performance.

Sense of agency refers to the feeling of controlling one's own actions, and, through these actions, events in the outside world. Sense of agency is widely held to involve a retrospective inference based on matching actual effects of an action with its expected effects. We hypothesise a second, prospective aspect of sense of agency, reflecting the fluency of action selection, based on results from subliminal priming of actions. When people responded to a target that was compatible with a preceding subliminal prime, they felt stronger sense of control over a subsequent colour effect than when the preceding prime was incompatible. Importantly, compatible and incompatible primes had the same predictive statistical relation to the colour effect. We next investigated whether differences in sense of control could be based on monitoring motor performance. By varying the timings of mask and target, we compared sense of control between a Positive Compatibility condition, where compatible primes facilitated performance, and a Negative Compatibility condition, where compatible primes impaired performance. We found that compatible priming again enhanced sense of control, irrespective of its effects on performance. We present a simple model of the prospective aspect of sense of agency, in which early signals reflecting action selection processing make a direct, experiential contribution to sense of control. Sense of agency may be partly based on an experience-based 'feeling of doing', analogous to the metacognitive 'feeling of knowing'

Managing Resources by Grazing in Grasslands Dominated by Dominant Shrub Species

The European natural grasslands are attracting new attention because of their environmental value as habitats for threatened fauna and flora species and their contribution to the diversity of landscapes. Those responsible for the implementation of the European agri-environmental policy are hence encouraging livestock farmers to adopt grazing practices that contribute to the conservation of grassland biodiversity especially by limiting encroachment by dominant shrubs. However, current scientific knowledge and technical information are often insufficient to connect flock feeding and the impact of grazing on shrub dynamics and livestock farmers are not very enthusiastic about restoring or conserving “plant mosaics” including shrubs that support biodiversity in their fields. This paper presents results of an interdisciplinary study on interactions between small ruminant feeding strategy and population dynamics of dominant shrub species with the objective of managing by grazing the structure of plant community and thus to provide the renewal of resources on a multi-year scale

Murine isoforms of retinoic acid receptor gamma with specific patterns of expression.

We have characterized seven murine retinoic acid receptor gamma cDNA isoforms (mRAR-gamma 1 to -gamma 7) generated by alternative splicing of at least seven exons. These isoforms differ from one another in their 5' untranslated region and in two cases (mRAR-gamma 1 and -gamma 2) differ in their N-terminal A region, which is known to be important for differential transactivation by other nuclear receptors. mRAR-gamma 1 and -gamma 2, the predominant isoforms, are differentially expressed in adult tissues and during embryogenesis. Most notably, skin contains almost exclusively mRAR-gamma 1 transcripts. The conservation of the RAR-gamma isoforms from mouse to human together with their patterns of expression suggests that they perform specific functions, which may account for the pleiotropic effect of retinoic acid in embryogenesis and development

Information about action outcomes differentially affects learning from self-determined versus imposed choices

The valence of new information influences learning rates in humans: good news tends to receive more weight than bad news. We investigated this learning bias in four experiments, by systematically manipulating the source of required action (free versus forced choices), outcome contingencies (low versus high reward) and motor requirements (go versus no-go choices). Analysis of model-estimated learning rates showed that the confirmation bias in learning rates was specific to free choices, but was independent of outcome contingencies. The bias was also unaffected by the motor requirements, thus suggesting that it operates in the representational space of decisions, rather than motoric actions. Finally, model simulations revealed that learning rates estimated from the choice-confirmation model had the effect of maximizing performance across low- and high-reward environments. We therefore suggest that choice-confirmation bias may be adaptive for efficient learning of action–outcome contingencies, above and beyond fostering person-level dispositions such as self-esteem

Role of highly branched, high molecular weight polymer structures in directing uniform polymer particle formation during nanoprecipitation

The new macromolecular architecture, hyperbranched polydendrons, are composed of a broad distribution of molecular weights and architectural variation; however, nanoprecipitation of these materials yields highly uniform, dendron-functional nanoparticles. By isolating different fractions of the diverse samples, the key role of the most highly branched structures in directing nucleation and growth has been explored and determined.</div