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Entropy-based Guidance of Deep Neural Networks for Accelerated Convergence and Improved Performance

Neural networks have dramatically increased our capacity to learn from large, high-dimensional datasets across innumerable disciplines. However, their decisions are not easily interpretable, their computational costs are high, and building and training them are uncertain processes. To add structure to these efforts, we derive new mathematical results to efficiently measure the changes in entropy as fully-connected and convolutional neural networks process data, and introduce entropy-based loss terms. Experiments in image compression and image classification on benchmark datasets demonstrate these losses guide neural networks to learn rich latent data representations in fewer dimensions, converge in fewer training epochs, and achieve better test metrics.Comment: 13 pages, 4 figure

Using Creative Methodology to Explore LGBTQ+ Love and Relationship Experiences across the lifespan:Developing Inclusive and Healthy Spaces through Positive Intergenerational Exchange

Introduction: Important lessons can be learned from the intergenerational sharing of lifetime love and relationship stories between multigenerational LGBTQ+ people, to inform education, healthcare, and policy. However, such exploratory studies have been limited. The aim of this co-creation study was to explore younger and older peoples’ LGBTQ+ love and relationship experiences using creative methodology.Methods: Three 2-hour virtual fictional writing and storytelling workshops were conducted at the height of the COVID-19 pandemic in Edinburgh, Scotland. Participants included 2 middle-aged adults; 3 older adults aged 55+; and 5 youths who identified as either lesbian, gay, bisexual, transgender or queer. Participants’ stories were audio-recorded, transcribed and thematically-analyzed to capture understandings of intergenerational knowledge exchange and LGBTQ+ love and relationships across sociocultural and environmental contexts. Diverse experiences were unpacked and shared through a self-reflexive creative writing process.Findings: Participants identified the act of storytelling and fictional writing as particularly liberating, providing a platform for voice and reflexivity. The reflexive analysis highlighted the importance of reflexivity and the careful navigation of intersectionality and power within research contexts. Our introspective analysis resulted in valuable future directions for employing creative methodologies to further explore diverse experiences within LGBTQ+ research.Conclusions: Participants reported that being able to craft their stories was a freeing experience, enabling sense-making to occur. Using creative methodology was demonstrated as an effective way to facilitate intergenerational engagement, and bring to light the complexities of LGBTQ+ love and relationships across generations in a safe environment

Taking a PEEK into YOLOv5 for Satellite Component Recognition via Entropy-based Visual Explanations

The escalating risk of collisions and the accumulation of space debris in Low Earth Orbit (LEO) has reached critical concern due to the ever increasing number of spacecraft. Addressing this crisis, especially in dealing with non-cooperative and unidentified space debris, is of paramount importance. This paper contributes to efforts in enabling autonomous swarms of small chaser satellites for target geometry determination and safe flight trajectory planning for proximity operations in LEO. Our research explores on-orbit use of the You Only Look Once v5 (YOLOv5) object detection model trained to detect satellite components. While this model has shown promise, its inherent lack of interpretability hinders human understanding, a critical aspect of validating algorithms for use in safety-critical missions. To analyze the decision processes, we introduce Probabilistic Explanations for Entropic Knowledge extraction (PEEK), a method that utilizes information theoretic analysis of the latent representations within the hidden layers of the model. Through both synthetic in hardware-in-the-loop experiments, PEEK illuminates the decision-making processes of the model, helping identify its strengths, limitations and biases

Transcription factor interactions explain the context-dependent activity of CRX binding sites

The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while negative homotypic interactions between sites cause CREs composed of multiple CRX sites to function as silencers. The effects of negative homotypic interactions can be overcome by the presence of other TFBSs that either interact cooperatively with CRX sites or make independent positive contributions to activity. The context-dependent activity of CRX sites is thus determined by the balance between positive heterotypic interactions, independent contributions of TFBSs, and negative homotypic interactions. Our findings explain observed patterns of activity among genomic CRX-bound enhancers and silencers, and suggest that enhancers may require diverse TFBSs to overcome negative homotypic interactions between TFBSs

High Redshift Metals I.: The Decline of C IV at z > 5.3

We present the results from our search for C IV in the intergalactic medium at redshifts z=5.3-6.0. We have observed four z~6 QSOs with Keck/NIRSPEC in echelle mode. The data are the most sensitive yet taken to search for C IV at these redshifts, being 50% complete at column densities log(N_{CIV})=13.4. We find no C IV systems in any of the four sightlines. Taking into account our completeness, this translates into a decline in the number density of C IV absorbers in the range 13.0 < log(N_{CIV}) < 15.0 of at least a factor 4.4 (95% confidence) from z~2-4.5, where the number density is relatively constant. We use our lack of detections to set limits on the slope and normalization of the column density distribution at z=5.3-6.0. The rapid evolution of C IV at these redshifts suggests that the decrease in the number density may largely be due to ionization effects, in which case many of the metals in the z~4.5 IGM could already be in place at z~5.3, but in a lower ionization state. The lack of weak systems in our data, combined with the presence of strong C IV absorbers along at least one other sightline, further suggests that there may be large-scale variations in the enrichment and/or ionization state of the z~6 IGM, or that C IV absorbers at these redshifts are associated with rare, UV-bright star-forming galaxies.Comment: 11 pages, 8 figures, submitted to Ap

Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox

Mutant U2AF1-induced alternative splicing of H2afy (macroH2A1) regulates B-lymphopoiesis in mice

Somatic mutations in spliceosome genes are found in ∼50% of patients with myelodysplastic syndromes (MDS), a myeloid malignancy associated with low blood counts. Expression of the mutant splicing factor U2AF1(S34F) alters hematopoiesis and mRNA splicing in mice. Our understanding of the functionally relevant alternatively spliced target genes that cause hematopoietic phenotypes in vivo remains incomplete. Here, we demonstrate that reduced expression of H2afy1.1, an alternatively spliced isoform of the histone H2A variant gene H2afy, is responsible for reduced B cells in U2AF1(S34F) mice. Deletion of H2afy or expression of U2AF1(S34F) reduces expression of Ebf1 (early B cell factor 1), a key transcription factor for B cell development, and mechanistically, H2AFY is enriched at the EBF1 promoter. Induced expression of H2AFY1.1 in U2AF1(S34F) cells rescues reduced EBF1 expression and B cells numbers in vivo. Collectively, our data implicate alternative splicing of H2AFY as a contributor to lymphopenia induced by U2AF1(S34F) in mice and MDS