Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the wiring evolution in differentiable neural architecture search

Controversy exists on whether differentiable neural architecture search methods discover wiring topology effectively. To understand how wiring topology evolves, we study the underlying mechanism of several existing differentiable NAS frameworks. Our investigation is motivated by three observed searching patterns of differentiable NAS: 1) they search by growing instead of pruning; 2) wider networks are more preferred than deeper ones; 3) no edges are selected in bi-level optimization. To anatomize these phenomena, we propose a unified view on searching algorithms of existing frameworks, transferring the global optimization to local cost minimization. Based on this reformulation, we conduct empirical and theoretical analyses, revealing implicit inductive biases in the cost's assignment mechanism and evolution dynamics that cause the observed phenomena. These biases indicate strong discrimination towards certain topologies. To this end, we pose questions that future differentiable methods for neural wiring discovery need to confront, hoping to evoke a discussion and rethinking on how much bias has been enforced implicitly in existing NAS methods.
Multi-domain semantic segmentation with pyramidal fusion

We present our submission to the semantic segmentation contest of the Robust Vision Challenge held at ECCV 2020. The contest requires submitting the same model to seven benchmarks from three different domains. Our approach is based on the SwiftNet architecture with pyramidal fusion. We address inconsistent taxonomies with a single-level 193-dimensional softmax output. We strive to train with large batches in order to stabilize optimization of a hard recognition problem, and to favour smooth evolution of batchnorm statistics. We achieve this by implementing a custom backward step through log-sum-prob loss, and by using small crops before freezing the population statistics. Our model ranks first on the RVC semantic segmentation challenge as well as on the WildDash 2 leaderboard. This suggests that pyramidal fusion is competitive not only for efficient inference with lightweight backbones, but also in large-scale setups for multi-domain application.
Research: is an 'ideal' questionnaire possible?

Writing a research protocol and designing a questionnaire are not as easy as might be thought. Producing the 'ideal' questionnaire can be fraught with difficulties, and the guidelines provided are intended to avoid potential pitfalls. Designing a questionnaire takes time and patience. The importance of a pre-test and pilot study cannot be overemphasised and resultant modifications to the questions will increase the validity, reliability and responsiveness of a questionnaire and lend support to any findings following appropriate statistical interpretation of the data. The advantages of the questionnaire research method, together with the disadvantages and the problems associated with poor response rates, are discussed.
Democratizing AI: non-expert design of prediction tasks

Non-experts have long made important contributions to machine learning (ML) by contributing training data, and recent work has shown that non-experts can also help with feature engineering by suggesting novel predictive features. However, non-experts have only contributed features to prediction tasks already posed by experienced ML practitioners. Here we study how non-experts can design prediction tasks themselves, what types of tasks non-experts will design, and whether predictive models can be automatically trained on data sourced for their tasks. We use a crowdsourcing platform where non-experts design predictive tasks that are then categorized and ranked by the crowd. Crowdsourced data are collected for top-ranked tasks and predictive models are then trained and evaluated automatically using those data. We show that individuals without ML experience can collectively construct useful datasets and that predictive models can be learned on these datasets, but challenges remain. The prediction tasks designed by non-experts covered a broad range of domains, from politics and current events to health behavior, demographics, and more. Proper instructions are crucial for non-experts, so we also conducted a randomized trial to understand how different instructions may influence the types of prediction tasks being proposed. In general, understanding better how non-experts can contribute to ML can further leverage advances in Automatic machine learning and has important implications as ML continues to drive workplace automation.
The efficacy of natural selection in producing optimal sex ratio adjustments in a fig wasp species

Ever since Darwin's discovery of natural selection, we expect traits to evolve to increase organisms' fitness. As a result, we can use optimization models to make a priori predictions of phenotypic variation, even when selection is frequency-dependent. A notable example is the prediction of female-biased sex ratios resulting from local mate competition (LMC) and inbreeding. LMC models incorporate the effects of LMC and inbreeding. Fig wasp sex ratio adjustments fit LMC predictions well. However, the appropriateness of LMC models to fig wasps has been questioned, and the role that a coincidental by-product plays in creating the apparent fit has been clearly illustrated. Here, we show that the sex ratio adjustments of a fig wasp are the result of a dual mechanism. It consists of a standard facultative LMC response favoured by natural selection, as well as a mechanism that may be the result of selection, but that could also be a coincidental by-product. If it is a by-product, the fitness increase is coincidental and natural selection's role was limited to fine-tuning it for higher fitness returns. We further document a case of an apparent fitness-reducing sex ratio adjustment. We conclude that the use of the adaptationist approach demands that our understanding of traits must be remodelled continually to rectify spurious assumptions.
Long non-coding RNA-polycomb intimate rendezvous

The interaction between polycomb-repressive complexes 1/2 (PRC1/2) and long non-coding RNA (lncRNA), such as the X inactive specific transcript Xist and the HOX transcript antisense RNA (HOTAIR), has been the subject of intense debate. While cross-linking, immuno-precipitation and super-resolution microscopy argue against direct interaction of Polycomb with some lncRNAs, there is increasing evidence supporting the ability of both PRC1 and PRC2 to functionally associate with RNA. Recent data indicate that these interactions are in most cases spurious, but nonetheless crucial for a number of cellular activities. In this review, we suggest that while PRC1/2 recruitment by HOTAIR might be direct, in the case of Xist, it might occur indirectly and, at least in part, through the process of liquid–liquid phase separation. We present recent models of lncRNA-mediated PRC1/2 recruitment to their targets and describe potential RNA-mediated roles in the three-dimensional organization of the nucleus.
Towards a reliable measure of motor working memory: revisiting Wu and Coulson's (2014) movement span task

Some researchers have argued that motor working memory is relatively independent from visuospatial working memory and underlies the learning and processing of motor tasks, like gesture comprehension. To allow systematic testing of these claims, Wu & Coulson 2014 Psychol. Sci. 26, 1717–1727. (doi:10.1177/0956797615597671) proposed a novel measure of motor working memory, the movement span task. Some studies have reported that the movement span task has a high degree of validity. The purpose of the present study was to attempt to replicate Wu & Coulson 2014 Psychol. Sci. 26, 1717–1727. (doi:10.1177/0956797615597671) in the following ways: (1) the high correlation between movement span and movement recall scores and (2) the lack of correlation between the movement span task on the one hand and visuospatial and verbal working memory on the other. In the present study, we found a high correlation between the movement span and recall scores as well as most measures of visuospatial memory. However, the size of these correlations was similar to that reported by Wu and Coulson, suggesting that the significance may be related to sample size. In other words, motor working memory may be weakly related to visuospatial memory. By contrast, there were weak correlations between the movement span task and verbal memory. In sum, we found the same pattern of results observed by Wu & Coulson 2014, 1717–1727. (doi:10.1177/0956797615597671).
Cellular bicarbonate accumulation and vesicular proton transport promote calcification in the sea urchin larva

The sea urchin embryo develops a calcitic endoskeleton through intracellular formation of amorphous calcium carbonate (ACC). Intracellular precipitation of ACC, requires HCO3−/CO32− concentrating as well as proton export mechanisms to promote calcification. These processes are of fundamental importance in biological mineralization, but remain largely unexplored. Here, we demonstrate that the calcifying primary mesenchyme cells (PMCs) use Na+/H+-exchange (NHE) mechanisms to control cellular pH homeostasis during maintenance of the skeleton. During skeleton re-calcification, pHi of PMCs is increased accompanied by substantial elevation in intracellular [HCO3−] mediated by the Na+/HCO3− cotransporter Sp_Slc4a10. However, PMCs lower their pHi regulatory capacities associated with a reduction in NHE activity. Live-cell imaging using green fluorescent protein reporter constructs in combination with intravesicular pH measurements demonstrated alkaline and acidic populations of vesicles in PMCs and extensive trafficking of large V-type H+-ATPase (VHA)-rich acidic vesicles in blastocoelar filopodial cells. Pharmacological and gene expression analyses underline a central role of the VHA isoforms Sp_ATP6V0a1, Sp_ATP6V01_1 and Sp_ATPa1-4 for the process of skeleton re-calcification. These results highlight novel pH regulatory strategies in calcifying cells of a marine species with important implications for our understanding of the mineralization process in times of rapid changes in oceanic pH.
CycleRank, or there and back again: personalized relevance scores from cyclic paths on directed graphs

Surfing the links between Wikipedia articles constitutes a valuable way to acquire new knowledge related to a topic by exploring its connections to other pages. In this sense, Personalized PageRank is a well-known option to make sense of the graph of links between pages and identify the most relevant articles with respect to a given one; its performance, however, is hindered by pages with high indegree that function as hubs and obtain high scores regardless of the starting point. In this work, we present CycleRank, a novel algorithm based on cyclic paths aimed at finding the most relevant nodes related to a topic. To compare the results of CycleRank with those of Personalized PageRank and other algorithms derived from it, we perform three experiments based on different ground truths. We find that CycleRank aligns better with readers’ behaviour as it ranks in higher positions the articles corresponding to links that receive more clicks; it tends to identify in higher position related articles highlighted by editors in ‘See also’ sections; and it is more robust to global hubs of the network having high indegree. Finally, we show that computing CycleRank is two orders of magnitude faster than computing the other baselines.
Echolocation call frequency variation in horseshoe bats: molecular basis revealed by comparative transcriptomics

Recently diverged taxa with contrasting phenotypes offer opportunities for unravelling the genetic basis of phenotypic variation in nature. Horseshoe bats are a speciose group that exhibit a derived form of high-duty cycle echolocation in which the inner ear is finely tuned to echoes of the narrowband call frequency. Here, by focusing on three recently diverged subspecies of the intermediate horseshoe bat (Rhinolophus affinis) that display divergent echolocation call frequencies, we aim to identify candidate loci putatively involved in hearing frequency variation. We used de novo transcriptome sequencing of two mainland taxa (himalayanus and macrurus) and one island taxon (hainanus) to compare expression profiles of thousands of genes. By comparing taxa with divergent call frequencies (around 15 kHz difference), we identified 252 differentially expressed genes, of which six have been shown to be involved in hearing or deafness in human/mouse. To obtain further validation of these results, we applied quantitative reverse transcription–PCR to the candidate gene FBXL15 and found a broad association between the level of expression and call frequency across taxa. The genes identified here represent strong candidate loci associated with hearing frequency variation in bats.
Frontoparietal Network Connectivity During an N-Back Task in Adults With Autism Spectrum Disorder

Background Short-term and working memory (STM and WM) deficits have been demonstrated in individuals with autism spectrum disorder (ASD) and may emerge through atypical functional activity and connectivity of the frontoparietal network, which exerts top-down control necessary for successful STM and WM processes. Little is known regarding the spectral properties of the frontoparietal network during STM or WM processes in ASD, although certain neural frequencies have been linked to specific neural mechanisms. Methods We analysed magnetoencephalographic data from 39 control adults (26 males; 27.15 ± 5.91 years old) and 40 adults with ASD (26 males; 27.17 ± 6.27 years old) during a 1-back condition (STM) of an n-back task, and from a subset of this sample during a 2-back condition (WM). We performed seed-based connectivity analyses using regions of the frontoparietal network. Interregional synchrony in theta, alpha, and beta bands was assessed with the phase difference derivative and compared between groups during periods of maintenance and recognition. Results During maintenance of newly presented vs. repeated stimuli, the two groups did not differ significantly in theta, alpha, or beta phase synchrony for either condition. Adults with ASD showed alpha-band synchrony in a network containing the right dorsolateral prefrontal cortex, bilateral inferior parietal lobules (IPL), and precuneus in both 1- and 2-back tasks, whereas controls demonstrated alpha-band synchrony in a sparser set of regions, including the left insula and IPL, in only the 1-back task. During recognition of repeated vs. newly presented stimuli, adults with ASD exhibited decreased theta-band connectivity compared to controls in a network with hubs in the right inferior frontal gyrus and left IPL in the 1-back condition. Whilst there were no group differences in connectivity in the 2-back condition, adults with ASD showed no frontoparietal network recruitment during recognition, whilst controls activated networks in the theta and beta bands. Conclusions Our findings suggest that since adults with ASD performed well on the n-back task, their appropriate, but effortful recruitment of alpha-band mechanisms in the frontoparietal network to maintain items in STM and WM may compensate for atypical modulation of this network in the theta band to recognise previously presented items in STM.
Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab vs. Chemotherapy as First-Line Therapy in Advanced Non-Small Cell Lung Cancer

Background: The CheckMate 227 trial has indicated that nivolumab plus ipilimumab compared with chemotherapy significantly increases long-term survival in the first-line setting of advanced non-small-cell lung cancer (NSCLC). Methods: A Markov model was built to estimate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy as the first-line therapy in patients with advanced NSCLC based on outcomes data from the CheckMate 227 trial. We calculated the cost and health outcomes at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in populations with different programmed death ligand 1 (PD-L1) expression levels (≥50, ≥1, and <1%) or a high tumor mutational burden (TMB) (≥10 mutations per megabase). Sensitivity analysis were used to test the model stability. Results: The outcomes showed that the incremental costs and QALYs by using nivolumab plus ipilimumab were $124180.76 and 1.16, $70951.42 and 0.53, $144093.63 and 0.83 for the advanced NSCLC patients with a PD-L1 expression ≥50%, ≥1%, and <1%, which led to an incremental cost-effective ratio (ICER) of $107403.72, $133732.20, and $172589.15 per QALY, respectively. For patients with a high TMB, nivolumab plus ipilimumab contributed an extra 2.04 QALYs at a cost of $69182.50 per QALY. Conclusion: Nivolumab plus ipilimumab as first-line therapy makes a better cost-effective strategy than chemotherapy in advanced NSCLC patients with PD-L1 expression levels ≥50% and ≥1% or a high TMB, at a willingness-to-pay threshold of $150,000 per QALY, but not in the patients with a PD-L1 expression <1%.
Muscle-Organ Crosstalk: Focus on Immunometabolism

Skeletal muscle secretes several hundred myokines that facilitate communication from muscle to other organs, such as, adipose tissue, pancreas, liver, gut, and brain. The biological roles of myokines include effects on e.g., memory and learning, as well as glucose and lipid metabolism. The present minireview focuses on recent developments showing that exercise-induced myokines are involved in immunometabolism of importance for the control of e.g., tumor growth and chronic inflammation. In this review, immunometabolism is discussed as the non-immune related pathologies leading to an immune response and some degree of inflammation, which promotes metabolic abnormalities.
Effects of fructose feeding on maternal and amniotic fluid corticotropin releasing hormone and C-reactive protein in pregnant female Sprague-dawley rats

Exposure to a compromised intra uterine environment has been known to alter fetal growth and metabolic processes with long term consequences for health. Maternal nutrition prior to and during gestation plays a role in fetal programming, however the mechanisms underlying these changes have however not been fully elucidated. The study was carried out to evaluate the effects of fructose feeding on maternal serum and amniotic fluid insulin, Corticotropin Releasing Hormone (CRH) and C - reactive protein (CRP), insulin-like growth factors (IGF-1 and 2) on days 12, 15 and 18 of pregnancy in control and fructose fed rats. Virgin female rats were randomly divided into control and fructose-fed. Female rats were mated with proven male rats and the presence of sperm cells in the virginal smear the following morning was taken as day 1 of pregnancy. Maternal blood samples and amniotic fluid were obtained on days 12, 15 and 18 of pregnancy for insulin, CRH, CRP and IGF-1 and 2 using ELISA techniques. Maternal and amniotic fluid CRH, CRP and IGF-1 levels were significantly higher (p<0.05) in the fructose-fed rats compared to the control rats. IGF-2 level was not significantly different in maternal and amniotic fluid in both groups. The results suggest that stress and inflammatory mechanisms may be implicated in the role maternal nutrition plays in developmental plasticity.
Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis

The human gastrointestinal tract harbors most of the microbial cells inhabiting the body, collectively known as the microbiota. These microbes have several implications for the maintenance of structural integrity of the gastrointestinal mucosal barrier, immunomodulation, metabolism of nutrients, and protection against pathogens. Dysfunctions in these mechanisms are linked to a range of conditions in the gastrointestinal tract, including functional gastrointestinal disorders, ranging from irritable bowel syndrome, to functional constipation and functional diarrhea. Irritable bowel syndrome is characterized by chronic abdominal pain with changes in bowel habit in the absence of morphological changes. Despite the high prevalence of irritable bowel syndrome in the global population, the mechanisms responsible for this condition are poorly understood. Although alterations in the gastrointestinal microbiota, low-grade inflammation and immune activation have been implicated in the pathophysiology of functional gastrointestinal disorders, there is inconsistency between studies and a lack of consensus on what the exact role of the microbiota is, and how changes to it relate to these conditions. The complex interplay between host factors, such as microbial dysbiosis, immune activation, impaired epithelial barrier function and motility, and environmental factors, including diet, will be considered in this narrative review of the pathophysiology of functional gastrointestinal disorders.
Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle

The neuromuscular junction (NMJ) is a prototypic chemical synapse between the spinal motor neuron and the motor endplate. Gene expression profiles of the motor endplate are not fully elucidated. Collagen Q (ColQ) is a collagenic tail subunit of asymmetric forms of acetylcholinesterase and is driven by two distinct promoters. pColQ1 is active throughout the slow-twitch muscle, whereas pColQ1a is active at the motor endplate of fast-twitch muscle. We made a transgenic mouse line that expresses nuclear localization signal (NLS)-attached Cre recombinase under the control of pColQ1a (pColQ1a-Cre mouse). RiboTag mouse expresses an HA-tagged ribosomal subunit, RPL22, in cells expressing Cre recombinase. We generated pColQ1a-Cre:RiboTag mouse, and confirmed that HA-tagged RPL22 was enriched at the NMJ of tibialis anterior (TA) muscle. Next, we confirmed that Chrne and Musk that are specifically expressed at the NMJ were indeed enriched in HA-immunoprecipitated (IP) RNA, whereas Sox10 and S100b, markers for Schwann cells, and Icam1, a marker for vascular endothelial cells, and Pax3, a marker for muscle satellite cells, were scarcely detected. Gene set enrichment analysis (GSEA) of RNA-seq data showed that “phosphatidylinositol signaling system” and “extracellular matrix receptor interaction” were enriched at the motor endplate. Subsequent analysis revealed that genes encoding diacylglycerol kinases, phosphatidylinositol kinases, phospholipases, integrins, and laminins were enriched at the motor endplate. We first characterized the gene expression profile under translation at the motor endplate of TA muscle using the RiboTag technique. We expect that our gene expression profiling will help elucidate molecular mechanisms of the development, maintenance, and pathology of the NMJ.