Can resources save rationality? ‘Anti-Bayesian’ updating in cognition and perception

Resource rationality may explain suboptimal patterns of reasoning; but what of “anti-Bayesian” effects where the mind updates in a direction opposite the one it should? We present two phenomena — belief polarization and the size-weight illusion — that are not obviously explained by performance- or resource-based constraints, nor by the authors’ brief discussion of reference repulsion. Can resource rationality accommodate them

ProPanDL: A Modular Architecture for Uncertainty-Aware Panoptic Segmentation

We introduce ProPanDL, a family of networks capable of uncertainty-aware panoptic segmentation. Unlike existing segmentation methods, ProPanDL is capable of estimating full probability distributions for both the semantic and spatial aspects of panoptic segmentation. We implement and evaluate ProPanDL variants capable of estimating both parametric (Variance Network) and parameter-free (SampleNet) distributions quantifying pixel-wise spatial uncertainty. We couple these approaches with two methods (Temperature Scaling and Evidential Deep Learning) for semantic uncertainty estimation. To evaluate the uncertainty-aware panoptic segmentation task, we address limitations with existing approaches by proposing new metrics that enable separate evaluation of spatial and semantic uncertainty. We additionally propose the use of the energy score, a proper scoring rule, for more robust evaluation of spatial output distributions. Using these metrics, we conduct an extensive evaluation of ProPanDL variants. Our results demonstrate that ProPanDL is capable of estimating well-calibrated and meaningful output distributions while still retaining strong performance on the base panoptic segmentation task

Invariant Aspartic Acid in Muscle Nicotinic Receptor Contributes Selectively to the Kinetics of Agonist Binding

We examined functional contributions of interdomain contacts within the nicotinic receptor ligand binding site using single channel kinetic analyses, site-directed mutagenesis, and a homology model of the major extracellular region. At the principal face of the binding site, the invariant αD89 forms a highly conserved interdomain contact near αT148, αW149, and αT150. Patch-clamp recordings show that the mutation αD89N markedly slows acetylcholine (ACh) binding to receptors in the resting closed state, but does not affect rates of channel opening and closing. Neither αT148L, αT150A, nor mutations at both positions substantially affects the kinetics of receptor activation, showing that hydroxyl side chains at these positions are not hydrogen bond donors for the strong acceptor αD89. However substituting a negative charge at αT148, but not at αT150, counteracts the effect of αD89N, demonstrating that a negative charge in the region of interdomain contact confers rapid association of ACh. Interpreted within the structural framework of ACh binding protein and a homology model of the receptor ligand binding site, these results implicate main chain amide groups in the domain harboring αW149 as principal hydrogen bond donors for αD89. The specific effect of αD89N on ACh association suggests that interdomain hydrogen bonding positions αW149 for optimal interaction with ACh

Combining Gene Expression Data from Different Generations of Oligonucleotide Arrays

Background: One of the important challenges in microarray analysis is to take full advantage of previously accumulated data, both from one's own laboratory and from public repositories. Through a comparative analysis on a variety of datasets, a more comprehensive view of the underlying mechanism or structure can be obtained. However, as we discover in this work, continual changes in genomic sequence annotations and probe design criteria make it difficult to compare gene expression data even from different generations of the same microarray platform. Results: We first describe the extent of discordance between the results derived from two generations of Affymetrix oligonucleotide arrays, as revealed in cluster analysis and in identification of differentially expressed genes. We then propose a method for increasing comparability. The dataset we use consists of a set of 14 human muscle biopsy samples from patients with inflammatory myopathies that were hybridized on both HG-U95Av2 and HG-U133A human arrays. We find that the use of the probe set matching table for comparative analysis provided by Affymetrix produces better results than matching by UniGene or LocusLink identifiers but still remains inadequate. Rescaling of expression values for each gene across samples and data filtering by expression values enhance comparability but only for few specific analyses. As a generic method for improving comparability, we select a subset of probes with overlapping sequence segments in the two array types and recalculate expression values based only on the selected probes. We show that this filtering of probes significantly improves the comparability while retaining a sufficient number of probe sets for further analysis. Conclusions: Compatibility between high-density oligonucleotide arrays is significantly affected by probe-level sequence information. With a careful filtering of the probes based on their sequence overlaps, data from different generations of microarrays can be combined more effectively

Nicotinic Receptor Interloop Proline Anchors β1-β2 and Cys loops in Coupling Agonist Binding to Channel Gating

Nicotinic acetylcholine receptors (AChRs) mediate rapid excitatory synaptic transmission throughout the peripheral and central nervous systems. They transduce binding of nerve-released ACh into opening of an intrinsic channel, yet the structural basis underlying transduction is not fully understood. Previous studies revealed a principal transduction pathway in which αArg 209 of the pre-M1 domain and αGlu 45 of the β1–β2 loop functionally link the two regions, positioning αVal 46 of the β1–β2 loop in a cavity formed by αPro 272 through αSer 269 of the M2–M3 loop. Here we investigate contributions of residues within and proximal to this pathway using single-channel kinetic analysis, site-directed mutagenesis, and thermodynamic mutant cycle analysis. We find that in contributing to channel gating, αVal 46 and αVal 132 of the signature Cys loop couple energetically to αPro 272. Furthermore, these residues are optimized in both their size and hydrophobicity to mediate rapid and efficient channel gating, suggesting naturally occurring substitutions at these positions enable a diverse range of gating rate constants among the Cys-loop receptor superfamily. The overall results indicate that αPro 272 functionally couples to flanking Val residues extending from the β1–β2 and Cys loops within the ACh binding to channel opening transduction pathway

Bayesian Model Calibration and Sensitivity Analysis for Oscillating Biological Experiments

Understanding the oscillating behaviors that govern organisms' internal biological processes requires interdisciplinary efforts combining both biological and computer experiments, as the latter can complement the former by simulating perturbed conditions with higher resolution. Harmonizing the two types of experiment, however, poses significant statistical challenges due to identifiability issues, numerical instability, and ill behavior in high dimension. This article devises a new Bayesian calibration framework for oscillating biochemical models. The proposed Bayesian model is estimated relying on an advanced Markov chain Monte Carlo (MCMC) technique which can efficiently infer the parameter values that match the simulated and observed oscillatory processes. Also proposed is an approach to sensitivity analysis based on the intervention posterior. This approach measures the influence of individual parameters on the target process by using the obtained MCMC samples as a computational tool. The proposed framework is illustrated with circadian oscillations observed in a filamentous fungus, Neurospora crassa.Comment: manuscript 33 pages, appendix 6 page

The effects of a 12-week jump rope exercise program on abdominal adiposity, vasoactive substances, inflammation, and vascular function in adolescent girls with prehypertension

Introduction Childhood obesity is strongly associated with cardiovascular disease (CVD) development. It is necessary to combat unfavorable outcomes of obesity at a young age by utilizing effective interventions, such as exercise. Purpose We sought to examine the effects of a jump rope exercise program on CVD risk factors, including body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls. Methods Forty girls (age 14–16) were recruited and randomly assigned to a jump rope exercise group (EX, n = 20) or control group (CON, n = 20). Body composition, nitrate and nitrite levels, endothelin-1 (ET-1), C-reactive protein (CRP), systolic blood pressure and diastolic blood pressure (SBP, DBP), and arterial stiffness were measured before and after 12 weeks. Results There were significant group by time interactions following the 12-week program for body composition (from 33.8 ± 3.6 to 30.2 ± 3.1%), central adiposity (from 86.4 ± 4 to 83.3 ± 5 cm), SBP (from 126 ± 3.3 to 120 ± 2.1 mmHg), and brachial-to-ankle pulse wave velocity (from 8.2 ± 1.0 to 7.4 ± 0.2 m/s). Nitrate/nitrite levels increased (from 54.5 ± 5.1 to 57.2 ± 5.2 µmol) along a reduction in CRP levels (from 0.5 ± 0.4 to 0.2 ± 0.1 mg/L). There were no significant changes in ET-1 (P = 0.22). Conclusions These findings indicate that jump rope exercise may be an effective intervention to improve these CVD risk factors in prehypertensive adolescent girls. Jumping rope is an easily accessible exercise modality that may have important health implications for CVD prevention in younger populations

A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position in the Fragile-X region of the X chromosome in placental mammals. Surprisingly, the miRNAs encoded by this cluster (Fx-mir) have a predilection for targeting the immediately adjacent gene, Fmr1, an unexpected finding given that miRNAs usually act in trans, not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP, the protein product of Fmr1, is downregulated when Fx-mir miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx-mir family members act cooperatively to regulate the translation of batteries of mRNAs in a developmentally regulated manner in SCs

A Novel Measure of Moral Boundaries: Testing Perceived In-Group/Out-Group Value Differences in a Midwestern Sample

The literature on group differences and social identities has long assumed that value judgments about groups constitute a basic form of social categorization. However, little research has empirically investigated how values unite or divide social groups. The authors seek to address this gap by developing a novel measure of group values: third-order beliefs about in- and out-group members, building on Schwartz value theory. The authors demonstrate that their new measure is a promising empirical tool for quantifying previously abstract social boundaries. Results from a midwestern sample show an important dichotomy such that in-groups were attributed the more positive and altruistic transcendence and openness values, while out-groups were associated conservation and enhancement, the value domains revolving around a self-focus and social restraint. Furthermore, religious attendance and political ideology also emerged as strong predictors of value boundaries, whereas socioeconomic indicators were less influential. Significance and implications are discussed.</div