Model-based clustering with data correction for removing artifacts in gene expression data

The NIH Library of Integrated Network-based Cellular Signatures (LINCS) contains gene expression data from over a million experiments, using Luminex Bead technology. Only 500 colors are used to measure the expression levels of the 1,000 landmark genes measured, and the data for the resulting pairs of genes are deconvolved. The raw data are sometimes inadequate for reliable deconvolution leading to artifacts in the final processed data. These include the expression levels of paired genes being flipped or given the same value, and clusters of values that are not at the true expression level. We propose a new method called model-based clustering with data correction (MCDC) that is able to identify and correct these three kinds of artifacts simultaneously. We show that MCDC improves the resulting gene expression data in terms of agreement with external baselines, as well as improving results from subsequent analysis.Comment: 28 page

A Posterior Probability Approach for Gene Regulatory Network Inference in Genetic Perturbation Data

Inferring gene regulatory networks is an important problem in systems biology. However, these networks can be hard to infer from experimental data because of the inherent variability in biological data as well as the large number of genes involved. We propose a fast, simple method for inferring regulatory relationships between genes from knockdown experiments in the NIH LINCS dataset by calculating posterior probabilities, incorporating prior information. We show that the method is able to find previously identified edges from TRANSFAC and JASPAR and discuss the merits and limitations of this approach

Kinetics of cone specific G-protein signaling in avian photoreceptor cells

Cone photoreceptor cells of night-migratory songbirds seem to process the primary steps of two different senses, vision and magnetoreception. The molecular basis of phototransduction is a prototypical G protein-coupled receptor pathway starting with the photoexcitation of rhodopsin or cone opsin thereby activating a heterotrimeric G protein named transducin. This interaction is well understood in vertebrate rod cells, but parameter describing protein–protein interactions of cone specific proteins are rare and not available for migratory birds. European robin is a model organism for studying the orientation of birds in the earth magnetic field. Recent findings showed a link between the putative magnetoreceptor cryptochrome 4a and the cone specific G-protein of European robin. In the present work, we investigated the interaction of European robin cone specific G protein and cytoplasmic regions of long wavelength opsin. We identified the second loop in opsin connecting transmembrane regions three and four as a critical binding interface. Surface plasmon resonance studies using a synthetic peptide representing the second cytoplasmic loop and purified G protein α-subunit showed a high affinity interaction with a KD value of 21 nM. Truncation of the G protein α-subunit at the C-terminus by six amino acids slightly decreased the affinity. Our results suggest that binding of the G protein to cryptochrome can compete with the interaction of G protein and non-photoexcited long wavelength opsin. Thus, the parallel presence of two different sensory pathways in bird cone photoreceptors is reasonable under dark-adapted conditions or during illumination with short wavelengths

Effect of medial arch-heel support in inserts on reducing ankle eversion: a biomechanics study

Background. Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running. Methods. Thirteen pronators and 13 normal subjects participated in standing, walking and running trials in each of the following conditions: (1) barefoot, and shod condition with insert with (2) no, (3) low, (4) medium, and (5) high medial arch-heel support. Motions were captured and processed by an eight-camera motion capture system. Maximum ankle eversion was calculated by incorporating the raw coordinates of 15 anatomical positions to a self-compiled Matlab program with kinematics equations. Analysis of variance with repeated measures with post-hoc Tukey pairwise comparisons was performed on the data among the five walking conditions and the five running conditions separately. Results. Results showed that the inserts with medial arch-heel support were effective in dynamics trials but not static trials. In walking, they successfully reduced the maximum eversion by 2.1 degrees in normal subjects and by 2.5-3.0 degrees in pronators. In running, the insert with low medial arch support significantly reduced maximum eversion angle by 3.6 and 3.1 degrees in normal subjects and pronators respectively. Conclusion. Medial arch-heel support in inserts is effective in reducing ankle eversion in walking and running, but not in standing. In walking, there is a trend to bring the over-pronated feet of the pronators back to the normal eversion range. In running, it shows an effect to restore normal eversion range in 84% of the pronators

Multi-Temporal Analysis and Scaling Relations of 100,000,000,000 Network Packets

Our society has never been more dependent on computer networks. Effective utilization of networks requires a detailed understanding of the normal background behaviors of network traffic. Large-scale measurements of networks are computationally challenging. Building on prior work in interactive supercomputing and GraphBLAS hypersparse hierarchical traffic matrices, we have developed an efficient method for computing a wide variety of streaming network quantities on diverse time scales. Applying these methods to 100,000,000,000 anonymized source-destination pairs collected at a network gateway reveals many previously unobserved scaling relationships. These observations provide new insights into normal network background traffic that could be used for anomaly detection, AI feature engineering, and testing theoretical models of streaming networks.Comment: 6 pages, 6 figures,3 tables, 49 references, accepted to IEEE HPEC 202

NEID Reveals that The Young Warm Neptune TOI-2076 b Has a Low Obliquity

TOI-2076 b is a sub-Neptune-sized planet ($R=2.39 \pm 0.10 \mathrm{R_\oplus}$) that transits a young ($204 \pm 50 \mathrm{MYr}$) bright ($V = 9.2$) K-dwarf hosting a system of three transiting planets. Using spectroscopic observations with the NEID spectrograph on the WIYN 3.5 m Telescope, we model the Rossiter-McLaughlin effect of TOI-2076 b, and derive a sky-projected obliquity of $\lambda=-3_{-15}^{+16\:\circ}$. Using the size of the star ($R=0.775 \pm0.015 \mathrm{R_\odot}$), and the stellar rotation period ($P_{\mathrm{rot}}=7.27\pm0.23$ days), we estimate a true obliquity of $\psi=18_{-9}^{+10\:\circ}$ ($\psi < 34^\circ$ at 95% confidence), demonstrating that TOI-2076 b is on a well-aligned orbit. Simultaneous diffuser-assisted photometry from the 3.5 m Telescope at Apache Point Observatory rules out flares during the transit. TOI-2076 b joins a small but growing sample of young planets in compact multi-planet systems with well-aligned orbits, and is the fourth planet with an age $\lesssim 300$ Myr in a multi-transiting system with an obliquity measurement. The low obliquity of TOI-2076 b and the presence of transit timing variations in the system suggest the TOI-2076 system likely formed via convergent disk migration in an initially well-aligned disk.Comment: Submitted to ApJL, 13 pages, 4 figures, 3 table

TOI-4201: An Early M-dwarf Hosting a Massive Transiting Jupiter Stretching Theories of Core-Accretion

We confirm TOI-4201 b as a transiting Jovian mass planet orbiting an early M dwarf discovered by the Transiting Exoplanet Survey Satellite. Using ground based photometry and precise radial velocities from NEID and the Planet Finder Spectrograph, we measure a planet mass of 2.59$^{+0.07}_{-0.06}$ M$_{J}$, making this one of the most massive planets transiting an M-dwarf. The planet is $\sim$0.4\% the mass of its 0.63 M$_{\odot}$ host and may have a heavy element mass comparable to the total dust mass contained in a typical Class II disk. TOI-4201 b stretches our understanding of core-accretion during the protoplanetary phase, and the disk mass budget, necessitating giant planet formation to either take place much earlier in the disk lifetime, or perhaps through alternative mechanisms like gravitational instability.Comment: To be submitted to AAS journals on 14th July 202

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung