Gene-based association testing of dichotomous traits using generalized functional linear mixed models for family data

Gene-based association testing with rare variants requires arbitrarily aggregating or collapsing the information of the rare variants in genes into a single measure. As genotyping data can be viewed as a realization of a stochastic process that varies along the chromosome, it is more natural to summarize the genetic information using the approaches of functional data analysis. In functional data analysis, discrete genotypes are fitted by a continuous curve by using a collection of smooth basis functions. Existing generalized functional linear models (FLM) have been developed for unrelated samples to test for association between a dichotomous trait and genetic variants in a gene. In most situations, these models have higher power than well-known kernel-based methods (SKAT and SKAT-O). Here we extend this approach to accommodate family-based data using the GLOGS (genome-wide logistic mixed model/score test) approach developed by Stanhope and Abney, and develop family-based generalized functional linear mixed models (GFLMMs). This involves parallel computations to integrate out a multidimensional polygenic effect. Simulation results indicate that in most scenarios our new statistics are better than other similar statistics (famSKAT or F-SKAT), but not better than the retrospective kernel and burden statistics developed by Schaid and colleagues. We also embed FLM-smoothed genotypes in the retrospective statistics, improving the power of the kernel-based approach. We illustrate the behavior of these statistics by applying them to an age-related macular degeneration (AMD) family data set, where, as expected, we observe strong association between AMD and CFH and ARMS2, two known AMD susceptibility genes. Our proposed GFLMM provides a new tool for conducting family-based research studies in public health for complex or multifactorial diseases. The findings may improve the knowledge of existing AMD susceptibility genes and make a positive contribution to AMD treatment and prevention

Network Externality and Trust in Agent-Based Social Commerce

The social commerce platform engages users in an agent-led network, leveraging local ties and communal trust. Agents are neighborhood influencers facilitating user referral, community engagement, and product marketing. We study the economic value of the agents to the platform based on their native endowed network externality and the trust formulated from the interaction with the users. Using detailed performance and referral data from a leading social commerce platform in Indonesia, we find that (1) agents with a higher level of endowed network externality outperform the ones with a lower level; (2) a more trustworthy and, surprisingly, less connected agent produces higher community sales; and (3) user’s perceived benevolence of the agent positively moderates the referral effect. The results suggest that the platform faces a trade-off between capitalizing on agents’ social connections and nurturing community trust

Grotesque Impressions Enhance the Gaze Cueing Effect

A non-predictive gaze cue produces a reflexive shift of attention to the gazed-at location. The present study used a modified version of Posner's attentional cueing paradigm (a gaze cueing paradigm) to investigate role of grotesque facial expressions on a gaze cueing effect involving induced fear. Grotesque faces were created by vertically shifting the position of one of the two eyes (Experiment 1, N =28) or both eyes (Experiment 2, N =28).  The grotesque faces of Experiment 1 produced a larger facilitative effect of a gaze cue than did original faces, whereas the less grotesque faces of Experiment 2 did not.  Cooper & Wojan (2000) have shown that one-eye moved faces produce much more grotesque impressions than two-eye moved faces. Results suggest that a grotesque facial expression, which may induce fear, automatically attracts observers' attention and facilitates processing of the gaze, ultimately enhancing the gaze cueing effect

Grotesque Impressions Enhance the Gaze Cueing Effect

A non-predictive gaze cue produces a reflexive shift of attention to the gazed-at location. The present study used a modified version of Posner's attentional cueing paradigm (a gaze cueing paradigm) to investigate role of grotesque facial expressions on a gaze cueing effect involving induced fear. Grotesque faces were created by vertically shifting the position of one of the two eyes (Experiment 1, N =28) or both eyes (Experiment 2, N =28).  The grotesque faces of Experiment 1 produced a larger facilitative effect of a gaze cue than did original faces, whereas the less grotesque faces of Experiment 2 did not.  Cooper & Wojan (2000) have shown that one-eye moved faces produce much more grotesque impressions than two-eye moved faces. Results suggest that a grotesque facial expression, which may induce fear, automatically attracts observers' attention and facilitates processing of the gaze, ultimately enhancing the gaze cueing effect

Binding energies of benzene on coinage metal surfaces: Equal stability on different metals

Interfaces between organic molecules and inorganic solids adapt a prominent role in fundamental science, catalysis, molecular sensors, and molecular electronics. The molecular adsorption geometry, which is dictated by the strength of lateral and vertical interactions, determines the electronic structure of the molecule/substrate system. In this study, we investigate the binding properties of benzene on the noble metal surfaces Au(111), Ag(111), and Cu(111), respectively, using temperature-programmed desorption and first-principles calculations that account for non-locality of both electronic exchange and correlation effects. In the monolayer regime, we observed for all three systems a decrease of the binding energy with increasing coverage due to repulsive adsorbate/adsorbate interactions. Although the electronic properties of the noble metal surfaces are rather different, the binding strength of benzene on these surfaces is equal within the experimental error (accuracy of 0.05 eV), in excellent agreement with our calculations. This points toward the existence of a universal trend for the binding energy of aromatic molecules resulting from a subtle balance between Pauli repulsion and many-body van der Waals attraction

Tuning the work function of stepped metal surfaces by adsorption of organic molecules

Understanding the binding mechanisms for aromatic molecules on transition-metal surfaces, especially with defects such as vacancies, steps and kinks, is a major challenge in designing functional interfaces for organic devices. One important parameter in the performance of organic/inorganic devices is the barrier of charge carrier injection. In the case of a metallic electrode, tuning the electronic interface potential or the work function for electronic level alignment is crucial. Here, we use density-functional theory (DFT) calculations with van der Waals (vdW) interactions treated with both screened pairwise (vdWsurf) and many-body dispersion (MBD) methods, to systematically study the interactions of benzene with a variety of stepped surfaces. Our calculations confirm the physisorptive character of Ag(2 1 1), Ag(5 3 3), Ag(3 2 2), Ag(7 5 5) and Ag(5 4 4) surfaces upon the adsorption of benzene. The MBD effects reduce the adsorption energies by about 0.15 eV per molecule compared to the results from the DFT + vdWsurf method. In addition, we find that the higher the step density, the larger the reduction of the work function upon the adsorption of benzene. We also study the effect of vdW interactions on the electronic structure using a fully selfconsistent implementation of the vdWsurf method in the Kohn–Sham DFT framework. We find that the self-consistent vdWsurf effects increase the work function due to the lowered Fermi level and the increased vacuum level. As a result, the benzene/Ag(2 1 1) system has the lowest work function (3.67 eV) among the five adsorption systems, significantly smaller than the work function of the clean Ag(1 1 1) surface (4.74 eV). Our results provide important insights into the stability and electronic properties of molecules adsorbed on stepped metal surfaces, which could help in designing more appropriate interfaces with low work functions for electron transfer

Establishment of predictive nomogram and web-based survival risk calculator for desmoplastic small round cell tumor: A propensity score-adjusted, population-based study

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study’s objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times: 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy

DavarOCR: A Toolbox for OCR and Multi-Modal Document Understanding

This paper presents DavarOCR, an open-source toolbox for OCR and document understanding tasks. DavarOCR currently implements 19 advanced algorithms, covering 9 different task forms. DavarOCR provides detailed usage instructions and the trained models for each algorithm. Compared with the previous opensource OCR toolbox, DavarOCR has relatively more complete support for the sub-tasks of the cutting-edge technology of document understanding. In order to promote the development and application of OCR technology in academia and industry, we pay more attention to the use of modules that different sub-domains of technology can share. DavarOCR is publicly released at https://github.com/hikopensource/Davar-Lab-OCR.Comment: Short paper, Accept by ACM MM202

Catalysis beyond frontier molecular orbitals: Selectivity in partial hydrogenation of multi-unsaturated hydrocarbons on metal catalysts

The mechanistic understanding and control over transformations of multi-unsaturated hydrocarbons on transition metal surfaces remains one of the major challenges of hydrogenation catalysis. To reveal the microscopic origins of hydrogenation chemoselectivity, we performed a comprehensive theoretical investigation on the reactivity of two a,b-unsaturated carbonyls—isophorone and acrolein—on seven (111) metal surfaces: Pd, Pt, Rh, Ir, Cu, Ag, and Au. In doing so, we uncover a general mechanism that goes beyond the celebrated frontier molecular orbital theory, rationalizing the C--C bond activation in isophorone and acrolein as a result of significant surface-induced broadening of high-energy inner molecular orbitals. By extending our calculations to hydrogen-precovered surface and higher adsorbate surface coverage, we further confirm the validity of the “inner orbital broadening mechanism” under realistic catalytic conditions. The proposed mechanism is fully supported by our experimental reaction studies for isophorone and acrolein over Pd nanoparticles terminated with (111) facets. Although the position of the frontier molecular orbitals in these molecules, which are commonly considered to be responsible for chemical interactions, suggests preferential hydrogenation of the C--O double bond, experiments show that hydrogenation occurs at the C--C bond on Pd catalysts. The extent of broadening of inner molecular orbitals might be used as a guiding principle to predict the chemoselectivity for a wide class of catalytic reactions at metal surfaces