Revealing evolutionary constraints on proteins through sequence analysis

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein, represented by an additive trait, can give rise to such a sector. As an illustration of a selected trait, we consider the elastic energy of an important conformational change within an elastic network model, and we show that selection acting on this energy leads to correlations among residues. For this concrete example and more generally, we demonstrate that the main signature of functional sectors lies in the small-eigenvalue modes of the covariance matrix of the selected sequences. However, secondary signatures of these functional sectors also exist in the extensively-studied large-eigenvalue modes. Our simple, general model leads us to propose a principled method to identify functional sectors, along with the magnitudes of mutational effects, from sequence data. We further demonstrate the robustness of these functional sectors to various forms of selection, and the robustness of our approach to the identification of multiple selected traits.Comment: 37 pages, 28 figure

RNA-SequenLens for Visualizing RNA Secondary Structures

Runner up of the Design ContestInternational audienceIn this paper, we present RNA-SequenLens to facilitate the visualization and comparison of RNA secondary structures.With RNA-SequenLens, all possible base pairings of a RNA sequence can be visualized at the desired probability threshold. Different RNA secondary structures can be easily compared. The interactive demo is available at https://youtu.be/C6EDC8LZJX

Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo.

BackgroundMany patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.ResultsTMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.ConclusionOur results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC

Entrepreneurs’ Activities on Social Media and Venture Financing

Social media has been an incredible platform for startups to develop meaningful connections with stakeholders and customers. We investigate ways in which entrepreneurs use social media to drive both the level of engagement for their startup and the subsequent level of venture financing. Our empirical analysis demonstrates how differences in entrepreneurs’ tweets—i.e., differences in the level informativity, persuasiveness, and transformativity—is associated with different levels of startup engagement and venture financing. We show differences in entrepreneurs’ activity with the social media platform—i.e., the number of tweets, the number of mentions of other accounts, and the number of retweets—further drives engagement and venture financing. We test our model by collecting an extensive dataset of over 7,000,000 tweets from entrepreneurs and startups that have been through accelerators. Results indicate associates between the social media activities of entrepreneurs, startup engagement, and venture financing

Professional Development Support for the Online Instructor: Perspectives of U.S. and German Instructors

With the increase in number of courses being offered online, there is an increase in the need for professional development support for instructors to teach online. The purpose of this study is to examine faculty perceptions on professional development needs for online teaching, specifically in the U.S. and in Germany. Based on a qualitative open-ended survey, four themes emerged on the professional development needs of instructors for administrative support, personnel support, pedagogical support and technology support. This study discusses specific areas of support in these themes and provides implications for administrators, faculty, and support staff

NeRF in the Palm of Your Hand: Corrective Augmentation for Robotics via Novel-View Synthesis

Expert demonstrations are a rich source of supervision for training visual robotic manipulation policies, but imitation learning methods often require either a large number of demonstrations or expensive online expert supervision to learn reactive closed-loop behaviors. In this work, we introduce SPARTN (Synthetic Perturbations for Augmenting Robot Trajectories via NeRF): a fully-offline data augmentation scheme for improving robot policies that use eye-in-hand cameras. Our approach leverages neural radiance fields (NeRFs) to synthetically inject corrective noise into visual demonstrations, using NeRFs to generate perturbed viewpoints while simultaneously calculating the corrective actions. This requires no additional expert supervision or environment interaction, and distills the geometric information in NeRFs into a real-time reactive RGB-only policy. In a simulated 6-DoF visual grasping benchmark, SPARTN improves success rates by 2.8$\times$ over imitation learning without the corrective augmentations and even outperforms some methods that use online supervision. It additionally closes the gap between RGB-only and RGB-D success rates, eliminating the previous need for depth sensors. In real-world 6-DoF robotic grasping experiments from limited human demonstrations, our method improves absolute success rates by $22.5\%$ on average, including objects that are traditionally challenging for depth-based methods. See video results at \url{https://bland.website/spartn}

Discursive construction of spiritual values and cultural standards in Sang Pemimpi Film

Spirituality is a contentious human phenomenon that encompasses personal, sociocultural, and transcendent interconnection. In Indonesian society, spiritual experiences are often associated with religion. They are also part of the cultural standards, the way of thinking, feeling, and behaving shared by most of a culture's members. This research aims to examine the spiritual and cultural values of Belitung's Muslim society through the Sang Pemimpi film. The research method in this study was critical discourse analysis, a qualitative approach based on a critical paradigm. This study combines Theo van Leeuwen's critical and multimodality discourse analysis techniques. Spiritual values and cultural standards are used as theoretical elements. The character in the film's text with the background of the Muslim society and the Belitung people's culture is the focus of this study. According to the film analysis, spirituality is formed by socio-cultural interactions in people's daily lives. The Muslim community in Belitung adapts well to religious and cultural differences in their social relationships with other ethnic groups, including the Chinese ethnic groups. According to the findings of this study, religiosity and communal domains are the aspects that appear the most in the film

Examination of Cybersecurity Technologies, Practices, Challenges, and Wish List in K-12 School Districts

With the growth in digital teaching and learning, there has been a sharp rise in the number of cybersecurity attacks on K-12 school networks. This has demonstrated a need for security technologies and cybersecurity education. This study examined security technologies used, effective security practices, challenges, concerns, and wish list of technology leaders in K-12 settings. Data collected from 23 district websites and from interviews with 12 district technology leaders were analyzed. Top security practices included cloud-based technologies, segregated network/V-LAN, two-factor authentication, limiting access, and use of Clever or Class Link. Top challenges included keeping users informed, lack of buy-in from staff and decision-makers, lack of expertise to implement modern best practices, and cost of resources. Top concerns included possible cyberattacks, leaked student data, and lack of user awareness. Finally, their wish list included technology personnel, access to Clever of Class Link, external system diagnostic checks, professional development for staff, and replacing aging infrastructure. The findings have implications for K-12 administrators, technology leaders, and teachers

NMR Spectroscopy Analysis Reveals Differential Metabolic Responses in Arabidopsis Roots and Leaves Treated with a Cytokinesis Inhibitor

In plant cytokinesis, de novo formation of a cell plate evolving into the new cell wall partitions the cytoplasm of the dividing cell. In our earlier chemical genomics studies, we identified and characterized the small molecule endosidin-7, that specifically inhibits callose deposition at the cell plate, arresting late-stage cytokinesis in arabidopsis. Endosidin-7 has emerged as a very valuable tool for dissecting this essential plant process. To gain insights regarding its mode of action and the effects of cytokinesis inhibition on the overall plant response, we investigated the effect of endosidin-7 through a nuclear magnetic resonance spectroscopy (NMR) metabolomics approach. In this case study, metabolomics profiles of arabidopsis leaf and root tissues were analyzed at different growth stages and endosidin-7 exposure levels. The results show leaf and root-specific metabolic profile changes and the effects of endosidin-7 treatment on these metabolomes. Statistical analyses indicated that the effect of endosidin-7 treatment was more significant than the developmental impact. The endosidin-7 induced metabolic profiles suggest compensations for cytokinesis inhibition in central metabolism pathways. This study further shows that long-term treatment of endosidin-7 profoundly changes, likely via alteration of hormonal regulation, the primary metabolism of arabidopsis seedlings. Hormonal pathway-changes are likely reflecting the plant’s responses, compensating for the arrested cell division, which in turn are leading to global metabolite modulation. The presented NMR spectral data are made available through the Metabolomics Workbench, providing a reference resource for the scientific community