The Bursty Dynamics of the Twitter Information Network

In online social media systems users are not only posting, consuming, and resharing content, but also creating new and destroying existing connections in the underlying social network. While each of these two types of dynamics has individually been studied in the past, much less is known about the connection between the two. How does user information posting and seeking behavior interact with the evolution of the underlying social network structure? Here, we study ways in which network structure reacts to users posting and sharing content. We examine the complete dynamics of the Twitter information network, where users post and reshare information while they also create and destroy connections. We find that the dynamics of network structure can be characterized by steady rates of change, interrupted by sudden bursts. Information diffusion in the form of cascades of post re-sharing often creates such sudden bursts of new connections, which significantly change users' local network structure. These bursts transform users' networks of followers to become structurally more cohesive as well as more homogenous in terms of follower interests. We also explore the effect of the information content on the dynamics of the network and find evidence that the appearance of new topics and real-world events can lead to significant changes in edge creations and deletions. Lastly, we develop a model that quantifies the dynamics of the network and the occurrence of these bursts as a function of the information spreading through the network. The model can successfully predict which information diffusion events will lead to bursts in network dynamics

On the Convexity of Latent Social Network Inference

In many real-world scenarios, it is nearly impossible to collect explicit social network data. In such cases, whole networks must be inferred from underlying observations. Here, we formulate the problem of inferring latent social networks based on network diffusion or disease propagation data. We consider contagions propagating over the edges of an unobserved social network, where we only observe the times when nodes became infected, but not who infected them. Given such node infection times, we then identify the optimal network that best explains the observed data. We present a maximum likelihood approach based on convex programming with a l1-like penalty term that encourages sparsity. Experiments on real and synthetic data reveal that our method near-perfectly recovers the underlying network structure as well as the parameters of the contagion propagation model. Moreover, our approach scales well as it can infer optimal networks of thousands of nodes in a matter of minutes.Comment: NIPS, 201

First results from a VLBA proper motion survey of H2O masers in low-mass YSOs: the Serpens core and RNO15-FIR

This article reports first results of a long-term observational program aimed to study the earliest evolution of jet/disk systems in low-mass YSOs by means of VLBI observations of the 22.2 GHz water masers. We report here data for the cluster of low-mass YSOs in the Serpens molecular core and for the single object RNO~15-FIR. Towards Serpens SMM1, the most luminous sub-mm source of the Serpens cluster, the water maser emission comes from two small (< 5 AU in size) clusters of features separated by ~25 AU, having line of sight velocities strongly red-shifted (by more than 10 km/s) with respect to the LSR velocity of the molecular cloud. The two maser clusters are oriented on the sky along a direction that is approximately perpendicular to the axis of the radio continuum jet observed with the VLA towards SMM1. The spatial and velocity distribution of the maser features lead us to favor the interpretation that the maser emission is excited by interaction of the receding lobe of the jet with dense gas in the accretion disk surrounding the YSO in SMM1. Towards RNO~15-FIR, the few detected maser features have both positions and (absolute) velocities aligned along a direction that is parallel to the axis of the molecular outflow observed on much larger angular scales. In this case the maser emission likely emerges from dense, shocked molecular clumps displaced along the axis of the jet emerging from the YSO. The protostar in Serpens SMM1 is more massive than the one in RNO~15-FIR. We discuss the case where a high mass ejection rate can generate jets sufficiently powerful to sweep away from their course the densest portions of circumstellar gas. In this case, the excitation conditions for water masers might preferably occur at the interface between the jet and the accretion disk, rather than along the jet axis.Comment: 18 pages (postscript format); 9 figures; to be published into Astronomy & Astrophysics, Main Journa

The IKKâ related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists

The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogeneâ induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through siteâ specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGFâ receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i.e., TLR3; TLR4), revealing a stimulusâ selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knockâ in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFNâ β production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1â mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation.SynopsisTBK1, an IKKâ related kinase that drives interferon production as well cancer cell proliferation and survival, phosphorylates mTOR to activate mTORC1 in response to EGF and innate immune agonists, suggesting unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity and tumorigenesis.TBK1 interacts with mTORC1 and phosphorylates mTOR on S2159 to increase its catalytic activity.Cells lacking TBK1 or expressing a mTOR S2159A allele exhibit reduced mTORC1 signaling in response to EGFâ receptor and TLR3/4 activation.Primary macrophages derived from genome edited mTOR S2159A mice exhibit reduced mTORC1 signaling in response to TLR3/4 activation.Primary macrophages treated with rapamycin as well as those derived from mTORS2159A mice produce reduced levels of IFNâ β due to impaired nuclear translocation of the transcription factor IRF3.Innate immune kinase TBK1â dependent activation of mTORC1 occurs in response to pathogen recognition and EGF receptor activation and drives interferon production, thus highlighting the role of mTOR for innate immunity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/1/embj201696164.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/2/embj201696164.reviewer_comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/3/embj201696164_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141029/4/embj201696164-sup-0001-EVFigs.pd

Angular Momentum and the Formation of Stars and Black Holes

The formation of compact objects like stars and black holes is strongly constrained by the requirement that nearly all of the initial angular momentum of the diffuse material from which they form must be removed or redistributed during the formation process. The mechanisms that may be involved and their implications are discussed for (1) low-mass stars, most of which probably form in binary or multiple systems; (2) massive stars, which typically form in clusters; and (3) supermassive black holes that form in galactic nuclei. It is suggested that in all cases, gravitational interactions with other stars or mass concentrations in a forming system play an important role in redistributing angular momentum and thereby enabling the formation of a compact object. If this is true, the formation of stars and black holes must be a more complex, dynamic, and chaotic process than in standard models. The gravitational interactions that redistribute angular momentum tend to couple the mass of a forming object to the mass of the system, and this may have important implications for mass ratios in binaries, the upper stellar IMF in clusters, and the masses of supermassive black holes in galaxies.Comment: Accepted by Reports on Progress in Physic

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry

Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real-world” setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), Patient‐Centered Outcomes Research Institute (PCORI) (ME‐2019C1‐15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN