Miracle-dz/UniFAR-FTUs huggingface dataset:
When Corporations Are People: Agent Talk and the Development of Organizational Actorhood, 1890–1934

Research in organizational theory takes as a key premise the notion that organizations are “actors. ” Organizational actorhood, or agency, depends, in part, on how external audiences perceive organizations. In other words, organizational agency requires that external audiences take organizations to be agents. Yet little empirical research has attempted to measure these attributions: when do audiences assume that organizations are agents and how have these attributions changed over time? In this article, I suggest that scholars can triangulate across computational methods—including named entity recognition, dependency parsing, topic models, and dictionary methods—to analyze attributions of agency in text, discourse that I term “agent talk. ” I demonstrate the utility of this approach by analyzing how business organizations were discussed as agents during a key period of organizational development, the turn of the twentieth century. Analyzing articles from two of the leading national newspapers, the Wall Street Journal and New York Times, I examine agent talk in everyday business discourse. I find that agent talk generally increased over the early twentieth century, as organizations were depicted as active subjects in text and personified as speakers. Moreover, I find that this discourse was concentrated in social and legal semantic contexts: in particular, contexts relating to labor, regulation, and railroads. Finally, I show the uneven growth of this rhetoric over time, as organizations across different semantic arenas were personified as speakers. Overall, these results show how measures of discourse can provide a window into how and when audiences endow organizations with actorhood.
Mobile genetic element-encoded putative DNA primases composed of A-family polymerase—SSB pairs

Mobile genetic elements can encode a wide variety of genes that support their own stability and mobility as well as genes that provide accessory functions to their hosts. Such genes can be adopted from host chromosomes and can be exchanged with other mobile elements. Due to their accessory nature, the evolutionary trajectories of these genes can differ from those of essential host genes. The mobilome therefore provides a rich source of genetic innovation. We previously described a new type of primase encoded by S. aureus SCCmec elements that is composed of an A-family polymerase catalytic domain in complex with a small second protein that confers single-stranded DNA binding. Here we use new structure prediction methods in conjunction with sequence database searches to show that related primases are widespread among putative mobile genetic elements in the Firmicutes. Structure predictions show that the second protein adopts an OB fold (common among single-stranded DNA binding (SSB) proteins) and these predictions were far more powerful than simple sequence comparisons in identifying its homologs. The protein-protein interaction surface varies among these polymerase – SSB complexes and appears to have arisen repeatedly by exploiting partial truncations of the polymerase’s N-terminal accessory domains.
Isolation of strains and their genome sequencing to analyze the mating system of Ophiocordyceps robertsii

The fungal genus Ophiocordyceps contains a number of insect pathogens. One of the best known of these is Ophiocordyceps sinensis, which is used in Chinese medicine and its overharvesting threatens sustainability; hence, alternative sources are being sought. Ophiocordyceps robertsii, found in Australia and New Zealand, has been proposed to be a close relative to O. sinensis, but little is known about this species despite being also of historical significance. Here, O. robertsii strains were isolated into culture and high coverage draft genome sequences obtained and analyzed. This species has a large genome expansion, as also occurred in O. sinensis. The mating type locus was characterized, indicating a heterothallic arrangement whereby each strain has an idiomorphic region of two (MAT1-2-1, MAT1-2-2) or three (MAT1-1-1, MAT1-1-2, MAT1-1-3) genes flanked by the conserved APN2 and SLA2 genes. These resources provide a new opportunity for understanding the evolution of the expanded genome in the homothallic species O. sinensis, as well as capabilities to explore the pharmaceutical potential in a species endemic to Australia and New Zealand. One sentence summary Ophiocordyceps robertsii is a close relative of O. sinensis and has a large genome but with a heterothallic mating system.
Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes

Introduction While Yap and Wwtr1 regulate resident cardiac fibroblast to myofibroblast differentiation following cardiac injury, their role specifically in activated myofibroblasts remains unexplored. Methods We assessed the pathophysiological and cellular consequence of genetic depletion of Yap alone (Yapfl/fl;PostnMCM) or Yap and Wwtr1 (Yapfl/fl;Wwtr1fl/+;PostnMCM) in adult mouse myofibroblasts following myocardial infarction and identify and validate novel downstream factors specifically in cardiac myofibroblasts that mediate pathological remodeling. Results Following myocardial infarction, depletion of Yap in myofibroblasts had minimal effect on heart function while depletion of Yap/Wwtr1 resulted in smaller scars, reduced interstitial fibrosis, and improved ejection fraction and fractional shortening. Single cell RNA sequencing of interstitial cardiac cells 7 days post infarction showed suppression of pro-fibrotic genes in fibroblasts derived from Yapfl/fl,Wwtr1fl/+;PostnMCM hearts. In vivo myofibroblast depletion of Yap/Wwtr1 as well in vitro knockdown of Yap/Wwtr1 dramatically decreased RNA and protein expression of the matricellular factor Ccn3. Administration of recombinant CCN3 to adult mice following myocardial infarction remarkably aggravated cardiac function and scarring. CCN3 administration drove myocardial gene expression of pro-fibrotic genes in infarcted left ventricles implicating CCN3 as a novel driver of cardiac fibrotic processes following myocardial infarction. Discussion Yap/Wwtr1 depletion in myofibroblasts attenuates fibrosis and significantly improves cardiac outcomes after myocardial infarction and we identify Ccn3 as a factor downstream of Yap/Wwtr1 that contributes to adverse cardiac remodeling post MI. Myofibroblast expression of Yap, Wwtr1, and Ccn3 could be further explored as potential therapeutic targets for modulating adverse cardiac remodeling post injury.
Partition complex structure can arise from sliding and bridging of ParB dimers

Chromosome segregation is vital for cell replication and in many bacteria is controlled by the ParABS system. A key part of this machinery is the association of ParB proteins to the parS-containing centromeric region to form the partition complex. Despite much work, the formation and structure of this nucleoprotein complex has remained unclear. However, it was recently discovered that CTP binding allows ParB dimers to entrap and slide along the DNA, as well as leading to more efficient condensation through ParB-mediated DNA bridging. Here, we use semi-flexible polymer simulations to show how these properties of sliding and bridging can explain partition complex formation. We find that transient ParB bridges can organise the DNA into either a globular state or into hairpins and helical structures, depending on the bridge lifetime. In separate stochastic simulations, we show that ParB sliding reproduces the experimentally measured multi-peaked binding profile of Caulobacter crescentus, indicating that bridging and other potential roadblocks are sufficiently short-lived that they do not hinder ParB spreading. Indeed, upon coupling the two simulation frameworks into a unified sliding and bridging model, we find that short-lived ParB bridges do not hinder ParB sliding and the model can reproduce both the ParB binding profile as well as the condensation of the nucleoprotein complex. Overall, our model clarifies the mechanism of partition complex formation and predicts its fine structure. We speculate that the DNA hairpins produced by ParB bridging underlie the secondary function of ParB to load the Structural Maintenance of Chromosome (SMC) complex onto the DNA.
Prediction and curation of missing biomedical identifier mappings with Biomappings

Motivation Biomedical identifier resources (ontologies, taxonomies, controlled vocabularies) commonly overlap in scope and contain equivalent entries under different identifiers. Maintaining mappings for these relationships is crucial for interoperability and the integration of data and knowledge. However, there are substantial gaps in available mappings motivating their semi-automated curation. Results Biomappings implements a curation cycle workflow for missing mappings which combines automated prediction with human-in-the-loop curation. It supports multiple prediction approaches and provides a web-based user interface for reviewing predicted mappings for correctness, combined with automated consistency checking. Predicted and curated mappings are made available in public, version-controlled resource files on GitHub. Biomappings currently makes available 8,560 curated mappings and 41,178 predicted ones, providing previously missing mappings between widely used resources covering small molecules, cell lines, diseases and other concepts. We demonstrate the value of Biomappings on case studies involving predicting and curating missing mappings among cancer cell lines as well as small molecules tested in clinical trials. We also present how previously missing mappings curated using Biomappings were contributed back to multiple widely used community ontologies. Availability The data and code are available under the CC0 and MIT licenses at https://github.com/biopragmatics/biomappings. Contact benjamin_gyori@hms.harvard. edu
Hall effect in incompressible magnetic reconnection

[1] Theoretical models of magnetic reconnection have been traditionally developed within the framework of magnetohydrodynamics (MHD). However, in low-density astrophysical plasmas like those found in the magnetopause and the magnetotail, kinetic effects such as the Hall current are expected to play a significant role. We present results from externally driven magnetic reconnection simulations, within the framework of incompressible Hall MHD in 2 1/2 dimensions. We evaluate the relevance of the Hall current in the reconnection process by performing a set of simulations with different values of the Hall parameter. We compute the corresponding reconnection rates as a function of time and explore the spatial structure of the fields in the surroundings of the diffusion region.
Simulation of Stochastic Partial Differential Equations and Stochastic Active Contours

This thesis discusses several aspects of the simulation of stochastic partial differential equations. First, two fast algorithms for the approximation of infinite dimensional Gaussian random fields with given covariance are introduced. Later Hilbert space-valued Wiener processes are constructed out of these random fields. A short introduction to infinite-dimensional stochastic analysis and stochastic differential equations is given. Furthermore different definitions of numerical stability for the discretization of stochastic partial differential equations are presented and the numerical stability of the heat equation with additive and multiplicative noise is explicitely computed using semigroup theory. Finally stochastic active contours are used for segmentation. This thesis generalizes work done by Juan et al. and does the simulation of different stochastic partial differential equations. The results are compared to equations without stochastics.
The CD73 immune checkpoint promotes tumor cell metabolic fitness

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism, and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.
Color and Spatial Frequency Provide Functional Signatures of Retinotopic Visual Areas

Primate vision relies on retinotopically organized cortex defined by representations of hemifield (upper versus lower visual field), eccentricity (fovea versus periphery), and area (V1, V2, V3, V4). To test for the functional signatures of these organizing principles, we used fMRI to measure responses to colored gratings with varying spatial frequency, color, and saturation across rentinotopically defined parcels in macaque monkeys. Using an approach we call Sparse Supervised Embedding (SSE), we identified stimulus features that differed most across the cortical parcels. Constraining the model according to each voxel’s eccentricity revealed the expected variation of spatial frequency and S-cone modulation with eccentricity. Constraining according to voxel dorsal-ventral location and retinotopic area, revealed two additional components which together provide unexpected functional signatures. First earlier visual areas were more sensitive to contrast and saturation compared to later areas. Second, ventral parcels responded less to luminance contrast and more to color, particularly along the orange-blue intermediate axis in cone-opponent color space. This dorsal-ventral asymmetry resembles differences between candidate dorsal and ventral subdivisions of human V4 but extends to include all retinotopic visual areas, with a magnitude that increased from V1 to V4. Overall, our study demonstrates SSE as a data-driven tool for generating hypotheses about cortical function and behavior, and provides insight into the functional roles of different retinotopic areas. Significance Statement This study explores the functional roles of visual areas (V1, V2, V3, V4, V3a, MT) parceled by eccentricity preference and visual hemifield. We employ a new approach called Sparse Supervised Embedding (SSE), a promising technique for visualizing and understanding complex neuroimaging datasets. Analyzing fMRI responses to different color grating stimuli, we uncover a functional organization across these parcels, shedding light on their roles in visual computation. This study enhances our knowledge of processing in early visual cortex and how it varies across the retinotopic map. It also aids in resolving apparent differences between prior human and macaque studies.
Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of Methyl CpG-binding Protein 2 (MECP2) on the X chromosome in girls. Reactivation of the silent wild-type MECP2 allele from the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female patients with RTT. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 from Xi in RTT human embryonic stem cells (hESCs) and derived neurons. Demethylation of the MECP2 promoter by dCas9-Tet1 with target sgRNA reactivated MECP2 from Xi in RTT hESCs without detectable off-target effects at the transcriptional level. Neurons derived from methylation-edited RTT hESCs maintained MECP2 reactivation and reversed the smaller soma size and electrophysiological abnormalities, two hallmarks of RTT. In RTT neurons, insulation of the methylation edited MECP2 locus by dCpf1-CTCF with target CRISPR RNA enhanced MECP2 reactivation and rescued RTT-related neuronal defects, providing a proof-of-concept study for epigenome editing to treat RTT and potentially other dominant X-linked diseases. One-Sentence Summary Reactivation of MECP2 from the inactive X chromosome by multiplex epigenome editing rescues Rett syndrome neurons in vitro.
Carotenoid-dependent plumage coloration is associated with reduced male care in passerine birds

The immense diversity of plumage coloration exhibited by birds is the result of either pigments deposited in the feathers or microstructural arrangements of feather barbules. Some of the most common pigments are carotenoids that produce bright yellow, orange and red colors. Carotenoids differ from other pigments since birds cannot synthesize them de novo and must obtain them from the diet. Carotenoid pigments are usually associated with signaling and sexual selection, although they also have antioxidant properties and play a role in the immune response. Here we hypothesize that carotenoid-dependent plumage coloration functions as a signal of a male’s tendency to invest in offspring care because they play an important role in the self-maintenance and may provide key information about individual quality; allowing females to obtain information about a males’ tendency to invest in offspring care. Using phylogenetic comparative analyses across 350 passerine birds we show that species that consume carotenoid-rich foods have more carotenoid-dependent plumage coloration than species with carotenoid-poor diets. In addition, carotenoid-dependent plumage coloration is associated with a decreased male investment in offspring care. Our results suggest investment into carotenoid-dependent plumage coloration trades off against male investment into offspring care and will likely have broad implications for our understanding of the ecological contexts that facilitate various evolutionary processes such as sexual selection or signaling associated with plumage colors.
CRMnet: A deep learning model for predicting gene expression from large regulatory sequence datasets

Recent large datasets measuring the gene expression of millions of possible gene promoter sequences provide a resource to design and train optimised deep neural network architectures to predict expression from sequences. High predictive performance due to the modelling of dependencies within and between regulatory sequences is an enabler for biological discoveries in gene regulation through model interpretation techniques. To understand the regulatory code that delineates gene expression, we have designed a novel deep-learning model (CRMnet) to predict gene expression in Saccharomyces cerevisiae. Our model outperforms the current benchmark models and achieves a Pearson correlation coefficient of 0.971. Interpretation of informative genomic regions determined from model saliency maps, and overlapping the saliency maps with known yeast motifs, support that our model can successfully locate the binding sites of transcription factors that actively modulate gene expression. We compare our model’s training times on a large compute cluster with GPUs and Google TPUs to indicate practical training times on similar datasets.
Administration of amniotic fluid stem cell extracellular vesicles promotes development of fetal hypoplastic lungs by immunomodulating lung macrophages

Congenital diaphragmatic hernia (CDH) is a devastating condition characterized by incomplete closure of the diaphragm and herniation of abdominal organs into the chest. As a result, fetuses have pulmonary hypoplasia, whose severity is the main determinant of poor outcome. The pathogenesis of pulmonary hypoplasia secondary to CDH is at least in part explained by lack or dysregulation of miRNAs that are known to regulate lung developmental processes. Herein, we report that intra-amniotic administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs) rescues lung growth and maturation in a fetal rat model of CDH. To understand which fetal lung cells and biological pathways are affected by AFSC-EVs, we conducted whole lung single nucleus RNA-sequencing. We discovered that CDH lungs have a multilineage inflammatory signature with macrophage enrichment, and confirmed these findings in autopsy samples of lungs from human fetuses with CDH. Transcriptomic analysis of CDH fetal rat lungs also showed that AFSC-EV treatment reduced macrophage density and inflammation to normal levels. Analyzing the miRNAs contained in the AFSC-EV cargo with validated mRNA targets, we found that the downregulated genes in AFSC-EV treated CDH lungs were involved in inflammatory response and immune system processes. This study reports a single cell atlas of normal and hypoplastic CDH fetal rat lungs and provides evidence that AFSC-EVs restore lung development by addressing multiple pathophysiological aspects of CDH. One Sentence Summary Amniotic fluid stem cell extracellular vesicle treatment for fetal lung macrophage modulation
Unraveling the viral dark matter of the rumen microbiome with a new global virome database

Like in the human gut and other environments, viruses are probably also diverse and modulate the microbiome (both population and function) in the rumen of ruminants, but it remains largely unknown. Here we mined 975 published rumen metagenomes for viral sequences, created the first rumen virome database (RVD), and perform ecogenomic meta-analyses of these data. This identified 397,180 species-level viral operational taxonomic units (vOTUs) and allowed for a 10-fold increase in classification rate of rumen viral sequences compared with other databases. Most of the classified vOTUs belong to the order Caudovirales, but distinct from those in the human gut. Rumen viruses likely have ecosystem impacts as they were predicted to infect dominant fiber degraders and methane producers, and they carry diverse auxiliary metabolic genes and antibiotic resistance genes. Together, the RVD database and these findings provide a baseline framework for future research on how viruses may impact the rumen ecosystem.
On Convexity and Linear Mode Connectivity in Neural Networks

In many cases, neural networks trained with stochastic gradient descent (SGD) that share an early and often small portion of the training trajectory have solutions connected by a linear path of low loss. This phenomenon, called linear mode connectivity (LMC), has been leveraged for pruning and model averaging in large neural network models, but it is not well understood how broadly or why it occurs. LMC suggests that SGD trajectories somehow end up in a “convex” region of the loss landscape and stay there. In this work, we confirm that this eventually does happen by finding a high-dimensional convex hull of low loss between the endpoints of several SGD trajectories. But to our surprise, simple measures of convexity do not show any obvious transition at the point when SGD will converge into this region. To understand this convex hull better, we investigate the functional behaviors of its endpoints. We find that only a small number of correct predictions are shared between all endpoints of a hull, and an even smaller number of correct predictions are shared between the hulls, even when the final accuracy is high for every endpoint. Thus, we tie LMC more tightly to convexity, and raise several new questions about the source of this convexity in neural network optimization.