We study the relation between investment behavior and competitor financial constraints. Using interfirm patent citations and text-based product market similarities to identify intransitive competitor ...networks, we find that firms increase investment spending, patenting activity, and opportunistic hiring when competitor constraints become more binding. In addition, firms shift their investment composition (product market and patent portfolios) to compete more aggressively with relatively constrained competitors. To mitigate endogeneity concerns, we exploit the 2004 AJCA tax holiday and the 1989 junk bond crisis as exogenous shocks to competitor constraints, and we find similar effects.
Count (and count-like) data in finance Cohn, Jonathan B.; Liu, Zack; Wardlaw, Malcolm I.
Journal of financial economics,
November 2022, 2022-11-00, Volume:
146, Issue:
2
Journal Article
Peer reviewed
This paper assesses different econometric approaches to working with count-based outcome variables and other outcomes with similar distributions, which are increasingly common in corporate finance ...applications. We demonstrate that the common practice of estimating linear regressions of the log of 1 plus the outcome produces estimates with no natural interpretation that can have the wrong sign in expectation. In contrast, a simple fixed-effects Poisson model produces consistent and reasonably efficient estimates under more general conditions than commonly assumed. We also show through replication of existing papers that economic conclusions can be highly sensitive to the regression model employed.
We investigate how access to capital relates to the firms' investment decisions and project characteristics. We use project-level hydraulic fracturing (fracking) data from the energy industry to show ...that privately held firms more intensely invest in newer, non-proven areas while publicly-traded firms tilt investment toward well-established, proven areas. Furthermore, we find that exogenous improvements in private firms' access to finance decrease the investment wedge between private and public firms. Our results suggest that private firms minimize their financial disadvantages by targeting investment opportunities that have greater uncertainty.
Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on ...tissue-specific gene regulation.
The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation). The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM) detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes.
We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.
MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether ...MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.
Interferons (IFN) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (ISGs), most of which have ...uncharacterized functions and mechanisms. We identified cholesterol-25-hydroxylase (CH25H) as a broadly antiviral ISG. CH25H converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). 25HC treatment in cultured cells broadly inhibited growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses under BSL4 conditions. It suppressed viral growth by blocking membrane fusion between virus and cell. In animal models, Ch25h-deficient mice were more susceptible to MHV68 lytic infection. Moreover, administration of 25HC in humanized mice suppressed HIV replication and reversed T cell depletion. Thus, our studies demonstrate a unique mechanism by which IFN achieves its antiviral state through the production of a natural oxysterol to inhibit viral entry and implicate membrane-modifying oxysterols as potential antiviral therapeutics.
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► CH25H inhibits viral growth by production of an oxysterol, 25-hydroxycholesterol ► 25HC inhibits replication of VSV, HSV, HIV, MHV68, EBOV, NiV, RSSEV, and RVFV ► 25HC inhibits viral fusion of VSV and HIV ► In vivo, 25HC suppresses HIV growth and Ch25h is required for antiviral immunity
The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells ...in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten-/-central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
Alternative splicing is highly regulated in tissue‐specific and development‐specific patterns, and it has been estimated that 15% of disease‐causing point mutations affect pre‐mRNA splicing. In this ...review, we consider the cis‐acting splice site and trans‐acting splicing factor mutations that affect pre‐mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa (RP) and various cone‐rod dystrophies. Mutations in alternatively spliced retina‐specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X‐linked RP and ocular variants of Stickler syndrome, respectively. Furthermore, mutations in general pre‐mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant RP. These findings suggest an important role for pre‐mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule‐based therapies, has the potential to lead to new treatments for retinal degenerative diseases.
We develop roadmaps to transform the all-purpose energy infrastructures (electricity, transportation, heating/cooling, industry, agriculture/forestry/fishing) of 139 countries to ones powered by ...wind, water, and sunlight (WWS). The roadmaps envision 80% conversion by 2030 and 100% by 2050. WWS not only replaces business-as-usual (BAU) power, but also reduces it ∼42.5% because the work: energy ratio of WWS electricity exceeds that of combustion (23.0%), WWS requires no mining, transporting, or processing of fuels (12.6%), and WWS end-use efficiency is assumed to exceed that of BAU (6.9%). Converting may create ∼24.3 million more permanent, full-time jobs than jobs lost. It may avoid ∼4.6 million/year premature air-pollution deaths today and ∼3.5 million/year in 2050; ∼$22.8 trillion/year (12.7 ¢/kWh-BAU-all-energy) in 2050 air-pollution costs; and ∼$28.5 trillion/year (15.8 ¢/kWh-BAU-all-energy) in 2050 climate costs. Transitioning should also stabilize energy prices because fuel costs are zero, reduce power disruption and increase access to energy by decentralizing power, and avoid 1.5°C global warming.
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•Roadmaps for 139 countries to use 100% wind-water-solar in all energy sectors•Roadmaps avoid 1.5°C global warming and millions of annual air-pollution deaths•Roadmaps reduce social cost of energy and create 24.3 million net long-term jobs•Roadmaps reduce power disruption and increase worldwide access to energy
For the world to reverse global warming, eliminate millions of annual air-pollution deaths, and provide secure energy, every country must have an energy roadmap based on widely available, reliable, zero-emission energy technologies. This study presents such roadmaps for 139 countries of the world. These roadmaps are far more aggressive than what the Paris agreement calls for, but are still technically and economically feasible. The solution is to electrify all energy sectors (transportation, heating/cooling, industry, agriculture/forestry/fishing) and provide all electricity with 100% wind, water, and solar (WWS) power. If fully implemented by 2050, the roadmaps will enable the world to avoid 1.5°C global warming and millions of annual air-pollution deaths, create 24.3 million net new long-term, full-time jobs, reduce energy costs to society, reduce energy end-use by 42.5%, reduce power disruption, and increase worldwide access to energy.
We develop energy roadmaps to significantly slow global warming and nearly eliminate air-pollution mortality in 139 countries. These plans call for electrifying all energy sectors (transportation, heating/cooling, industry, agriculture/forestry/fishing) and providing the electricity with 100% wind, water, and solar (WWS) power. Fully implementing the roadmaps by 2050 avoids 1.5°C global warming and millions of deaths from air pollution annually; creates 24.3 million net new long-term, full-time jobs; reduces energy costs to society; reduces power requirements 42.5%; reduces power disruption; and increases worldwide access to energy.
Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked ...how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection. Oct4 suppresses neural ectodermal differentiation and promotes mesendodermal differentiation; Sox2 inhibits mesendodermal differentiation and promotes neural ectodermal differentiation. Differentiation signals continuously and asymmetrically modulate Oct4 and Sox2 protein levels, altering their binding pattern in the genome, and leading to cell fate choice. The same factors that maintain pluripotency thus also integrate external signals and control lineage selection. Our study provides a framework for understanding how complex transcription factor networks control cell fate decisions in progenitor cells.
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► Lineage-specific expression patterns identify factors governing germ layer fate choice ► Dynamics of ESC pluripotency factors Oct4 and Sox2 predict and control cell fate choice ► Altering Oct4 and Sox2 levels affects germ layer fate choice ► Modeling reveals that pluripotency circuit can integrate signals to determine fate
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