Slow Moving Capital

We study three cases in which specialized arbitrageurs lost significant amounts of capital and, as a result, became liquidity demanders rather than providers. The effects on security markets were large and persistent: Prices dropped relative to fundamentals and the rebound took months. While multi-strategy hedge funds who were not capital constrained increased their positions, a large fraction of these funds actually acted as net sellers consistent with the view that information barriers within a firm (not just relative to outside investors) can lead to capital constraints for trading desks with mark-to-market losses. Our findings suggest that real world frictions impede arbitrage capital.

Bankruptcy and the Collateral Channel

Do bankrupt firms impose negative externalities on their nonbankrupt competitors? We propose and analyze a collateral channel in which a firm’s bankruptcy reduces the collateral value of other industry participants, thereby increasing their cost of debt financing. We identify the collateral channel using novel data of secured debt tranches issued by U.S. airlines that include detailed descriptions of the underlying collateral pools. Our estimates suggest that industry bankruptcies have a sizeable impact on the cost of debt financing of other industry participants. We discuss how the collateral channel may lead to contagion effects that amplify the business cycle during industry downturns

Uma abordagem pontual acerca da Cultura e do Direito no Rio de Janeiro contemporâneo

O trabalho tem como cenário a cidade do Rio de Janeiro no período compreendido entre os anos de 1945/1964. A abordagem em si discute, de maneira geral, a convivência sócio institucional urbana pós segunda guerra mundial, envolvendo, de maneira particular, a cultura urbana prevalente nos aspectos político, jurídico e social. Discute de maneira bem pontual, as novas idealizações civilizatórias projetadas para o Brasil tendo como referência a nova ordem ocidental pós-moderna, principalmente naquilo que envolve os contextos político, econômico e social. No aspecto político, aborda o mosaico político-partidário daépoca e, principalmente, a Constituição Federal de 1946. No aspecto econômico, aborda a inserção do Brasil à nova ordem imposta pelo neo-capitalismo mundial, basicamente aquele oriundo do capital expansionista americano. No aspecto social, o texto observa o comportamento social, os costumes impactados pela nova mentalidade emergente. Dentro da perspectiva jurídica, o trabalho observa também a promulgação dos direitos sociais, dos direitos políticos e a idealização pela afirmação da cidadania como pressuposto obrigatório na reforma política empreendida no período

Red Blood Cell Distribution Width (RDW) Predicts COVID-19 Severity: A Prospective, Observational Study from the Cincinnati SARS-CoV-2 Emergency Department Cohort

Since previous evidence has demonstrated that red blood cell distribution width (RDW) may be a useful prognostic parameter in many critical illnesses and infectious diseases, we investigated the utility of RDW for monitoring patients with coronavirus disease 2019 (COVID-19). The study population consisted of 49 COVID-19 patients, including 16 (32.6%) with severe illness, 12 (24.5%) with severe acute kidney injury (AKI), and 8 (16.3%) requiring renal replacement therapy (RRT). The predictive value of blood tests, performed during emergency department evaluation, was then addressed. A progressive increase of RDW was observed with advancing COVID-19 severity. The area under the curve (AUC) of RDW was 0.73 for predicting severe illness, 0.80 for severe AKI, and 0.83 for RRT, respectively. In multivariate analysis, elevated RDW was associated with 9-fold and 16-fold increased odds of severe COVID-19 and AKI, respectively. The results of this study suggest that RDW should be part of routine laboratory assessment and monitoring of COVID-19

Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline

In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development

Non-proteolytic ubiquitin signaling mediated by Lys63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNF signaling and lipid metabolism in the adipose tissue through modulation of Lys63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells

Sudden Financial Arrest

This paper was presented as the Mundell-Fleming Lecture at the Tenth Jacques Polak Annual Research Conference at the International Monetary Fund in Washington held November 5–6, 2009.There are striking and terrifying similarities between the sudden failure of a heart and that of a financial system. In the medical literature, the former is referred to as sudden cardiac arrest. By analogy, I refer to its financial counterpart as a sudden financial arrest. In this article I describe the latter and its treatment guided by its medical counterpart