Modulation of cdk2, cyclin D1, p16INK4a, p21WAF and p27Kip1 expression in endothelial cells by TNF/IFN gamma.

BACKGROUND: Regional administration of high doses of tumor necrosis factor (TNF) and interferon gamma (IFN gamma) to metastatic melanoma patients causes selective disruption of the tumor vasculature. This effect is paralleled by decreased endothelial cell proliferation and suppressed integrin alpha V beta 3-mediated adhesion in vitro. Overexpression of the cyclin-dependent kinase (cdk) inhibitory protein p16INK4a was reported to interfere with integrin alpha V beta 3-dependent melanoma cell adhesion. MATERIALS AND METHODS: TNF- and IFN gamma-treated HUVEC were analyzed for cell cycle progression and for protein expression by flow cytometry and Western blotting, respectively. p16INK4a was overexpressed by transient transfection, and HUVEC adhesion was tested in short-term adhesion assays. RESULTS: TNF and IFN gamma synergistically induced a G1 arrest associated with reduced levels of cyclin D1 and cdk2, and increased expression of the cdk inhibitors p16INK4a, p21WAF and p27Kip1. p16INK4a overexpression, however, had no effect on alpha V beta 3-mediated adhesion. CONCLUSION: These results implicate the down-regulation of cyclin D1 and cdk-2, and up-regulation of p16INK4a, p21WAF and p27Kip1 in the suppression of endothelial cell proliferation induced by TNF/IFN gamma and demonstrate that increased p16INK4a levels are not sufficient to suppress alpha V beta 3-mediated endothelial cell adhesion.

Consumer Advisory Bulletin, Bank Credit Card Information, Fall 2003

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about: Bank Credit Card Information

Credit rationing and crowding out during the Industrial Revolution: Evidence from Hoare's Bank, 1702-1862

Crowding-out during the British Industrial Revolution has long been one of the leadingexplanations for slow growth during the Industrial Revolution, but little empirical evidence exists to support it. We argue that examinations of interest rates are fundamentally misguided, and that the eighteenth- and early nineteenth-century private loan market balanced through quantity rationing. Using a unique set of observations on lending volume at a London goldsmith bank, Hoare s, we document the impact of wartime financing on private credit markets. We conclude that there is considerable evidence that government borrowing, especially during wartime, crowded out private credit.

Consumer Advisory Bulletin, Guard Your Bank Accounts!, June 2005

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about: Guard Your Bank Accounts!

Financial liberalization, bank crises and growth: Assessing the links

This paper studies the effects of financial liberalization and banking crises on growth. It shows that financial liberalization spurs on average economic growth. Banking crises are harmful for growth, but to a lesser extent in countries with open financial systems and good institutions. The positive effect of financial liberalization is robust to different definitions. While the removal of capital account restrictions is effective by increasing financial depth, equity market liberalization affects growth directly. The empirical analysis is performed through GMM dynamic panel data estimations on a panel of 90 countries observed in the period 1975-1999.

Systemic risk, interbank relations and liquidity provision by the Central Bank

We model systemic risk in an interbank market. Banks face liquidityneeds as consumers are uncertain about where they need to consume. Interbank credit lines allow to cope with these liquidity shocks while reducing the cost of maintaining reserves. However, the interbank market exposes the system to a coordination failure(gridlock equilibrium) even if all banks are solvent. When one bankis insolvent, the stability of the banking system is affected in various ways depending on the patterns of payments across locations. We investigate the ability of the banking industry to withstand the insolvency of one bank and whether the closure ofone bank generates a chain reaction on the rest of the system. Weanalyze the coordinating role of the Central Bank in preventing payments systemic repercussions and we examine the justification ofthe Too-big-to-fail-policy.

Bank versus venture capital

Why do some start-up firms raise funds from banks andothers from venture capitalists? To answer this question,I develop a model of start-up financing when intellectualproperty rights are not well protected. The upside of VCfinancing is that the VC understands the business betterthan a bank. The downside, however, is that the VC maysteal the idea and use it himself. The results of themodel are consistent with empirical regularities onstart-up financing. The model implies that thecharacteristics of the firms financing from venturecapitalists are low-collateral, high-growth and high-profitability. The model also suggests that thetighter protection of intellectual property rightscontributes to the recent dramatic growth of the USventure capital industry.

A low dimensional Kalman filter for systems with lagged observables

This note describes how the Kalman filter can be modified to allow for thevector of observables to be a function of lagged variables without increasing the dimensionof the state vector in the filter. This is useful in applications where it is desirable to keepthe dimension of the state vector low. The modified filter and accompanying code (whichnests the standard filter) can be used to compute (i) the steady state Kalman filter (ii) thelog likelihood of a parameterized state space model conditional on a history of observables(iii) a smoothed estimate of latent state variables and (iv) a draw from the distribution oflatent states conditional on a history of observables.

Modulation of angiogenic and inflammatory response in glioblastoma by hypoxia.

Glioblastoma are rapidly proliferating brain tumors in which hypoxia is readily recognizable, as indicated by focal or extensive necrosis and vascular proliferation, two independent diagnostic criteria for glioblastoma. Gene expression profiling of glioblastoma revealed a gene expression signature associated with hypoxia-regulated genes. The correlated gene set emerging from unsupervised analysis comprised known hypoxia-inducible genes involved in angiogenesis and inflammation such as VEGF and BIRC3, respectively. The relationship between hypoxia-modulated angiogenic genes and inflammatory genes was associated with outcome in our cohort of glioblastoma patients treated within prospective clinical trials of combined chemoradiotherapy. The hypoxia regulation of several new genes comprised in this cluster including ZNF395, TNFAIP3, and TREM1 was experimentally confirmed in glioma cell lines and primary monocytes exposed to hypoxia in vitro. Interestingly, the cluster seems to characterize differential response of tumor cells, stromal cells and the macrophage/microglia compartment to hypoxic conditions. Most genes classically associated with the inflammatory compartment are part of the NF-kappaB signaling pathway including TNFAIP3 and BIRC3 that have been shown to be involved in resistance to chemotherapy.Our results associate hypoxia-driven tumor response with inflammation in glioblastoma, hence underlining the importance of tumor-host interaction involving the inflammatory compartment.

Banking as an emerging technology: Hoare's Bank, 1702-1742

London s financial market underwent dramatic change after 1700. More limitedthan Paris or Amsterdam in the seventeenth century, London became the leadingfinancial centre in Europe in the eighteenth century. There is an extensive andgrowing literature on the causes of this change, but comparatively little on thechange itself. This article provides detailed information on the operation of theLondon financial market around 1700 by describing the operations of a nascentLondon bank.

Private borrowing during the financial revolution: Hoare’s Bank and its customers, 1702-1724

The financial revolution improved the British government s ability to borrow, andthus its ability to wage war. North andWeingast argued that it also permitted privateparties to borrow more cheaply and widely.We test these inferences with evidencefrom a London bank.We confirm that private bank credit was cheap in the earlyeighteenth century, but we argue that it was not available widely. Importantly, thegovernment reduced the usury rate in 1714, sharply reducing the circle of privateclients that could be served profitably.

Post crisis challenges to bank regulation

The current crisis has swept aside not only the whole of the US investment banking industry butalso the consensual perception of banking risks, contagion and their implication for bankingregulation. As everyone agrees now, risks where mispriced, they accumulated in neuralgic pointsof the financial system, and where amplified by procyclical regulation as well as by the instabilityand fragility of financial institutions.The use of ratings as carved in stone and lack of adequate procedure to swiftly deal withsystemic institutions bankruptcy (whether too-big-to-fail, too complex to fail or too-many to fail).The current paper will not deal with the description and analysis of the crisis, already covered inother contributions to this issue will address the critical choice regulatory authorities will face. Inthe future regulation has to change, but it is not clear that it will change in the right direction. Thismay occur if regulatory authorities, possibly influenced by public opinion and political pressure,adopt an incorrect view of financial crisis prevention and management. Indeed, there are twoapproaches to post-crisis regulation. One is the rare event approach, whereby financial crises willoccur infrequently, but are inescapable.

Bank liquidity, interbank markets and monetary policy

A major lesson of the recent financial crisis is that the interbank lending marketis crucial for banks facing large uncertainty regarding their liquidity needs. Thispaper studies the efficiency of the interbank lending market in allocating funds. Weconsider two different types of liquidity shocks leading to different implications foroptimal policy by the central bank. We show that, when confronted with a distributional liquidity-shock crisis that causes a large disparity in the liquidity held amongbanks, the central bank should lower the interbank rate. This view implies that thetraditional tenet prescribing the separation between prudential regulation and monetary policy should be abandoned. In addition, we show that, during an aggregateliquidity crisis, central banks should manage the aggregate volume of liquidity. Twodifferent instruments, interest rates and liquidity injection, are therefore required tocope with the two different types of liquidity shocks. Finally, we show that failureto cut interest rates during a crisis erodes financial stability by increasing the riskof bank runs.

Is bank debt special for the transmission of monetary policy? Evidence from the stock market

We combine existing balance sheet and stock market data with two new datasets to studywhether, how much, and why bank lending to firms matters for the transmission of monetarypolicy. The first new dataset enables us to quantify the bank dependence of firms precisely,as the ratio of bank debt to total assets. We show that a two standard deviation increase inthe bank dependence of a firm makes its stock price about 25% more responsive to monetarypolicy shocks. We explore the channels through which this effect occurs, and find that thestock prices of bank-dependent firms that borrow from financially weaker banks display astronger sensitivity to monetary policy shocks. This finding is consistent with the banklending channel, a theory according to which the strength of bank balance sheets mattersfor monetary policy transmission. We construct a new database of hedging activities andshow that the stock prices of bank-dependent firms that hedge against interest rate riskdisplay a lower sensitivity to monetary policy shocks. This finding is consistent with aninterest rate pass-through channel that operates via the direct transmission of policy ratesto lending rates associated with the widespread use of floating-rates in bank loans and creditline agreements.